bluuebunny/crossref_metadata_2025 huggingface dataset:
P93 Dupilumab treatment in children with moderate-to-severe atopic dermatitis increases levels of bone mineralization biomarkers
Authors: Irvine Alan D , Paller Amy S , Horowitz Julie E , Farrell Annamaria , Hatsell Sarah , Ehmann Peter , McDonald Robert , Marco Ainara Rodriguez , Tian Tingting , Cyr Sonya L
Published: June 2023

Children with atopic dermatitis (AD) are at risk for lower bone mineral density (BMD) and lower alkaline phosphatase (ALP) levels than healthy children. Low BMD and ALP in children could contribute to a higher lifetime prevalence of fractures, osteopenia and osteoporosis. Dupilumab is a fully humanized monoclonal anti-interleukin (IL)-4R antibody approved for the treatment of AD in children. The objective of this analysis is to report the impact of dupilumab treatment on markers of bone mineralization in children aged 6–12 years with moderate-to-severe AD vs. reference intervals (RIs). Analysis was performed retrospectively on sera from participants in LIBERTY AD PEDS, a phase III placebo-controlled trial of 16 weeks (NCT03345914) and LIBERTY AD PED-OLE (NCT02612454), an open-label extension trial in which eligible patients received dupilumab until week 52. Biomarkers, including bone ALP (BALP), procollagen type 1 N-terminal propeptide (P1NP), C-terminal crosslinking telopeptide of β-1 collagen (β-CTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1), were analysed at baseline, 8, 12 and 16 weeks; only BALP was measured at 52 weeks. Both dupilumab dosing regimens led to significant increases in geometric mean (SE) levels of BALP at 8, 12 and 16 weeks compared with placebo. For the 100/200-mg Q2W group, at week 8 the BALP level was 72.7 (1.03) μg L−1 vs. 62.0 (1.05) μg L−1 (P < 0.0001), at week 12 it was 74.7 (1.03) μg L−1 vs. 64.3 (1.05) μg L−1 (P < 0.001) and at week 16 it was 78.0 (1.03) μg L−1 vs. 65.0 (1.04) μg L−1 (P < 0.001). For the 300-mg Q4W group, at week 8 the BALP level was 76.7 (1.03) μg L−1 vs. 62.0 (1.05) μg L−1 (P < 0.001), at week 12 it was 73.3 (1.04) μg L−1 vs. 64.3 (1.05) μg L−1 (P = 0.002) and at week 16 it was 77.3 (1.03) μg L−1 vs. 65.0 (1.04) μg L−1 (P < 0.001). At 52 weeks, BALP levels were statistically significantly increased compared with baseline [placebo vs. placebo transitioned to dupilumab: 64.2 (1.04) μg L−1 vs. 82.9 (1.04) μg L−1 (P < 0.001); 100/200 mg Q2W: 62.0 (1.05) μg L−1 vs. 83.8 (1.03) μg L−1 (P < 0.001); 300 mg Q4W: 64.1 (1.04) μg L−1 vs. 78.7 (1.04) μg L−1 (P < 0.001)] and also increased within RIs. From baseline to week 16, OC, P1NP and β-CTX levels improved from below to within the RIs, and levels of IGF-1 increased from the lower limit of the RI. However, data points were limited due to insufficient sera volumes, preventing statistical analyses for these biomarkers. The overall results suggest an increase in bone mineralization biomarkers in paediatric patients with moderate-to-severe AD following dupilumab treatment.

Funding sources:research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.
P94 Bimekizumab early treatment response translated into cumulative benefits in health-related quality of life in patients with moderate-to-severe plaque psoriasis: results from 2 years of the BE RADIANT phase IIIb trial
Authors: Hampton Philip , Brunner Patrick , Ghoreschi Kamran , Boehncke Wolf-Henning , Warham Rhys , Ciaravino Valerie , Szilagyi Balint , Staelens Fabienne , Foulkes Amy
Published: June 2023

Speed of response is a key treatment goal for patients with psoriasis. This analysis aimed to assess how early clinical response translated into cumulative health-related quality of life (HRQoL) benefit in patients with moderate-to-severe plaque psoriasis over 2 years of bimekizumab (BKZ) treatment. Included patients from BE RADIANT were randomized to BKZ 320 mg every 4 weeks (Q4W), continued to receive Q4W dosing or switched to Q8W at week 16 and entered the open-label extension (OLE) at week 48 (receiving BKZ Q4W or Q8W; NCT03536884). The proportions of patients achieving Psoriasis Symptoms and Impacts Measure (P-SIM) 0 in itching, skin pain and scaling, and Dermatology Life Quality Index 0 or 1 (DLQI 0/1), were estimated using modified nonresponder imputation (mNRI); missing data were imputed via NRI for patients discontinuing due to the lack of efficacy or treatment-related adverse events and multiple imputation otherwise. Cumulative HRQoL and symptom benefit through to week 96 was estimated using the area under the curve (AUC0–96) by week 16 Psoriasis Area and Severity Index (PASI)-100 status (NRI), with week 16 and week 96 responses also reported. AUC0–96 was used to calculate the estimated number of days that each response was achieved. Of the 336 patients randomized to BKZ who entered the OLE, 216 achieved PASI 100 at week 16. Of these, 187/216 patients had already achieved PASI 100 at one or more visit(s) before week 16. Of the PASI-100 responders at week 16, 71.8%, 92.1%, 89.4% and 88.0% also achieved P-SIM 0 for itching, skin pain and scaling and DLQI 0/1, respectively, vs. 39.1%, 77.7%, 56.6% and 74.6% of nonresponders. Of the week 16 PASI-100 responders at week 96, 67.1%, 85.4%, 80.6% and 89.3% achieved P-SIM 0 for itching, skin pain and scaling and DLQI 0/1, respectively, vs. 55.6%, 77.7%, 63.7% and 80.8% of nonresponders. The total AUC0–96 for achievement of P-SIM 0 in itching, skin pain and scaling and DLQI 0/1 was greater for week 16 PASI-100 responders through 2 years, corresponding to a greater number of days achieving these outcomes vs. nonresponders (Table 1). A high proportion of patients achieved complete skin clearance at week 16, translating to a greater number of days achieving P-SIM 0 in itching, skin pain and scaling and DLQI 0/1 vs. week 16 PASI-100 nonresponders through 2 years of BKZ treatment.Table 1AUC0-96 by week 16 PASI-100 response over 2 years (mNRI)Week 16 PASI-100 responders (n = 216)Week 16 PASI-100 nonresponders (n = 120)P-SIM 0P-SIM 0ItchingSkin painScalingDLQI 0/1ItchingSkin painScalingDLQI 0/1AUC0–9666398504784982674918753957837584Days465595549579344528405531

Acknowledgment: Medical writing: Costello Medical.

Funding sources: UCB Pharma.
P98 Real-world effectiveness of guselkumab in absolute Psoriasis Area and Severity Index-stratified patients with psoriasis: data from the British Association of Dermatologists Biologics and Immunomodulators Register
Authors: Ali Faraz , Wang Xiayi , Gillespie Justin , Topping Louise M
Published: June 2023

Guselkumab is a fully human monoclonal antibody that inhibits interleukin-23 by selectively targeting the p19 subunit. Long-term evaluations have demonstrated high levels of clinical response and improvement in patient-reported outcomes over 5 years of guselkumab treatment in patients with psoriasis. Psoriasis has a significant and negative impact on a patient’s quality of life, even among patients with a Psoriasis Area and Severity Index (PASI) score < 10. Both absolute PASI (aPASI) and the Dermatology Life Quality Index (DLQI) are widely used tools to assess disease impact, as well as treatment eligibility and response. This retrospective analysis evaluated the impact of guselkumab treatment over 1 year across aPASI-stratified patients with psoriasis in BADBIR, a national pharmacovigilance registry documenting longitudinal clinical data for individuals with psoriasis initiating systemic therapies. Retrospective analyses of the guselkumab cohort were carried out using BADBIR data collected up to September 2021. Data were analysed for patients who had initiated guselkumab treatment and had recorded aPASI and DLQI assessments at both baseline and the 12-month follow-up. Patients were stratified according to psoriasis severity at baseline: aPASI < 5, aPASI ≥ 5 to ≤ 10 and aPASI > 10 disease. Treatment effect was defined as the mean improvement in DLQI and aPASI scores for the overall group of guselkumab-treated patients and for subsets of patients with aPASI < 5, aPASI ≥ 5 to ≤ 10 and aPASI > 10 at baseline. Five patients were excluded owing to treatment cessation prior to the 12-month cutoff. Following 12 months of guselkumab treatment, patients with aPASI < 5, aPASI ≥ 5 to ≤ 10 and aPASI > 10 at baseline achieved a mean (SD) DLQI score of 2.18 (5.64), 2.79 (5.15) and 1.80 (3.56), representing a decrease of 62.0%, 74.8% and 89.1% from baseline, respectively. Additionally, patients with aPASI < 5, aPASI ≥ 5 to ≤ 10 and aPASI > 10 at baseline achieved a mean (SD) aPASI score of 0.96 (1.84), 3.16 (3.90) and 2.78 (4.93), representing a decrease of 40%, 58.6% and 84.5% from baseline, respectively. Among patients with an aPASI score < 10 at baseline (n = 53), 83.0% (n = 44) achieved aPASI score ≤ 3; of these, 67.9% (n = 36) achieved an aPASI score ≤ 2 and 54.7% (n = 29) achieved an aPASI score ≤ 1. These data demonstrate that guselkumab produces an effective and consistent response in patients with a broad range of disease severity at baseline, as reflected by mean improvements in aPASI and DLQI. Greater reductions in DLQI and aPASI scores were observed after 12 months of guselkumab treatment in patients with more severe psoriasis at baseline.
P100 Dermoscopy and clinicohistopathological profile of lichen planopilaris restricted to the face: a case series of six unusual cases
Authors: Kothari Rohit , Sandhu Sunmeet
Published: June 2023

Lichen planopilaris (LPP) is an autoimmune cicatricial alopecia that usually affects the scalp. LPP confined to the face is rare and the information on its dermoscopy is limited. We present the dermoscopy and clinicohistopathological profile of six patients, all but one of whom were men aged 32–60 years. A 12-year-old girl was the youngest patient in our series, as well as in the literature to the best of our knowledge. All patients presented with varying degrees of hyperpigmented atrophic patches and scarring alopecia restricted to the face. Two had a linear morphology, which is usually the most common presentation of facial LPP. In our series, the chin was the most frequently affected site, followed by the cheek and upper lips; the forehead was the least frequently involved. None of the patients had lesions elsewhere on the body, including the scalp. The duration of the lesions ranged from 1 to 6 months. All cases showed a brown-to-violaceous background and/or mild blotchy erythema, significantly reduced hair follicles, cicatricial alopecia and variable scaling and/or peripilar cast, brown dots, pigment pseudonetwork, pigment clumps and whitish scar-like areas on dermoscopy. Histopathology predominantly showed perifollicular inflammatory infiltrate, basal layer vacuolar degeneration and pigment incontinence, focal areas of perifollicular fibrosis corresponding to the erythema and peripilar cast, brown dots and pigment clumps, and scar-like areas. The men all described regular shaving, almost daily. The girl and two men described having a regular mustard oil massage over the face, which might have irritated and damaged the facial skin. The possibility of continuous microtrauma due to shaving and mustard oil application acting as a trigger leading to development of facial LPP cannot be ruled out. All patients received hydroxychloroquine, potent topical corticosteroids, intralesional steroids and/or oral steroids. Patient 3 was lost to follow-up; the rest are under regular follow-up with a favourable—albeit suboptimal—response. This case series highlights a rare presentation of LPP restricted to the face, with only a few similar cases with dermoscopy reported in the literature. Its diagnosis requires a high degree of suspicion in any case presenting with scarring alopecia and atrophic patches over the face. The treatment is difficult and aims to halt disease progression and/or hair regrowth if detected and treated early, preventing significant morbidity and anxiety in the patient.
P102 Severe atopic eczema is associated with reduced acne vulgaris in Bangladeshi children and young adults: a retrospective analysis from a cross-sectional study
Authors: Hughes Aaron , Barbosa Elsa , Cernova Jeva , Thomas Bjorn , O’Toole, Edel , O'Shaughnessy Ryan
Published: June 2023

Atopic eczema (AE) is the most common inflammatory dermatosis, affecting up to 20% of children. Loss of function (LoF) mutations in FLG are the most strongly implicated genetic risk factor for eczema. To understand the effect of FLG on the pathobiology of AE, we knocked down FLG in primary keratinocytes using short hairpin RNA and performed phosphoproteomic analysis, which showed downregulation of the AKT signalling pathway, confirmed using Western blotting to phospho-AKT and immunostaining of biopsies from patients with AE. Given that AKT signalling is increased in acne vulgaris, we hypothesized that loss of FLG may protect patients with AE from acne. The Tower Hamlets Eczema Assessment (THEA) study is a cross-sectional study that aims to phenotype and genotype 1000 Bangladeshi children and young adults with AE. So far, 620 participants have undergone genotyping, 37% of whom have LoF mutations in FLG. We selected patients from this cohort who were older than 12 years of age. In total, 204 patients (99 FLG wild type, 86 heterozygotes, 19 compound heterozygotes) were included. We identified a diagnosis of acne or previous prescription of topical acne therapies or tetracycline antibiotics from the patients’ general practice e-health records. We stratified the patients by genotype, Eczema Area and Severity Index (EASI) score, Patient Oriented Eczema Measure (POEM) score, transepidermal water loss (TEWL) and palmar hyperlinearity groups. The χ2-test was used to determine differences between groups. A lower proportion of patients with AE with FLG mutations had acne (27% wild type vs. 19% FLG mutations), which was more pronounced, but not statistically significant, in the compound heterozygote group (16%). We saw a nonsignificant reduction in acne in patients who had the top 25% of TEWL measurements, those with the most severe form of hyperlinearity and those with higher POEM scores. Patients with severe AE, measured as an EASI score > 21, had a more reduced incidence of acne than those with lower EASI scores (9% vs. 26%; P = 0.04). Overall, this suggests that patients with more severe AE are protected from developing acne. There was insufficient evidence to establish if this was mediated by a reduction in filaggrin (FLG) and AKT signalling. This may be because the groups were too small to determine this. Given that all patients with severe AE have reduced FLG expression regardless of genotype, it is possible that this is mediated through FLG–AKT signalling.
P105 Adult-onset mastocytosis: a retrospective review
Authors: Hiranput Siwaporn , Nallathamby Kasthuri , Malik Bilal Haider , Smith Lucy , Williams Abigail J , Ayub Habibah , Yesudian Paul Devakar
Published: June 2023

Mastocytosis is characterized by an abnormal proliferation of mast cells in different organs, with the skin being the most frequently affected site. Adult-onset mastocytosis often follows a chronic course and is more likely to have extracutaneous involvement. We undertook a retrospective case note review of adult patients with a diagnosis of mastocytosis in our dermatology department between 2021 and 2022. Fourteen patients were identified with a female-to-male ratio of 1.8 : 1. Median age at disease onset was 46 years (range 25–75). Lesions were described as maculopapular (n = 8), macular (n = 3), telangiectatic (n = 2) and urticated (n = 1). The torso was affected in 12 patients (86%). The most commonly reported symptom was pruritus (n = 9). Other complaints included flushing (n = 3), abdominal pain (n = 2), dizziness (n = 2), weight loss (n = 2), night sweats (n = 2), syncope (n = 1), musculoskeletal pain (n = 1) and symptoms of recurrent anaphylaxis (n = 1). Two patients were asymptomatic. Darier sign was elicited in five patients and negative in two (not documented in seven). Eight patients were assessed for lymphadenopathy and organomegaly, with no detected abnormality. Eleven patients had skin biopsies; 10 (91%) had mastocytosis in the skin confirmed on histology; one patient had a nondiagnostic histological finding, but mastocytosis was diagnosed on the basis of clinical presentation. Seven patients had elevated serum tryptase levels (> 20 ng mL−1) on at least one occasion. Bone densitometry was done in five patients with elevated serum tryptase: two had osteopenia and one had osteoporosis. Eleven patients underwent bone marrow examination. Mast cell infiltration of the bone marrow was detected in four patients; KIT mutations in bone marrow were subsequently identified in three patients. Twelve patients remain under long-term follow-up. Treatments prescribed included antihistamine (n = 10), epinephrine autoinjector (n = 6), topical steroids (n = 5), vitamin D (n = 5), calcium (n = 4), H2 blocker (n = 2), bisphosphonates (n = 2), phototherapy (n = 2), leukotriene antagonists (n = 2), cosmetic camouflage (n = 1), oral sodium cromoglicate (n = 1) and KIT–tyrosine kinase inhibitor (n = 1). Despite treatments, none of the patients had regression (partial or complete) of cutaneous disease, although no fatal outcome was observed. Four (29%) cases had a final diagnosis of indolent systemic mastocytosis (all had elevated serum tryptase levels, two had anaemia). Our findings were consistent with the literature, where serum tryptase levels rather than systemic symptoms were a reliable predictor of systemic mastocytosis. Interestingly, 10 (71%) patients had mastocytosis limited to the skin, which is in contrast to the published literature, where the majority of people with adult-onset mastocytosis have systemic forms of the disease.
P106 Hidradenitis suppurativa is associated with lower socioeconomic status using the MacArthur scale of subjective social status
Authors: Kearney Niamh , McGrath Barry , McCourt Collette , Hughes Rosalind , O’Kane Donal , Kirby Brian
Published: June 2023

Hidradenitis suppurativa (HS) is associated with lower socioeconomic status (SES). Previous studies in Europe, Australia and the USA identified that patients with HS are more likely to be unemployed and have lower mean incomes than the background population. Low SES is inextricably linked with poor health outcomes. The MacArthur scale of subjective social status is a simple ladder from 1 to 10 that describes perceived SES and is an even better predictor of health outcomes than objective measures of SES. Our aim was to evaluate SES in HS using the MacArthur scale and compare it with healthy controls. Patient recruitment took place in two dermatology clinics where all patients with HS were invited to participate in addition to an anonymous online survey distributed by HS patient-led organizations. Healthy control patients were recruited from a rapid-access lesion clinic. Statistical analysis was completed using Jamovi (version 2.0). Student’s t-test was used to compare means and Spearman’s test for correlation. We recruited 131 patients with HS with a mean age of 37.6 years and 82 healthy controls with a mean age of 48.7 years. Patients with HS were predominantly female (89.3%) as were healthy controls (62.2%). The mean (SD) MacArthur scale in the HS group was 4.85 (2.19) (range 1–10). It was higher in healthy control patients at 6.44 (1.36) (range 3–10; P < 0.001). In the HS cohort, the mean MacArthur scale was higher in employed patients (5.49 vs. 3.59; P < 0.001) and in patients who completed any education following school (5.19 vs. 4.12; P = 0.009). The MacArthur scale weakly but statistically significantly correlated with age (r = 0.158, P = 0.022) and was higher in male patients (6.14 vs. 5.27; P = 0.013). Owing to the influence of age and sex on the MacArthur scale, a group of 37 patients with HS with age- and sex-matched healthy controls was analysed. In this matched group, the mean MacArthur scale was lower in patients with HS (5.22 vs. 6.36; P = 0.018). This is the first study to assess SES in HS using the MacArthur scale of the subjective social status. Patients with HS had a significantly lower SES than healthy controls. The MacArthur scale accounted for both employment and education in the HS cohort. The ladder is easy to use and provides more information with regard to health outcomes than objective SES alone. Its use should be considered in HS research, particularly studies evaluating treatment response, disease and comorbidity outcomes.
BC03 Skincare in acne: are we letting our patients down?
Authors: Salih Hamisha , Moradi Saeeda , Gupta Pallavi
Published: June 2023

Acne vulgaris is a chronic and recurrent inflammatory condition of the pilosebaceous unit. A combination of topical and systemic agents is often required to achieve symptom control, improve quality of life and reduce the risk of scarring. The role of skincare products in the management of acne has been well defined in the literature as a key adjunct to other therapies. We conducted an observational retrospective study to explore the patient experience of acne skincare advice provided by their dermatologist. Patients in the acne clinic, to which they would be referred for treatment with oral isotretinoin, were invited to participate. A survey incorporating multiple choice questions and an open comment box was distributed electronically. Twenty-nine per cent of patients acknowledged the importance of skincare products in managing their acne. Only 39% of respondents felt they had the opportunity to discuss skincare during their consultation. Over 86% of patients had been prescribed oral isotretinoin at least once; however, 60% had not received any skincare advice from their dermatologist. Only 31% of patients felt more confident with their skincare routine after their dermatology consultation than they did before. The internet and social media were the most popular sources of information for accessing skincare advice, with over 77% of patients identifying it as their main informant. Yet the majority of patients (88%) were likely to adhere to skincare advice if instructed by their dermatologist, clearly preferring this to social media. The most recurring theme from open comments was the desire to discuss skincare with their dermatologist and get signposted to a more reliable source of information for skincare. The data suggest that clinicians are failing to address or discuss skincare with patients, leaving them at the mercy of social media and at risk of exposure to scientifically unproven or incorrect advice. Integrating such advice when reviewing patients with acne would not only help with the management of their condition post-treatment with oral isotretinoin but also improve patient satisfaction and avoid misinformation. As a single-centre study, our results may not be representative of all patients, and the data collected were dependent on patient recall. Our results highlight the need for dermatologists to disseminate evidence-based skincare advice specific to acne-prone skin to their patients. Going forward, we aim to provide all our patients with acne with an information leaflet on skincare to complement their medical treatment.
BC05 Technological and clinical demonstration of a skin ageing analysis prototype
Authors: Pradeep Pratyush , Birch-Machin Mark , Anderson Kirstie , Moor Jessica
Published: June 2023

The skin undergoes intrinsic and extrinsic ageing, with extrinsic ageing caused by environmental factors including inadequate sleep. Preliminary studies have suggested a link between sleep quality and skin ageing. Noninvasive devices have been developed that are able to measure and quantify markers of skin ageing, such as collagen levels and wrinkle formation. A handheld optical coherence tomography (OCT) test, sourced from Industrial Technology Research Institute, is one such device that allows for the measurement of dermal collagen levels. We describe a pilot study to assess the feasibility of combining several methods to quantify skin ageing in those with and without sleep disturbance, to understand which specific markers of skin ageing are affected by poor sleep. Questionnaires were distributed to 10 female workers and completed by each participant to understand their sleep and sun protection habits. There were two groups: women working fixed day shifts (aged 41–53 years) or fixed night shifts (aged 22–63 years). Skin swabs, VISIA® and OCT were used to measure markers of skin ageing of both cheeks: DNA amplification, wrinkles (percentile) and collagen (percentage), respectively. The entire testing could be completed by each participant within 15 minutes. The results were then compared between the different groups. The testing was well tolerated in this small sample. There was a statistically significant difference between day and night workers in their percentile of wrinkles using the VISIA (left cheek: P = 0.039; right cheek: P = 0.015), with night workers showing fewer signs of wrinkle formation. No statistically significant difference in DNA amplification was observed between day and night workers using skin swabs (left cheek: P = 0.27; right cheek: P = 0.32). Using OCT, no statistically significant difference was observed in collagen percentage between day and night workers (left cheek: P = 0.73; right cheek: P = 0.98). Skin swabs, OCT and VISIA were well tolerated, with no adverse events seen. The VISIA showed a significant difference in markers of skin ageing between day and night workers. Night shift workers may have shown fewer signs of wrinkle formation due to confounding factors such as age and smoking. No significant difference was observed with skin swabs and OCT, which may be related to the small sample size. The skin swabs, VISIA and OCT together can be quickly used to test the impact of sleep or any other extrinsic factor on skin ageing. This study has provided useful pilot data that can be scaled for future, larger studies.
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

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>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

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>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>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

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>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

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

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

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 > 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

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 > 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

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.