{"title":"Predictors and Management of Inadequate Response to JAK Inhibitors in Alopecia Areata","authors":"Xiaolin Zhang, Yiqun Jiang","doi":"10.1007/s40257-024-00884-x","DOIUrl":"10.1007/s40257-024-00884-x","url":null,"abstract":"<div><p>Alopecia areata is a common autoimmune disorder characterized by non-scarring hair loss on the scalp or other hair-bearing surface. In recent years, Janus kinase (JAK) inhibitors have shown promise in the treatment of alopecia areata by disrupting the signaling pathways involved in immune-mediated hair follicle damage. However, some patients with alopecia areata exhibit insufficient responses to JAK inhibitors. This review aims to explore the predictive factors for poor responses to JAK inhibitors in patients with alopecia areata and to discuss alternative treatment strategies in such cases. Patients with a longer duration of the current episode and higher baseline severity are at an increased risk of inadequate JAK inhibitor responses. Oral administration rather than topical application, and extended treatment durations, correlate with a favorable response. Notably, the poor response to JAK inhibitors in alopecia areata may be related to the amount and functional depletion of regulatory T cells resulting from an augmented T helper-2-type immune response. For patients with poor responses to JAK inhibitors, treatment adjustments may include increasing the dosage, extending the treatment duration, combination therapies, or switching to alternative JAK inhibitors. For patients with atopic comorbidities or psychological problems, it is important to select corresponding treatment options to optimize patient outcomes. Further research is needed to establish more reliable predictors and improve overall patient care.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 6","pages":"975 - 986"},"PeriodicalIF":8.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118823","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":"Advances in the Application of Noninvasive Skin Imaging Techniques in Acne Scars","authors":"Xiaoli Ning, Lingfan Jiang, Ruixing Yu, Yujun Sheng, Mengmeng Li, Hongfei Ouyang, Jingkai Xu, Yong Cui","doi":"10.1007/s40257-024-00882-z","DOIUrl":"10.1007/s40257-024-00882-z","url":null,"abstract":"<div><p>Acne scarring is a common sequela of acne vulgaris, which seriously affects facial esthetics. The treatment options for acne scars vary depending on the development stage, color, type, and location of scarring. The objective and precise assessment of acne scars is a prerequisite for treatment, and it is also an important means of monitoring the treatment effect. The traditional methods to evaluate the types and severity grade of acne scars are primarily based on subjective assessment by physicians, which lacks objectivity and accuracy. Novel noninvasive skin imaging techniques, such as skin surface imaging analysis systems, dermoscopy, reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), and multiphoton tomography (MPT), provide new tools for the rapid and objective assessment of acne scars. This article reviews the progress of skin imaging techniques in the diagnosis, classification, and efficacy evaluation of acne scars.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 5","pages":"823 - 835"},"PeriodicalIF":8.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970439","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}
Luis F. Andrade, Zaim Haq, Parsa Abdi, Sarah G. Brooks, Veronica Voronina, Michael J. Diaz, Gil Yosipovitch
{"title":"Association of Cardiovascular Disease and Chronic Spontaneous Urticaria: A Case–Control Study","authors":"Luis F. Andrade, Zaim Haq, Parsa Abdi, Sarah G. Brooks, Veronica Voronina, Michael J. Diaz, Gil Yosipovitch","doi":"10.1007/s40257-024-00881-0","DOIUrl":"10.1007/s40257-024-00881-0","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 5","pages":"849 - 851"},"PeriodicalIF":8.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888267","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}
Katie K. Lovell, Rushan I. Momin, Harneet Singh Sangha, Steven R. Feldman, Rita O. Pichardo
{"title":"Dapsone Use in Dermatology","authors":"Katie K. Lovell, Rushan I. Momin, Harneet Singh Sangha, Steven R. Feldman, Rita O. Pichardo","doi":"10.1007/s40257-024-00879-8","DOIUrl":"10.1007/s40257-024-00879-8","url":null,"abstract":"<div><p>Dapsone, initially synthesized for textile dyeing, gained recognition in the 1930s for its antibacterial properties, leading to its utilization in dermatology for leprosy and dermatitis herpetiformis. Despite US Food and Drug Administration (FDA) approval for these conditions, dapsone’s off-label uses have expanded, making it a valuable option in various dermatologic conditions. This review seeks to highlight the common uses of dapsone in its FDA indications and off-label indications. Diseases in which dapsone is considered first-line therapy or adjunctive therapy are reviewed, with highlights from the resources included. An overview of dapsone’s pharmacokinetics, pharmacodynamics, indications, dosages, and safety profile are also reviewed. Dapsone’s versatility and safety profile make it a cost-effective treatment option in dermatology, particularly for patients with limited access to specialized medications. Ongoing clinical trials are also described exploring dapsone’s efficacy in novel dermatologic uses. Dapsone has been a valuable adjunctive therapy across various dermatologic conditions for years and evidence for its use continues to expand.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 5","pages":"811 - 822"},"PeriodicalIF":8.6,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791696","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}
Julia L. Gao, Tracey S. Otto, Martina L. Porter, Alexa B. Kimball
{"title":"Hidradenitis Suppurativa: New Targets and Emerging Treatments","authors":"Julia L. Gao, Tracey S. Otto, Martina L. Porter, Alexa B. Kimball","doi":"10.1007/s40257-024-00880-1","DOIUrl":"10.1007/s40257-024-00880-1","url":null,"abstract":"<div><p>Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can be challenging to treat. Biologics and targeted small molecules have become an increasingly popular area of investigation for therapeutic development for moderate-to-severe HS, though only three biologics—adalimumab, secukinumab, and bimekizumab—have received US Food and Drug Administration (FDA) or European Medicines Evaluation Agency approval for treating HS. Promising agents under investigation are targeting interleukin 17A/F, JAK/STAT pathway, interleukin 36, interleukin 1, and more.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 5","pages":"765 - 778"},"PeriodicalIF":8.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764877","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}
Nicole D. Boswell, Shikha Singla, Kenneth B. Gordon
{"title":"Sequencing of Targeted Therapy in Psoriasis: Does it Matter?","authors":"Nicole D. Boswell, Shikha Singla, Kenneth B. Gordon","doi":"10.1007/s40257-024-00874-z","DOIUrl":"10.1007/s40257-024-00874-z","url":null,"abstract":"<div><p>With the continued development of biologics for the treatment of psoriasis, some patients have achieved optimal control, but a recommended biologic sequence if a biologic fails to initially improve the skin, termed primary nonresponse, or loses efficacy after initial improvement, termed secondary nonresponse, is still lacking. Primary and secondary nonresponse can occur with any class of biologics, and the type of nonresponse can drive the choice of whether to switch within a biologic class or to a different biologic class. The choice of biologic can also be challenging when managing psoriasis and concomitant psoriatic arthritis, as treatment differs on the basis of the severity of both diseases and further classification of axial and peripheral joint involvement. When choosing a biologic, each patient’s comorbidities and preferences are also taken into account to provide the optimal therapy. With this lack of an established biologic sequence after biologic failure, the objective of our review is to define a therapy sequence for the tumor necrosis factor (TNF), interleukin-17 (IL-17), and interleukin-23 (IL-23) inhibitor classes in the treatment of psoriasis and psoriatic arthritis. Our proposed biologic sequence was derived through an analysis of the efficacy of each biologic class, primary and secondary nonresponse rates from clinical trials, and clinical experience with expert opinion.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 5","pages":"795 - 810"},"PeriodicalIF":8.6,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603157","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":"Lichen Planus: What is New in Diagnosis and Treatment?","authors":"Burak Tekin, Fangyi Xie, Julia S. Lehman","doi":"10.1007/s40257-024-00878-9","DOIUrl":"10.1007/s40257-024-00878-9","url":null,"abstract":"<div><p>Lichen planus (LP), an idiopathic, multifaceted chronic inflammatory disease with a heterogeneous clinical presentation, affects approximately 0.5–1% of the population. The various clinical manifestations of LP fall into three broad categories, namely cutaneous, appendageal, and mucosal, with further subclassification depending on the morphology and distribution patterns of individual lesions. There is mounting evidence that LP has systemic associations, including autoimmune conditions, glucose intolerance, dyslipidemia, and cardiovascular disorders. Cutaneous hypertrophic and mucosal forms of LP are at a heightened risk for malignant transformation. Familiarity with these potential associations in conjunction with long-term follow-up and regular screening could lead to a timely diagnosis and management of concomitant conditions. In addition, the frequent quality of life (QoL) impairment in LP underscores the need for a comprehensive approach including psychological evaluation and support. Several treatment strategies have been attempted, though most of them have not been adopted in clinical practice because of suboptimal benefit-to-risk ratios or lack of evidence. More recent studies toward pathogenesis-driven treatments have identified Janus kinase inhibitors such as tofacitinib, phosphodiesterase-4 inhibitors such as apremilast, and biologics targeting the interleukin-23/interleukin-17 pathway as novel therapeutic options, resulting in a dramatic change of the treatment landscape of LP. This contemporary review focuses on the diagnosis and management of LP, and places emphasis on more recently described targeted treatment options.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 5","pages":"735 - 764"},"PeriodicalIF":8.6,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562439","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":"Efficacy and Safety of Brodalumab, an Anti-interleukin-17 Receptor A Monoclonal Antibody, for Palmoplantar Pustulosis: 16-Week Results of a Randomized Clinical Trial","authors":"Yukari Okubo, Satomi Kobayashi, Masamoto Murakami, Shigetoshi Sano, Natsuko Kikuta, Yoshiumi Ouchi, Tadashi Terui","doi":"10.1007/s40257-024-00876-x","DOIUrl":"10.1007/s40257-024-00876-x","url":null,"abstract":"<div><h3>Background</h3><p>Palmoplantar pustulosis (PPP), a refractory skin disease characterized by repeated eruptions of sterile pustules and vesicles on palms and/or soles, involves interleukin-17 pathway activation. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, is being investigated for use in PPP treatment.</p><h3>Objective</h3><p>The aim was to assess the efficacy and safety of brodalumab in Japanese PPP patients with moderate or severe pustules/vesicles.</p><h3>Methods</h3><p>A phase 3, randomized, double-blind, placebo-controlled trial was conducted between July 2019 and August 2022, at 41 centers in Japan. Patients aged 18–70 years with a diagnosis of PPP for ≥ 24 weeks, a PPP Area Severity Index (PPPASI) score of ≥ 12, a PPPASI subscore of pustules/vesicles of ≥ 2, and inadequate response to therapy were included. Participants were randomized 1:1 to receive brodalumab 210 mg or placebo, subcutaneously (SC) at baseline, weeks 1 and 2, and every 2 weeks (Q2W) thereafter until week 16. Changes from baseline to week 16 in the PPPASI total score (primary endpoint) and other secondary skin-related endpoints and safety endpoints were assessed.</p><h3>Results</h3><p>Of the 126 randomized patients, 50 of 63 in the brodalumab group and 62 of 63 in the placebo group completed the 16-week period. Reasons for discontinuation were adverse event (<i>n</i> = 6), withdrawal by patient/parent/guardian (<i>n</i> = 3), progressive disease (<i>n</i> = 3), and lost to follow-up (<i>n</i> = 1) in the brodalumab group and Good Clinical Practice deviation (<i>n</i> = 1) in the placebo group. Change from baseline in the PPPASI total score at week 16 was significantly higher (<i>p</i> = 0.0049) with brodalumab (least-squares mean [95% confidence interval {CI}] 13.73 [10.91–16.56]) versus placebo (8.45 [5.76–11.13]; difference [95% CI] 5.29 [1.64–8.94]). At week 16, brodalumab showed a trend of rapid improvement versus placebo for PPPASI-50/75/90 response (≥ 50%/75%/90% improvement from baseline) and Physician’s Global Assessment 0/1 score: 54% versus 24.2%, 36.0% versus 8.1%, 16.0% versus 0.0%, and 32.0% versus 9.7%, respectively. Infection was the dominant treatment-emergent adverse event (TEAE); the commonly reported TEAEs were otitis externa (25.4%/1.6%), folliculitis (15.9%/3.2%), nasopharyngitis (14.3%/4.8%), and eczema (14.3%/12.9%) in the brodalumab/placebo groups, respectively. The severity of most TEAEs reported was Grade 1 or 2 and less frequently Grade ≥ 3.</p><h3>Conclusions</h3><p>Brodalumab SC 210 mg Q2W demonstrated efficacy in Japanese PPP patients. The most common TEAEs were mild infectious events.</p><h3>Trial Registration</h3><p>NCT04061252 (Date of Trial Registration: August 19, 2019)</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 5","pages":"837 - 847"},"PeriodicalIF":8.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490599","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}
Yasmine Oprea, Daniel R. Antohi, Morgan Vague, Caroline Delbourgo Patton, Benedict Wu, Alex G. Ortega‐Loayza
{"title":"Human Inborn Errors of Immunity in Pyoderma Gangrenosum: A Systematic Review","authors":"Yasmine Oprea, Daniel R. Antohi, Morgan Vague, Caroline Delbourgo Patton, Benedict Wu, Alex G. Ortega‐Loayza","doi":"10.1007/s40257-024-00875-y","DOIUrl":"10.1007/s40257-024-00875-y","url":null,"abstract":"<div><h3>Background and Objective</h3><p>Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that can be associated with primary immunodeficiency. The pathogenesis of PG has not yet been elucidated, although contributions from dysregulation of the immune system in patients with apparent genetic predispositions have been postulated. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review with the objective of identifying inborn errors of immunity in the presence of PG as well as their clinical characteristics of severity including number of PG lesions and anatomic areas affected, and treatment outcomes.</p><h3>Methods</h3><p>A literature search was performed using PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science through August 24, 2023, for studies published in English using the search terms: “pyoderma gangrenosum,” “inborn error of immunity,” “immune defect*,” and a list of genetic mutations potentially associated with PG.</p><h3>Results</h3><p>Seventy-four cases of PG associated with inborn errors of immunity were identified. The results demonstrate an association of PG with a variety of inborn errors of immunity, including genetic mutations not classically associated with the condition. Genetic mutations such as <i>BTK</i>, <i>IL1RN</i>, <i>ITGB2</i>, <i>LPIN2</i>, <i>MEFV</i>, <i>NFkB1</i>, <i>NLRP3</i>, <i>NLRP12</i>, <i>NOD2</i>, <i>PSMB8</i>, <i>PLCG2</i>, <i>PSTPIP1</i>, <i>RAG1</i>, <i>TTC37</i>, and <i>WDR1</i>, as well as complement component 2<i>/</i>complement component 4 (C2/C4) and complement component 7 (C7) deficiencies were identified in the presence of either idiopathic or syndromic PG. Of note, mutations in genes such as <i>PSMB8</i>, <i>NLRP3</i>, and <i>IL1RN</i> were found to be associated with a more severe and atypical course of PG, whereas mutations in <i>RAG1</i> as well as those causing a C2/C4 deficiency were associated with the mildest clinical presentations of PG. Mutations in <i>NFkB1</i>, <i>ITGB2</i>, and <i>PSTPIP1</i> were associated with the most heterogeneous clinical presentations.</p><h3>Conclusions</h3><p>Human inborn errors of immunity may be implicated in the genetic predisposition to PG and may influence the clinical presentation. Due to the rarity of these diseases, further work must be done to describe the association between inborn errors of immunity and PG. Identifying inborn errors of immunity that may contribute to the development of PG may assist in further elucidating the mechanism of PG, guiding targeted treatment, and improving clinical outcomes for these patients.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 5","pages":"701 - 716"},"PeriodicalIF":8.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475704","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}