British Journal of Dermatology最新文献

{"title":"Efficacy and safety of tildrakizumab in patients with early- vs late-onset psoriasis.","authors":"April W Armstrong, Andrew Blauvelt, Mark Lebwohl, Akihiko Asahina, Ranga Gogineni, Christopher E M Griffiths","doi":"10.1093/bjd/ljaf171","DOIUrl":"10.1093/bjd/ljaf171","url":null,"abstract":"<p><strong>Background: </strong>Age of psoriasis onset is bimodally distributed with distinct peaks at <40 (early onset) and ≥40 years (late onset). Although age of psoriasis onset is associated with distinct disease profiles, few well-controlled studies report efficacy of biologics in patients with early- vs late-onset disease. Efficacy and safety of tildrakizumab, an interleukin-23 p19 inhibitor, for the treatment of moderate-to-severe plaque psoriasis were investigated in the Phase 3 trials reSURFACE 1 and reSURFACE 2.</p><p><strong>Objectives: </strong>To determine efficacy and safety of tildrakizumab in patients with early- vs late-onset psoriasis through 28 weeks of treatment.</p><p><strong>Methods: </strong>This was a post hoc subgroup analysis of patients from reSURFACE 1 and reSURFACE 2. Patients ≥50 years of age were grouped by age of psoriasis onset at <40 vs ≥40 years. Efficacy endpoints included absolute Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), and proportions of patients who achieved a ≥75%/≥90%/100% improvement from baseline in PASI (PASI 75/90/100), Physician Global Assessment score of 0 or 1 (PGA 0/1), and DLQI of 0 or 1 (DLQI 0/1), adjusted for potential confounders. Safety was assessed from treatment-emergent adverse events (TEAEs).</p><p><strong>Results: </strong>Higher percentages and adjusted responder rate estimates of patients with late- (n = 130) vs early-onset psoriasis (n = 111) achieved absolute PASI <1 (36.2% vs 27.9%; estimate, 32.2% vs 25.0%), PASI 90 (50.8% vs 39.6%; estimate, 49.4% vs 40.2%), and PASI 100 (21.5% vs 8.1%; estimate, 13.7% vs 7.9%) at Week 28 (all P <0.05). Age of onset did not significantly affect change from baseline in absolute PASI or DLQI, or achievement of PASI <5, PASI <3, PASI 75, DLQI 0/1, or PGA 0/1 (all P > 0.05). Efficacy findings were supported in a subset of patients matched by disease duration. Among patients with early- vs late-onset psoriasis, TEAEs and serious TEAEs occurred in 65.8% vs 66.2% and 3.6% vs 6.9%, respectively.</p><p><strong>Conclusions: </strong>Treatment with tildrakizumab was effective with no safety signals in both patient subgroups. Patients with late-onset psoriasis were more likely to achieve complete or near-complete clearance than were patients with early-onset psoriasis.</p><p><strong>Clinical trial registration: </strong>NCT01722331 and NCT01729754.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss-of-function variants in DUSP1 encoding dual specificity phosphatase 1 cause palmoplantar keratoderma.","authors":"Kiril Malovitski, Yarden Feller, Moshe Giladi, Ajit B Janagond, Namratha Shivaraj, Gurushantappa Kadakol, Lubna Khair, Sari Assaf, Janan Mohamad, Rawaa Ishtewy, Alexander Ildardashty, Liat Samuelov, Ofer Sarig, Arun C Inamadar, Eli Sprecher","doi":"10.1093/bjd/ljaf181","DOIUrl":"https://doi.org/10.1093/bjd/ljaf181","url":null,"abstract":"<p><strong>Background: </strong>Dual specificity phosphatase 1 (DUSP1) has recently been shown to regulate keratinocytes (KCs) proliferation through ERK signaling.</p><p><strong>Aims: </strong>We aimed at delineating the genetic basis underlying inherited palmoplantar keratoderma (PPK) in two families.</p><p><strong>Material and methods: </strong>We used whole exome and direct sequencing, RT-qPCR, protein modeling, immunofluorescence confocal microscopy, immunoblotting, three-dimensional skin equivalents and the dispase dissociation assay.</p><p><strong>Results: </strong>Whole exome sequencing revealed two variants in DUSP1 (c.809T>G, p.Leu270Arg and c.251T>A, p.Val84Glu) encoding DUSP1, in four individuals with PPK belonging to two unrelated families affected by a semi-dominant form of PPK. Bioinformatics and protein modeling predicted the variants to be pathogenic. Primary human KCs transfected with constructs expressing the PPK-causing pathogenic variants in DUSP1 showed decreased DUSP1 expression and concomitant increased expression of p-ERK1/2 as well as reduced DSG1 expression. Accordingly, primary human KCs downregulated for DUSP1 displayed disrupted cell-to-cell adhesion, increased p-ERK1/2 and reduced DSG1 expression. Three-dimensional organotypic skin equivalents downregulated for DUSP1 demonstrated reduced DSG1 expression and increased epidermal thickness, reminiscent of the human phenotype. ERK1/2 inhibition rescued this abnormal phenotype.</p><p><strong>Conclusions: </strong>The present study attributes to DUSP1 a hitherto unrecognized role in epidermal differentiation and expand the spectrum of genetic defects known to cause inherited PPK.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical ruxolitinib for treatment of mycosis fungoides and lymphomatoid papulosis.","authors":"Marion Wobser, Matthias Goebeler, Andreas Rosenwald, Katja Maurus","doi":"10.1093/bjd/ljaf180","DOIUrl":"https://doi.org/10.1093/bjd/ljaf180","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormone Therapy and Increased Risk of Psoriasis in Reproductive-age and Postmenopausal Women: A Nationwide Cohort Study and Target Trial Emulation.","authors":"Hui-Wen Yang, Yi-Hsien Chen, Sheng-Yin To, Yuan-Liang Wen, Senyeong Kao, Liang-Hsuan Chen, Li-Ting Kao","doi":"10.1093/bjd/ljaf179","DOIUrl":"https://doi.org/10.1093/bjd/ljaf179","url":null,"abstract":"<p><strong>Background: </strong>Hormonal therapy (HT) is widely administered for contraception and menopausal symptom management. However, its impact on psoriasis risk remains unclear, requiring an evaluation across diverse age groups to inform clinical practice and optimize treatment strategies.</p><p><strong>Objective: </strong>To investigate the association between HT and the risk of psoriasis in reproductive-age and postmenopausal women.</p><p><strong>Methods: </strong>This study utilized both nationwide cohort design and target trial emulation, analyzing data from Taiwan's National Health Insurance Database (2001-2021). Women over 20 years old without a prior history of psoriasis, ovarian cancer, or breast cancer were included, segmented into reproductive-age (≤50 years) and postmenopausal (>50 years) groups. Women who initiated HT were assigned as the exposed group, while women without HT formed the comparison group. The primary outcome was the incidence of psoriasis over a five-year period. The study applied inverse probability of treatment weighting (IPTW) and Cox proportional hazards models to estimate hazard ratios (HRs). Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to enhance the robustness of the findings.</p><p><strong>Results: </strong>In the postmenopausal cohort, comprising 1,482,302 HT users and 1,313,799 nonusers, the IPTW-adjusted HR for psoriasis in the ITT analysis was 1.48 (95% CI 1.44-1.52). The PP analysis indicated a more pronounced risk, with an HR of 5.93 (95% CI 5.66-6.22). Among the reproductive-age cohort, which included 3,849,721 HT users and 1,585,461 nonusers, the IPTW-adjusted HR in the ITT analysis was 1.93 (95% CI 1.90-1.99). In the PP analysis, the risk increased, showing an HR of 7.85 (95% CI 7.56-8.15). These findings highlight the significantly elevated psoriasis risk associated with HT, especially in younger women.</p><p><strong>Conclusion: </strong>This study establishes an association between HT and an increased risk of psoriasis in both reproductive-age and postmenopausal women using a nationwide cohort design and target trial emulation. These findings further highlight the potential influence of hormonal factors on psoriasis development. Clinicians should remain attentive to early signs of psoriasis in women receiving HT to ensure timely recognition and management.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Unmet Needs in Brachioradial Pruritus.","authors":"Giulia Coscarella, Yael Rosen, Nathanael Singer, Eli Eyal, Linor Haimson, Orna Goren, Esther Hagai, Manuel Pereira, Sonja Stander, Gil Yosipovitch","doi":"10.1093/bjd/ljaf182","DOIUrl":"https://doi.org/10.1093/bjd/ljaf182","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the MAPK Pathway for NRAS Mutant Melanoma: From Mechanism to Clinic.","authors":"Yi Wang, Guangchao Xu, Hongwei Xia","doi":"10.1093/bjd/ljaf178","DOIUrl":"https://doi.org/10.1093/bjd/ljaf178","url":null,"abstract":"<p><p>Mutant NRAS is the second-most common type of mutation in melanoma. The prognosis is poor in the patients with NRAS mutant melanoma, and effective targeted treatment strategies are still lacking. Mutant NRAS mainly acts through activating the RAF-MEK-ERK signaling to promote the carcinogenesis in melanoma. In recent years, significant clinical advancements have been achieved by targeting the NRAS-MAPK pathway, with novel therapies such as the MEK inhibitor tunlametinib and the combination therapy of the pan-RAF inhibitor naporafenib with trametinib leading the way. In this review, we will systematically summarize the recent advances in the direct targeting of mutant NRAS proteins and their downstream RAF and MEK proteins, as well as targeting the MAPK pathway in combination with other therapeutic targets, including the immunotherapy, to treat NRAS mutant melanoma. Additionally, we will further discuss the current issues and emerging countermeasures related to targeted therapy for NRAS mutant melanoma.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanoma in England: incidence is up, mortality is down.","authors":"David C Whiteman","doi":"10.1093/bjd/ljaf175","DOIUrl":"https://doi.org/10.1093/bjd/ljaf175","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Living network meta-analysis to compare nemolizumab against other available targeted systemic treatments for atopic dermatitis.","authors":"Aaron M Drucker, Chantel Walwyn, Cherry Chu, Zenas Z N Yiu, Bram Rochwerg, Sonya Di Giorgio, Bernd W M Arents, Tanya Mohan, Tim Burton, Phyllis I Spuls, Jochen Schmitt, David Prieto-Merino, Carsten Flohr","doi":"10.1093/bjd/ljaf166","DOIUrl":"https://doi.org/10.1093/bjd/ljaf166","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of bullous pemphigoid with methotrexate is associated with a decreased mortality risk.","authors":"Päivi Leisti, Anna Pankakoski, Laura Huilaja, Jari Jokelainen, Outi Varpuluoma, Jaana Panelius, Kaisa Tasanen","doi":"10.1093/bjd/ljaf172","DOIUrl":"https://doi.org/10.1093/bjd/ljaf172","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mutation burden of narrowband ultraviolet B phototherapy (NB-UVB) in human skin; relevance to NB-UVB lifetime exposures and skin cancer surveillance.","authors":"Joanna C Fowler, Roshan K Sood, George Coltart, Chester Lai, Noeline Nadarajah, John W Holloway, Matthew J J Rose-Zerilli, Brian Diffey, Philip H Jones, Eugene Healy","doi":"10.1093/bjd/ljaf173","DOIUrl":"https://doi.org/10.1093/bjd/ljaf173","url":null,"abstract":"<p><strong>Background: </strong>Ultraviolet radiation (UVR) is used as treatment for psoriasis and other skin diseases, but UVR can induce DNA mutations which may lead to skin cancer development. While skin cancers have been documented in patients treated with phototherapy, a limited number of epidemiological studies have examined skin cancer incidence in people receiving narrowband ultraviolet B (NB-UVB) treatment. Information on mutagenicity of NB-UVB would help inform about the potential skin cancer risks of this treatment.</p><p><strong>Objectives: </strong>To determine the mutation burden in human skin resulting from a NB-UVB treatment course and use this data to estimate the total number of NB-UVB exposures whereupon skin cancer surveillance should commence.</p><p><strong>Methods: </strong>Biopsies of normal skin were obtained before and after a course of NB-UVB from 16 patients with psoriasis. Epidermal DNA was sequenced using nanorate sequencing (NanoSeq) to determine the mutational signatures and mutation burden from NB-UVB.</p><p><strong>Results: </strong>The NB-UVB treatment course increased the number of mutations in skin. Median increase in mutation burden was 0.55 substitutions/Mb in infrequently sun-exposed (buttock) and 0.89 substitutions/Mb in frequently sun-exposed (forearm) skin, P= 0.0001, n=14 patients and P=0.0098, n=10 patients respectively. Change in mutation burden due to NB-UVB ranged from 1.16 to 10.5-fold in buttock skin and 0.93 to 2.33-fold in forearm skin. This increase was mainly attributable to UVR-exposure linked mutational signatures, SBS7a and SBS7b, with some evidence that mutational burden related to genetic background of the individual. Modelling the change in mutation burden from NB-UVB relative to minimal erythema dose (MED) in comparison with average mutation burden in keratinocyte skin cancers allowed estimation of total lifetime exposures at which patients are likely to require skin cancer surveillance; for patients with MED equal to 2 standard erythemal doses (SEDs), skin cancer surveillance should be offered at 422, 165 and 58 NB-UVB exposures for those receiving low, typical, and high levels of sun exposure, respectively.</p><p><strong>Conclusions: </strong>A treatment course of NB-UVB causes UVR-induced mutations in normal skin of patients with psoriasis. Relating mutation burden to MED and sun behaviour habits allows estimation of when to commence skin cancer surveillance according to total lifetime NB-UVB exposures.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}