British Journal of Dermatology最新文献

{"title":"Bimekizumab efficacy and safety through 3 years in patients with moderate-to-severe plaque psoriasis: long-term results from the BE RADIANT phase IIIb trial open-label extension period.","authors":"Richard B Warren, Mark Lebwohl, Diamant Thaçi, Melinda Gooderham, Andreas Pinter, Carle Paul, Paolo Gisondi, Balint Szilagyi, Katy White, Delphine Deherder, Fabienne Staelens, Jérémy Lambert, Bruce Strober","doi":"10.1093/bjd/ljaf032","DOIUrl":"10.1093/bjd/ljaf032","url":null,"abstract":"<p><strong>Background: </strong>Overexpression of interleukin (IL)-17A and IL-17F significantly influences psoriasis pathology. Until recently, biologics targeting IL-17A alone, like secukinumab, were used to treat psoriasis. Bimekizumab is a monoclonal IgG1 antibody that targets both IL-17A and IL-17F. BE RADIANT was the first phase III trial to investigate switching from selective inhibition of IL-17A to dual inhibition of IL-17A and IL-17F. Bimekizumab has previously shown superior achievement of complete skin clearance [100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100)] vs. secukinumab through 48 weeks. Switching from secukinumab to bimekizumab resulted in improved clinical responses. Over 2 years, no new safety signals were observed.</p><p><strong>Objectives: </strong>To report the 3-year efficacy and safety of bimekizumab in patients with moderate-to-severe plaque psoriasis receiving continuous bimekizumab or switching from secukinumab after 1 year.</p><p><strong>Methods: </strong>The BE RADIANT phase IIIb randomized controlled trial had a 48-week double-blinded period, in which patients received bimekizumab [320 mg every 4 weeks (Q4W)] or secukinumab (300 mg weekly to week 4, then Q4W). At week 16, patients randomized to bimekizumab underwent re-randomization to receive Q4W or Q8W maintenance dosing. From week 48 onward (open-label extension), all received bimekizumab.</p><p><strong>Results: </strong>In total, 336 patients randomized to bimekizumab and 318 randomized to secukinumab at baseline entered the open-label extension. More patients randomized to bimekizumab achieved PASI 100 (modified nonresponder imputation) at year 1 (74.9%) vs. those randomized to secukinumab (52.8%). PASI 100 response rates were maintained over 3 years in patients treated with bimekizumab (68.8%) and increased in those randomized to secukinumab switching to bimekizumab (68.8%). Bimekizumab was well tolerated to 3 years. In patients who received ≥ 1 bimekizumab dose, the most common treatment-emergent adverse events (TEAEs) over 3 years were nasopharyngitis, oral candidiasis and upper respiratory tract infection (exposure-adjusted incidence rates 12.2, 10.0 and 5.5/100 patient-years, respectively). Rates of TEAEs of interest, including serious infections, inflammatory bowel disease, and suicidal ideation and behaviour, did not increase with longer exposure to bimekizumab from 1 to 3 years.</p><p><strong>Conclusions: </strong>More than two-thirds of patients randomized to bimekizumab and those who switched from secukinumab to bimekizumab achieved and maintained complete skin clearance over 3 years of treatment. Over 3 years, bimekizumab was well tolerated and TEAE rates did not increase with longer exposure.</p><p><strong>Trial registration: </strong>NCT03536884.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"44-55"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036539","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":"Focusing on antigen-specific T cells.","authors":"Takashi Inozume, Satoshi Fukushima","doi":"10.1093/bjd/ljaf050","DOIUrl":"10.1093/bjd/ljaf050","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"6-7"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363660","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":"A role for arginase in skin epithelial differentiation and antimicrobial peptide production.","authors":"Denis C Szondi, Rachel A Crompton, Linus Oon, Nagavidya Subramaniam, Khek-Chian Tham, Sze Han Lee, Helen Williams, Joanne Pennock, Thiam C Lim, Carine Bonnard, Jason Wong, Leah A Vardy, Sheena M Cruickshank","doi":"10.1093/bjd/ljaf057","DOIUrl":"10.1093/bjd/ljaf057","url":null,"abstract":"<p><strong>Background: </strong>Arginase 1 (ARG1) is an enzyme expressed by keratinocytes that drives several functions linked to skin barrier function. However, the mechanisms underpinning keratinocyte ARG1 function in barrier homeostasis have not been fully elucidated. Atopic dermatitis (AD) is linked to impaired skin barrier via altered keratinocyte differentiation and susceptibility to infection.</p><p><strong>Objectives: </strong>To investigate the role of ARG1 in keratinocyte differentiation and antimicrobial responses.</p><p><strong>Methods: </strong>In vitro two-dimensional differentiation assays using ARG knockdown or ARG inhibited keratinocytes were used to explore the function of ARG1 in keratinocyte differentiation and barrier formation. ARG1 was also assessed in an ex vivo model of AD.</p><p><strong>Results: </strong>ARG1 was strongly expressed in the apical layers of human skin, corresponding to high ARG1 expression in late differentiated -keratinocytes. ARG was downregulated in an ex vivo AD model relative to control, suggesting that altered ARG1 is clinically relevant. ARG1 -inhibition in keratinocytes led to a significant decrease in the late differentiation markers filaggrin, involucrin and loricrin, and significant downregulation of antimicrobial peptides (AMPs), lipocalin 2, kallikreins and small proline-rich proteins. ARG forms part of the urea cycle and the action of ARG on L-arginine causes the production of L-ornithine and urea. In turn, L-ornithine is catabolized for putrescine production. Supplementation with ARG products, putrescine and urea could rescue late keratinocyte differentiation and AMP expression in ARG-deficient cells.</p><p><strong>Conclusions: </strong>ARG1 activity plays a major role in keratinocyte differentiation and AMP production. ARG1 is downregulated in an AD model, and in cell systems its function can be rescued by the ARG1 downstream products putrescine and urea. Manipulation of the ARG1 pathway may have the potential to be used for the management of skin conditions such as AD.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"125-135"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412922","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":"Reassuring results from skin cancer risk in Swedish patients with vitiligo and alopecia areata.","authors":"Alexandra M Mortimore, Erin McMeniman","doi":"10.1093/bjd/ljaf118","DOIUrl":"10.1093/bjd/ljaf118","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"4-5"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976644","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":"Naevoid hyperkeratosis of the nipple and/or areola.","authors":"Lin Zheng, Jingzhu Bai, Ruihua Fang","doi":"10.1093/bjd/ljae501","DOIUrl":"10.1093/bjd/ljae501","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"190"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869390","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":"Bright yellow dots in children with alopecia areata.","authors":"André Luiz Vairo Donda, Rodrigo Pirmez, Antonella Tosti, Colombina Vincenzi, Daniel Fernandes Melo","doi":"10.1093/bjd/ljae498","DOIUrl":"10.1093/bjd/ljae498","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"191"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871380","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":"Variants in KLF4 affecting residue Asp441 cause an autosomal dominant syndromic ichthyosis.","authors":"Zijuan Wang, Jun Liu, Oded Wechsberg, Lina Liang, Catherine E Keegan, Christina Sloan-Heggen, You Mo, Yangyang Luo, Huijun Wang, Zhimiao Lin","doi":"10.1093/bjd/ljaf062","DOIUrl":"10.1093/bjd/ljaf062","url":null,"abstract":"<p><strong>Background: </strong>Congenital ichthyoses comprise a group of skin scaling diseases with clinical and genetic heterogeneity. They can be subclassified into syndromic and nonsyndromic forms. Syndromic ichthyoses affect organs beyond the skin. An increasing number of causative genes have been identified.</p><p><strong>Objectives: </strong>To identify the causative gene and the underlying pathogenesis of a previously unreported syndromic ichthyosis.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES), combined with Sanger sequencing, was used to identify the genetic defect. Protein structural modelling and dual-luciferase reporter assays were used to investigate the effects of the pathogenic variants on Krüppel-like factor 4 (KLF4). A human embryonic stem cell (hESC) H9 line harbouring the pathogenic variant was developed into a skin organoid for morphological observation and RNA sequencing analysis. The expression of candidate target genes was further validated in patient skin samples using quantitative reverse transcriptase polymerase chain reaction and immunofluorescence.</p><p><strong>Results: </strong>We enrolled four unrelated patients with a syndromic ichthyosis that predominantly manifested as ichthyosis, palmoplantar keratoderma, hypotrichosis, periorificial keratosis, nail dystrophy and extracutaneous involvement. WES identified two heterozygous missense variants, c.1322A>G (p.Asp441Gly) and c.1323T>A (p.Asp441Glu), in KLF4 in all four patients. Protein modelling predicted that the substitutions of the affected residue, Asp441, were likely to affect the stability of the local α-helix structure. Both variants exhibited reduced transcriptional activity. Skin organoids derived from hESC-H9 cells harbouring the heterozygous c.1323T>A variant displayed defects in epithelial morphogenesis and abnormal expression of keratinocyte differentiation-related genes and Wnt signalling genes. Decreased expression of KLK7 and WNT10A, which are vital for skin desquamation and multiorgan development, respectively, was detected in patient skin lesions.</p><p><strong>Conclusions: </strong>Loss-of-function variants affecting residue Asp441 of KLF4 cause an autosomal dominant syndromic ichthyosis with multiorgan involvement. These variants impair KLF4 transcriptional activity, leading to the downregulation of multiple genes, particularly KLK7 and WNT10A. This may disrupt the skin desquamation process and affect multiorgan development in the patients.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"136-146"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448373","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":"Risk of herpes zoster and postherpetic neuralgia in patients with psoriasis treated with biologics: a nationwide study using a target trial emulation framework.","authors":"Chaw-Ning Lee, Miyuki Hsing-Chun Hsieh, Che-Yu Chen, Chao-Chun Yang, Tzu-Chi Liao, Edward Chia-Cheng Lai","doi":"10.1093/bjd/ljaf101","DOIUrl":"10.1093/bjd/ljaf101","url":null,"abstract":"<p><strong>Background: </strong>Patients with psoriasis have a higher baseline risk of herpes zoster (HZ) than the general population. This has raised concerns that tumour necrosis factor (TNF)-α inhibitor use may be associated with an increased risk of HZ. However, the risk profiles for newer biologics, including interleukin (IL)-17, IL-12/23 and IL-23 inhibitors, remain uncertain.</p><p><strong>Objectives: </strong>To compare the risks of HZ and postherpetic neuralgia (PHN) in patients with psoriasis using different biologics (ustekinumab, secukinumab, ixekizumab, guselkumab, etanercept and adalimumab) vs. traditional systemic treatments (TSTs).</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database (2011-2021). We included patients with psoriasis or psoriatic arthritis aged ≥ 20 years who had been treated with biologics or TSTs for at least 6 months. We classified patients by individual biologics or TST and followed them for up to 2.5 years from drug initiation until the occurrence of outcome events or death. The primary outcome was a diagnosis of HZ. We used inverse probability of treatment weighting to adjust for covariates, including patient age, sex, comorbidities and comedications. We used Cox proportional hazards models to evaluate the risk of HZ with different biologics.</p><p><strong>Results: </strong>We identified 815, 1870, 1095, 2327, 261, 303 and 98 patients with psoriasis who were taking etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab and guselkumab, respectively. Compared with patients receiving TSTs, for those receiving ustekinumab and guselkumab the risk of HZ trended lower [ustekinumab: weighted hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.61-1.11; guselkumab: weighted HR 0.48, 95% CI 0.22-1.02], while for those receiving adalimumab it was statistically significantly higher (weighted HR 1.63, 95% CI 1.22-2.18). Additionally, ustekinumab was associated with a reduced risk of PHN (HR 0.22, 95% CI 0.08-0.64). There were no statistically significant differences in the risk of HZ between TSTs and either etanercept, secukinumab, ixekizumab or brodalumab.</p><p><strong>Conclusions: </strong>Our findings suggest that ustekinumab and guselkumab may be associated with a reduced risk of HZ and PHN vs. TSTs in patients with psoriasis. This study could have significance for real-world practice.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"105-114"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668980","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":"Estimating the proportions of allele frequencies for SERPINA12 pathogenic variants in Japanese patients with Nagashima-type palmoplantar keratosis/keratoderma.","authors":"Aoi Ebata, Takuya Takeichi, Kazuki Nishida, Basile Chretien, Akira Miyazaki, Takenori Yoshikawa, Yuika Suzuki, Kana Tanahashi, Ryo Fukaura, Mariko Seishima, Yasushi Suga, Yoshinao Muro, Yuka Nakazawa, Tomoo Ogi, Masashi Akiyama","doi":"10.1093/bjd/ljaf111","DOIUrl":"10.1093/bjd/ljaf111","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"184-185"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728638","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":"Management of congenital ichthyoses: guidelines of care: Part two: 2024 update.","authors":"Juliette Mazereeuw-Hautier, Amy S Paller, Edel O'Toole, Isabelle Dreyfus, Christine Bodemer, Masashi Akiyama, Andrea Diociaiuti, Maya El Hachem, Judith Fischer, Rogelio Gonzalez-Sarmiento, Carlos Gutiérrez-Cerrajero, Hagen Ott, Cristina Has, Nathalie Jonca, Céline Granier Tournier, Ana Martinez, Heiko Traupe, Carmen Maria Salavastru, Matthias Schmuth, Eli Sprecher, Kathrin Giehl, Mandy Aldwin, Ruth Anton Morales, Saturnino Santos, Marie-Anne Morren, Anne Audouze, Raman Malhotra, Karin Veldman, Joanna Narbutt, Kira Süßmuth, Antoni Gostynski, Angela Hernandez-Martin","doi":"10.1093/bjd/ljaf077","DOIUrl":"10.1093/bjd/ljaf077","url":null,"abstract":"<p><p>In 2019, a group of experts published the first European guidelines for the management of congenital ichthyoses after a multidisciplinary expert meeting held in 2016. An update of these guidelines and literature search was planned every 5 years, given the clinical, molecular and therapeutic advances, including the use of biologic therapies. We present here updated guidelines that have been developed by a reorganized multidisciplinary group of international experts after a systematic review of recent literature, discussions and consensus reached at an expert conference held in June 2023. The guidelines provide summarized evidence and expert-based recommendations that aim to guide clinicians in the management of these rare and often complex diseases. These guidelines consist of two sections. Part one is reported elsewhere. Here, Part two covers the management of complications (eye, ear-nose-throat, pruritus, pain, cutaneous infections, vaccinations, growth failure and nutritional deficiency, hair and nail anomalies, reaction to hot and cold climates, physical limitations, comorbidities) and the particularities of the neonatal period and Netherton syndrome.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"28-43"},"PeriodicalIF":11.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794673","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}