American Journal of Clinical Dermatology最新文献

{"title":"A Maximum-Use Trial of Ruxolitinib Cream in Children Aged 2-11 Years with Moderate to Severe Atopic Dermatitis.","authors":"Linda Stein Gold, Robert Bissonnette, Seth Forman, Andrea Zaenglein, YuTzu Kuo, Brett Angel, Xuejun Chen, Howard Kallender, Amy S Paller","doi":"10.1007/s40257-024-00909-5","DOIUrl":"https://doi.org/10.1007/s40257-024-00909-5","url":null,"abstract":"<p><strong>Background: </strong>Ruxolitinib cream has demonstrated anti-inflammatory and antipruritic activity and was well tolerated in a phase 3 study in patients aged 2-11 years with mild to moderate atopic dermatitis (AD).</p><p><strong>Objective: </strong>This study examined the safety, tolerability, pharmacokinetics, efficacy, and quality of life (QoL) with ruxolitinib cream under maximum-use conditions and with longer-term use.</p><p><strong>Methods: </strong>Eligible patients were aged 2-11 years with moderate to severe AD [Investigator's Global Assessment (IGA) score 3-4], and ≥ 35% affected body surface area (BSA). Patients applied 1.5% ruxolitinib cream twice daily to all baseline-identified lesions during the 4-week maximum-use period, then to active lesions only up to week 52 (patients with ≤ 20% affected BSA from week 8). Safety was assessed by frequency and severity of adverse events. Pharmacokinetic parameters were assessed as secondary endpoints, and efficacy and QoL were exploratory endpoints.</p><p><strong>Results: </strong>Overall, 29 patients (median age 5 years) were enrolled. Treatment-emergent adverse events were reported in 9/29 patients (31.0%); there were no adverse events of special interest (i.e., no serious infections, malignancies, major adverse cardiovascular events, or thromboses) during the study period. Mean steady-state plasma concentration during the maximum-use period was below the known half-maximal inhibitory concentration of Janus kinase-mediated myelosuppression in adults. Reductions in affected BSA and IGA observed at week 4 were sustained with as-needed use through 52 weeks. Improvements in patient-reported outcomes and QoL measures were consistent with efficacy results.</p><p><strong>Conclusion: </strong>These results support the safety of ruxolitinib cream in children (2-11 years) with AD, including those with extensive disease, and are consistent with previous efficacy findings.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT05034822, first registered 30 August 2021.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930611","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":"Acknowledgement to Referees.","authors":"","doi":"10.1007/s40257-024-00914-8","DOIUrl":"https://doi.org/10.1007/s40257-024-00914-8","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875526","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":"Prognostic Biomarkers in Evolving Melanoma Immunotherapy.","authors":"Robin Reschke, Alexander H Enk, Jessica C Hassel","doi":"10.1007/s40257-024-00910-y","DOIUrl":"https://doi.org/10.1007/s40257-024-00910-y","url":null,"abstract":"<p><p>Melanoma, a highly aggressive form of skin cancer, has seen significant advancements in treatment through the introduction of immunotherapy. However, the variability in patient responses underscores the need for reliable biomarkers to guide treatment decisions. This article reviews key biomarkers in melanoma immunotherapy, such as PD-L1 expression, tumor mutational burden (TMB), and gene expression profiles (GEPs). It also explores emerging biomarkers, including LAG-3 expression, immune cell phenotyping in tissue and blood, gut microbiota, and circulating tumor DNA (ctDNA). Notably, ctDNA may offer valuable insights into the efficacy of T cell-engaging bispecific molecules, such as tebentafusp. The review provides a comprehensive overview of the evolving landscape of melanoma biomarkers, their role in personalizing treatment, and future research directions, including neoadjuvant immune checkpoint inhibition.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871060","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":"Frontal Fibrosing Alopecia: An Update.","authors":"Andrew G Messenger, Leila Asfour, Matthew Harries","doi":"10.1007/s40257-024-00912-w","DOIUrl":"https://doi.org/10.1007/s40257-024-00912-w","url":null,"abstract":"<p><p>In this review, we discuss recent developments in our understanding of frontal fibrosing alopecia, a disease that has become increasingly common and widespread since its first description in 1994. An inherited predisposition to frontal fibrosing alopecia, previously suspected from the occurrence of familial cases, has been confirmed through genetic studies. Nevertheless, the epidemiology continues to implicate environmental factors in the aetiology. The search has focussed mainly on personal skin care products such as facial moisturisers and UV filters, and there is also some evidence implicating exogenous oestrogens, but confirmation of direct causal links has so far proved elusive. The pathologic mechanisms underlying follicular deletion are being clarified, including the nature of the inflammatory component, the loss of follicular immune privilege in the bulge region and the role of epithelial-mesenchymal transition in the scarring process. Lichen planus pigmentosus, a common accompaniment to frontal fibrosing alopecia in those with darker skin, is probably a feature of the same pathology affecting interfollicular epidermis, rather than a co-morbidity, and may offer new clues to the aetiology. Treatment is still based largely on retrospective case series and variable endpoints. However, methods for assessing frontal fibrosing alopecia and monitoring treatment responses have been strengthened and randomised controlled trials with novel agents (e.g. Janus kinase inhibitors) are in progress. As the main aim of effective treatment is to prevent disease progression, early diagnosis will remain an important target, as will prevention in the longer term.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852078","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":"Obesity in Hidradenitis Suppurativa: Are GLP-1 Receptor Agonists the New Frontier?","authors":"Jennifer Strong, Marcia S Driscoll","doi":"10.1007/s40257-024-00911-x","DOIUrl":"https://doi.org/10.1007/s40257-024-00911-x","url":null,"abstract":"<p><p>Hidradenitis suppurativa (HS) is an inflammatory skin disorder presenting with painful and draining nodules in intertriginous areas that may progress to sinus tracts. There is an increased prevalence of obesity in HS, and obesity may predispose patients to HS. Weight loss has been associated with improvement of HS symptoms. However, weight loss through diet modification, exercise or bariatric surgery has mixed results. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have been investigated for weight loss in HS. These drugs are effective for weight loss and reduce weight-related comorbidities, with few significant side effects. Early studies of liraglutide and semaglutide in HS have demonstrated improvement in disease severity and quality of life. GLP-1 receptor agonists are a promising therapy for patients with HS and may improve symptoms through decreased mechanical stress and moderation of inflammation.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845593","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":"Overcoming Resistance Mechanisms to Melanoma Immunotherapy.","authors":"David X Zheng, David J Bozym, Giuseppe Tarantino, Ryan J Sullivan, David Liu, Russell W Jenkins","doi":"10.1007/s40257-024-00907-7","DOIUrl":"https://doi.org/10.1007/s40257-024-00907-7","url":null,"abstract":"<p><p>The advent of immune checkpoint inhibition has revolutionized treatment of advanced melanoma. While most patients derive survival benefit from established immunotherapies, notably monoclonal antibodies blocking cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1, a subset does not optimally respond due to the manifestation of innate or acquired resistance to these therapies. Combination regimens have proven efficacious relative to single-agent blockade, but also yield high-grade treatment toxicities that are often dose-limiting for patients. In this review, we discuss the significant strides made in the past half-decade toward expanding the melanoma immunotherapy treatment paradigm. These include newly approved therapies, adoption of neoadjuvant immunotherapy, and studies in the clinical trials pipeline targeting alternative immune checkpoints and key immunoregulatory molecules. We then review how developments in molecular and functional diagnostics have furthered our understanding of the tumor-intrinsic and -extrinsic mechanisms driving immunotherapy resistance, as well as highlight novel biomarkers for predicting treatment response. Throughout, we discuss potential approaches for targeting these resistance mechanisms in rational combination with established immunotherapies to improve outcomes for patients with melanoma.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783980","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":"Role of Inflammation and Cytokine Dysregulation in Depression in Patients with Inflammatory Skin Conditions.","authors":"Olivia M Katamanin, Isabella J Tan, Jillian Barry, Mohammad Jafferany","doi":"10.1007/s40257-024-00905-9","DOIUrl":"https://doi.org/10.1007/s40257-024-00905-9","url":null,"abstract":"<p><p>The growing field of psychodermatology examines the interplay between dermatological and psychiatric comorbidities. While current literature recognizes that cutaneous and psychiatric conditions often coexist within patients, the relationship between dysregulated inflammation and depression in patients with inflammatory skin conditions has not been thoroughly explored. This review seeks to describe the connection between cutaneous disease and depression via shared inflammatory cytokine pathways. A review of current literature was conducted, and studies addressing the co-occurrence of depression and inflammatory skin diseases were included. This review focuses on depression in patients with psoriasis, atopic dermatitis, and hidradenitis suppurativa. Studies that focused on the prevalence of depression in these populations, shared inflammatory pathways, and co-management of cutaneous and psychiatric disorders were chosen. The literature revealed a high prevalence of depression in individuals with inflammatory skin conditions compared with those without cutaneous disease. Recent studies described how proinflammatory cytokines in inflammatory skin diseases can elicit inflammation in the brain, leading to depressive symptoms. Certain subsets of cytokines that mediate inflammatory pathways were associated with both cutaneous inflammation and depression, highlighting shared pathology. Antiinflammatory medications targeting shared cytokines found reductions in both cutaneous and depressive symptoms. Practitioners have emphasized interdisciplinary approaches to treating both conditions, including psychotherapy and pharmacological methods. There is a clear association between inflammatory cutaneous diseases and depression. Co-management of these conditions, including interdisciplinary methods, is essential for patients' well-being. Future research addressing similar links between other cutaneous and psychiatric conditions could yield new treatment opportunities as well.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Experience of Spesolimab for Generalized Pustular Psoriasis Flares in Adult Patients: A Multicenter Retrospective Study.","authors":"Jensen Yeung, Siddhartha Sood","doi":"10.1007/s40257-024-00906-8","DOIUrl":"https://doi.org/10.1007/s40257-024-00906-8","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749537","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":"A Review of the Etiologies and Key Clinical Features of Secondary Hyperhidrosis.","authors":"Parnia Behinaein, Katherine Gavagan, Jacob Waitzman, Aunna Pourang, Geoffrey Potts","doi":"10.1007/s40257-024-00908-6","DOIUrl":"https://doi.org/10.1007/s40257-024-00908-6","url":null,"abstract":"<p><p>Secondary hyperhidrosis is a multifactorial condition that poses unique diagnostic and management challenges. Distinguishing secondary from primary hyperhidrosis remains difficult due to overlapping symptoms. This review consolidates existing evidence on the numerous underlying causes and pathophysiologic mechanisms of secondary hyperhidrosis across various disciplines. Secondary hyperhidrosis typically manifests in the fourth decade of life or later, whereas primary hyperhidrosis usually begins earlier. Generalized hyperhidrosis often suggests a secondary cause, though the distribution can vary, including focal symmetric/asymmetric or regional patterns depending on the underlying condition. Key clinical features such as lack of family history and associated symptoms provide additional clues favoring a secondary etiology. Recognizing these distinct characteristics is crucial for accurate differentiation between secondary and primary hyperhidrosis, thereby guiding appropriate evaluation and management of the underlying cause.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738064","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":"Multiple Keratoacanthomas Associated with Genetic Syndromes: Narrative Review and Proposal of a Diagnostic Algorithm.","authors":"Alexandra Dobre, Roxana-Ioana Nedelcu, Gabriela Turcu, Alice Brinzea, Irina Struna, Gabriela Tudorache, Alen Ali, Ionela Hulea, Elena Balasescu, Tudor Emanuel Fertig, Mihaela Gherghiceanu, Catherine Harwood, Daniela Adriana Ion, Ana-Maria Forsea","doi":"10.1007/s40257-024-00900-0","DOIUrl":"https://doi.org/10.1007/s40257-024-00900-0","url":null,"abstract":"<p><p>Keratoacanthoma (KA) is a relatively common, fast-growing epithelial tumour, with characteristic behaviour and clinical variability. Although it appears as a solitary lesion in a majority of cases, multiple KAs do occur, secondary to skin exposure to ultraviolet radiation, chemical carcinogens or certain medications, but may also be associated with various genetic syndromes. Thus, multiple KAs may serve as an early clinical alarm sign. Prompt diagnosis of the underlying cause and identification of the mechanism of development are critical for the secondary prevention of associated organ disorders or neoplasias, the improvement of patient quality of life and familial counselling. Although research in this field has seen important progress in the last few years, there are still many pathogenic processes that have not been elucidated. Additionally, the literature on this topic is limited to individual case reports and small case series, making it difficult for clinicians to parse available data and select the essential information. Therefore, this work aims to review current knowledge, summarizing existing studies, with focus on multiple KAs associated with genetic syndromes, and proposes a diagnostic algorithm for these rare cases to help guide clinicians in their practice. Lastly, we aim to highlight the main gaps in understanding the underlying mechanisms and suggest further research avenues.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685792","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}