British Journal of Dermatology最新文献

{"title":"Keratin variants in monilethrix.","authors":"Daniela Ortner-Tobider, Thomas Trafoier, Verena Moosbrugger-Martinz, Susanne Tollinger, Robert Gruber, Matthias Schmuth","doi":"10.1093/bjd/ljae340","DOIUrl":"10.1093/bjd/ljae340","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"863-864"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079204","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 magnitude and healthcare costs of melanoma in situ and thin invasive melanoma overdiagnosis in Australia.","authors":"Daniel Lindsay, Katy J L Bell, Catherine M Olsen, David C Whiteman, Thanya Pathirana, Louisa G Collins","doi":"10.1093/bjd/ljae296","DOIUrl":"10.1093/bjd/ljae296","url":null,"abstract":"<p><strong>Background: </strong>Research suggests that a high proportion of melanoma in situ (MIS) may be overdiagnosed, potentially contributing to overtreatment, patient harm and inflated costs for individuals and healthcare systems. However, Australia-wide estimates of the magnitude of melanoma overdiagnosis are potentially outdated and there has been no estimation of the cost to the healthcare system.</p><p><strong>Objectives: </strong>To estimate the magnitude and cost of overdiagnosed MIS and thin invasive melanomas in Australia.</p><p><strong>Methods: </strong>Using two different methods to calculate lifetime risk, we used routinely collected national-level data to estimate overdiagnosed MIS and thin invasive melanomas (stage IA) in Australia in 2017 and 2021, separately for men and women. We multiplied the number of overdiagnosed melanomas by the estimated annual cost of a MIS or thin invasive melanoma, to quantify the financial burden of melanoma overdiagnosis to the Australian healthcare system in the year following diagnosis.</p><p><strong>Results: </strong>We estimated that 67-70% of MIS were overdiagnosed in 2017, rising to 71-76% in 2021, contributing to between 19 829 [95% confidence interval (CI) 19 553-20 105] and 20 811 (95% CI 20 528-21 094) cases of overdiagnosed MIS. In 2021, the estimated costs in Australia ranged between $17.7 million Australian dollars (AUD; 95% CI 17.4-17.9 million) and AUD$18.6 million (95% CI 18.3-18.8 million). We estimated that 22-29% of thin invasive melanomas were overdiagnosed in 2017, rising to 28-34% in 2021, contributing to between 2831 (95% CI 2726-2935) and 3168 (95% CI 3058-3279) overdiagnosed thin invasive melanomas. In 2021, the estimated costs from thin invasive melanoma overdiagnoses ranged between AUD$2.5 million (95% CI 2.4-2.6 million) and AUD$2.8 million (95% CI 2.7-2.9 million).</p><p><strong>Conclusions: </strong>Melanoma overdiagnosis is a growing clinical and public health problem in Australia, producing significant economic costs in the year following overdiagnosis. Limiting melanoma overdiagnosis may prevent unnecessary healthcare resource use and improve financial sustainability within the Australian healthcare system.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"906-913"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723154","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":"Cytokeratin 17 expression is commonly observed in keratinocytic skin tumours and controls tissue homeostasis impacting human papillomavirus protein expression.","authors":"Daniel Hasche, Martin Hufbauer, Ilona Braspenning-Wesch, Sonja Stephan, Steffi Silling, Gabriele Schmidt, Stephan Krieg, Alexander Kreuter, Baki Akgül","doi":"10.1093/bjd/ljae255","DOIUrl":"10.1093/bjd/ljae255","url":null,"abstract":"<p><strong>Background: </strong>The structured expression of several keratins in the skin is associated with differentiation status of the epidermal layers, whereas other keratins are upregulated only during wound healing, in skin disorders and in cancers. One of these stress keratins, K17, is correlated with poor prognosis in various cancer types and its loss has been shown to decelerate tumour growth. K17 expression can also be detected in cutaneous squamous cell carcinomas, where ultraviolet irradiation and infection with cutaneous human papillomaviruses are important cofactors. It was previously reported that K17 is upregulated in papillomavirus (PV)-induced benign skin lesions in mice and induces an immunological status that is beneficial for tumour growth.</p><p><strong>Objectives: </strong>In order to investigate whether K17 upregulation is induced by PVs, we analysed K17 levels in skin tumour specimens of different animal models and humans.</p><p><strong>Methods: </strong>Various immunofluorescence stainings were performed to identify K17 expression as well as levels of E-cadherin, vimentin and CD271. Tissues were further analysed by polymerase chain reaction (PCR), quantitative (q)PCR and enzyme-linked immunosorbent assay to control for PV activity. K17 knockdown cells were generated and effects on viral life cycle were investigated by infection assays, qPCR and Western blotting.</p><p><strong>Results: </strong>We showed that K17 is commonly expressed in skin tumours and that its presence is not directly linked to viral oncoprotein expression. Rather, K17 expression seems to be a marker of epithelial differentiation and its absence in tumour tissue is associated with an epithelial-to-mesenchymal transition. We further demonstrated that the absence of K17 in skin tumours increases markers of cancer stem-like cells and negatively affects viral protein synthesis.</p><p><strong>Conclusions: </strong>Collectively, our data indicate that K17 expression is a common feature in skin tumorigenesis. While K17 is not primarily targeted by PV oncoproteins, our in vivo and in vitro data suggest that it is an important regulator of epithelial differentiation and thus may play a role in controlling viral protein synthesis.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"949-963"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327217","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":"Phenotypic and genotypic risk factors for invasive melanoma by sex and body site.","authors":"Catherine M Olsen, Nirmala Pandeya, Rachel E Neale, Matthew H Law, David C Whiteman","doi":"10.1093/bjd/ljae297","DOIUrl":"10.1093/bjd/ljae297","url":null,"abstract":"<p><strong>Background: </strong>Cutaneous melanoma incidence varies consistently across body sites between men and women, but the underlying causes of these differences remain unclear. To date, no prospective studies have examined risk factors for melanoma separately for men and women according to body site.</p><p><strong>Objectives: </strong>We aimed to examine the association between identified constitutional, genetic and environmental risk factors for invasive melanoma of different body sites among men and women.</p><p><strong>Methods: </strong>We compared the association between constitutional, genetic and environmental risk factors for invasive melanoma on different body sites separately for men and women in a population-based prospective cohort study of 17 774 men and 21 070 women aged between 40 and 69 years who were residents of Queensland, Australia at baseline in 2011. Participants were followed until December 2021. We examined risk factors including hair colour, tanning ability, naevus density and proxies for high cumulative sun exposure, all self-reported at baseline. We also examined polygenic risk score (PRS) derived from summary statistics from a melanoma genome-wide association study meta-analysis.</p><p><strong>Results: </strong>During a median 10.4 years of follow-up, 455 men and 331 women developed an incident invasive melanoma; the mean age at diagnosis was lower in women than in men (62.6 vs. 65.0 years). The most common body site was the trunk in men (45.1%), and the upper (36.8%) and lower limbs (27.4%) in women. High naevus density and proxy measures of high cumulative sun exposure were similarly associated with melanoma at all sites in men and women. In both sexes, high genetic risk was associated with melanoma on all body sites except the head and neck. We observed differences between men and women in the association between PRS and melanoma of the trunk [highest vs. lowest tertile of PRS: hazard ratio (HR) 2.78, 95% confidence interval (CI) 1.64-4.69 for men; HR 1.55, 95% CI 0.63-3.80 for women] and nonsignificant but large differences for the lower limbs (HR 5.25, 95% CI 1.80-15.27 for men; HR 1.75, 95% CI 0.88-3.47 for women).</p><p><strong>Conclusions: </strong>While there are a number of potential explanations for these findings, this raises the possibility that genetic factors other than those related to pigmentation and naevus phenotypes may play a role in the predilection for melanoma to arise on different sites in men and women.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"914-923"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723156","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 scabies in children under 15 kg and pregnant or breastfeeding women: recommendations supported by the Centre of Evidence of the French Society of Dermatology.","authors":"Aurelie Morand, Amandine Weill, Juliette Miquel, Olivier Chosidow, Bernard Guillot, Julio Tannous, Ludovic de Gentile, Emmanuel Parant, Béatrice Quinet, Marie Boyer, Annabel Maruani, Nathalie Bodak, Alice Phan, Arezki Izri, Barthélémy Tosello, Florence Bretelle, Elisabeth Elefant, Franck Boralevi, Catherine Letord, Thomas Hubiche, Stephanie Mallet","doi":"10.1093/bjd/ljae288","DOIUrl":"10.1093/bjd/ljae288","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"1014-1016"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726911","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 role of cytokeratin 17 in skin tumorigenesis and human papillomavirus persistence.","authors":"Marianne de Brito, Edel A O'Toole","doi":"10.1093/bjd/ljae294","DOIUrl":"10.1093/bjd/ljae294","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"862-863"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757283","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":"Audacity of gene therapy.","authors":"Marketa Dimitrov, Christen L Ebens, Jakub Tolar","doi":"10.1093/bjd/ljae332","DOIUrl":"10.1093/bjd/ljae332","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"1009-1011"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003641","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":"An expert consensus on managing dupilumab-related ocular surface disorders in people with atopic dermatitis 2024.","authors":"Michael R Ardern-Jones, Sara J Brown, Carsten Flohr, Parwez Hossain, Alan D Irvine, Graham A Johnston, Mark Lane, Sinéad M Langan, Philip Laws, Daniel O'Driscoll, Donal O'Kane, Alice Payne, Gabriela Petrof, Andrew E Pink, Saaeha Rauz, Scott Robbie, Sri K Gore, Mili Shah, Richard T Woolf, Chenxi Wang, Stoyana Tumbeva, M Firouz Mohd Mustapa","doi":"10.1093/bjd/ljae344","DOIUrl":"10.1093/bjd/ljae344","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is the most common inflammatory skin condition and affects people of all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasized in real-world observations, an unexpected increased frequency of ocular adverse effects has become apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if adverse effects arise. The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD). A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with expertise in DROSD, patient representatives and the BAD Clinical Standards Unit. A literature search was conducted and the results reviewed. All recommendations were reviewed, discussed and voted on. The recommendations pertain to dermatology and ophthalmology management, and apply to people of all ages, unless otherwise stated. Importantly, initiation of dupilumab for AD should not be delayed for most eye disorders except acute new problems (e.g. infections) or potentially severe conditions (e.g. a history of corneal transplant; ophthalmology advice should be sought first). There is insufficient evidence to recommend lubricant drops prophylactically. Dermatologists should assess eye complaints to diagnose DROSD; a severity grading system is provided. DROSD management differs slightly in those aged < 7 years, as ocular complications may affect neuro-ocular development. Therefore, irrespectively of DROSD severity, this population should be referred for ophthalmology advice. In those aged ≥ 7 years, dermatologists should feel confident to trial treatment and reserve ophthalmology advice for severe or nonresponding cases. Discussion about dupilumab withdrawal should be prompted by a significant impact on quality of life, threat to sight, or other complications. Although dupilumab is a highly effective agent for treating AD, the risk of ocular adverse effects should not inhibit clinicians or patients from using it, but clinicians should be aware of them. If a patient develops DROSD, there are clear pathways to assess severity and offer initial management. Where this is ineffective, dermatologists should assess the urgency and seek advice from or initiate referral to ophthalmology. While the evidence reviewed for these guidelines reflects the extensive literature on dupilumab, we believe our advice has relevance for ocular surface disorders in patients with AD treated with tralokinumab and lebrikizumab.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"865-885"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139335","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":"Atypical chemokine receptor 1-positive endothelial cells mediate leucocyte infiltration and synergize with secreted frizzled-related protein 2/asporin-positive fibroblasts to promote skin fibrosis in systemic sclerosis.","authors":"Yan Huang, Weilin Pu, Lei Wang, Qianqian Ma, Yanyun Ma, Qingmei Liu, Shuai Jiang, Xiangyue Zhao, Yuting Zhang, Qiuyu He, Yulong Tang, Jing Liu, Jui-Ming Lin, Xiangguang Shi, Wenzhen Tu, Yuanyuan Chen, Jinran Lin, Yiyi Gong, Wenyu Wu, Jiucun Wang","doi":"10.1093/bjd/ljae286","DOIUrl":"10.1093/bjd/ljae286","url":null,"abstract":"<p><strong>Background: </strong>Skin fibrosis is the typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS); it has an unclear aetiology and few effective treatments. Although excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, evidence has suggested that vascular damage is the initiating event and that various cell types, including fibroblasts, work together to contribute to the pathogenesis of skin fibrosis.</p><p><strong>Objectives: </strong>To explore the relationship between vascular endothelial cell lesions and immune cell infiltration, along with the interactions between various cell types within the fibrotic skin ecosystem.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was performed on skin biopsies from three healthy donors and seven patients with SSc. Additional data from three patients with localized scleroderma available in the Gene Expression Omnibus (GSE160536) were integrated by Harmony. CellChat (version 1.5.0) was used to analyse the cell communication network. A Transwell® assay and a bleomycin (BLM) mouse model were used to explore the role of atypical chemokine receptor 1 (ACKR1; 'Duffy antigen') in immune cell infiltration. Milo single-cell Western blot was used to show fibroblast subcluster activation.</p><p><strong>Results: </strong>A total of 62 295 cells were obtained and subpopulations of stromal and immune cells identified. Interaction network analysis found that multiple chemokines secreted by macrophages, pericytes and proinflammatory fibroblasts could bind with ACKR1, which was highly expressed by endothelial cells in lesional skin. The Transwell® assay revealed that overexpression of ACKR1 in human umbilical vein endothelial cells facilitated leucocyte infiltration following treatment with interleukin-8. BLM mice showed enhanced ACKR1 expression, massive immune cell infiltration and skin fibrosis that was attenuated by ACKR1 inhibition. Furthermore, infiltrated macrophages expressing high levels of transforming growth factor (TGF)-β1 or platelet-derived growth factor B (PDGFB) could activate secreted frizzled-related protein 2 (SFRP2)/asporin (ASPN)+ fibroblasts to contribute to the excessive accumulation of extracellular matrix. It was also found that the SOX4-ASPN axis plays an important role in the TGF-β signalling cascade and the aetiology of skin fibrosis.</p><p><strong>Conclusions: </strong>Our results reveal that high expression of ACKR1 by endothelial cells in fibrotic skin tissue promotes immune cell infiltration and that SFRP2/ASPN+ fibroblasts synergize to exacerbate skin fibrosis.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"964-978"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619392","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":"Supplemental vitamin D on trial: no evidence of benefit as an adjuvant treatment for melanoma.","authors":"Remco van Doorn","doi":"10.1093/bjd/ljae302","DOIUrl":"10.1093/bjd/ljae302","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"858-859"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747505","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}