American Journal of Clinical Dermatology最新文献

{"title":"The Impact of Family History on Clinical Presentation and Biologic Treatment Response in Patients with Psoriasis: A Multicenter Prospective Cohort Study","authors":"Yuxiong Jiang,&nbsp;Xiaoke Liu,&nbsp;Rui Ma,&nbsp;Dawei Huang,&nbsp;Yu Wang,&nbsp;Xiaoyuan Zhong,&nbsp;Lingling Yao,&nbsp;Shuang Xu,&nbsp;Ying Li,&nbsp;Xilin Zhang,&nbsp;Jiajing Lu,&nbsp;Yuling Shi","doi":"10.1007/s40257-025-00918-y","DOIUrl":"10.1007/s40257-025-00918-y","url":null,"abstract":"<div><h3>Background</h3><p>Family history (FH) of psoriasis has been implicated as a risk factor for developing psoriasis. However, whether FH also carries information on clinical presentation and treatment response to biological agents in patients with psoriasis remains unclear.</p><h3>Objective</h3><p>This prospective, multicenter observational study aimed to analyze the clinical presentation and efficacy differences between patients with psoriasis with and without a FH.</p><h3>Patients and Methods</h3><p>The SPEECH registry is an observational, multicenter, and prospective registry that has been collecting data on psoriasis treatment since November 2022. This study included adult patients diagnosed with moderate-to-severe plaque psoriasis initiating treatment with biologics, including guselkumab, secukinumab, ixekizumab, ustekinumab, and adalimumab. FH of psoriasis was identified through patient self-report in which a positive FH was defined as a first-degree relative having psoriasis. The primary outcome measures include 75% improvement in Psoriasis Area and Severity Index (PASI75) and the Physician’s Global Assessment score of cleared/minimal (PGA 0/1) after 3 months of treatment. Logistic regression was employed to determine the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the achievement of response in selected outcomes for patients with a FH compared with those without a FH.</p><h3>Results</h3><p>The study included a total of 859 patients, of whom 22.9% had a FH of psoriasis. Patients with psoriasis who had a FH experienced an earlier onset of the disease and more severe anxiety symptoms than those without a FH. After 3 months of treatment, patients with psoriasis with a FH exhibited a higher likelihood of achieving PASI75 (aOR 1.60 [95% CI 1.02, 2.51]) and PGA 0/1 (aOR 1.54 [95% CI 1.03, 2.31]). Notably, these differences persisted after 6 months of treatment, confirming the sustained effectiveness of biologic treatments in patients with a positive FH. Further mediation analysis uncovered a significant indirect effect of FH on the treatment response to biologics through age of onset (<i>p</i> = 0.028), and the proportion mediated was 20.5%.</p><h3>Conclusion</h3><p>FH of psoriasis may affect the clinical course of patients and enhance their treatment response to biologics, highlighting the importance of FH assessment in optimizing treatment outcome and guiding clinical decision of biologic selection. Future studies on biologic treatment responses in psoriasis should consider family history as a significant confounding factor.</p><h3>Chinese Clinical Trial Registry</h3><p>ChiCTR2000036186.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 2","pages":"291 - 300"},"PeriodicalIF":8.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021765","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":"Characterization of Clinicopathological Features and Autoantibody Profiles in Patients with Cutaneous Lupus Erythematous: A Single-Center Retrospective Study","authors":"Svati Pazhyanur,&nbsp;Olivia Lamberg,&nbsp;Megan Hauptman,&nbsp;Jessica Cristiu,&nbsp;Noreen Khan,&nbsp;Allison C. Billi,&nbsp;Mio Nakamura","doi":"10.1007/s40257-024-00916-6","DOIUrl":"10.1007/s40257-024-00916-6","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Cutaneous lupus erythematosus (CLE) is an autoimmune condition characterized by a wide range of clinical manifestations and limited treatment options. There is little research on the impact of commonly used diagnostic tests including antinuclear antibodies (ANA) and extractable nuclear antigens (ENA) on disease course or responsiveness to treatment.&lt;/p&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;p&gt;This single-center retrospective cohort study aims to address this gap by characterizing clinicopathological characteristics, patient demographics, and treatment response among patients with CLE.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;The study included patients with a diagnosis of CLE based on the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes evaluated in the outpatient clinics of the Department of Dermatology at Michigan Medicine between 1 January 2012 and 31 December 2022. Chart review was conducted to collect patient and clinical data including CLE subtype, patient demographics, disease course, presence of SLE, ANA and ENA results, and CLE treatments and response.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;390 patients with CLE were included, 86% (&lt;i&gt;n&lt;/i&gt; = 334) of whom had biopsy-proven CLE. Most patients were female (77%), non-Hispanic (97%), and Caucasian (58%). Of all patients, 35% (&lt;i&gt;n&lt;/i&gt; = 138) were ANA negative. The most common CLE treatments were antimalarials (86%, &lt;i&gt;n&lt;/i&gt; = 336), topical steroids (85%, &lt;i&gt;n&lt;/i&gt; = 331), systemic steroids (42%, &lt;i&gt;n&lt;/i&gt; = 164), and mycophenolate mofetil (30%, &lt;i&gt;n&lt;/i&gt; = 119). Treatment response was determined by clinician documentation and ranged from stabilization of disease to complete remission. Treatments with the highest CLE response rates included systemic steroids (84%, &lt;i&gt;n&lt;/i&gt; = 138), antimalarials (63%, &lt;i&gt;n&lt;/i&gt; = 212), belimumab (54%, &lt;i&gt;n&lt;/i&gt; = 29), and topical steroids (50%, &lt;i&gt;n&lt;/i&gt; = 165). Factors associated with lower response rates to antimalarials using chi-squared tests included anti-double stranded (ds) DNA (&lt;i&gt;n&lt;/i&gt; = 54, 57% response among anti-dsDNA+ versus &lt;i&gt;n&lt;/i&gt; = 165, 74% response among anti-dsDNA−), anti-Smith (&lt;i&gt;n&lt;/i&gt; = 33, 54% versus &lt;i&gt;n&lt;/i&gt; = 82, 72%), anti-RNP (&lt;i&gt;n&lt;/i&gt; = 48, 56% versus &lt;i&gt;n&lt;/i&gt; = 67, 73%), anti-SmRNP (&lt;i&gt;n&lt;/i&gt; = 44, 54% versus &lt;i&gt;n&lt;/i&gt; = 171, 74%), anti-chromatin (&lt;i&gt;n&lt;/i&gt; = 33, 50% versus &lt;i&gt;n&lt;/i&gt; = 179, 74%), SLE (&lt;i&gt;n&lt;/i&gt; = 81, 57% versus &lt;i&gt;n&lt;/i&gt; = 143, 79%), and ACLE subtype (&lt;i&gt;n&lt;/i&gt; = 28, 58% versus &lt;i&gt;n&lt;/i&gt; = 195, 71%). When controlling for demographics, CLE subtype, and presence of SLE using a logistic regression, factors associated with lower antimalarial response rates included anti-dsDNA (OR 0.5), anti-Smith (OR 0.5), and anti-chromatin (OR 0.6)&lt;/p&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Our results suggest that numerous patient characteristics, namely the presence of ACLE, SLE, and its most commonly implicated autoantibodies (i.e., anti-dsDNA and anti-Smith), are associated with lower response rates to first-line therapies, including topica","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 2","pages":"265 - 273"},"PeriodicalIF":8.6,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998650","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":"Biomarkers in Atopic Dermatitis: A Review of the Role of IL-13 and the Impact of Tralokinumab Treatment","authors":"Joe Gorelick,&nbsp;Andrea Nguyen,&nbsp;Shannon K R Schneider,&nbsp;Britta C. Martel,&nbsp;Daniel E. Madsen,&nbsp;April W. Armstrong","doi":"10.1007/s40257-024-00913-9","DOIUrl":"10.1007/s40257-024-00913-9","url":null,"abstract":"<div><p>Atopic dermatitis (AD) is a chronic, inflammatory skin disease that can significantly affect quality of life. Presence, severity, and therapeutic response of AD are traditionally reported through clinical assessments including the Eczema Area and Severity Index or Investigator’s Global Assessment. These clinical rating scales are visual assessments used in clinical trials to denotate AD severity. Alternatively, biomarkers open the potential to further enhance diagnosis of AD, assess disease status and severity, and potentially enable tailored treatment options for patients. Biomarkers can be classified according to their clinical use, clinical presentation, and underlying/endogenous molecular mechanisms. Specifically, interleukin (IL)-13, which has been shown to be a key biomarker in AD pathogenesis, can be used for prediction of AD development and to monitor clinical severity/response to treatment. Treatment with tralokinumab, a human monoclonal antibody that binds directly to—and subsequently blocks signaling of—IL-13, has been shown to reduce inflammation, re-balance the skin microbiome, and improve the skin barrier in patients with AD. In this review, key AD-related biomarkers, the role of IL-13 in driving AD pathogenesis, and the impact of IL-13 inhibition by tralokinumab on other AD-related biomarkers are discussed.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 2","pages":"199 - 211"},"PeriodicalIF":8.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-024-00913-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 Herald Patch: Exploring the Complex Landscape of Pityriasis Rosea","authors":"Kayla D. Mashoudy,&nbsp;Sarah Kim,&nbsp;Leah Farhadi,&nbsp;Scott A. Elman","doi":"10.1007/s40257-024-00915-7","DOIUrl":"10.1007/s40257-024-00915-7","url":null,"abstract":"<div><p>Pityriasis rosea (PR) is a prevalent dermatological condition characterized by a distinctive herald patch, followed by secondary eruptions, often forming a “Christmas tree” pattern on the trunk. Despite its recognizable clinical presentation, the etiology of PR remains uncertain, with hypotheses pointing to both infectious and noninfectious origins. Human herpesviruses (HHV) 6 and 7 have been implicated, with evidence suggesting viral reactivation as a potential trigger. Epidemiologically, PR affects children, adolescents, and young adults, with a higher incidence in females. The condition is observed globally, with varying incidence rates and seasonal variations, suggesting an infectious component. While PR is generally benign and self-limiting, it can cause significant discomfort owing to pruritus, and atypical presentations and recurrences complicate diagnosis and management. This review evaluates the current understanding of PR’s pathogenesis, highlighting both infectious and noninfectious hypotheses, including viral reactivation and immune response mechanisms. It also examines treatment options, such as antivirals and phototherapy, which have shown varying degrees of effectiveness. Further research is needed to clarify etiological factors and to explore the efficacy and safety of various treatment modalities. Understanding these aspects is crucial for improving patient outcomes and developing targeted therapies, especially for atypical or recurrent cases.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 2","pages":"237 - 250"},"PeriodicalIF":8.6,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-024-00915-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Maximum-Use Trial of Ruxolitinib Cream in Children Aged 2–11 Years with Moderate to Severe Atopic Dermatitis","authors":"Linda Stein Gold,&nbsp;Robert Bissonnette,&nbsp;Seth Forman,&nbsp;Andrea Zaenglein,&nbsp;YuTzu Kuo,&nbsp;Brett Angel,&nbsp;Xuejun Chen,&nbsp;Howard Kallender,&nbsp;Amy S. Paller","doi":"10.1007/s40257-024-00909-5","DOIUrl":"10.1007/s40257-024-00909-5","url":null,"abstract":"<div><h3>Background</h3><p>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><h3>Objective</h3><p>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><h3>Methods</h3><p>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><h3>Results</h3><p>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><h3>Conclusion</h3><p>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><h3>ClinicalTrials.gov Identifier</h3><p>NCT05034822, first registered 30 August 2021.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 2","pages":"275 - 289"},"PeriodicalIF":8.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-024-00909-5.pdf","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":"OA","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":"10.1007/s40257-024-00914-8","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 1","pages":"1 - 5"},"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,&nbsp;Alexander H. Enk,&nbsp;Jessica C. Hassel","doi":"10.1007/s40257-024-00910-y","DOIUrl":"10.1007/s40257-024-00910-y","url":null,"abstract":"<div><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></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 2","pages":"213 - 223"},"PeriodicalIF":8.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-024-00910-y.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontal Fibrosing Alopecia: An Update","authors":"Andrew G. Messenger,&nbsp;Leila Asfour,&nbsp;Matthew Harries","doi":"10.1007/s40257-024-00912-w","DOIUrl":"10.1007/s40257-024-00912-w","url":null,"abstract":"<div><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></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 2","pages":"155 - 174"},"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,&nbsp;Marcia S. Driscoll","doi":"10.1007/s40257-024-00911-x","DOIUrl":"10.1007/s40257-024-00911-x","url":null,"abstract":"<div><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></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 2","pages":"175 - 182"},"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,&nbsp;David J. Bozym,&nbsp;Giuseppe Tarantino,&nbsp;Ryan J. Sullivan,&nbsp;David Liu,&nbsp;Russell W. Jenkins","doi":"10.1007/s40257-024-00907-7","DOIUrl":"10.1007/s40257-024-00907-7","url":null,"abstract":"<div><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></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 1","pages":"77 - 96"},"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}