British Journal of Dermatology最新文献

{"title":"Phase 2 Trial of Topical Application of the Hedgehog Inhibitor Patidegib in Patients With Gorlin Syndrome.","authors":"John T Lear, Catherine A Harwood, Zeeshaan Hasan, Jonathan Kentley, Jason Thomson, Andre Khoo, Alix Alderman, Mark DeSouza, Ervin H Epstein, Gerd G Kochendoerfer, Jean Y Tang","doi":"10.1093/bjd/ljae444","DOIUrl":"https://doi.org/10.1093/bjd/ljae444","url":null,"abstract":"<p><strong>Background: </strong>Patients with Gorlin (basal cell nevus) syndrome (GS) have numerous phenotypic abnormalities due to over-activity of the hedgehog (HH) signaling pathway, most commonly due to a heritable mutation in the PTCH1 gene, which encodes a major inhibitor of this pathway. HH inhibitors (HHi) taken orally can reverse some of the manifestations, most prominent of which is the development of numerous cutaneous basal cell carcinomas (BCCs). In order to improve the benefit:risk ratio, we have developed a gel containing a small cyclopamine-derived molecule that can be applied topically in expectation that this mode of delivery can reduce the burden of BCCs without producing the systemic adverse effects that cause patients to stop treatment with oral HHis.</p><p><strong>Objectives: </strong>This study attempts to determine whether or not Patidegib Topical Gel, 2% or 4%, can accumulate in high enough concentrations to have local anti-BCC efficacy but not so high that systemic drug levels produce the adverse effects that are typical of oral HHi treatment.</p><p><strong>Methods: </strong>We conducted a small, randomized, double blinded Phase 2A trial at two sites in the United Kingdom to assess the clinical and molecular efficacy and adverse effects of 6 months of twice daily application of Patidegib Topical Gel to the entire face as well as to treatment-targeted surgically-eligible BCCs at other anatomical sites.</p><p><strong>Results: </strong>Post hoc analyses suggested that Patidegib Topical Gel reduced the number of new surgically-eligible BCCs and the level of HH signaling with minimal adverse effects.</p><p><strong>Conclusions: </strong>Patidegib Topical Gel warrants further clinical development.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638269","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":"Interactive effect of genetic and environmental risk factors on Psoriasis: current evidence and future directives.","authors":"Nidhi Singh, Tamara Schikowski","doi":"10.1093/bjd/ljae450","DOIUrl":"https://doi.org/10.1093/bjd/ljae450","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638222","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":"Real-world data confirms limited efficacy of dual anti-PD-1 and CTLA-4 immune checkpoint blockade in acral lentiginous melanoma.","authors":"David X Zheng, Russell W Jenkins","doi":"10.1093/bjd/ljae445","DOIUrl":"https://doi.org/10.1093/bjd/ljae445","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638290","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":"Haematogenous seeding in mycosis fungoides and Sézary syndrome: Current evidence and clinical implications.","authors":"Robert Gniadecki, Emmanuella Guenova, Christiane Querfeld, Jan P Nicolay, Julia Scarisbrick, Lubomir Sokol","doi":"10.1093/bjd/ljae441","DOIUrl":"https://doi.org/10.1093/bjd/ljae441","url":null,"abstract":"<p><p>Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of diseases characterised by abnormal neoplastic T-cell growth in the skin. Mycosis fungoides (MF), the most common CTCL, manifests as erythematous skin patches and/or plaques, tumours or erythroderma. The disease may involve blood, lymph nodes and rarely viscera. Sézary syndrome (SS) is a unique leukaemia/lymphoma syndrome related to MF, which presents with blood and skin involvement at diagnosis. The pathogenesis of MF/SS is not fully elucidated. The presence of skin lesions at distant sites underpins a hypothesis that MF/SS lesions may develop through haematogenous seeding. Phenotypic similarities between malignant and normal T-cells led to the notion that disease-initiating mutations occur in specific subtypes of mature T-cells, which are responsible for most CTCLs. However, this mature T-cell precursor model is not always consistent with clinical observations and research on MF/SS pathogenesis. Here, we review evidence supporting an alternative model of pathogenesis for MF/SS involving haematogenous seeding as a key process responsible for the initiation and progression of the disease. According to this hypothesis, malignant transformation occurs at an early stage of T-cell development (probably in bone marrow or thymus), yielding circulating neoplastic T-cells which colonise the skin where the microenvironment is most permissive for proliferation and evolution. These mutated precursor cells seed the skin where they find a suitable niche to develop into clinically perceptible disease. Subsequently, malignant T-cells can re-enter the bloodstream, re-seed pre-existing lesions and seed new areas of the skin, causing synchronous and convergent changes in the transcriptomic profile of lesions and tumours, and clinical disease progression - 'consecutive haematogenous seeding' captures this temporal phenomenon. This model radically changes the current understanding of CTCL pathogenesis, transforming it from a primarily cutaneous disease with secondary involvement of blood, to a systemic disease, where the spread of malignant cells through the blood to the skin is not a phenomenon of advanced disease but is an essential component of pathogenesis. This understanding of MF/SS could have several clinical implications, including standardising our approach to assessing blood tumour burden, potential advances in prognosis and monitoring, and investigating combination treatments to improve patient outcomes.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638218","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":"Emerging Challenges in Global Health Dermatology: measuring impact and sustainability.","authors":"Morvarid Zehtab, L Claire Fuller, Wendemagegn Enbiale, Karolyn A Wanat, Luca Borradori, Henry W Lim, Esther E Freeman","doi":"10.1093/bjd/ljae435","DOIUrl":"https://doi.org/10.1093/bjd/ljae435","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638210","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":"Exploring the driver events of eccrine poromas and porocarcinomas: A retrospective, cross-institutional study of 54 cases.","authors":"Mark J Arends, Martin Del Castillo Velasco-Herrera, Saamin Cheema, Kim Wong, Jacqueline M Boccacino, Ian Vermes, Kirsty Roberts, Elizabeth Anderson, Michiel P J van der Horst, Nicolas de Saint Aubain, Ahmed K Alomari, Carlos Monteagudo, Steven D Billings, Derek Frew, Emily Clarke, William Merchant, Neil Rajan, Peter Ferguson, Carolin Mogler, Ingrid Ferreira, Thomas Brenn, Louise van der Weyden, David J Adams","doi":"10.1093/bjd/ljae447","DOIUrl":"https://doi.org/10.1093/bjd/ljae447","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638213","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 roles of IL-17A and IL-17F in hidradenitis suppurativa pathogenesis: evidence from human in vitro preclinical experiments and clinical samples.","authors":"Joseph Rastrick, Hannah Edwards, Alex S Ferecskó, Gaëlle Le Friec, Avneet Manghera, Matthew Page, Stevan Shaw","doi":"10.1093/bjd/ljae442","DOIUrl":"https://doi.org/10.1093/bjd/ljae442","url":null,"abstract":"<p><strong>Background: </strong>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 IL-17A and IL-17F have been shown to be upregulated in patients with HS. Previous studies demonstrated that the monoclonal IgG1 antibody bimekizumab selectively inhibits IL-17F in addition to IL-17A.</p><p><strong>Objectives: </strong>To further investigate the roles of IL-17A and IL-17F in HS pathogenesis.</p><p><strong>Methods: </strong>RNA sequencing was conducted on skin biopsies taken at baseline and after treatment at Week 12 of the phase 2 proof of concept study of bimekizumab in patients with moderate to severe HS. Differentially expressed genes were identified between baseline lesional and non-lesional 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 the supernatant of stimulated Th17 cells in combination with anti-IL-17A, anti-IL-17F, anti-IL-17A and anti-IL-17F, or IgG control antibodies. Total mRNA was analysed by RNA sequencing (RNAseq). Cellular supernatants from the stimulated HHFKs were used as a source of Th17-induced chemoattractants in neutrophil chemotaxis assays.</p><p><strong>Results: </strong>RNAseq revealed that the most prominently upregulated genes within HS lesions included those associated with neutrophil biology. Bimekizumab treatment resulted in reduced expression of these genes. Extent of reduction in gene expression was dependent on HiSCR50 fulfilment. In vitro, dual inhibition of IL-17A and IL-17F had greater attenuation of Th17-induced HS-associated genes and neutrophil migration in HHFKs compared to IL-17A or IL-17F inhibition alone. In situ hybridisation revealed IL-17A and IL-17F producing cells in HS lesions can lack IL-23R and IL-1β could induce IL-23-independent IL-17F expression in vitro. Furthermore, mucosal-associated invariant cells in HS tunnels expressed IL-17F and IL-1R1. IL-1β, IL-17A and IL-17F expressing cells were found to be co-localised in HS lesions.</p><p><strong>Conclusions: </strong>These data support the hypothesis that IL-17A and IL-17F play central roles in HS, a neutrophilic dermatosis. The presence of IL-1β may partly explain the high expression of IL-17F in lesional HS tissue.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615112","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":"Correction to: COL10A1 expression distinguishes a subset of cancer-associated fibroblasts present in the stroma of high-risk basal cell carcinoma.","authors":"","doi":"10.1093/bjd/ljae440","DOIUrl":"https://doi.org/10.1093/bjd/ljae440","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615110","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":"Disabling Pansclerotic Morphea: A century of discovery.","authors":"Vivian K Hua, Johanna Chang, Ronald M Laxer, Lori Broderick","doi":"10.1093/bjd/ljae443","DOIUrl":"https://doi.org/10.1093/bjd/ljae443","url":null,"abstract":"<p><p>Disabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder at the severe end of the localized scleroderma spectrum which primarily affects children under 14 years of age. The disease is characterized by rapid sclerosis with circumferential involvement that frequently extends to the fascia, muscle, and bone. Disease progression often involves development of sclerotic plaques, chronic skin ulcers, and painful joint contractures leading to patient immobility with a high mortality rate. Internal organ fibrosis is typically absent. The aggressive and systemic nature of the disease leads patients to seek multidisciplinary care where current therapies are targeted towards immunomodulation and measures to preserve mobility while limiting infection, but often have limited efficacy. Here, we summarize all DPM patients in the English literature, common clinical symptoms, laboratory investigations, and treatments reported to date. Assessment of published cases suggest that the number of therapies does not influence disease outcome and that female patients were younger at the time of reported death. Clinician familiarity and awareness of common DPM symptoms are important for an accurate and early diagnosis. Furthermore, knowledge of the treatments that have been reported to be effective in mitigating disease progression may be helpful in expanding the treatment options available to patients.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615111","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":"Juvenile xanthogranuloma underneath a toenail: an unusual localization.","authors":"Xiaoting Song, Hang Li, Shuxia Yang","doi":"10.1093/bjd/ljae421","DOIUrl":"https://doi.org/10.1093/bjd/ljae421","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603407","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}