tbuckley/cabot-search huggingface dataset:
CPC11 A case of C3 bullous dermatosis
Authors: Bindi Gaglani, Paola De Mozzi, Sophia Watts
Journal: British Journal of Dermatology (2024)

Abstract A 44-year-old Asian man was seen as an urgent referral in dermatology for insidious-onset multiple pruritic tense serous-filled blisters. These were of varying sizes and occurred over acral sites and the body, sparing mucosal sites. He has a history of eczema as a child, which was in remission now, and no other medical problems and no regular medications. He denied any bowel problems. A punch biopsy showed subepidermal blistering with few eosinophils and a perivascular lymphocytic infiltrate. A perilesional indirect immunofluorescence was negative for IgG, IgM, IgA and C3 initially, and was repeated later to show granular C3 deposition at the basement membrane. Indirect immuno­fluorescence and enzyme-linked immunosorbent assay were negative, as was as an autoimmune screen including antinuclear antibodies, extractable nuclear antigen, dsDNA and coeliac screen. The condition was very sensitive to oral steroids, with relapse of the condition after slow wean of prednisolone. C3 bullous dermatosis is a rare form of bullous dermatosis first described by Hashimoto et al. in 2016 (Hashimoto T, Tsuruta D, Yasukochi A et al. Granular C3 dermatosis. Acta Derm Venereol 2016; 96: 748–53). Since its initial report, only 21 such patients have been reported in the literature in total. This condition appears to exhibit clinical characteristics resembling dermatitis herpetiformis in the absence of other diagnostic criteria for coeliac disease. It also presents histopathological features marked by subepidermal blister formation, oedema, and liquefaction degeneration accompanied by infiltrations of lymphocytes, eosinophils and neutrophils in varying combinations. Despite its benign disease progression, it demonstrates a positive response to oral dapsone and topical steroids. Additionally, granular deposition of C3 and C5–C9 is observed, while other complement components do not show significant deposition. Notably, there is a slight reduction in the expression of C3 in the epidermis.
PA12 Fats and figures: how abnormal lipids unravel the truth
Authors: Yee Ping Teoh, Adam Gold, Paul D Yesudian
Journal: British Journal of Dermatology (2024)

Abstract Oral isotretinoin is the most effective treatment for severe acne vulgaris. However, its use may be limited by adverse drug reactions, including hyperlipidaemia. A 22-year-old man with a 2-year history of severe nodulocystic acne involving the face, chest and back was commenced on low-dose prednisolone and isotretinoin. His acne did not respond as expected to the isotretinoin. Baseline screening of lipids, and liver function tests were unremarkable. Lipid monitoring during therapy revealed progressively worsening hyperlipidaemia with a peak low-density lipoprotein cholesterol (LDL-C) of 10.6 mmol L−1 (normal &amp;lt; 3.0 mmol L−1), triglycerides 4.1 mmol L−1 (normal &amp;lt; 2.0 mmol L−1) and reduced high-density lipoprotein cholesterol (HDL-C) of 0.2 mmol L−1 (normal &amp;gt; 1.0 mmol L−1). Biochemists intervened, suspecting possible familial hypercholesterolaemia. On further questioning, the patient admitted to self-administering multiple anabolic steroids and testosterone, as well as consuming high-protein supplements. Laboratory testing revealed markedly elevated testosterone levels, above the laboratory limit &amp;gt; 52 nmol L−1 (normal range 9.0–31.0 nmol L−1). The differential diagnoses for isolated high LDL include familial hypercholesterolaemia and hypothyroidism. However, the combination of very low HDL and high LDL cholesterol suggests secondary aetiologies such as exogenous testosterone or anabolic steroid use in young men. In older individuals, multiple myeloma or haematological cancers can similarly present, although LDL is often normal in cancer. The underlying aetiology of anabolic-steroid-induced lowering of HDL is thought to be mediated via an increase in activity of hepatic triglyceride lipase (HTGL), an enzyme that facilitates catabolism of HDL. HTGL stimulates breakdown of HDL particles, significantly decreasing HDL-C levels. However, the mechanism behind the adverse effect of anabolic steroids on increased LDL-C levels remains to be completely elucidated. Previous case reports reveal that there may be unintentional ingestion of anabolic steroids that have been added to consumer products like whey proteins. Conversely, patients may not disclose substance use without direct questioning. This case highlights important considerations for interpreting and managing abnormal lipid profiles in patients receiving isotretinoin treatment for acne. Unexplained markedly elevated LDL-C, especially accompanied by very low HDL-C, should prompt evaluation of testosterone levels, as it may indicate undisclosed exogenous testosterone or anabolic steroid use.
PA25 Sleep disruption in caregivers of infants with atopic dermatitis
Authors: Cathal O’Connor, Kate O’Halloran, Alan D Irvine, Deirdre Murray, Jonathan Hourihane, Michelle Murphy, Geraldine Boylan
Journal: British Journal of Dermatology (2024)

Abstract Atopic dermatitis (AD) commonly presents in infancy and is characterized by dermatitis, itch and sleep disturbance. The burdens of disease and treatment in AD are very high. Caregivers of infants with AD are loaded with provision of medical care, emotional distress and sleep disruption. The aim of this study was to assess the sleep of parents of infants with AD in the first year of life by comparing them with parents of healthy age-matched control infants, using both quantitative and qualitative measures. Parental sleep and infant sleep were quantitatively assessed using the Pittsburgh Sleep Quality Index and Brief Infant Sleep Questionnaire at 6, 9 and 12 months. Data on infant AD severity and infant itch were collected using the Eczema Area and Severity Index and a numerical rating scale. Detailed interviews were conducted at 12 months with 10 parents of infants with AD. There were 31 cases and 32 controls. Mothers of cases slept less than mothers of control infants at all timepoints: 6.3, 6.8 and 6.7 h at 6, 9 and 12 months (vs. 7.1, 7.3 and 7.5 h). Sleep onset latency was longer for mothers of infants with AD at 6 months (27.1 vs. 12.8 min, P &amp;lt; 0.05) and 12 months (20.8 vs. 12.6 min, P &amp;lt; 0.05). Sleep efficiency was worse for cases at all timepoints. Fathers had longer sleep onset latency and worse sleep efficiency than controls at 9 months. Themes regarding parental sleep disruption included the relationships between AD severity, itch and sleep disruption; bedtime routine; daytime loss of function; impact on parental relationship, infant bonding and family planning; sleep futility; and strategies to cope with sleep disruption. Mothers, but not fathers, of infants with AD experience significant sleep disruption in the first year of life. Factors that affect parental sleep include infant AD severity and itch.
PA26 Severe pyoderma gangrenosum in a child and the response to adalimumab
Authors: Ahmed Zwain, Alexander Crawford, Avinash Belgi, Caroline Morgan, Suzannah August
Journal: British Journal of Dermatology (2024)

Abstract Pyoderma gangrenosum (PG) is an uncommon ulcerating skin condition that can be associated with underlying problems such as inflammatory bowel disease, rheumatic or haematological diseases and malignancy. The peak incidence is between age 20 and 50 years, and it is rare in children (Graham JA, Hansen KK, Rabinowitz LG, Esterly NB. Pyoderma gangrenosum in infants and children. Pediatr Dermatol 1994; 11: 10–17). A 7-year-old boy presented with multiple erythematous and ulcerated plaques affecting the lower back and abdomen. He had recovered from chickenpox 3 weeks previously. He had been admitted under the paediatric team but had not responded to intravenous antibiotics. A skin biopsy was carried out under general anaesthesia, which showed dense dermal neutrophilic inflammation on histology. Investigations showed no evidence of inflammatory bowel disease, atypical viral infection, granulomatous disease, connective tissue disease or lymphoma. The ulcers became increasingly extensive and painful. A diagnosis of PG was made, and intravenous methylprednisolone was given followed by oral and topical cortico­steroids. There was an initial improvement, but the ulcers flared on reduction of the corticosteroid dose. Ciclosporin was therefore added but there was no improvement after 2 months of therapy, with the ulceration progressing to involve a large proportion of the abdominal skin. Adalimumab was then commenced and there was a marked improvement in the ulceration within 3–4 weeks of starting treatment. It has been shown that adalimumab is effective in children with PG (Kechichian E, Haber R, Mourad N et al. Pediatric pyoderma gangrenosum: a systematic review and update. Int J Dermatol 2017; 56: 486–95). Our patient showed a dramatic response to adalimumab with complete healing of large areas of ulceration after 2 months of therapy, enabling complete cessation of ciclosporin and oral corticosteroids. PG is a rare condition in childhood but can lead to devastating cutaneous ulceration. Adalimumab is a well-tolerated and effective treatment in this patient group.
PA16 Isotretinoin under the lens
Authors: Amy Long, Sean O’Malley, Claire Quigley, Sinead Collins
Journal: British Journal of Dermatology (2024)

Abstract Isotretinoin has been a widely prescribed medication in the field of dermatology for almost 50 years. It has been heavily scrutinized because of its teratogenicity, association with mood disturbance, and now its potential for sexual dysfunction. Ophthalmic adverse sequelae, although frequent, are the subject of less scrutiny. A 22-year-old woman was referred urgently to dermatology with a 6-month history of severe nodulocystic facial acne and extensive ice pick scarring. She had not responded to a combination retinoid and benzyl peroxide cream and an oral tetracycline antibiotic. She had an intrauterine device for contraception, and her medical history was otherwise unremarkable. Her most recent eye exam was 4 years previously for a mild convergent squint. Low-dose isotretinoin was commenced in conjunction with oral erythromycin. Her dose of isotretinoin was uptitrated until control of her acne was achieved. Six weeks into treatment, a routine ocular exam revealed bilateral early cataracts. Congenital cataracts could be excluded, and no other associated risk factors could be determined. In view of the temporal relationship a potential causal association with isotretinoin was postulated. She remained on isotretinoin after a discussion regarding the risk and benefit was had. She completed a further 4 months of therapy, averaging 0.25 mg kg−1 daily, with full clearance of her acne. She had no progression of the cataracts at a 6-month ophthalmological follow-up. Despite many ocular side-effects being generally reversible and mild, there is potential for significant harm and ocular morbidity to be caused by isotretinoin. Adverse events range from surface evaporative disease and blepharoconjunctivitis more commonly, to reports of rarer events such as cataracts. Data on cataracts in the context of isotretinoin are scant and largely historical. With the added pharmacovigilance accompanying the new UK Medicines and Healthcare products Regulatory Agency’s guidance on isotretinoin, there may be an opportunity to record the impact of the ocular and mucocutaneous adverse events that have been less well studied [Commission in Human Medicines. Report of the Commission on Human Medicines Isotretinoin Implementation Advisory Expert Working Group. Available at: https://www.gov.uk/government/publications/report-of-the-commission-on-human-medicines-isotretinoin-implementation-advisory-expert-working-group (last accessed 19 April 2024)]. Our case serves to remind prescribers of isotretinoin of potential serious ocular toxicity associated with this common drug, and to include ocular symptoms in our checklist of adverse events.
PA02 A case series of refractory, paediatric atopic dermatitis effectively treated with dupilumab in combination with abrocitinib
Authors: Wei Chern Gavin Fong, Kaung Htet Hla Win, Rhea Lopes, Alpa Kanji, Jane Ravenscroft, Ting Seng Tang, Carsten Flohr
Journal: British Journal of Dermatology (2024)

Abstract A range of systemic treatment options are available for children with atopic dermatitis (AD) who do not respond to standard topical therapy. However, real-world data have revealed a subset of patients who remain significantly affected despite treatment with all of the available topical and systemic therapies, including novel therapeutic agents such as dupilumab and Janus kinase (JAK) inhibitors. To achieve disease control, these individuals may require novel approaches such as utilizing systemic treatments in combination. However, there is insufficient published evidence about the efficacy and safety of this approach. We present three paediatric cases with severe refractory AD who required combined systemic therapy with dupilumab and abrocitinib to achieve adequate disease control and improvement in quality of life. The third patient had coexistent extensive alopecia areata, which also responded well to treatment. These individuals had exhausted all conventional systemic therapies, and had undergone treatment with both dupilumab and abrocitinib individually and in various combinations with methotrexate. However, despite this, they continued to experience inadequate disease control and significant adverse effects. It was only when the combination of dupilumab and abrocitinib was introduced that they finally achieved noticeable and sustained improvements in AD control. The heightened observed efficacy of dupilumab and abrocitinib in combination may be attributed to the inhibition of interleukin-4 and interleukin-13 at two separate stages, at the receptor (dupilumab) and intracellularly (abrocitinib). Furthermore, an additional advantage of this combined regimen is that JAK inhibitors, with their broader mechanism of action, may attenuate cytokines implicated in comorbid diseases such as dupilumab-related eye disease, seen in our first two cases, and alopecia areata in our third case. In conclusion, the concurrent use of dupilumab with abrocitinib represents a potentially effective and tolerated therapeutic approach for children with severe, refractory AD who exhibit inadequate control with other treatments. Larger studies are warranted to ascertain the long-term efficacy and safety of this treatment strategy.
Poster presentationsPA10 Hidradenitis suppurativa and trisomy 21: a case series
Authors: Lisa Murphy, Anne-Marie Tobin
Journal: British Journal of Dermatology (2024)

Abstract It has long been postulated that there is a link between hidradenitis suppurativa (HS) and Down syndrome (DS); however, there are limited data in the literature examining the disease trajectory for these patients and the underlying mechanism. We performed a multicentre retrospective chart review to assess whether there is a particular phenotype of HS associated with patients with DS. Nine patients were included in total. The average age of presentation among our cohort was 17.4 years. Overall, 44% of patients had a raised body mass index, 22% had a positive family history for HS and none of the patients currently smoked. Most patients (89%) had trialled at least one oral antibiotic for their HS. The results of our review suggest that DS would appear to be an independent risk factor for developing HS. It would also appear to have an earlier age of presentation and to occur independently of the traditional risk factors for developing HS. It is hypothesized that trisomy 21 contributes to a genetic dysregulation that predisposes patients to this condition. This supports the findings suggested by similar studies.
Revised criteria for the diagnosis and staging of Alzheimer’s disease
Authors: Clifford R. Jack, Scott J. Andrews, Thomas G. Beach, Teresa Buracchio, Billy Dunn, Ana Graf, Oskar Hansson, Carole Ho, William Jagust, Eric McDade, Jose Luis Molinuevo, Ozioma C. Okonkwo, Luca Pani, Michael S. Rafii, Philip Scheltens, Eric Siemers, Heather M. Snyder, Reisa Sperling, Charlotte E. Teunissen, Maria C. Carrillo
Journal: Nature Medicine (2024)
PA21 A child with longitudinal melanonychia secondary to subungual naevus showing regression during treatment with a single-agent MEK inhibitor (trametinib)
Authors: Jonathan Guckian, Susan Picton, Andrew Muinonen-Martin, Angana Mitra, Sangeetha Shanmugam
Journal: British Journal of Dermatology (2024)

Abstract A 3-year-old boy with type IV skin presented in May 2021 with a 5-month history of a pigmented line in his right fourth fingernail. Examination revealed a 1-mm uniform darkly pigmented band (1.2 mm at proximal aspect) of triangular longitudinal melanonychia with positive pseudo-Hutchinson and negative Hutchinson sign. A clinical diagnosis of benign subungual naevus was made. The patient had a background of neurofibromatosis type 1 and ganglioglioma of the brainstem and right cerebellar peduncle treated with chemotherapy. First- and second-line regimens – vincristine plus carboplatin in 2019–2020, and TPCV (thioguanine, procarbazine, lomustine and vincristine) in 2020 to April 2021 – had been trialled unsuccessfully before dermatology review. In October 2021, the patient commenced trametinib 0.5 mg once daily for his progressive ganglioglioma. Within 4 months, the longitudinal melanonychia had involuted significantly. Dermoscopy demonstrated faded melanonychia with a small residual blueish linear pigmentation remaining proximally (reduced to 0.8 mm). Pseudo-Hutchinson sign was now negative. The patient’s trametinib was discontinued for around 10 days in July 2022 due to mucositis and sepsis and his melanonychia subsequently darkened and extended further distally over the following 3 months. In November 2022 his trametinib dose was decreased to 0.37 mg due to ongoing mucositis and infection. However, the dark band was not as pronounced as at the initial presentation. He remained on the reduced trametinib dose, and by January 2024 the melanonychia had faded and appeared as a 1-mm uniform pale-brown longitudinal streak. He also developed multiple new naevi on his face, trunk, buttocks and genital area during this period. Trametinib, a mitogen-activated protein kinase kinase (MEK) inhibitor, has been used in targeted therapies against various malignancies, including in combination with BRAF inhibitors against metastatic melanoma. A lesser-reported complication of targeted therapies includes ‘lightening’ of pigmented naevi. Hypopigmentation, or involution or regression has been reported in patients receiving single-agent BRAF inhibitor or combined BRAF–MEK therapy. However, ours is the first reported case of a single-agent MEK inhibitor causing regression of a subungual naevus as a side-effect. The mechanism behind naevus involution in patients receiving targeted therapy is unclear, with proposed models focusing on the impact of BRAF rather than MEK inhibition. This case highlights a stark temporal relationship between trametinib therapy and the involution and subsequent redevelopment of a benign longitudinal melanonychia. This adds to our growing understanding of the impact of targeted therapies on melanocytic naevi, which patients and doctors should be aware of.
PA18 Audit of direct booking of urgent dermatology slots by the emergency department
Authors: Jonathan Carter-Hurst, Muna Nadeem, Helen Goodyear
Journal: British Journal of Dermatology (2024)

Abstract Children with skin disorders frequently present to emergency departments (EDs) with onward referral to dermatology. Recognizing the urgency of some presentations, and to minimize requests from ED for an immediate dermatology opinion, we created one dedicated ED slot on all consultant dermatology clinics, which was directly bookable by the ED. If the slot was unfilled it could be used for other urgent referrals. This system worked well over many years, but recently clinicians have noted long waits by ED patients. To analyse slot use, we undertook a retrospective audit from 1 April 2022 to 31 March 2023. We identified 219 appointments for 210 individuals. Twelve episodes, none of which were ED referrals, were excluded from analysis due to inadequate or erroneous data. The remaining 207 referrals were from ED (85, 41.1%), general practitioners (92, 44.4%), internal specialties (15, 7.2%), external hospitals (9, 4.3%) or our own department (6, 2.9%). The commonest non-ED referrals were melanocytic naevi (34, 27.9%), infantile haemangiomas (21, 17.2%) and eczema (18, 14.8%). The most frequent ED referrals were eczema flares (29%), infected eczema (15%) and ‘nonspecific rashes’ (12%). The median symptom duration was 4 weeks (range 1 day to several years). Treatment given in ED was considered appropriate in most cases (56%) but could not be assessed in 28% because of ED clinician diagnostic uncertainty. In 11% of cases, ED sought on-call dermatology advice before booking appointments. The median wait from referral to appointment was 2 weeks (range 0–7), with an attendance rate of 84.7%. In 20% of attendances, the problem had already resolved. The audit team’s assessment of referrals was that most were warranted, with further treatment commenced in 74.1% and ongoing clinic follow-up in nearly 75%. In conclusion, our work highlights that these outpatient slots designed for ED use were being utilized for other referrals, resulting in excessive waits by ED patients with urgent needs. This reflects outpatient waiting list pressures including 2-week-wait referrals. We propose to reinforce booking rules to the call centre and to reinstate regular dermatology teaching in ED to optimize urgent first-line management.