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Background: Acne vulgaris (AV) is the eighth most common nonfatal disease globally. Previous work identified an association between AV and increased filaggrin (FLG) protein expression in the follicular epidermis, but further work did not find a clear link between loss-of-function (LoF) FLG gene mutations and protection from AV., Objectives: To explore any association between AV and FLG LoF mutations in a cohort of genotyped patients of Bangladeshi ancestry with atopic eczema (AE) in East London., Methods: A retrospective notes review was performed on 245 patients who had been genotyped for FLG LoF mutations and undergone -clinical assessment. A χ2-test or Fisher's exact test was used to determine differences in AV history between FLG LoF genotype groups., Results: We found a significant reduction in history of AV in patients with AE with FLG LoF mutations (19 of 82) relative to those without FLG mutations (47 of 129) (23% vs. 36.4%; P = 0.02). We showed a nonsignificant reduction in AV diagnosis in patients with impaired barrier function (measured by transepidermal water loss) and palmar hyperlinearity. We found that patients with severe AE were less likely to have a history of AV only if they had an existing FLG LoF mutation (P = 0.02)., Conclusions: In the context of AE, our work suggests that FLG LoF mutations protect patients from developing AV., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Pachyonychia congenita (PC) is an autosomal dominant genodermatosis characterized by a triad of chronic severe plantar pain, focal palmoplantar keratoderma and hypertrophic nail dystrophy. Plantar pain can be debilitating and have a profound impact on quality of life. Current therapeutic options for pain in PC are limited to lifestyle adjustment and mechanical techniques, with a small subgroup of patients benefiting from oral retinoids. This review investigates the pathogenesis of pain in PC and provides a summary of the current and future therapeutic options., Competing Interests: Conflicts of interest E.O’T. has received funding from Palvella Therapeutics (consultancy, clinical trial), Timber Pharmaceuticals (consultancy), Unilever (research), the LEO Foundation (research) and Kamari Pharma (research grant, consultancy and clinical trial). All funding is to the university/hospital. M.D.B. held a position funded by the Chan Zuckerberg Initiative and is now a Medical Research Council clinical training fellow. R.L.M. held a position funded by Palvella Therapeutics to work on a pachyonychia congenita clinical trial. All funding goes to the university/hospital., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Atopic dermatitis (AD) is a chronic, inflammatory skin condition which affects over 200 million people worldwide, with patients commonly presenting with dry, itchy and sore skin. The challenge in finding optimal treatment for AD stems from the heterogenous nature of the disease and its multifaceted aetiology: skin barrier dysfunction, immune system dysregulation, genetic factors, environmental factors and alterations in skin microorganisms. Traditional treatments for AD such as corticosteroids, calcineurin inhibitors and immunosuppressants have several limitations such as reoccurrence of symptoms when discontinued, lack of targeted action and risk of adverse effects. The aim of this literature review was to explore and summarise the role of aryl hydrocarbon receptor (AHR) agonists (namely Tapinarof) as potential future therapy for AD. AHR agonists hope to overcome the limitations of traditional AD therapies and exert their therapeutic value by maintaining integrity of the skin barrier, defending against oxidative stress, modulating immune activity and inflammation and restoring a healthy skin microbiome. Tapinarof, a topical AHR agonist, is showing promising results and is currently in phase 3 trials (ADORING 3). For Tapinarof to be integrated into the AD treatment pathway, further research must be conducted on its efficacy, durability, potential remittive effect and safety across different AD subtypes in a large, diverse patient population. In addition, Tapinarof's cost-effectiveness compared to its topical counterparts needs to be considered and multidisciplinary collaboration is required between researchers, clinicians and policy makers., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Competing Interests: Conflicts of interest J.M. is Editor-in-Chief of the BJD; E.A.O’T. is on the BJD’s Editorial Advisory Board. The other authors declare no conflicts of interest.

Competing Interests: Conflicts of interest R.L.McC. has held a position funded by Palvella Therapeutics to work on a clinical trial (all unrelated to this work with all funding going to the university. D.G. has been a speaker for Lilly and La Roche-Posay (none applicable to this work). M.T. has been a speaker for AbbVie, Almirall, Eucerin, Janssen and Sanofi (none applicable to this work). E.O’T. has received research funding from Kamari Pharma and Unilever; consultancy fees from Azitra, Palvella Therapeutics and Kamari Pharma; and speaker’s fees from Almirall (all unrelated to this work with all funding going to the university). M.S. declares no conflicts of interest.

Background: Hyperlinear palms are described as a feature of loss-of-function (LoF) variants in filaggrin (FLG)., Objectives: To explore the phenotype of participants (age < 31 years) with atopic eczema of Bangladeshi ancestry from East London and investigate which factors best associate with LoF FLG variants., Methods: A cross-sectional study with participants recruited between May 2018 and December 2020. Patterns of palmar linearity were categorized and modelled with the Eczema Area and Severity Index (EASI), transepidermal water loss (TEWL), skin hydration (SH) and LoF FLG variants., Results: There were 506 complete cases available. Five palm patterns were noted. The 'prominent diamond' pattern associated best with EASI [marginal effects (ME) 2.53, 95% confidence interval (CI) 1.74-3.67], SH (ME 0.85, 95% CI 0.78-0.96) and TEWL (ME 1.32, 95% CI 1.11-1.62). Using five palm patterns had some ability to discriminate LoF FLG variants [area under the receiver operator characteristic (AUROC) 76.32%, 95% CI 71.91-80.73], improving to 77.99% (73.70-82.28) with the addition of SH. In subgroup analysis with only fine perpendicular/prominent diamond patterns the AUROC was 89.11% (95% CI 84.02-94.19)., Conclusions: This was a single-centre study design with humans classifying clinical patterns. The stability of temperature and humidity was not guaranteed across TEWL and SH measurements despite using a climate-controlled room. Palm patterns associate with EASI and TEWL. The fine perpendicular/prominent diamond patterns are markers to detect the absence/presence of LoF FLG variants, respectively., Competing Interests: Conflicts of interest E.A.O’T. has received research funding paid to the university from Kamari Pharma and Unilever, consulting fees paid to the university from Azitra Inc., Kamari Pharma, Palvella Therapeutics and Timber Pharma unrelated to this work. All other authors have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Atopic eczema (AE) is a chronic relapsing, pruritic disease that greatly affects the child and family's quality of life (QoL). It is usually common and severe among children of Bangladeshi ethnicity., Objectives: This is a cross-sectional quantitative study in patients with AE of Bangladeshi origin, which aims to analyse different components of the family, children and adult quality-of-life indices and their relationship to patient age, sex, eczema severity and distribution, other allergic associations, parental education and socioeconomic level., Methods: Children and young adults of Bangladeshi origin aged 0-30 years, clinically diagnosed with AE were recruited as part of the Tower Hamlets Eczema Assessment project, a clinical phenotyping study of AE in the Bangladeshi population living in East London. Questionnaires completed by children/parents included the Family Dermatology Life Quality Index (FDLQI), Infant's Dermatology Quality of Life (IDQOL) and the Children's Dermatology Life Quality Index (CDLQI). Young adults completed the Dermatology Life Quality Index (DLQI). The disease severity was assessed objectively using the Eczema Area Severity Index (EASI). Patients and parents who did not read or speak English were aided by Bengali/Sylheti-speaking research assistants., Results: Overall, 460 Bangladeshi children and 98 adults with AE were recruited. Burden of care, extra housework and emotional distress were the highest affected domains in parental QoL, while itching and sleep were the highest for children. Significant factors influencing FDLQI score were EASI [marginal effect (ME) 1.01, 95% confidence interval (CI) 1.00-1.03; P = 0.004], age (ME 0.98, 95% CI 0.97-0.99; P = 0.004), extensor eczema distribution (ME 1.25, 95% CI 1.03-1.52; P = 0.023), parental English fluency (ME 1.29, 95% CI 1.10-1.52; P = 0.002) and atopic comorbidities (ME 1.10, 95% CI 1.04-1.17; P = 0.001). Parental socioeconomic class was a nonsignificant factor. IDQOL/CDLQI was influenced significantly by the child's age (ME 0.99, 95% CI 0.97-1.00, P = 0.023), 'nonclear' eczema distribution clusters especially the 'severe extensive' cluster (ME 1.46, 95% CI 1.15-1.84; P = 0.002) and nonsignificantly by EASI and parental English literacy and socioeconomic levels. DLQI was affected significantly by nonclear eczema distribution groups especially 'severe extensive' (ME 2.49, 95% 1.76-3.53; P < 0.001) and nonsignificantly by patient age, and female sex., Conclusions: AE is a chronic disease where many external factors other than disease severity affect QoL of patients and their families, -especially in under-represented minority groups who face different linguistic and cultural barriers., Competing Interests: Conflicts of interest E.O.T. - research funding to university from Kamari Pharma and Unilever, consulting fees to university from Palvella Therapeutics, Azitra Inc, Timber Pharma and Kamari Pharma unrelated to this work. The other authors declare they have no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Competing Interests: Conflicts of interest: the authors declare they have no conflicts of interest.

We showed previously that primary keratinocytes selected for low desmoglein 3 (Dsg3) expression levels exhibited increased colony-forming efficiency and heightened proliferative potential relative to cells with higher Dsg3 expression levels, characteristics consistent with a more "stem/progenitor cell-like" phenotype. Here, we have confirmed that Dsg3(dim) cells derived from cultured primary human adult keratinocytes have comparability with alpha(6)(bri)/CD71(dim) stem cells in terms of colony-forming efficiency. Moreover, these Dsg3(dim) cells exhibit increased reconstituting ability in in vitro organotypic culture on de-epidermalized dermis (DED); they are small, actively cycling cells, and they express elevated levels of various p63 isoforms. In parallel, using the two immortalized keratinocyte cell lines HaCaT and NTERT, we obtained essentially similar though occasionally different findings. Thus, reduced colony-forming efficiency by Dsg3(bri) cells consistently was observed in both cell lines even though the cell cycle profile and levels of p63 isoforms in the bri and dim populations differed between these two cell lines. Dsg3(dim) cells from both immortalized lines produced thicker and better ordered hierarchical structural organization of reconstituted epidermis relative to Dsg3(bri) and sorted control cells. Dsg3(dim) HaCaT cells also show sebocyte-like differentiation in the basal compartment of skin reconstituted after a 4-week organotypic culture. No differences in percentages of side population cells (also a putative marker of stem cells) were detected between Dsg3(dim) and Dsg3(bri) populations. Taken together our data indicate that Dsg3(dim) populations from primary human adult keratinocytes and long-term established keratinocyte lines possess certain stem/progenitor cell-like properties, although the side population characteristic is not one of these features. Disclosure of potential conflicts of interest is found at the end of this article.