Journal of the European Academy of Dermatology and Venereology最新文献

{"title":"Bridging the gap: From clinical intuition to structured cutaneous squamous cell carcinoma classification","authors":"Christoffer Gebhardt","doi":"10.1111/jdv.20548","DOIUrl":"https://doi.org/10.1111/jdv.20548","url":null,"abstract":"<p>The paper ‘Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts’ by Gaudy-Marqueste presents a groundbreaking approach to classifying cutaneous squamous cell carcinoma (cSCC), addressing critical shortcomings in existing staging systems.<span><sup>1</sup></span> This innovative methodology has important implications for enhancing clinical decision-making and refining the design of future clinical research.</p><p>The study's approach of using unsupervised clustering of real cSCC cases by a group of 18 international specialists from different relevant disciplines, enhancing its validity and applicability, is particularly noteworthy. By tapping into the collective unconscious expertise of clinicians, the researchers have developed a classification system that is inherently aligned with real-world clinical decision-making processes. This approach contrasts with traditional staging systems that are often based on specific tumour characteristics and risk factors.<span><sup>1</sup></span></p><p>The resulting six-group classification system—comprising easy-to-treat, complex-to-treat due to tumour and/or patient characteristics, multiple tumours, locally advanced without regional metastases, regional metastases and visceral metastases—offers a practical framework for clinicians. This structure can help streamline tumour board discussions and facilitate more consistent decision-making across different healthcare settings. The high concordance (94%) in case allocation between new practitioners and experts demonstrates the classification's intuitive nature and potential for widespread adoption.<span><sup>1</sup></span></p><p>One of the most significant contributions of this classification system is its potential impact on clinical trial design. By providing a method to create more homogeneous patient groups, it addresses a longstanding challenge in cSCC research. This could lead to more targeted and efficient clinical trials, potentially accelerating the development of new treatments and improving patient outcomes.<span><sup>2</sup></span></p><p>The study's success in finding a mathematical consensus, resulting in a five-cluster classification of ‘difficult-to-treat’ cases, despite the high heterogeneity of cSCC cases is remarkable. This achievement suggests that the classification system captures fundamental aspects of cSCC presentation and behaviour that are relevant across diverse patient populations. Such a universally applicable system could greatly enhance global collaboration in cSCC research and treatment.</p><p>Importantly, this new classification system is designed to complement, rather than replace, existing staging systems like the American Joint Committee on Cancer (AJCC) and Brigham and Women's Hospital (BWH) systems. For instance, while AJCC 8 has limitations in predicting poor outcomes, and BWH demonstrates better positive predictive value,<span><sup>3</sup></span> neith","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 3","pages":"461-462"},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventing penile cancer and poor outcomes","authors":"C. B. Bunker, A. Muneer","doi":"10.1111/jdv.20544","DOIUrl":"https://doi.org/10.1111/jdv.20544","url":null,"abstract":"<p>In this issue, O'Connell et al.<span><sup>1</sup></span> address factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma, reporting on a retrospective multicentre cohort study.</p><p>At first sight, their study and its findings, especially those concerning staging, would seem to be more useful for urologists and oncologists than readers of this journal. However, it is important for dermatovenereologists to be informed and updated about penile cancer, because, although rare, it is an important cause of avoidable morbidity, mortality and litigation. Disease of the male genitalia is indubitably our concern. The aims and objectives of the practice of male genital dermatology are headed by the prevention or mitigation of penile cancer and its potentially dire consequences.</p><p>Regarding the study itself, firstly, the numbers are small which is anxiogenic considering the statistical analyses employed. Secondly, the retrospective analysis will invariably introduce attrition bias. These points notwithstanding, some of the crude data (Table 1) are fascinating viz. (i) 8 of 148 patients with poor outcomes (local recurrence metastasis or disease-related death) were circumcised as neonates and 19 as adults; these are striking figures given what we believe about the protective impact of circumcision: perhaps they were overweight with a buried penis and possessed of a neo-foreskin,<span><sup>2</sup></span> (ii) 136 of 265 patients had no history of prior penile disease; again, striking given that we know that virtually all penile cancer is associated with lichen sclerosus or HPV or both,<span><sup>3</sup></span> implying a failure of prevention, early diagnosis and effective interventional management, each of which may be attributed to both patient-related and clinician-related ignorance or inattention (or, of course, poor or inadequate documentation). Some of the crude data are confusing, for example in Table 1, the numbers for phimosis, balanitis/posthitis, psoriasis, urethral stricture/HPV-related premalignant lesion do not seem to add up—perhaps some patients had two or more entities; we cannot fathom whether this affects the analysis. What may well affect the analyses is that the Nx patients labelled as N0 could be skewing the data and introducing bias, as these are potentially the cases with undiagnosed micrometastatic disease. Without the benefit of inguinal node sampling, either with dynamic sentinel node biopsy or inguinal lymphadenectomy, Nx should not be correlated with N0 disease. The analysis indicates that the majority of patients underwent limited or extensive localized surgery without pathological nodal staging which introduces a significant bias when interpreting the risk of metastatic disease.</p><p>What of the purported findings, that a history of balanitis, history of phimosis, perineural invasion, corporal invasion and poor differentiation are independent risk factors associated with poor","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 3","pages":"457-458"},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologics targeting interleukin (IL)-23 and the risk of cardiovascular events: Where are we?","authors":"F. Poizeau, H. Ait-Oufella, H. Bachelez","doi":"10.1111/jdv.20128","DOIUrl":"https://doi.org/10.1111/jdv.20128","url":null,"abstract":"<p>Florence Poizeau</p><p>Hafid Ait-oufella</p><p>Hervé Bachelez</p><p>In a recent phase III trial assessing the efficacy and safety of the IL-23p19 inhibitor mirikizumab compared to placebo and secukinumab among moderate-to-severe plaque psoriasis patients, six cerebro-cardiovascular events occurred in the mirikizumab arm within the first 16 weeks versus none in the other arms.<span><sup>1</sup></span> The sponsor, Eli Lilly, decided to stop the development of mirikizumab in this indication. This rare signal raises the complex issue of the impact of IL-23 blockade on the risk of major adverse cardiovascular events (MACEs).</p><p>IL-23, composed of p40 and p19 subunits, plays a pathogenic role in psoriasis by driving the differentiation of naïve T cells towards IL-17-producing T cells. Monoclonal antibodies targeting p40 (IL-12/23 inhibitors) include ustekinumab and briakinumab, while p19 inhibitors include guselkumab, risankizumab, tildrakizumab and mirikizumab.</p><p>Experimental studies investigating the contribution of IL-23 to atherosclerosis have yielded conflicting findings. According to some models, IL-23p19 has a mainly anti-atherogenic function through effects on the gut microbiota and the intestinal barrier function.<span><sup>2</sup></span> Other models have shown that IL-17 responses, which are driven by IL-23, promote collagen synthesis by vascular smooth muscle cells, and maintain plaque stability.<span><sup>3</sup></span> However, no intrinsic effect of IL-23 has been reported on plaque vulnerability to date.</p><p>The cardiovascular events in the mirikizumab trial echo previous concerns with the IL-12/23p40 inhibitor briakinumab, the development of which was stopped in phase III. The controversy extended to ustekinumab following a meta-analysis of data from phases II/III clinical trials, with both agents exhibiting an increased risk of MACE, although randomized controlled trials (RCTs) lack power to study rare events.<span><sup>4</sup></span> Recently, an additional safety signal was issued when post-marketing surveillance flagged the IL-23p19 inhibitor risankizumab because of a disproportionately large number of cerebrovascular events, although under-reporting limits significance.<span><sup>5, 6</sup></span></p><p>Several cohort studies have concluded that ustekinumab and IL-23p19 inhibitors are safe with respect to the MACE risk, but here again conflicting results were reported.<span><sup>7</sup></span> We will discuss three major pitfalls of observational studies evaluating the cardiovascular safety of biologics: (i) the transient nature of the risk (also called a ‘trigger effect’), (ii) interaction (i.e. ‘effect modification’) and (iii) confounding by indication. First, estimating incidence rates or hazard ratios assumes that the MACE risk is constant over time during biological treatment, whilst immunocardiologists suggest that IL-17 and/or IL-23 blockade could be detrimental in the short-term but beneficial in the long-term","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 3","pages":"447-448"},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No allergy, but mast cells are involved: MRGPRX2 in chronic inflammatory skin diseases","authors":"Martin Metz","doi":"10.1111/jdv.20541","DOIUrl":"https://doi.org/10.1111/jdv.20541","url":null,"abstract":"<p>About 10 years ago, the mas-related G protein-coupled receptor X2 (MRGPRX2) was reported to be crucial for pseudo-allergic drug reactions,<span><sup>1</sup></span> suggesting that IgE-mediated activation of mast cells (MC) may not be the only way how MC can contribute to the pathophysiology of diseases. In fact, both MRGPRX2 and MCs may be important in inflammatory skin diseases without an allergic background. In this issue, Kumar and colleagues summarize what is known about the role of MRGPRX2 in pruritus and skin diseases.<span><sup>2</sup></span></p><p>Clinical data on the effects of pharmacological blockade of MRGPRX2 are still lacking, but there is increasing evidence for a potential role of the receptor in various skin diseases. The authors provide several arguments for the important role of MRGPRX2 in chronic spontaneous urticaria, atopic dermatitis, rosacea, psoriasis, chronic pruritus, and chronic prurigo.<span><sup>2</sup></span> Most importantly, an increased expression of MRGPRX2 agonists has been identified in all of these diseases. The majority of these agonists are either neuropeptides, such as substance P and vasoactive intestinal polypeptide, or peptides involved in antimicrobial defence (e.g. cortistatin, β-defensins and LL-37).<span><sup>3</sup></span> Many resident skin cells such as keratinocytes, sensory nerves, and macrophages, but also inflammatory cells recruited to sites of chronic skin inflammation can release MRGPRX2 agonists. This may also shed some light on the potential of skin MCs to contribute to non-allergic skin diseases: Although the receptor has also been detected in some other cell types, by far the highest expression of MRGPRX2 is found on skin MCs.<span><sup>4</sup></span> Since all MRGPRX2 agonists can activate MCs to release proteases, cytokines, and histamine,<span><sup>5</sup></span> the observed increase of MRGPRX2 agonists in various inflammatory skin diseases is likely to contribute to at least some aspects (e.g. pruritus) of the respective skin diseases by activating and degranulating skin MCs. Another argument of Kumar et al. for an important involvement of MRGPRX2 is the observed increased sensitivity to provocation with exogenous and endogenous MRGPRX2 agonists in patients with chronic spontaneous urticaria. This increased sensitivity to MRGPRX2 agonists may be due to the increased number of MRGPRX2 expressing cells (i.e. mast cells) observed in the skin of patients with chronic spontaneous urticaria, but also in many other chronic inflammatory skin diseases.</p><p>Several MRGPRX2 antagonists have already been tested in preclinical models in vitro and in humanized mouse models in vivo, and have been shown to effectively block MRGPRX2 agonist-mediated activation of MCs.<span><sup>2</sup></span> Currently ongoing (NCT06077773, NCT06050928) and further planned clinical trials investigating the efficacy of MRGPRX2 antagonists in chronic spontaneous and chronic inducible urticaria will provide insi","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 3","pages":"451-452"},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world evidence for comprehensive evaluation of guselkumab in the treatment of psoriasis","authors":"Diamant Thaçi","doi":"10.1111/jdv.20554","DOIUrl":"https://doi.org/10.1111/jdv.20554","url":null,"abstract":"<p>Diamant Thaçi</p><p>While randomized controlled trials (RCTs) remain the gold standard of evidence-based medicine, real-world evidence (RWE) is becoming increasingly important.<span><sup>1</sup></span> Despite potential challenges with data sources, such as missing/limited data and the lack of patient randomization, RWE is considered more relatable to daily clinical practice and aids investigation of long-term effectiveness and treatment safety.<span><sup>1</sup></span> This is particularly relevant for chronic conditions like moderate-to-severe psoriasis, which usually requires long-term treatment and is associated with numerous comorbidities.</p><p>Guselkumab, a human monoclonal antibody that inhibits interleukin-23, was approved for the treatment of moderate-to-severe psoriasis in 2017. This supplemental issue of <i>JEADV</i> discusses guselkumab RWE as an important evidence source to complement RCTs in psoriasis, presenting five non-interventional studies (PERSIST,<span><sup>2</sup></span> G-EPOSS,<span><sup>3</sup></span> GULLIVER,<span><sup>4</sup></span> SPRING<span><sup>5</sup></span> and a study by Tskhvarashvili et al.<span><sup>6</sup></span>) comprising >1400 guselkumab-treated patients across five European countries.<span><sup>2-6</sup></span> Together, they describe effectiveness, health-related quality of life (HRQoL) and safety outcomes with guselkumab treatment, as well as drug persistence, in a real-world setting.</p><p>The limitations of RWE noted above emphasize the importance of conducting non-interventional studies with robust methodology. PERSIST, G-EPOSS and GULLIVER were prospective, multicentre, observational studies conducted in Germany<span><sup>2, 3</sup></span> and Italy.<span><sup>4</sup></span> They had predefined patient eligibility criteria and study endpoints, and their population sizes were planned using rigorous statistical methodology. SPRING and the Tskhvarashvili et al. study were multicentre, retrospective studies conducted in Spain<span><sup>5</sup></span> and Finland/Sweden,<span><sup>6</sup></span> respectively, with defined patient eligibility criteria. Tskhvarashvili et al. conducted sensitivity analyses to account for biases in drug availability, changing treatment practices and uncertainty in drug discontinuation dates.<span><sup>6</sup></span></p><p>Although RCTs typically provide rigorous evaluation of a drug's efficacy and safety profile, the controlled conditions and stringent patient eligibility criteria may limit the generalizability of the results obtained.<span><sup>1</sup></span> For example, patients enrolled in the guselkumab RCTs VOYAGE 1 and 2 were required to have a baseline Psoriasis Area and Severity Index (PASI) ≥ 12;<span><sup>7, 8</sup></span> as such, baseline PASI was lower in the guselkumab non-interventional studies.<span><sup>2-5</sup></span> Additionally, patients typically have received fewer biologics prior to enrolment in RCTs, compared with RWE studies, which can i","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 S1","pages":"3-5"},"PeriodicalIF":8.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: EuroGuiderm Guideline on lichen sclerosus-introduction into lichen sclerosus.","authors":"G Kravvas, R Watchorn, A Spencer, C B Bunker","doi":"10.1111/jdv.20612","DOIUrl":"https://doi.org/10.1111/jdv.20612","url":null,"abstract":"","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Botulinum toxin type A efficacy on pain and suppuration in hidradenitis suppurativa.","authors":"Noor F Goandal, Gregor B E Jemec, Ditte M L Saunte","doi":"10.1111/jdv.20611","DOIUrl":"https://doi.org/10.1111/jdv.20611","url":null,"abstract":"","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of second primary cancers in patients with Merkel cell carcinoma: A systematic review and meta-analysis.","authors":"Ioannis-Alexios Koumprentziotis, Aikaterini Tsiogka, Natalia Rompoti, Stergios Soulaidopoulos, Vasiliki Nikolaou, Stamatios Gregoriou, Electra Nicolaidou, Alexander Stratigos","doi":"10.1111/jdv.20615","DOIUrl":"https://doi.org/10.1111/jdv.20615","url":null,"abstract":"","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mission impossible? Caveats in interpreting and comparing long-term efficacy in biologic studies for moderate-to-severe plaque psoriasis.","authors":"Richard G Langley, Alexander Egeberg, Melinda Gooderham, Robert Bissonnette, Julien Ringuet, Sunil Kalia, Laura Park-Wyllie, Nastaran Abbarin, Diana Tran, Anthony Zara, Ya Wen Yang, Bruce Strober","doi":"10.1111/jdv.20555","DOIUrl":"https://doi.org/10.1111/jdv.20555","url":null,"abstract":"","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactional genital leukokeratosis as a new clinico-histological variant of penile squamous hyperplasia in young men.","authors":"Syrine Benammou, Romain Salle, Bénédicte Cavelier-Balloy, Sébastien Fouéré, Jean-David Bouaziz, Tu-Anh Duong, Jean-Noël Dauendorffer","doi":"10.1111/jdv.20613","DOIUrl":"https://doi.org/10.1111/jdv.20613","url":null,"abstract":"","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}