British Journal of Dermatology最新文献

{"title":"Safety and efficacy of the selective tyrosine kinase 2/Janus kinase 1 inhibitor TLL-018 in moderate-to-severe plaque psoriasis: a phase Ib, randomized, double-blind, placebo-controlled study.","authors":"Jia-Qi Chen, Min Zheng, Wen-Hao Yin, Ping Wang, Xiao-Wei Shi, Tie-Chi Lei, Zhi-Ming Li, Meng Pan, Yu-Ling Shi, Yu-Zhen Li, Congxin Liang, Xiao-Yong Man","doi":"10.1093/bjd/ljaf185","DOIUrl":"10.1093/bjd/ljaf185","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis treatments that provide rapid and extensive itch relief as well as lesion clearance are currently inadequate.</p><p><strong>Objectives: </strong>To evaluate the efficacy and safety of the tyrosine kinase 2/Janus kinase 1 inhibitor TLL-018 in patients with moderate-to-severe psoriasis.</p><p><strong>Methods: </strong>This phase Ib, double-blind, placebo-controlled study (NCT05342428) randomized participants to receive TLL-018 10 mg, 20 mg, 30 mg or placebo 2 : 2 : 2 : 1 orally twice daily for 12 weeks. The study included 73 patients with moderate-to-severe psoriasis. Eligible patients were aged 18-75 years and were diagnosed with moderate-to-severe psoriasis at least 6 months prior to screening, as defined by a Psoriasis Area and Severity Index (PASI) of ≥ 12, a body surface area ≥ 10% and a Physician's Global Assessment (PGA) of ≥ 3. The primary endpoint was safety of TLL-018. The efficacy endpoints were proportions of patients at week 12 achieving a ≥ 75% improvement from baseline in PASI (PASI 75), PGA of 0 or 1 (PGA 0/1) and Dermatology Life Quality Index of 0 or 1.</p><p><strong>Results: </strong>A total of 73 participants were treated. TLL-018 was well tolerated, and most treatment-emergent adverse events were mild/moderate. At week 12, 40% of patients (8 of 20) achieved PASI 75 with TLL-018 10 mg, 48% (10 of 21) with 20 mg, 62% (13 of 21) with 30 mg and 9% (1 of 11) with placebo. The proportions of patients with PGA 0/1 were 35%, 43%, 71% and 0%, respectively. Of the 21 patients in the TLL-018 30-mg group, 10 (48%) achieved a ≥ 90% improvement from baseline in PASI.</p><p><strong>Conclusions: </strong>TLL-018 was well tolerated and showed promising efficacy at week 12 compared with placebo in patients with moderate-to-severe plaque psoriasis.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"670-677"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076125","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":"Syndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy.","authors":"Amy S Paller, Joyce Teng, Juliette Mazereeuw-Hautier, Ángela Hernández-Martín, Céline Granier Tournier, Alain Hovnanian, Mandy Aldwin-Easton, Gianluca Tadini, Janice Schwartz, Eli Sprecher, Kiril Malovitski, Akemi Ishida-Yamamoto, Keith Choate, Masashi Akiyama, Edel A O'Toole, Judith Fischer, Christine Bodemer, Antoni Gostynski, Matthias Schmuth","doi":"10.1093/bjd/ljaf123","DOIUrl":"10.1093/bjd/ljaf123","url":null,"abstract":"<p><p>Since the 2010 classification of ichthyoses, our understanding of hereditary epidermal differentiation disorders (EDDs) has markedly increased, allowing for consideration of new therapeutic targets based on disease pathogenesis. A new gene- and protein product function-based classification focuses on shared mechanisms of disease pathogenesis, with the possibility that grouped disorders may respond similarly to new therapeutics. These EDDs have been subdivided into syndromic (sEDD), nonsyndromic with features limited to skin and appendages, and predominantly palmoplantar skin involvement (nonsyndromic and syndromic). sEDDs have clinically important extracutaneous features related to the gene alteration. Often, recognition based on skin manifestations facilitates early gene-based diagnosis, discussion of prognosis, genetic counselling and the initiation of therapy. All sEDDs are rare; the most common are STS-sEDD (formerly known as X-linked ichthyosis) and SPINK5-sEDD (formerly known as Netherton syndrome). Given the rarity, frequent association with early demise and variable clinical features of sEDDs, the natural history of the diseases with advancing age and genotype-phenotype relationships are poorly defined. Of the 51 sEDDs, associated neurological (n = 36; 71%) and/or ophthalmological (n = 25; 49%) findings are most common, and 39% (n = 20) have associated hair abnormalities. The widespread use of topical lovastatin for cholesterol synthesis-related sEDDs represents the prototype of pathogenesis-based therapy. This concept of upstream inhibition to prevent metabolite accumulation and supplementation with the pathway end product potentially applies to other sEDDs, such as those affecting ceramide synthesis and transport. Topical or systemically administered inhibition of activated pathways is another potential approach, exemplified by the emerging treatment of SPINK5-sEDD with kallikrein inhibitors. Many sEDDs may be amenable to gene editing or the introduction of functional cDNA. However, even systemic treatments targeting cutaneous diseases may not address extracutaneous manifestations that arise during embryological development.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"592-618"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784549","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":"Monoclonal gammopathy of thrombotic significance.","authors":"Laurence Mainville, David Croitoru","doi":"10.1093/bjd/ljaf144","DOIUrl":"10.1093/bjd/ljaf144","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"807"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966306","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":"Proposing an immune-inclusive lens to the new epidermal differentiation disorders classification.","authors":"Rahul Mahajan, Hitaishi Mehta, Dipankar De, Sanjeev Handa","doi":"10.1093/bjd/ljaf187","DOIUrl":"10.1093/bjd/ljaf187","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"799-800"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076121","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":"Nonsyndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy.","authors":"Masashi Akiyama, Keith Choate, Ángela Hernández-Martín, Mandy Aldwin-Easton, Christine Bodemer, Antoni Gostyński, Alain Hovnanian, Akemi Ishida-Yamamoto, Kiril Malovitski, Edel A O'Toole, Amy S Paller, Matthias Schmuth, Janice Schwartz, Eli Sprecher, Joyce M C Teng, Céline Granier Tournier, Juliette Mazereeuw-Hautier, Gianluca Tadini, Judith Fischer","doi":"10.1093/bjd/ljaf154","DOIUrl":"10.1093/bjd/ljaf154","url":null,"abstract":"<p><p>Epidermal differentiation disorders (EDDs) encompass inherited conditions characterized by abnormal epidermal differentiation, including nonsyndromic and syndromic subtypes with more extensive cutaneous involvement or palmoplantar keratoderma. Nonsyndromic EDDs (nEDDs) are defined as disorders that primarily affect large areas of skin and adnexal structures without alterations in extracutaneous tissues resulting from the underlying genetic change. To facilitate the development of targeted therapies and to provide clinicians with clearer therapeutic guidance, we have developed a new nomenclature for EDDs that includes the causative altered gene and the nEDD subgroup designation, sometimes with a clinical or histological descriptor or acronym. Historically, many nEDDs have been named on the basis of phenotypic characteristics or associations that are now considered outdated or inappropriate. For example, the term 'harlequin ichthyosis' evokes potentially stigmatizing images. Similarly, the word 'ichthyosis' is derived from the Greek ichthys, meaning fish, and the Greek hystrix, meaning porcupine, further emphasizing the need to abandon derogatory terminology. As a result, the clinical relevance of the previous classification, which included eponymous and/or descriptive titles, has diminished. In the new, gene-based classification, old terms considered pejorative, such as ichthyosis, vulgaris, hystrix and harlequin have been eliminated and eponyms have been replaced. Among the 53 genetically distinct nEDDs are conditions formerly known as autosomal recessive congenital ichthyosis, erythrokeratodermia variabilis et progressiva, Hailey-Hailey disease and Darier-White disease. This review outlines the updated nomenclature and classifications of nEDDs, linked to detailed clinical descriptions and representative photographs to guide practitioners.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"619-641"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966404","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":"Paediatric arsenical keratosis.","authors":"Xu Li, Lili Zhi","doi":"10.1093/bjd/ljaf150","DOIUrl":"10.1093/bjd/ljaf150","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"808"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961644","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":"Steroid acne: fluorescence under ultraviolet light.","authors":"Lin Wang, Cheng Tan","doi":"10.1093/bjd/ljaf107","DOIUrl":"10.1093/bjd/ljaf107","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"805"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676842","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":"Blueberry muffin rash in neonatal leukaemia.","authors":"Zeqiao Zhang, Zhimiao Lin","doi":"10.1093/bjd/ljaf116","DOIUrl":"10.1093/bjd/ljaf116","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"806"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728637","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":"10.1093/bjd/ljaf175","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"588"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","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":"Incidence and mortality of melanoma in situ and malignant melanoma in England between 2001 and 2020.","authors":"Dimitrios Karponis, Birgitta van Bodegraven, Khaylen Mistry, Vasiliki Nikolaou, Alexander J Stratigos, Nick J Levell, Zoe C Venables","doi":"10.1093/bjd/ljaf136","DOIUrl":"10.1093/bjd/ljaf136","url":null,"abstract":"<p><strong>Background: </strong>An increase in the incidence of melanoma has been reported globally since the late twentieth century, while mortality from melanoma is no longer increasing in England and other countries. Improved therapeutics have reduced mortality. However, this phenomenon implicates 'overdiagnosis', where thinner melanomas of unclear malignant potential are being diagnosed possibly due to 'diagnostic drift'.</p><p><strong>Objectives: </strong>To assess the age-standardized and age-specific incidence and mortality trends for melanoma in situ (MIS) and malignant melanoma (MM) in England between 2001 and 2020 by age and gender.</p><p><strong>Methods: </strong>We analysed routinely collected data from the National Disease Registration Service for MIS and MM in England between 2001 and 2020. We used joinpoint regression analysis to calculate the trends and average annual percentage change (APC) in age-standardized (using the 2013 European Standard Population) incidence (EASIR) and mortality (EASMR) and age-specific incidence (ASIR) and mortality (ASMR) rates, by age and gender per 100 000 person years (PYs).</p><p><strong>Results: </strong>Between 2001 and 2020, 86 792 cases of MIS and 220 286 cases of MM were recorded in England. The EASIR (per 100 000 PYs) for MM increased most rapidly during 2001-6 (from 14.6 to 19.6; APC 6.3%); the rate of increase slowed during 2006-14 (APC 4.1%; EASIR2014 26.7) and decelerated further between 2014 and 2019 (APC 1.4%; EASIR2019 28.7). The EASIR for MIS (per 100 000 PYs) increased rapidly during 2001-15 (from 4.5 to 12.5; APC 7.5%) and subsequently slowed between 2015 and 2019 (to EASIR2019 13.3; APC 1.9%). In individuals 0-24 years old, the ASIR of MM and MIS has been decreasing since the late 2000s, whereas the ASIR of MM in those aged > 50 years is rising, with the greatest increases seen in those aged > 70 years. Since the early 2010s, EASMRs from MM have remained higher in men. ASMRs have reduced in adults < 74 years of age; however, rates have continued to increase in those > 75 years old.</p><p><strong>Conclusions: </strong>The deceleration in the incidence rates of MM and MIS may be due to stabilization of any diagnostic drift, ethnicity diversity and reduced sun-seeking behaviours, particularly in younger generations. Mortality rates from MM have decreased since therapeutic developments in the early 2010s, and in younger generations before this. MM incidence and mortality are increasing most rapidly in men aged > 75 years, the age group with the highest incidence and expected growth in the future. These results support the importance of early melanoma detection, public health sun-awareness campaigns and better melanoma diagnostics.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"687-695"},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977218","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}