The 50 most-cited articles in British Journal of Dermatology, 2024

The field of dermatology is experiencing the rapid deployment of artificial intelligence (AI), from mobile applications (apps) for skin cancer detection to large language models like ChatGPT that can answer generalist or specialist questions about skin diagnoses. With these new applications, ethical concerns have emerged. In this scoping review, we aimed to identify the applications of AI to the field of dermatology and to understand their ethical implications. We used a multifaceted search approach, searching PubMed, MEDLINE, Cochrane Library and Google Scholar for primary literature, following the PRISMA Extension for Scoping Reviews guidance. Our advanced query included terms related to dermatology, AI and ethical considerations. Our search yielded 202 papers. After initial screening, 68 studies were included. Thirty-two were related to clinical image analysis and raised ethical concerns for misdiagnosis, data security, privacy violations and replacement of dermatologist jobs. Seventeen discussed limited skin of colour representation in datasets leading to potential misdiagnosis…

Prurigo nodularis (PN) is an inflammatory skin condition characterized by intensely pruritic nodules on the skin. Patients with PN suffer from an intractable itch-scratch cycle leading to impaired sleep, psychosocial distress and a significant disruption in quality of life. The pathogenesis of PN is associated with immune and neural dysregulation, mediated by inflammatory cytokines [such as interleukin (IL)-4, -13, -17, -22 and -31] and neuropeptides (such as substance P and calcitonin gene-related peptide). There is a role for type 2 inflammation in PN in addition to T-helper (Th)17 and Th22-mediated inflammation. The neuroimmune feedback loop in PN involves neuropeptides released from nerve fibres that cause vasodilation and further recruitment of inflammatory cells. Inflammatory cells, particularly mast cells and eosinophils, degranulate and release neurotoxins, as well as nerve growth factor, which may contribute to the neuronal hyperplasia seen in the dermis of patients with PN and neural sensitization. Recent studies have also indicated underlying genetic susceptibility to PN…

BACKGROUND: Acne vulgaris is a common skin condition affecting adolescents and young adults worldwide, yet data on the burden and trends of this disease remain limited. We aimed to investigate trends in the burden of acne vulgaris among adolescents and young adults aged 10-24 years at global, regional and national levels. METHODS: We retrieved data from the Global Burden of Disease Study 2021 for individuals aged 10-24 years in 204 countries and territories from 1990 to 2021. We analysed the numbers, age-standardized rates and average annual percentage changes (AAPCs) of the prevalence, incidence and disability-adjusted life years (DALYs) for acne vulgaris at the global, regional and national levels. Additionally, we examined these global trends by age, sex and Sociodemographic Index (SDI). RESULTS: Globally, the age-standardized prevalence rate of acne vulgaris among adolescents and young adults increased from 8563.4 per 100 000 population [95% uncertainty interval (UI) 7343.5-9920.1] in 1990 to 9790.5 (95% UI 8420.9-11 287.2) per 100 000 population in 2021, with an AAPC of 0.43…

BACKGROUND: In the phase III POETYK PSO-1 and PSO-2 trials, deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, was well tolerated and efficacious over 1 year in patients with psoriasis. OBJECTIVE: To evaluate deucravacitinib safety and efficacy over 2 years in patients participating in the phase III trials. METHODS: In the POETYK long-term extension (LTE), an ongoing phase IIIb open-label trial, adults with moderate-to-severe plaque psoriasis who completed PSO-1 or PSO-2 receive deucravacitinib 6 mg once daily. Safety was assessed via adverse events (AEs) and laboratory parameter abnormalities. Efficacy endpoints, including ≥ 75% reduction from baseline Psoriasis Area and Severity Index score (PASI 75) and static Physician's Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients originally randomized to deucravacitinib, patients who crossed over from placebo at week 16 and patients who achieved PASI 75 at week 24 (peak efficacy). RESULTS: At data cutoff (1 October 2021), 1519 patients had received at least one dose of…

BACKGROUND: Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients with AD continue to experience flares and substantial clinical burden, despite ongoing systemic treatment. OBJECTIVES: To assess the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) as per its label, and present the week 16 primary analysis results. METHODS: Level Up is a phase IIIb/IV global randomized open-label efficacy assessor-blinded study evaluating UPA vs. DUPI in adolescents and adults with moderate-to-severe AD who had an inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (period 1). Patients on UPA were started on 15 mg and dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥ 4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on or after week 4, or an EASI…

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a severe spectrum of rare mucocutaneous reactions that are primarily drug-induced and characterized by significant morbidity and mortality. These conditions manifest in extensive skin detachment, distinguishing them from other generalized skin eruptions. The rarity and severity of SJS/TEN underscore the importance of accurate diagnostic criteria and effective treatments, which are currently lacking consensus. This review proposes new diagnostic criteria to improve specificity and global applicability. Recent advances in understanding the immunopathogenesis of SJS/TEN are explored, emphasizing the role of drug-specific T-cell responses and human leucocyte antigen polymorphisms in disease onset. The review also addresses current therapeutic approaches, including controversies surrounding the use of immunosuppressive agents and the emerging role of tumour necrosis factor-α inhibitors. Novel therapeutic strategies targeting specific pathogenic mechanisms, such as necroptosis and specific immune cell pathways,…

BACKGROUND: Janus kinase inhibitors (JAKi) have the potential to alter the landscape of atopic dermatitis (AD) management dramatically, owing to promising efficacy results from phase III trials and their rapid onset of action. However, JAKi are not without risk, and their use is not appropriate for all patients with AD, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD. OBJECTIVES: To provide a consensus expert opinion statement from the International Eczema Council (IEC) that provides a pragmatic approach to prescribing JAKi, including choosing appropriate patients and dosing, clinical and laboratory monitoring and advice about long-term use. METHODS: An international cohort of authors from the IEC with expertise in JAKi selected topics of interest were placed into authorship groups covering 10 subsections. The groups performed topic-specific literature reviews, consulted up-to-date adverse event (AE) data, referred to product labels and provided analysis and expert opinion. The manuscript guidance…

BACKGROUND: Use of artificial intelligence (AI), or machine learning, to assess dermoscopic images of skin lesions to detect melanoma has, in several retrospective studies, shown high levels of diagnostic accuracy on par with - or even outperforming - experienced dermatologists. However, the enthusiasm around these algorithms has not yet been matched by prospective clinical trials performed in authentic clinical settings. In several European countries, including Sweden, the initial clinical assessment of suspected skin cancer is principally conducted in the primary healthcare setting by primary care physicians, with or without access to teledermoscopic support from dermatology clinics. OBJECTIVES: To determine the diagnostic performance of an AI-based clinical decision support tool for cutaneous melanoma detection, operated by a smartphone application (app), when used prospectively by primary care physicians to assess skin lesions of concern due to some degree of melanoma suspicion. METHODS: This prospective multicentre clinical trial was conducted at 36 primary care centres in…

Atopic dermatitis (AD) is a heterogeneous inflammatory condition involving multiple immune pathways mediated by pathogenic T cells. OX40 ligand (OX40L) and OX40 are costimulatory immune checkpoint molecules that regulate effector and memory T-cell activity and promote sustained immune responses in multiple immunological pathways, including T helper (Th)2, Th1, Th17 and Th22. As such, OX40L/OX40 signalling between antigen-presenting cells (APCs) and activated T cells postantigen recognition promotes pathogenic T-cell proliferation and survival. Under inflammatory conditions, OX40L is upregulated on APCs, enhancing the magnitude of antigen-specific T-cell responses and secretion of proinflammatory cytokines. In AD, OX40L/OX40 signalling contributes to the amplification and chronic persistence of T-cell-mediated inflammation. Recent therapeutic success in clinical trials has highlighted the importance of the OX40L/OX40 axis as a promising target for the treatment of AD. Here, we discuss the many factors that are involved in the expression of OX40L and OX40, including the cytokine…

BACKGROUND: Alopecia areata (AA) is a chronic autoimmune disease that leads to a high psychiatric, economic and systemic disease burden. A comprehensive understanding of AA epidemiology is essential for evaluating healthcare source utilization; however, a systematic approach to summarizing epidemiological data on AA is lacking. OBJECTIVES: To investigate systematically the global, regional and national incidence and prevalence of AA. METHODS: A structured search was conducted using the databases MEDLINE, Embase, Cochrane Library, Web of Science, SciELO and Korean Journal Database from their date of inception to 4 October 2023. Studies that reported the prevalence or incidence of AA were included. We used a Bayesian hierarchical linear mixed model to analyse prevalence estimates. The primary outcomes of our study were the global, regional and national prevalence of physician-diagnosed AA for the overall population, for adults and for children. The incidence data were summarized descriptively. RESULTS: In total, 88 studies from 28 countries were included in the analysis. The reported…

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies. OBJECTIVES: To explore the effects of spesolimab treatment in patients with HS. METHODS: This randomized double-blind placebo-controlled proof-of-clinical-concept (PoCC) study was conducted at 25 centres across 12 countries from 3 May 2021 to 21 April 2022. Patients had moderate-to-severe HS for ≥ 1 year before enrolment. Patients were randomized (2 : 1) to receive a loading dose of 3600-mg intravenous spesolimab (1200 mg at weeks 0, 1 and 2) or matching placebo, followed by maintenance with either 1200-mg subcutaneous spesolimab every 2 weeks from weeks 4 to 10 or matching placebo. The primary endpoint was the percentage change from baseline in total abscess and inflammatory nodule (AN) count at week 12. Secondary endpoints were the absolute change from baseline in the International Hidradenitis Suppurativa Severity Score System (IHS4), percentage…

Hidradenitis suppurativa (HS) has a significant impact on patients’ quality of life (QoL) and mortality. We report the use of semaglutide and its impact on disease control and QoL in 30 patients with obesity attending an HS specialty clinic. These retrospective data suggest that the addition of semaglutide to standard HS treatments results in improvement in QoL and fewer HS flares. The retrospective nature of the study is a limitation. Placebo-controlled randomized clinical trials should be done in HS to assess the efficacy of semaglutide in this debilitating condition.

Lay Summary Alopecia areata (AA) is a long-term condition that can occur in both children and adults. AA can appear as patches of baldness on the scalp. Sometimes, nail growth is also affected. Hair on other parts of the body may also fall out, such as the beard, eyebrows and eyelashes. Total loss of scalp hair is called alopecia totalis (AT). Complete loss of scalp, facial and body hair is called alopecia universalis (AU). The British Association of Dermatologists gathered a group of experts in managing people of all ages with AA. The group consisted of 11 dermatologists, 1 psychologist, 2 people with AA and a team with expertise in preparing guidelines. This group of experts reviewed relevant studies published until 19 October 2023. Using the evidence, the group produced recommendations using rigorous standards for guideline development. The guideline development group produced 49 recommendations for management of people with AA. They also made 7 recommendations for future research and suggested 11 audit points for hospitals. Based on the guideline, the group prepared an updated…

BACKGROUND: Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor-α monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils. OBJECTIVES: To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment. METHODS: The 24-week, randomized, double-blind, placebo-controlled, phase IIb portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomized to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in Itch Severity Score (ISS)7 at week 12. The key secondary endpoint was change from baseline in Urticaria Activity Score (UAS)7 at week 12. Additional secondary endpoints included other metrics to assess CSU at week 24, blood eosinophil levels, and pharmacokinetics and…

BACKGROUND: The ALLEGRO phase IIa and IIb/III (NCT02974868 and NCT03732807) studies have demonstrated that ritlecitinib is effective and well tolerated in adults and adolescents with alopecia areata (AA) up to 48 weeks. OBJECTIVES: To assess the efficacy of ritlecitinib through month 24 and safety through data cutoff in the ALLEGRO phase IIb/III study and the ongoing long-term open-label phase III ALLEGRO-LT study (NCT04006457). METHODS: Patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss from ALLEGRO IIb/III who rolled over to ALLEGRO-LT after up to 48 weeks were included. Proportions of patients with responses based on clinician-reported Severity of Alopecia Tool (SALT) scores of ≤ 20 and ≤ 10, eyebrow assessment (EBA) and eyelash assessment (ELA), patient global impression of change (PGI-C) and patient satisfaction with hair growth were reported through month 24 for patients who received ritlecitinib 50 mg daily with or without a 200-mg 4-week daily loading dose. Observed and imputed data [last observation carried forward (LOCF)] were reported up to 9 December 2022. Safety…

BACKGROUND: Bullous pemphigoid (BP) affects elderly individuals with multiple comorbidities, making conventional treatments unsuitable. OBJECTIVES: Evaluate the effectiveness and safety of dupilumab in the treatment of BP. METHODS: A multicentre ambispective cohort study was conducted across 34 hospitals. Patients with BP treated with dupilumab were included. Most of the patients (97.1%) received an initial 600-mg dose followed by 300 mg every 2 weeks. The primary outcome was the proportion of patients achieving complete remission (CR) within 4 weeks, defined as an Investigator's Global Assessment score of 0 or 1. CR at weeks 16, 24 and 52, adverse events (AEs), reductions in Peak Pruritus Numerical Rating Scale (PP-NRS) and systemic glucocorticoid use were also assessed. RESULTS: The study included 103 patients with a median age of 77.3 years; 58.3% were male. CR was achieved by 53.4% within 4 weeks and 95.7% by week 52. The PP-NRS score reduced by 70.0% by week 4 and was completely controlled by week 24. Thirteen patients presented with AEs, most of which were mild. Systemic…

Atopic dermatitis (AD) is the most common inflammatory skin condition and affects people of all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasized in real-world observations, an unexpected increased frequency of ocular adverse effects has become apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if adverse effects arise. The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD). A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with expertise in DROSD, patient representatives and the BAD Clinical Standards Unit. A literature search was conducted and the results reviewed. All recommendations were reviewed, discussed and voted on. The recommendations pertain to dermatology and…

Hidradenitis suppurativa (HS) is a complex inflammatory disease, with rapid advances being made in our understanding of the complex immunological pathogenesis of the condition. New insights into the genomic landscape of HS have identified a number of genes that contribute to the development of HS in a polygenic manner, contributing to inflammatory dysregulation and alterations in epidermal stem cell fate in the follicular unit. These genomic variations can explain unique aspects of the disease such as the development and presence of epithelialized tunnels and abnormalities in wound healing. From genetic and translational studies, it is likely that these genetic alterations predispose to an innate immune dysregulation that can be triggered through sex hormone-responsive transcription factors with hormonal changes such as puberty, pregnancy and the menstrual cycle. The role of sex hormones in HS also has direct effects upon the development and maturation of inflammatory cells such as monocytes, which has the potential to explain differential patient response to treatments such as…

BACKGROUND: Very few studies have evaluated the global prevalence of pruritus. OBJECTIVES: To assess its prevalence according to age, sex, ethnicity and geographic region. METHODS: An international cross-sectional study was conducted in 20 countries from January to April 2023. Participants were asked to complete a questionnaire on sociodemographics, and to confirm the presence or absence of a skin disease in the last 12 months and the presence or absence of pruritus in the last 7 days. RESULTS: The studied sample included 50 552 individuals. The worldwide prevalence of pruritus was 39.8%. The age group ≥ 65 years had the highest prevalence (43.3%). The prevalence was 40.7% among women and 38.9% among men (P < 0.001). There was no significant difference between ethnicities (P = 0.14). Compared with North America (41.2%), the prevalence of pruritus was significantly lower in Europe (35.9%, P < 0.001), Australia (38.4%, P = 0.017), East Asia (40.2%, P = 0.04) and Latin America (36.5%, P < 0.001), and higher in Africa (45.7%, P = 0.007). No significant difference was found with the…

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a substantial disease burden. Secukinumab has previously been reported to have sustained efficacy with a favourable safety profile in patients with moderate-to-severe HS. It is unknown whether prior biologic exposure affects the efficacy and safety of secukinumab. OBJECTIVES: To investigate the efficacy and safety of secukinumab in patients with moderate-to-severe HS based on prior exposure to -biologics. METHODS: This was an analysis of the SUNSHINE and SUNRISE phase III trials of secukinumab in patients with moderate-to-severe HS. Patients were randomized at baseline to receive secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo for 16 weeks. After week 16, patients on the SECQ2W and SECQ4W schedules remained on the same treatment regimen, while patients randomized to placebo were switched to either SECQ2W or SECQ4W up to week 52. Assessments based on prior exposure to biologics included Hidradenitis Suppurativa Clinical Response (HiSCR), abscess and inflammatory nodule (AN)…

BACKGROUND: Psoriasis and insulin resistance (IR) are closely related, but it remains unclear whether IR affects the treatment of patients with psoriasis. OBJECTIVE: To investigate whether IR impairs the treatment response to biologic agents in patients with moderate-to-severe plaque psoriasis. METHODS: This project was based on a prospective cohort study design. Data were collected from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH), which is a prospective cohort exploring treatment strategies for psoriasis in China. IR was assessed using triglyceride glucose-body mass index (TyG-BMI). Psoriasis severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Multiple logistic regression was used to explore the differences between patients with high and low levels of IR. Subgroup and sensitivity analyses were performed to examine the robustness of the study results. RESULTS: A total of 290 patients were included in the analysis. Based on median TyG-BMI, the patients were divided into two groups: high and low IR. The high…

BACKGROUND: Psoriasis is a common chronic inflammatory disease with an unclear aetiology. Keratinocytes in psoriasis are susceptible to exogenous triggers that induce inflammatory cell death. OBJECTIVES: To investigate whether gasdermin E (GSDME)-mediated pyroptosis in keratinocytes contributes to the pathogenesis of psoriasis. METHODS: Skin samples from patients with psoriasis and from healthy controls were collected to evaluate the expression of GSDME, cleaved caspase-3 and inflammatory factors. We then analysed the data series GSE41662 to further compare the expression of GSDME between lesional and nonlesional skin samples in those with psoriasis. In vivo, a caspase-3 inhibitor and GSDME-deficient mice (Gsdme-/-) were used to block caspase-3/GSDME activation in an imiquimod-induced psoriasis model. Skin inflammation, disease severity and pyroptosis-related proteins were analysed. In vitro, tumour necrosis factor (TNF)-α-induced caspase-3/GSDME-mediated pyroptosis in the HACAT cell line was explored. RESULTS: Our analysis of the GSE41662 data series found that GSDME was…

We describe 14 cases of native refractory dermatophytes caused by Trichophyton indotineae diagnosed at a hospital in China since 2021, primarily diagnosed in the past 1 year and from the same province. Trichophyton indotineae isolates were resistant to multiple antifungals and harboured Phe397Leu or Leu393Ser substitutions in the squalene epoxidase enzyme. Short-term rapid emergence of multidrug-resistant T. indotineae in China poses increasing threats to public safety and warrants continued public health surveillance.

BACKGROUND: Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab - a monoclonal antibody that neutralizes IL-13 - reduces inflammation and clinical disease activity, less is known about its effects on barrier function. OBJECTIVES: To characterize the effects of tralokinumab treatment on skin barrier function. METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, nonlesional and sodium lauryl sulfate-irritated skin of 16 patients with AD over the course of 16 weeks of tralokinumab treatment. RESULTS: All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 33% (P = 0.01) and SCH increased by 58% (P = 0.004), along with a histological reduction in spongiosis (P = 0.003), keratin 16 expression and epidermal thickness (P = 0.001). In parallel, there was a…

BACKGROUND: Large language models (LLMs) have a potential role in providing adequate patient information. OBJECTIVES: To compare the quality of LLM responses with established Dutch patient information resources (PIRs) in answering patient questions regarding melanoma. METHODS: Responses from ChatGPT versions 3.5 and 4.0, Gemini, and three leading Dutch melanoma PIRs to 50 melanoma-specific questions were examined at baseline and for LLMs again after 8 months. Outcomes included (medical) accuracy, completeness, personalization, readability and, additionally, reproducibility for LLMs. Comparative analyses were performed within LLMs and PIRs using Friedman's Anova, and between best-performing LLMs and gold-standard (GS) PIRs using the Wilcoxon signed-rank test. RESULTS: Within LLMs, ChatGPT-3.5 demonstrated the highest accuracy (P = 0.009). Gemini performed best in completeness (P < 0.001), personalization (P = 0.007) and readability (P < 0.001). PIRs were consistent in accuracy and completeness, with the general practitioner's website excelling in personalization (P = 0.013) and…

BACKGROUND: Psoriasis is a T cell-mediated chronic inflammatory skin condition characterized by the interaction of T cells with various cell types, forming an inflammatory microenvironment that sustains psoriatic inflammation. Homeostasis of these tissue-resident T cells is supported by fibroblasts, the primary structural cells in the dermis. In psoriasis, there is increased expression of matrix metalloproteinase 2 (MMP2), mediating structural alterations in skin tissues and modulating inflammation. Additionally, the CD100-plexin-B2 (PLXNB2) axis is known to enhance psoriasis inflammation via keratinocytes, and CD103 levels are associated with the severity of psoriasis upon relapse. OBJECTIVES: To elucidate the role of fibroblasts and the MMP2-CD100 axis in modulating psoriasis inflammation. METHODS: CD100 expression and function in psoriasis were assessed using immunofluorescence, enzyme-linked immunosorbent assay, single-cell transcriptome sequencing, cellular interaction analyses and quantitative reverse transcriptase polymerase chain reaction. CD8+ T cells from people with…

BACKGROUND: Anti-programmed cell death 1 antibodies (PD-1 Abs) are widely used for advanced melanoma, but information on the efficacy of anti-PD-1 Abs is limited in the Asian population. There remains an unmet need to improve the therapeutic effects of anti-PD-1 Ab-treatment, particularly in patients with melanoma who are refractory to anti-PD-1 Abs. The aim of this study was to evaluate anti-PD-1 Ab-treatment in combination with TM5614 (a plasminogen activator inhibitor-1 inhibitor) in patients with unresectable melanoma. METHODS: The TM5614-MM study was a multicentre, open-label, single-arm, phase II clinical trial to evaluate the efficacy and safety of nivolumab in combination with TM5614 in patients with advanced, unresectable malignant melanoma recruited at seven Japanese institutes between 13 September 2021 and 31 March 2023. Patients with metastatic or unresectable melanoma previously treated with anti-PD-1 Abs were enrolled. Nivolumab 480 mg was administered intravenously every 4 weeks for 8 weeks, while TM5614 was administered orally at a dose of 120 mg (0-4 weeks) and 180…

BACKGROUND: Increasing melanoma incidence with less increasing mortality is observed in several countries. This discrepancy is not well understood. OBJECTIVES: In this study, our aim was to discuss factors [ultraviolet radiation (UVR) exposure, melanoma treatment, diagnostic activity, overdiagnosis, pathologists' diagnostic threshold and clinicians' propensity to remove suspect skin lesions] that might influence melanoma incidence and mortality in Denmark. METHODS: This was a register study with the number of melanocyte-related lesions and melanoma mortality based on comprehensive national pathology and mortality databases for the period 1999-2019. We investigated melanocyte-related diagnoses and mortality in a population of 5.5 million with a national healthcare system. Age-adjusted melanoma mortality and age-adjusted incidence of benign naevi, atypical lesion, or melanoma in situ and of invasive melanoma were computed for data analysis. RESULTS: In total, 1 434 798 biopsies were taken from 704 682 individuals (65% female). The mean age at biopsy was 39.8 years in males and 37.6 in…

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease associated with significant comorbidities and poor quality of life. Despite uncertainty about pathways driving inflammation in HS lesions, the cytokines interleukin (IL)-17A and IL-17F have been shown to be upregulated in patients with HS. Previous studies have demonstrated that the monoclonal IgG1 antibody bimekizumab selectively inhibits IL-17F in addition to IL-17A. OBJECTIVES: To further investigate the roles of IL-17A and IL-17F in HS pathogenesis. METHODS: RNA sequencing (RNAseq) was conducted on skin biopsies taken at baseline and after treatment at week 12 of a phase II proof-of-concept study of bimekizumab in patients with moderate-to-severe HS. Differentially expressed genes were identified between baseline lesional and nonlesional samples and between lesional samples before and after bimekizumab treatment, to describe molecular disease mechanisms and treatment effect. Human hair follicular keratinocytes (HHFK) were cultured and treated with a supernatant of stimulated T helper…

BACKGROUND: Congenital ichthyoses comprise a heterogeneous group of genetic diseases that require lifelong treatment and have a major impact on patients' quality of life. Conventional treatments reduce scaling and skin discomfort; however, they usually have little or no effect on erythema and pruritus. The identification of cytokine alterations in congenital ichthyoses has raised the possibility of repurposing currently available biologics. Several case reports have reported success with different biologics. OBJECTIVES: To report the real-life effects of biologics on congenital ichthyoses. METHODS: This was a retrospective observational international multicentric study of patients with congenital ichthyoses treated with at least one biologic for a minimum of 3 months. The effect of the biologics was evaluated using an Investigator Global Assessment for change (IGA-C) scale. A comprehensive literature search was performed in parallel. RESULTS: Ninety-eight patients were included [mean (SD) age of 19.7 years, 50 female patients]. Patients with Netherton syndrome (NS) or congenital…

BACKGROUND: Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials. OBJECTIVES: To evaluate the efficacy and safety of xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated. RESULTS: At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and…

BACKGROUND: It is increasingly clear that triglyceride-rich lipoproteins are proinflammatory and cause low-grade systemic inflammation. However, it is currently unknown whether elevated plasma triglycerides are causally related to the development of psoriasis, a skin disorder driven by chronic inflammation. OBJECTIVES: To determine if elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis. METHODS: Consecutive individuals from the Copenhagen General Population Study were included. We used plasma triglycerides (n = 108 043) and a weighted triglyceride allele score (n = 92 579) on nine known triglyceride-altering genetic variants. Genetic results were replicated in 337 159 individuals from the UK Biobank. Psoriasis was defined using the International Classification of Diseases, version 10 (ICD-10) code for hospital contact in the main analyses, and prescription of topical antipsoriatics for mild psoriasis in the sensitivity analysis. RESULTS: During a follow-up of median (range) 9.3 (0.1-15.1) years from 2003…

More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We…

BACKGROUND: The psychological burden of cutaneous malignant melanoma (CM) is all-encompassing, affecting treatment adherence, recurrence and mortality. However, the prevalence and risk factors of anxiety and depression in CM remain unclear. OBJECTIVES: To establish a benchmark pooled prevalence of anxiety and depression in CM, to provide magnitudes of association for clinical, therapeutic and demographic correlates, and to elucidate temporal trends in anxiety and depression from the time of diagnosis. METHODS: This review followed the MOOSE guidelines. MEDLINE, Embase, PsychINFO, Web of Science and the Cochrane Library were queried from database inception to 24 August 2023. Study selection, data extraction and quality assessment were performed by two independent authors, utilizing both the Joanna Briggs Institute (JBI) and National Institutes of Health risk-of-bias tools for the latter. The GRADE approach was used to rate the certainty of evidence. Prevalence rates, 95% confidence intervals (CIs) and prediction intervals (PIs) were derived using a random-effects model and estimating…

BACKGROUND: Skin fibrosis is the typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS); it has an unclear aetiology and few effective treatments. Although excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, evidence has suggested that vascular damage is the initiating event and that various cell types, including fibroblasts, work together to contribute to the pathogenesis of skin fibrosis. OBJECTIVES: To explore the relationship between vascular endothelial cell lesions and immune cell infiltration, along with the interactions between various cell types within the fibrotic skin ecosystem. METHODS: Single-cell RNA sequencing was performed on skin biopsies from three healthy donors and seven patients with SSc. Additional data from three patients with localized scleroderma available in the Gene Expression Omnibus (GSE160536) were integrated by Harmony. CellChat (version 1.5.0) was used to analyse the cell communication network. A Transwell® assay and a bleomycin (BLM) mouse model were used to explore the role of…

BACKGROUND: A phase III clinical trial in Japanese children aged 6-12 years with atopic dermatitis (AD) and inadequately controlled moderate-to-severe pruritus found that 16 weeks of nemolizumab treatment [30 mg every 4 weeks (Q4W)] was clinically effective and tolerable, with early improvement in pruritus and associated skin signs and a positive impact on patient quality of life (QoL). OBJECTIVES: To report the findings from the long-term extension period of the study, and evaluate the efficacy and safety profiles of nemolizumab when administered concomitantly with topical agents over 68 weeks. METHODS: The study included a 16-week randomized placebo-controlled double-blind parallel-group period during which patients received nemolizumab 30 mg or placebo Q4W; those who completed this period could enter a 52-week long-term treatment period during which all patients received nemolizumab Q4W. Efficacy endpoints assessed treatment impact on pruritus, AD signs and QoL. Treatment-emergent adverse events (TEAEs) were tabulated to evaluate long-term safety. The study was registered with…

BACKGROUND: Prurigo nodularis (PN), a chronic inflammatory skin condition, adversely affects the quality of life of affected individuals. Current treatment options for PN in Japan are limited. OBJECTIVES: To evaluate the optimal dose, efficacy and safety of long-term treatment with nemolizumab in patients with PN in Japan. METHODS: In a 16-week double-blind phase II/III study, patients aged ≥ 13 years with PN were randomly assigned (1 : 1 : 1) to nemolizumab 30-mg, 60-mg or placebo groups, with concomitant topical corticosteroids, every 4 weeks. The primary efficacy endpoint was the percentage change in the weekly mean Peak Pruritus Numerical Rating Scale (PP-NRS) score (range 0-10, with higher scores indicating worse itching) from baseline to week 16. Secondary efficacy endpoints assessed the impact of treatment on pruritus, PN severity, sleep and quality of life. RESULTS: At week 16, the least-squares mean percentage change from baseline in the PP-NRS score was -61.1% in the nemolizumab 30-mg group (n = 77), -56.0% in the 60-mg group (n = 76), and -18.6% in the placebo group (n =…

BACKGROUND: Artificial intelligence (AI) is reshaping healthcare, using machine and deep learning (DL) to enhance disease management. Dermatology has seen improved diagnostics, particularly in skin cancer detection, through the integration of AI. However, the potential of AI in automating immunofluorescence imaging for autoimmune bullous skin diseases (AIBDs) remains untapped. While direct immunofluorescence (DIF) supports diagnosis, its manual interpretation can hinder efficiency. The use of DL to classify DIF patterns automatically, including the intercellular (ICP) and linear pattern (LP), holds promise for improving the diagnosis of AIBDs. OBJECTIVES: To develop AI algorithms for automated classification of AIBD DIF patterns, such as ICP and LP, in order to enhance diagnostic accuracy, streamline disease management and improve patient outcomes through DL-driven immunofluorescence interpretation. METHODS: We collected immunofluorescence images from skin biopsies of patients suspected of having an AIBD between January 2022 and January 2024. Skin tissue was obtained via a 5-mm…

BACKGROUND: According to current guidelines, systemic or topical corticosteroids are both recommended as first-line treatments for bullous pemphigoid (BP). There is evidence to suggest that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections and relapse, between systemic and topical corticosteroid treatments. OBJECTIVES: To evaluate the risk of death, MACE, infections and relapse in patients with BP treated with systemic or topical corticosteroids. METHODS: A population-based retrospective cohort study was performed using the TriNetX US Collaborative Network. As a measure against bias, propensity score matching for age, sex, 10 diseases and 6 medications was done, and 3 sensitivity analyses were conducted. RESULTS: All-time risk of death was increased in US patients with BP exposed to any dose of systemic corticosteroids (n = 2917) vs. patients treated with topical clobetasol propionate [n = 2932; hazard ratio…

Modulation of immune responses through immune checkpoint blockade has revolutionized cutaneous melanoma treatment. However, it is still the case that not all patients respond successfully to these therapies, indicating the presence of as yet unknown resistance mechanisms. Hence, it is crucial to find novel targets to improve therapy efficacy. One of the described resistance mechanisms is regulated by immune inhibitory Siglec receptors, which are engaged by the carbohydrates sialic acids expressed on tumour cells, contributing to programmed cell death protein-1 (PD1)-like immune suppression mechanisms. In this review, we provide an overview on the regulation of sialic acid synthesis, its expression in melanoma, and the contribution of the sialic acid-Siglec axis to tumour development and immune suppressive mechanisms in the tumour microenvironment. Finally, we highlight potential sialic acid-Siglec axis-related therapeutics to improve the treatment of melanoma.

BACKGROUND: A common complication of wounds is the excessive production of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. Currently, no treatments with good evidence for preventing excessive scar tissue formation are available. We explored the use of microneedle patches containing small interfering RNA (siRNA) to inhibit SPARC mRNA in reducing the volume of postoperative scars. OBJECTIVES: To compare differences in postoperative scar volume with the daily application of siRNA-embedded dissolving microneedle patches vs. silicone sheets. METHODS: This was an 8-week, single-blinded intraindividually controlled randomized trial at a tertiary dermatological centre. Patients with 2-week-old postoperative wounds were included. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at days 0, 30 and 60. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000558729). RESULTS: At day 30, scars treated with…

BACKGROUND: Alopecia areata (AA) is an immune-mediated form of hair loss that can occur at any age, often with a significant mental health burden. OBJECTIVES: We aimed to provide estimates of the lifetime incidence of AA, and the impacts on mental health, healthcare utilization and work-related outcomes, assessing variation across major sociodemographic subgroups. METHODS: AA cases were identified in primary care from the UK population-based Oxford-Royal College of General Practitioners Research and Surveillance Centre database (2009-2018). Lifetime incidence of AA was estimated at age 80 years using modified time-to-event models with age as the timescale, overall and stratified by sex, ethnicity, deprivation and geography. Mental health, healthcare utilization and work-related outcomes were assessed in the 2 years after AA diagnosis compared with matched unaffected controls, and stratified by the same sociodemographic subgroups. RESULTS: During the study period, 6961 people developed AA. Overall lifetime incidence of AA was 2.11% [95% confidence interval (CI) 2.06-2.16]. Females…

BACKGROUND: Hypertrophic scarring is a disease of abnormal skin fibrosis caused by excessive fibroblast proliferation. Existing drugs have not achieved satisfactory therapeutic effects. OBJECTIVES: To explore the molecular pathogenesis of hypertrophic scars and screen effective drugs for their treatment. METHODS: Existing human hypertrophic scar RNA sequencing data were utilized to search for hypertrophic scar-related gene modules and key genes through weighted gene co-expression network analysis (WGCNA). Candidate compounds were screened in a compound library. Potential drugs were screened by molecular docking and verified in human hypertrophic scar fibroblasts and a mouse mechanical force hypertrophic scar model. RESULTS: WGCNA showed that hypertrophic scar-associated gene modules influence focal adhesion, the transforming growth factor (TGF)-β signalling pathway and other biologic pathways. Integrin β1 (ITGB1) is the hub protein. Among the candidate compounds obtained by computer virtual screening and molecular docking, crizotinib, sorafenib and SU11274 can inhibit the…

BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon (IFN)-α (subtypes 2a and 2b) has been used to treat MF/SS since 1984; however, its production was recently stopped. The recombinant pegylated (PEG) form of IFN-α-2a remains the only alternative IFN treatment, although it has not been approved for use in MF/SS. OBJECTIVES: To assess the effectiveness and safety of PEG-IFN-α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in a real-world setting. METHODS: We conducted an international, multicentre retrospective study of patients with MF and SS (of any stage) treated with PEG-IFN-α-2a from July 2012 to February 2022. Patients were included across 11 centres in 10 countries. The primary endpoints were to determine the TTNT of PEG-IFN-α-2a and adverse events (AEs) in MF/SS. RESULTS: In total, 105 patients were included [mean (SD) age 61 (13.1) years]; 42 (40.0%) had stage…

BACKGROUND: UK studies examining vitiligo burden and vitiligo-related healthcare resource utilization (HCRU) are lacking. OBJECTIVE: To describe the incidence and prevalence of vitiligo, the demographic and clinical characteristics of patients with vitiligo, vitiligo burden, HCRU, incidence of mental health comorbidities and management strategies, including treatment patterns. METHODS: This retrospective study used UK Clinical Practice Research Datalink and Hospital Episode Statistics databases to analyse patients with vitiligo from 1 January 2010 to 31 December 2021. RESULTS: Among 17 239 incident patients, mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years [PY; range 0.10 (2020-COVID-19) to 0.19 (2010/2013/2018)]; among 66 217 prevalent patients, prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%) and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time included depression and/or anxiety (24.6%), depression…

Pemphigus vulgaris (PV) is a rare autoimmune bullous disease characterized by blistering of the skin and mucosa owing to the presence of autoantibodies against the desmosome proteins desmoglein 3 and occasionally in conjunction with desmoglein 1. Fundamental research into the pathogenesis of PV has revolutionized its treatment and outcome with rituximab, a B-cell-depleting therapy. The critical contribution of B cells to the pathogenesis of pemphigus is well accepted. However, the exact pathomechanism, mechanisms of onset, disease course and relapse remain unclear. In this narrative review, we provide an overview of the fundamental research progress that has unfolded over the past few centuries to give rise to current and emerging therapies. Furthermore, we summarize the multifaceted roles of B cells in PV, including their development, maturation and antibody activity. Finally, we explored how these various aspects of B-cell function contribute to disease pathogenesis and pave the way for innovative therapeutic interventions.

BACKGROUND: The SUNSHINE and SUNRISE phase III trials demonstrated sustained clinical efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa (HS) through 52 weeks. Patients completing the core trials could enter a 4-year extension trial. OBJECTIVES: To evaluate the long-term efficacy, safety/tolerability and maintenance of clinical response to secukinumab through week 104 in the extension trial. METHODS: Patients with a hidradenitis suppurativa (HS) clinical response (HiSCR) at week 52 of the core trials (extension trial baseline visit) entered a randomized withdrawal period. HiSCR responders receiving subcutaneous secukinumab 300 mg every 2 or 4 weeks (SECQ2W/SECQ4W) through week 52 in the core trials were randomized 2 : 1 to continue secukinumab (SECQ2W-R-Q2W or SECQ4W-R-Q4W) or receive placebo (SECQ2W-R-PBO or SECQ4W-R-PBO) through week 104. The primary endpoint was time to loss of response (LOR; newly defined for this trial) through week 104 in week 52 HiSCR responders (SECQ2W-R-Q2W vs. SECQ2W-R-PBO and SECQ4W-R-Q4W vs. SECQ4W-R-PBO). Time to LOR…

BACKGROUND: Skin cancer is the most common cancer worldwide. Early diagnosis is crucial to improving patient survival and morbidity. Artificial intelligence (AI)-assisted smartphone applications (apps) for skin cancer potentially offer accessible, early risk assessment of suspicious skin lesions. However, the integration of novel technologies into dermatology pathways raises ethical concerns. Although ethical principles for AI governance are well known, how these principles should be applied to real-life AI apps readily available for public use is less well understood. OBJECTIVES: To conduct an ethical use-case analysis of commercially available skin cancer apps, to better understand the ethical issues arising from their development and use in a real-world context. METHODS: Established methods for the ethical analysis of clinical AI applications were applied to two popular skin cancer apps in the UK: SkinVision and Scanoma. Systematic searches of published literature, regulatory documents and websites were conducted to review the evidence regarding app development, effectiveness and…

BACKGROUND: Deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, is approved in the USA, the European Union, Japan, South Korea, China and other countries for the treatment of moderate-to-severe plaque psoriasis. OBJECTIVES: To evaluate the efficacy and safety of deucravacitinib in Asian patients with moderate-to-severe plaque psoriasis. METHODS: In the 52-week blinded phase III POETYK PSO-3 trial (NCT04167462), patients were randomized 1 : 2 to placebo (n = 74) or deucravacitinib 6 mg once daily (n = 146) for 16 weeks followed by deucravacitinib alone. Co-primary endpoints were the achievement of a ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear; sPGA 0/1) at week 16. Efficacy and safety were evaluated throughout. RESULTS: At week 16, significantly higher proportions of patients receiving deucravacitinib compared with placebo achieved PASI 75 (68.8% vs. 8.1%; P < 0.001) and sPGA 0/1 (55.6% vs. 6.8%; P < 0.001). Response rates with deucravacitinib were…

BACKGROUND: Air pollution and genetic risk have been found to contribute to the onset and development of psoriasis. However, the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of incident psoriasis remains unknown. OBJECTIVES: To assess the association between joint exposure to multiple air pollutants and the risk of psoriasis, and its modification, according to genetic susceptibility. METHODS: This prospective study included 451 064 participants from the UK Biobank who had complete air pollution data and were free of psoriasis at baseline. All participants were enrolled from 2006 to 2010 and followed up to 2022. An air pollution score (APS) was calculated to assess joint exposure to multiple air pollutants, including fine particulate matter (PM) with diameters ≤ 2.5 μm (PM2.5), between 2.5 and 10 μm (PM2.5-10) and ≤ 10 μm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). To evaluate the genetic risk, a polygenic risk score (PRS) for psoriasis was constructed. Cox proportional hazard models were used to assess the…