{"title":"Inflammatory dermatoses and an era of new diagnostic dermatopathology.","authors":"John A McGrath, Chao-Kai Hsu","doi":"10.1093/bjd/ljae306","DOIUrl":"10.1093/bjd/ljae306","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"855-856"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787333","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 sex- and site-specific differences in melanoma.","authors":"Alan C Geller, Alexander J Stratigos","doi":"10.1093/bjd/ljae345","DOIUrl":"10.1093/bjd/ljae345","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"860"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124872","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}
Helen Alexander, Rayka Malek, David Prieto-Merino, Elizaveta Gribaleva, Manisha Baden, Paula Beattie, Sara Brown, Tim Burton, Shona Cameron, Bola Coker, Michael J Cork, Ross Hearn, John R Ingram, Alan D Irvine, Graham A Johnston, Alice Lambert, Mark Lunt, Irene Man, Louise Newell, Graham Ogg, Prakash Patel, Mandy Wan, Richard B Warren, Richard Woolf, Zenas Z N Yiu, Nick Reynolds, Michael R Ardern-Jones, Carsten Flohr
{"title":"A prospective observational cohort study comparing the treatment effectiveness and safety of ciclosporin, dupilumab and methotrexate in adult and paediatric patients with atopic dermatitis: results from the UK-Irish A-STAR register.","authors":"Helen Alexander, Rayka Malek, David Prieto-Merino, Elizaveta Gribaleva, Manisha Baden, Paula Beattie, Sara Brown, Tim Burton, Shona Cameron, Bola Coker, Michael J Cork, Ross Hearn, John R Ingram, Alan D Irvine, Graham A Johnston, Alice Lambert, Mark Lunt, Irene Man, Louise Newell, Graham Ogg, Prakash Patel, Mandy Wan, Richard B Warren, Richard Woolf, Zenas Z N Yiu, Nick Reynolds, Michael R Ardern-Jones, Carsten Flohr","doi":"10.1093/bjd/ljae287","DOIUrl":"10.1093/bjd/ljae287","url":null,"abstract":"<p><strong>Background: </strong>The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA.</p><p><strong>Objectives: </strong>To compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD.</p><p><strong>Methods: </strong>We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). The minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression analysis was used to compare the hazard ratios of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits.</p><p><strong>Results: </strong>We included 488 patients (311 adults and 177 children/adolescents) on dupilumab (n = 282), MTX (n = 149) or CyA (n = 57). CyA and MTX were primarily used as the first-line treatment, while dupilumab was mainly a second-line systemic treatment as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared with MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reduction in EASI, POEM and PP-NRS was even greater with CyA. The incidence rates of AEs were similar across groups (734, 654 and 594 per 10 000 person-month on CyA, dupilumab and MTX, respectively).</p><p><strong>Conclusions: </strong>This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"988-999"},"PeriodicalIF":11.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751157","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":"VEXAS syndrome was in front of us for decades.","authors":"Nicolas Giachetti, Valentin Lacombe","doi":"10.1093/bjd/ljae309","DOIUrl":"10.1093/bjd/ljae309","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"1022-1023"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787334","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":"Paternal exposure: two patients' perspectives in an evolving landscape of therapeutics. Can we now provide reassurance?","authors":"Bhaskar Narayan, Leila Asfour","doi":"10.1093/bjd/ljae319","DOIUrl":"10.1093/bjd/ljae319","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"1008-1009"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892889","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}
Daniela Ortner-Tobider, Thomas Trafoier, Verena Moosbrugger-Martinz, Susanne Tollinger, Robert Gruber, Matthias Schmuth
{"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}
Daniel Lindsay, Katy J L Bell, Catherine M Olsen, David C Whiteman, Thanya Pathirana, Louisa G Collins
{"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":"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}
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
{"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}
Daniel Hasche, Martin Hufbauer, Ilona Braspenning-Wesch, Sonja Stephan, Steffi Silling, Gabriele Schmidt, Stephan Krieg, Alexander Kreuter, Baki Akgül
{"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}