Prior to the approval of spesolimab as the first treatment for generalised pustular psoriasis, it was made available to patients via expanded access programmes in Japan, China and Argentina. As a secondary objective, the safety and tolerability of spesolimab was evaluated in the population of real-world patients with GPP.
BACKGROUND:Non-syndromic hereditary hypotrichosis (NSHH) is a genetically heterogeneous disorder characterized by sparse or absent hair growth. Comprehensive genotype-phenotype correlation analyses remain limited, particularly in the Chinese population. OBJECTIVES:To define the genetic and phenotypic spectrum of NSHH in a Chinese cohort and to explore genotype-phenotype correlations with potential clinical utility. METHODS:This observational multicenter study included 47 unrelated families (107 affected individuals) with clinically and genetically confirmed NSHH. Genetic analysis was performed using next-generation sequencing with Sanger validation. Clinical features, including age at onset, severity, hair shaft morphology, and extracranial hair involvement, were systematically analysed and correlated with causative genes. RESULTS:Eleven causative genes were identified in 47 unrelated families, with LIPH (n=18, 38.3%), LSS (n=10, 21.27%), and HRURF (n=7, 14.89%) being the most prevalent. NSHH showed marked phenotypic heterogeneity with genotype-dependent patterns in age at onset, severity, and hair shaft morphology. Congenital onset was common in LIPH, LSS, and HRURF, whereas postnatal onset was observed in APCDD1, KRT86, and HR. Preliminary genotype-phenotype analysis of LIPH demonstrated allele-specific effects, with c.736T>A associated variants linked to more severe hypotrichosis compared with c.742C>A. In HRURF, two recurrently affected regions were observed, involving the start codon and the region encoding amino acids 23-28. Based on these findings, a preliminary phenotype-driven candidate-gene prioritisation framework was proposed. Exploratory analysis of topical minoxidil showed variable treatment responses. CONCLUSIONS:This study defines the genetic architecture and genotype-phenotype correlations of NSHH in the Chinese population and provides a preliminary phenotype-driven framework that may assist clinical evaluation and candidate-gene prioritisation.
Insulin resistance is increasingly recognised as being closely linked to psoriasis severity and treatment response, rather than simply representing an associated metabolic comorbidity. Emerging evidence for GLP-1 receptor agonists further supports the potential for targeting metabolic dysfunction as part of psoriasis management.
BACKGROUND:Paper mills represent a growing threat to research integrity, producing fabricated manuscripts for sale at scale and infiltrating the biomedical literature. While this phenomenon has been described in other fields, its impact within dermatology remains poorly characterised. OBJECTIVES:To describe the landscape of paper mill-associated retractions in dermatology, raise awareness of their prevalence, and identify features that may facilitate early detection. METHODS:A cross-sectional analysis was conducted using the Retraction Watch Database and reported in accordance with STROBE statement for cross-sectional studies. (OSF registration: doi:10.17605/OSF.IO/382PT). Dermatology-related records were identified using pre-defined keywords. Only articles explicitly labelled as "paper mill" in the retraction reason were included. Data extracted included study design, topic, research integrity indicators, country of origin, journal metrics, publisher, and reasons for retraction. Time to retraction was analysed using Kaplan-Meier methods and compared using the log-rank test. RESULTS:A total of 118 paper mill-associated articles (9.8%) were identified among 1,209 dermatology retractions. No cases were observed prior to 2018, followed by a rapid rise peaking in 2023 (>50 retractions). Studies were predominantly experimental (67%) and focused on cutaneous oncology (47%). No paper-mill articles reported data availability or protocol pre-registration, and 79% lacked ethics approval. China accounted for 86% of cases. Articles were published across 50 journals, most in the first or second SCImago Journal Rank quartile (80%), with a mean impact factor of 3.0. The mean time to retraction was 957 days, with no significant difference compared with non-paper mill articles (P = 0.53). CONCLUSIONS:Paper mill activity in dermatology has emerged rapidly and is characterised by consistent deficits in research integrity, particularly in data transparency and ethical oversight. Strengthening editorial screening, mandating data availability statements, and collaborating across publishers and wider research ecosystem will be essential to mitigate the impact of paper mills and protect the reliability of the dermatology evidence base for patient benefit.
Paediatric nail matrix nevi show age-dependent clinical and dermoscopic patterns. In this retrospective cohort, acquired lesions more often presented as narrow, regular, single-colour bands than congenital or congenital-type lesions. These findings suggest that age at onset may help refine the evaluation of paediatric longitudinal melanonychia.
We performed a mixed-cohort study to establish the scalp lipid–microbe functional linkages in dandruff using untargeted quantitative lipidomic and shot-gun metagenomic technology. Our findings suggest that suppressing scalp microbes facilitates lipid removal and alleviates dandruff more effectively.
BACKGROUND:Generalized pustular psoriasis (GPP) is a rare, severe inflammatory skin disease characterized by acute flares. Recibokibart is a humanized IgG1 monoclonal antibody targeting the interleukin-36 (IL-36) receptor. In a phase 1b open-label study, a single intravenous dose of recibokibart was associated with an acceptable safety profile and rapid improvements in pustulation, overall skin disease severity, and systemic inflammatory markers through 12 weeks. OBJECTIVES:This study aimed to evaluate the efficacy and safety of recibokibart in patients with acute flares of GPP. METHODS:In this multicenter, randomized, double-blind, placebo-controlled phase 2 trial conducted in China, patients with moderate-to-severe acute GPP were randomly assigned in a 2:1 ratio to receive a single intravenous dose of recibokibart (1050 mg) or placebo at day 1. Patients with persistent disease activity at day 8 were eligible to receive open-label recibokibart, and patients with recurrent flares after achieving a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 0 or 1 could receive an additional open-label dose. The primary efficacy endpoint was the proportion of patients who achieved a GPPGA pustulation sub-score of 0 or 1 at week 1 (day 8). RESULTS:A total of 33 patients were randomized (recibokibart, n=22; placebo, n=11). At week 1 (day 8), the primary endpoint of achieving a GPPGA pustulation sub-score of 0 or 1 was met by 86.4% of patients in the recibokibart group versus 9.1% in the placebo group (between-group difference, 77.3%; 95% CI, 42.5-88.9; P<0.0001). At week 1 (day 8), greater improvements were observed with recibokibart across key secondary endpoints, including achievement of a GPPGA total score of 0 or 1 (63.6% vs. 0%), complete pustule clearance (54.5% vs. 0%), and mean percentage change from baseline in GPPASI (-59.3% vs. 0%). By week 4, 72.7% of patients treated with recibokibart achieved GPPASI 75. Clinical improvements were observed as early as 24 hours after treatment and were maintained through week 12, although assessments after day 8 included patients who received open-label treatment. The most frequently reported adverse events with recibokibart included hypoproteinemia, hypertriglyceridemia, hyperlipidemia, and pruritus. CONCLUSIONS:A single intravenous dose of recibokibart resulted in rapid improvement in pustular and overall skin disease severity in patients with acute GPP flares, with an acceptable safety profile.
Author’s response to “Beyond fibroblast activation: expanding the role of the AREG–EGFR axis in keloid pathogenesis’ by Li et al.
We investigated the confidence of pharmacy-based healthcare professionals in counselling parents on pediatric atopic dermatitis and studied which over-the-counter products they recommend. A national survey was conducted in France using an online questionnaire and a total of 406 pharmacy-based healthcare professionals responded to the questionnaire. Approximately half of the respondents reported a high confidence in managing AD in children. Most participants provided appropriate guidance on the use of moisturizers and cleansing oils, yet, advice regarding complementary therapy was more variable and often not aligned with current AD guidelines.
We comment on the recent study by Dong et al., which identified the AREG–EGFR axis as a key driver of fibroblast activation and extracellular matrix deposition in keloids. We expand their findings by discussing the potential roles of immune–stromal interactions, EGFR downstream signalling complexity, extracellular matrix mechanobiology, and ligand-specific targeting within the EGFR network. These perspectives may help refine the mechanistic understanding of AREG signalling and guide the development of more precise therapeutic strategies for keloids.
Author’s response to ‘High-dimensional overfitting and noisy diagnostic labels: reconsidering the role of BRAF copy number in primary dermal melanoma’ by Zhang et al.
Half of the participants in this randomized online experiment of 1655 Australian adults would prefer to not have a wide local excision (WLE) after a completely excised low-risk melanocytic lesion, if offered this option. Using the term ‘low-risk melanocytic neoplasm’ instead of ‘melanoma in situ’ reduced anxiety and the proportion choosing a WLE. Across all label groups, most participants preferred to attend routine 6-monthly clinic visits for follow-up, most likely reflecting the high prevalence of this in the Australian context.
BACKGROUND:The skin and its commensal microbiota are regularly exposed to ultraviolet radiation (UVR) in sunlight. While UVR is a major environmental factor affecting human skin, the influence of skin microbiota on skin's UVR response remains underexplored. OBJECTIVES:We have investigated the impact of the skin microbiota on UVR-induced inflammation (sunburn response) in healthy humans (Fitzpatrick skin type I-III, n = 10). METHODS:Ethanol-disinfected and non-disinfected upper back skin of 10 healthy volunteers were exposed to a geometric series of solar-simulated UVR (SSR, erythemally-weighted, 7-80mJ/cm2). Erythema was assessed 24 h post-exposure visually and using reflectance spectroscopy. Skin biopsies were collected 0.5 h and 24 h after exposure to 80 mJ/cm2 SSR and from unexposed skin. Keratinocyte apoptosis (TUNEL, cleaved caspase-3), proliferation (Ki67), and dermal inflammatory infiltrate (CD68, neutrophil elastase, CD4) were assessed by immunostaining. Gene expression and pathway enrichment were analysed using Xenium spatial transcriptomics. RESULTS:Disinfected and non-disinfected skin exhibited similar minimal erythema doses, with no significant difference in the UVR-erythema dose-response. Disinfection had no detectable effect on the measured outcomes in unexposed skin. At 0.5 h post-exposure, disinfected skin responded similarly to non-disinfected skin across all measured parameters. However, at 24 h post-exposure, disinfected skin showed significantly fewer TUNEL+ keratinocytes (P = 0.0005), CD68+ macrophages (P = 0.012), and neutrophil elastase+ neutrophils (P = 0.012), together with increased Ki67+ keratinocyte proliferation (P = 0.020) compared with non-disinfected skin. Spatial transcriptomic analysis supported these findings, showing upregulation of proliferation-associated genes and pathways in disinfected skin, whereas apoptosis- and inflammation-associated pathways were enriched in non-disinfected skin. CONCLUSIONS:These findings suggest that the healthy skin microbiota modulates human skin's response to UVR, promoting keratinocyte apoptosis and dermal infiltration of neutrophils and macrophages while reducing keratinocyte proliferation.
BACKGROUND:Vitiligo affects 0·5-2% of the global population and carries a substantial psychosocial burden. Topical ruxolitinib 1·5% cream is approved for non-segmental vitiligo based on phase-3 trial data, but real-world evidence across heterogeneous populations remains limited. OBJECTIVES:To evaluate the real-world effectiveness, safety, and patient-reported outcomes of topical ruxolitinib across 34 Italian dermatology centres, and to identify possible clinical predictors of treatment response. METHODS:Multicentre retrospective cohort study (July 2024-October 2025). Patients (≥12 years) with non-segmental vitiligo received ruxolitinib 1·5% cream twice daily. Primary outcomes were F-VASI75 and F-VASI90 at 24 and 52 weeks. Secondary outcomes were VNS, DLQI, VitiQoL, GAD-7, and PHQ-9. RESULTS:860 patients (mean age 47 years; 58% female; disease duration 13·5 years; 84% previously treated) completed 24-week assessment; 229 (26·6%) had reached 52 weeks at the time of data lock. F-VASI75 was achieved by 18·5% at 24 weeks, increasing to 38·4% at 52 weeks; F-VASI90 rose from 5·7% to 25·8%. In multivariable logistic regression, summer treatment initiation (adjusted OR 6·7, 95% CI 2·7-16·8) and Koebner phenomenon (adjusted OR 1·6, 95% CI 1·04-2·66) were independent predictors of F-VASI75 at 24 weeks. At baseline, 37% of patients had moderate-to-severe anxiety (GAD-7 ≥10); this fell to 11% at 24 weeks and 2% at 52 weeks. VitiQoL, DLQI, and PHQ-9 improved at all timepoints. Adverse events were mild in 98·9%; treatment discontinuation rate was 1·5%. CONCLUSIONS:In a large real-world population considerably more heterogeneous than registration trial cohorts, topical ruxolitinib showed progressive repigmentation through 52 weeks with excellent tolerability. Summer initiation and Koebner phenomenon independently predicted early response, findings that may inform patient counselling and the design of prospective studies. The parallel sustained reduction in anxiety and depression argues for standardised mental health assessment as a routine component of vitiligo care.
This case series, a re-evaluation of a historical patient cohort after 42 years, provides valuable insights into the natural history of porphyria turcica. It has been confirmed that patient 1 is one of the individuals clinically documented in the landmark cohort study published by Cripps and others in the BJD in 1984.
This report details ulcerating sarcoidosis as a rare dermatological manifestation of systemic sarcoidosis that was repeatedly misattributed to venous insufficiency ulcers and recurrent infection for more than 3 years. Initiation of subcutaneous methotrexate led to complete resolution of the patient's extensive ulcers. We believe this case provides valuable clinical teaching for general practitioners, internists, dermatologists and other BJD readers who encounter persistent or atypical lower limb ulcers, reinforcing the need for timely diagnostic evaluation when standard management fails.
