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

{"title":"Shifting the focus: Exploring happiness as a health outcome in dermatology","authors":"Flora Balieva","doi":"10.1111/jdv.20536","DOIUrl":"https://doi.org/10.1111/jdv.20536","url":null,"abstract":"<p>Happiness is under-researched in medicine. The World Happiness Report highlights the role of societal factors: income equality, social freedom and healthcare access in influencing population-level happiness.<span><sup>1</sup></span> The majority of dermatological research focuses on disability indices such as impairment in mental health, reduced health-related quality of life (HRQoL), economic burden and other negative measurements that impair well-being. In this issue of the JEADV, Ziehfreund, Wecker et al. present their study<span><sup>2</sup></span> in which they chose to adopt a positive perspective, exploring happiness as the key health outcome. The authors investigated happiness in 1039 patients with psoriasis and atopic dermatitis (AD).</p><p>The study employs a combination of subjective self-assessments using standardized instruments (Dermatology Life Quality Index (DLQI), Satisfaction with Life Scale (SWLS), subjective well-being with the Scale of Positive and Negative Experience (SPANE), a heuristic happiness single item scale and self-assessed disease severity) as well as objective clinical measures of disease severity (Psoriasis Area and Severity Index [PASI] and SCORing Atopic Dermatitis [SCORAD]) to integrate diverse data, which were then used to perform quantile regression. This approach offers valuable insights into the factors influencing happiness across a spectrum of experiences.</p><p>The authors selected their measurements based on prior existing publications and their own experience in the field, ensuring that results could be compared across studies and patient groups. Furthermore, the participants were recruited from eight European countries, providing insights into geographical differences in happiness levels and their relationship with dermatological health. This broad scope is a valuable contribution to cross-cultural research in dermatology.</p><p>Patients with AD reported greater impairment in HRQoL compared to patients with psoriasis. The authors attribute this difference to symptoms such as itch and fatigue. However, fatigue is more explored in psoriasis, while tiredness in AD is more likely to result from sleep loss due to severe itching.<span><sup>3</sup></span> Another reason for lower experienced happiness in patients with AD may be due to psoriasis patients having had access to effective biological treatments, available since the early 2000s, whereas similar treatments for AD have only recently become available.<span><sup>4</sup></span> The last two decades have offered psoriasis patients considerably better improvement in symptoms than for patients with AD, thus a different patient journey. In the study by Ziehfreund, Wecker et al.,<span><sup>2</sup></span> patients with AD exhibited more severe disease symptoms than patients with psoriasis, and current or previous use of systemic treatments was linked to higher happiness scores in some quantiles. These findings underscore the importance of adequate medical","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 3","pages":"455-456"},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481585","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":"Towards greener conferences: Addressing the sustainability of cosmeceutical samples","authors":"M. Keperti, M. Trakatelli","doi":"10.1111/jdv.20545","DOIUrl":"https://doi.org/10.1111/jdv.20545","url":null,"abstract":"<p>It is widely known that during large-scale events, such as the annual EADV Congress, a great number of cosmeceutical samples are distributed to the delegates. The environmental impact of such products raises significant concerns due to the wasteful nature of samples. The publication by Salimi and Tso<span><sup>1</sup></span> in this issue places in the forefront sustainability implications such practices entail and proposes practical solutions for reducing environmental harm giving us food for thought on how to run greener meetings in the future.</p><p>Indeed, the most common practices linked to cosmeceutical samples are the single-use packaging plastics, the indiscriminately distribution and the negligent disposition of the products.<span><sup>1</sup></span> The magnitude of the problem should not be underestimated. Conferences of such size attract thousands of attendees, each receiving promotional specimens in quantities far exceeding individual needs. A significant portion of these items ends up discarded, contributing to plastic waste. The reliance on non-recyclable packaging exacerbates the problem, as these materials often end up in landfills, releasing harmful chemicals into the environment and microplastics.<span><sup>2</sup></span></p><p>The authors clearly state feasible solutions to tackle this undesirable reality. Conference organizers are responsible for developing and implementing a green policy, part of which should be the inclusion of sustainable healthcare as a key conference agenda item. It is crucial that all the recyclable materials do not end up in landfills and so the conference could implement green policy, placing both recycling stations and boxes for reusable packaging. Delegates can also play an important part and make more sustainable choices by returning excess and unwanted items or even consider requesting samples from each company's local representative instead of collecting them at the conference.</p><p>On the other hand, industries must welcome the returned, unused samples from the delegates, as a part of the ‘reduce reuse recycle’ movement<span><sup>3</sup></span> or donate them to the local community or charity. If there isn't a local representative of the company in an individual's country, the industry should be ready to assist the delegate to gain access to the samples through digital marketing. A carrier bag should be optional or the delegates should be invited to bring their own, packaging materials must be recycled and recyclable, and biodegradable/organic materials ought to be chosen over single use materials.</p><p>In order to minimize distribution of excess samples the adoption of digital sampling methods is required. By using QR codes, delegates can request product samples delivered to their homes, reducing the need for bulk distribution and minimizing waste. This approach has the added advantage for the industry as it provides companies with valuable insights into consumer preferences and enables a ","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 3","pages":"463-464"},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20545","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481396","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":"Beyond the surface: Integrating sex and gender in dermatologic therapy","authors":"Ion Birkenmaier, Julia-Tatjana Maul","doi":"10.1111/jdv.20542","DOIUrl":"https://doi.org/10.1111/jdv.20542","url":null,"abstract":"<p>In recent decades, dermatology has seen significant progress in the development of targeted and biologic therapies for inflammatory skin diseases. Yet, as underscored by the systematic review by Preis et al.,<span><sup>1</sup></span> medical research and clinical practice have too often marginalized sex- and gender-based variations, creating a one-size-fits-all approach. This newly published work dives into how both biological (sex) and sociocultural (gender) factors alter disease trajectories, therapeutic outcomes and risk profiles in dermatological conditions such as psoriasis and atopic dermatitis.</p><p>A noteworthy finding of this systematic review is the discrepancy in treatment success and adverse events between men and women. In psoriasis, for instance, female sex was frequently linked to increased side effects,<span><sup>2</sup></span> as also shown in our more recent work from Switzerland.<span><sup>3</sup></span> Paradoxically, lower treatment response was seen in other studies.<span><sup>4</sup></span> These observations imply that weight-based dosing, hormonal milieu, psychosocial variables or adherence may skew women's clinical outcomes. While it remains difficult to separate strictly biological processes from sociocultural influences, the review highlights how chronic disease burden may be amplified in women, often leading to earlier discontinuation of systemic therapies.</p><p>In addition, the review documents that men tend to more readily receive systemic treatments and at a younger age, suggesting possible biases in the initiation and timing of intervention.<span><sup>5</sup></span> For women of childbearing age, concerns over teratogenic risks and physician hesitancy may delay the start of systemic therapies. Moreover, insufficient patient-level knowledge about psoriasis, as well as lack of clinical studies with safety data in pregnancy, is frequently cited as barriers. This delay can perpetuate the underutilization of potentially beneficial treatments in women, while men—though less likely to have childbearing concerns—may face other healthcare hurdles such as reluctance to seek early dermatologic consultation.</p><p>As the authors rightly note, existing data predominantly conflate ‘sex’ and ‘gender’ into a single category, making it difficult to measure how purely biological differences (e.g., hormonal fluctuations and body mass index) interact with social and psychological factors (e.g., stigma and cultural norms). Standardizing study designs to define ‘sex’ and ‘gender’ more precisely would greatly improve clarity around treatment outcomes. Indeed, the call for more granular trials resonates with the shift towards personalized medicine, wherein each patient's biological background and social context could inform optimized therapeutic pathways.</p><p>Finally, is it truly time for novel, sex-specific dermatologic guidelines? The authors present compelling evidence that a blanket ‘one-guideline-fits-all’ approach misses cri","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 3","pages":"453-454"},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481584","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":"Efficacy and safety of JAK inhibitors in treating lichen planopilaris or frontal fibrosing alopecia.","authors":"Chaofan Wang, Yiqun Jiang","doi":"10.1111/jdv.20614","DOIUrl":"https://doi.org/10.1111/jdv.20614","url":null,"abstract":"","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492582","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":"Closing the gap between possibilities and reality in psoriasis management","authors":"Rolland Gyulai","doi":"10.1111/jdv.20546","DOIUrl":"https://doi.org/10.1111/jdv.20546","url":null,"abstract":"<p>Psoriasis treatment has evolved tremendously during the last few decades. I remember, as a resident dermatologist during the mid-1990s, we treated most of our severe psoriasis patients by rotating low-to-medium efficacy therapies: topical treatments (salicylic acid, corticosteroids, dithranol) phototherapy, acitretin and less frequently cyclosporine or methotrexate. Many patients regularly spent weeks in the hospital, and treatment success was usually partial and temporary, lasting for only a few months. The introduction of first-generation biologics marked a significant shift in the management of psoriasis. Methotrexate, which was used as the comparator in clinical trials, became the standard non-biological treatment, and patients began to experience longer more complete remissions. During the last decade, several novel biologics entered the psoriasis field, which showed clear superiority over both conventional and previous-generation biologics. Some biologics have been registered even as first-line treatments, theoretically enabling the early introduction of highly effective therapy. These advancements have led to more ambitious treatment goals by both doctors and patients. Today, even a cure—that is long-term remission off-treatment—seems scientifically realistic.<span><sup>1</sup></span></p><p>Notwithstanding these groundbreaking achievements, dermatologists still face considerable challenges in providing optimal care for psoriasis patients. With expanding indications, exponentially growing patient populations and sky-rocketing medication prices, health funders around the world are struggling to fit therapeutic options into sustainable financing schemes.</p><p>The article by Speeckaert et al.<span><sup>2</sup></span> in this issue of the Journal attempts to elucidate whether and how the integration of novel developments in psoriasis management (such as redefined disease severity or treatment goals, newer biologics or biosimilars, personalized dosing or telemedicine) could lead to (more) sustainable psoriasis care. The authors employ a quasi-Delphi methodology and relate their research to the Belgian psoriasis management environment as an example. They conclude that several factors may contribute to better and still sustainable psoriasis management, such as the implementation of a treat-to-target approach, the use of minimal disease activity (defined as PASI90 or PGA ≤ 1; itch VAS ≤ 10 mm; absence of disturbing lesions; no moderate-to-severe adverse events; DLQI ≤ 1; full tolerability; incapacity in daily functioning VAS score ≤ 1) as optimal therapeutic objective, or the use of teleconsultations for patient follow-up.</p><p>The authors also offer a critique of the current Belgian reimbursement criteria, which mandate the utilization of three conventional antipsoriatic therapies (phototherapy, methotrexate and cyclosporine) prior to the administration of biologics. They propose that only phototherapy and one conventional therapy should be n","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 3","pages":"449-450"},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481338","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":"Reflectance confocal microscopy: Presurgical margin assessment improves lentigo maligna and lentigo maligna melanoma management","authors":"Christoph Sinz, Pascale Guitera","doi":"10.1111/jdv.20549","DOIUrl":"https://doi.org/10.1111/jdv.20549","url":null,"abstract":"<p>Elshot et al.<span><sup>1</sup></span> emphasized in their article a cardinal subject in the management of Lentigo maligna (LM) and Lentigo maligna melanoma (LMM), a subtype of melanoma which commonly occurs on sun-exposed skin of the face, scalp and neck region, especially in elderly men. It is known to be associated with a noticeable incomplete excision rate and a significant recurrence rate after wide local excision (WLE).<span><sup>2</sup></span> The main explanation for these issues is LM/LMM subclinical extension, invisible to clinical examination using dermoscopy and Wood's lamp, leading to an underestimation of its actual size. This study's main objective is to investigate the influence of presurgical mapping of biopsy-proven LM/LMM with handheld reflectance confocal microscopy (HH-RCM) with a focus on surgical treatment, follow-up outcomes and management decisions.</p><p>The promising results of this research draw attention on how HH-RCM could become a standard of care in the surgical and also non-surgical management of LM and LMM. One of the most striking, and promising, findings is that the resection margins after WLE in the presurgical HH-RCM group were cleared in 96.5% of cases. Moreover, this exceptional clearance rate was also associated with a median histologic margin of 3.0 mm which, if achieved, is expected to significantly reduce risk of local recurrence.<span><sup>2</sup></span></p><p>It has to be acknowledged that the local recurrence rate of 1.4% in this study is potentially due to a shorter follow-up as observed in previous studies stating longer post-interventional observation periods with local recurrence rates ranging from 8% to 20%.<span><sup>2</sup></span></p><p>According to another finding, RCM detected in 60% of the cases subclinical atypical cells beyond the initial surgical margins which underlines the superiority of RCM compared to clinical examination with dermoscopy alone.<span><sup>3</sup></span> Identifying subclinical extent goes hand in hand with an increased lesion size. It is arguable that this clinical underestimation of the actual lesion size is introducing lower histologic clearance rates after wide local excision (WLE) and higher recurrence rates due to a smaller extent of the histologic margins.</p><p>Additionally, the authors reported that 75% of initially misdiagnosed LM were actually invasive melanomas highlighting another interesting aspect of RCM mapping: Despite the limited visualization of deeper skin structures down to a depth of around 200 μm, RCM has still the potential to identify invasive LMM components.<span><sup>4</sup></span></p><p>Identifying invasive or subclinical components and a refusal of (further) surgery are the most common reasons for a modified management such as an adaption of the surgical method, treatment with topical imiquimod or radiation therapy. In all these scenarios, presurgical HH-RCM margin assessment with a described median mapping duration in this study of only","PeriodicalId":17351,"journal":{"name":"Journal of the European Academy of Dermatology and Venereology","volume":"39 3","pages":"459-460"},"PeriodicalIF":8.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.20549","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481588","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":"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}