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Dapsone Use in Dermatology 多apseone 在皮肤科中的应用。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-07-30 DOI: 10.1007/s40257-024-00879-8
Katie K. Lovell, Rushan I. Momin, Harneet Singh Sangha, Steven R. Feldman, Rita O. Pichardo

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.

他松最初是为纺织品染色而合成的,在 20 世纪 30 年代因其抗菌特性而获得认可,从而被皮肤科用于麻风病和疱疹性皮炎的治疗。尽管美国食品和药物管理局(FDA)批准了对这些病症的治疗,但他松的标示外用途也在不断扩大,使其成为治疗各种皮肤病的重要选择。本综述旨在重点介绍多松在 FDA 适应症和标签外适应症中的常见用途。本综述将对那些将他松视为一线疗法或辅助疗法的疾病进行综述,并包括相关资源中的重点内容。此外,还概述了他松的药代动力学、药效学、适应症、剂量和安全性。他泼松的多功能性和安全性使其成为皮肤科中一种经济有效的治疗选择,特别是对于那些难以获得专门药物治疗的患者。此外,还介绍了正在进行的临床试验,以探索达泼松在新型皮肤病治疗中的疗效。多年来,他泼松一直是各种皮肤病的重要辅助治疗药物,其使用证据也在不断增加。
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引用次数: 0
Hidradenitis Suppurativa: New Targets and Emerging Treatments 化脓性扁桃体炎:新靶点和新疗法
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-07-26 DOI: 10.1007/s40257-024-00880-1
Julia L. Gao, Tracey S. Otto, Martina L. Porter, Alexa B. Kimball

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.

化脓性扁平湿疹(HS)是一种慢性炎症性皮肤病,治疗难度很大。生物制剂和靶向小分子药物已成为治疗中重度HS的一个日益热门的研究领域,但目前只有三种生物制剂--阿达木单抗、secukinumab和bimekizumab--获得了美国食品药品管理局(FDA)或欧洲药品评价局的批准用于治疗HS。针对白细胞介素 17A/F、JAK/STAT 通路、白细胞介素 36、白细胞介素 1 等的药物正在研究中,前景看好。
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引用次数: 0
Sequencing of Targeted Therapy in Psoriasis: Does it Matter? 银屑病靶向治疗的排序:这重要吗?
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-07-13 DOI: 10.1007/s40257-024-00874-z
Nicole D. Boswell, Shikha Singla, Kenneth B. Gordon

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.

随着治疗银屑病的生物制剂的不断发展,一些患者的病情得到了最佳控制,但如果一种生物制剂最初未能改善皮肤(称为原发性无应答),或在最初改善后失去疗效(称为继发性无应答),则仍缺乏推荐的生物制剂顺序。任何一类生物制剂都可能出现原发性和继发性无应答,而无应答的类型会促使患者选择是在一类生物制剂中更换还是更换到另一类生物制剂。在治疗银屑病合并银屑病关节炎时,生物制剂的选择也具有挑战性,因为两种疾病的严重程度以及轴向和外周关节受累的进一步分类会导致治疗方法的不同。在选择生物制剂时,还要考虑每位患者的合并症和偏好,以提供最佳治疗。由于生物制剂治疗失败后缺乏既定的生物制剂治疗顺序,我们的综述旨在确定肿瘤坏死因子(TNF)、白细胞介素-17(IL-17)和白细胞介素-23(IL-23)抑制剂类药物在治疗银屑病和银屑病关节炎时的治疗顺序。我们提出的生物制剂治疗顺序是通过分析每类生物制剂的疗效、临床试验中的主要和次要无应答率以及专家意见的临床经验得出的。
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引用次数: 0
Lichen Planus: What is New in Diagnosis and Treatment? 扁平苔癣:诊断和治疗的新进展?
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-07-09 DOI: 10.1007/s40257-024-00878-9
Burak Tekin, Fangyi Xie, Julia S. Lehman

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.

扁平苔藓(LP)是一种特发性、多发性慢性炎症疾病,临床表现多种多样,约占总人口的 0.5-1%。扁平苔藓的各种临床表现可分为三大类,即皮肤类、阑尾类和粘膜类,并可根据单个病变的形态和分布模式进一步细分。越来越多的证据表明,LP 与全身性疾病有关,包括自身免疫性疾病、葡萄糖不耐受症、血脂异常和心血管疾病。皮肤肥厚型和粘膜型 LP 恶变的风险更高。熟悉这些潜在的关联,并进行长期随访和定期筛查,可以及时诊断和处理并发症。此外,LP 患者的生活质量(QoL)经常受到损害,这也强调了采取包括心理评估和支持在内的综合方法的必要性。目前已尝试了多种治疗策略,但由于疗效风险比不理想或缺乏证据,大多数治疗策略尚未被临床采用。最近,针对发病机制驱动治疗的研究发现,Janus 激酶抑制剂(如托法替尼)、磷酸二酯酶-4 抑制剂(如阿普瑞司特)和靶向白细胞介素-23/白细胞介素-17 通路的生物制剂是新的治疗选择,从而使 LP 的治疗格局发生了巨大变化。这篇当代综述的重点是 LP 的诊断和管理,并着重介绍了最新的靶向治疗方案。
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引用次数: 0
Clinical Efficacy and Safety of Interleukin-17 Inhibitors in Treating Patients with Erythrodermic Psoriasis: A Retrospective Cohort, Three-Center Study 白细胞介素-17抑制剂治疗红皮病型银屑病患者的临床疗效和安全性:一项回顾性队列、三中心研究。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-07-05 DOI: 10.1007/s40257-024-00873-0
Yu Lan, Xiaoyan Wu, Linya Ni, Yuhua Liu, Tianmeng Yan, Dejian Duan, Zhenying Zhang
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引用次数: 0
Efficacy and Safety of Brodalumab, an Anti-interleukin-17 Receptor A Monoclonal Antibody, for Palmoplantar Pustulosis: 16-Week Results of a Randomized Clinical Trial 抗白细胞介素-17受体A单克隆抗体Brodalumab治疗掌跖脓疱病的疗效和安全性:一项随机临床试验的16周结果。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-07-02 DOI: 10.1007/s40257-024-00876-x
Yukari Okubo, Satomi Kobayashi, Masamoto Murakami, Shigetoshi Sano, Natsuko Kikuta, Yoshiumi Ouchi, Tadashi Terui

Background

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.

Objective

The aim was to assess the efficacy and safety of brodalumab in Japanese PPP patients with moderate or severe pustules/vesicles.

Methods

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.

Results

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 (n = 6), withdrawal by patient/parent/guardian (n = 3), progressive disease (n = 3), and lost to follow-up (n = 1) in the brodalumab group and Good Clinical Practice deviation (n = 1) in the placebo group. Change from baseline in the PPPASI total score at week 16 was significantly higher (p = 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.

Conclusions

Brodalumab SC 210 mg Q2W demonstrated efficacy in Japanese PPP patients. The most common TEAEs were mild infectious events.

Trial Registration

NCT04061252 (Date of Trial Registration: August 19, 2019)

背景:掌跖脓疱病(PPP)是一种难治性皮肤病,其特征是手掌和/或足底反复爆发无菌性脓疱和水泡,涉及白细胞介素-17通路激活。Brodalumab是一种全人源抗白细胞介素-17受体A单克隆抗体,目前正在研究用于治疗PPP:目的:评估布达鲁单抗对患有中度或重度脓疱/囊肿的日本 PPP 患者的疗效和安全性:2019年7月至2022年8月期间,在日本41个中心开展了一项3期随机、双盲、安慰剂对照试验。纳入的患者年龄为18-70岁,确诊PPP≥24周,PPP面积严重程度指数(PPPASI)评分≥12分,脓疱/囊肿的PPPASI子评分≥2分,且对治疗反应不充分。参与者按1:1随机分配,在基线、第1周和第2周皮下注射(SC)210毫克或安慰剂,此后每2周注射一次(Q2W),直至第16周。评估从基线到第16周PPPASI总分(主要终点)和其他次要皮肤相关终点及安全性终点的变化:结果:在126名随机患者中,布达鲁单抗组63人中有50人完成了16周的治疗,安慰剂组63人中有62人完成了16周的治疗。停药原因包括:不良事件(6例)、患者/家长/监护人退出(3例)、疾病进展(3例)、brodalumab组失去随访(1例)和安慰剂组偏离良好临床实践(1例)。与安慰剂(8.45 [5.76-11.13]; 差异 [95% CI] 5.29 [1.64-8.94])相比,在第16周时,布达鲁单抗(最小二乘均值[95% 置信区间{CI}] 13.73 [10.91-16.56])的PPPASI总分与基线相比的变化显著更高(p = 0.0049)。第16周时,在PPPASI-50/75/90反应(与基线相比改善≥50%/75%/90%)和医生总体评估0/1评分方面,brodalumab与安慰剂相比呈现快速改善趋势:分别为54%对24.2%、36.0%对8.1%、16.0%对0.0%和32.0%对9.7%。感染是最主要的治疗突发不良事件(TEAE);在brodalumab组/安慰剂组中,常见的TEAE分别是外耳道炎(25.4%/1.6%)、毛囊炎(15.9%/3.2%)、鼻咽炎(14.3%/4.8%)和湿疹(14.3%/12.9%)。报告的大多数TEAEs的严重程度为1级或2级,≥3级的情况较少:结论:布罗达鲁单抗 SC 210 毫克 Q2W 对日本 PPP 患者具有疗效。最常见的TEAE为轻度感染事件:NCT04061252(试验注册日期:2019年8月19日)。
{"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,&nbsp;Satomi Kobayashi,&nbsp;Masamoto Murakami,&nbsp;Shigetoshi Sano,&nbsp;Natsuko Kikuta,&nbsp;Yoshiumi Ouchi,&nbsp;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}
引用次数: 0
Human Inborn Errors of Immunity in Pyoderma Gangrenosum: A Systematic Review 脓皮病中的人类先天性免疫错误:系统综述
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-07-01 DOI: 10.1007/s40257-024-00875-y
Yasmine Oprea, Daniel R. Antohi, Morgan Vague, Caroline Delbourgo Patton, Benedict Wu, Alex G. Ortega‐Loayza

Background and Objective

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.

Methods

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.

Results

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 BTK, IL1RN, ITGB2, LPIN2, MEFV, NFkB1, NLRP3, NLRP12, NOD2, PSMB8, PLCG2, PSTPIP1, RAG1, TTC37, and WDR1, as well as complement component 2/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 PSMB8, NLRP3, and IL1RN were found to be associated with a more severe and atypical course of PG, whereas mutations in RAG1 as well as those causing a C2/C4 deficiency were associated with the mildest clinical presentations of PG. Mutations in NFkB1, ITGB2, and PSTPIP1 were associated with the most heterogeneous clinical presentations.

Conclusions

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.

背景和目的:坏疽性脓皮病(PG)是一种罕见的溃疡性嗜中性皮肤病,可能与原发性免疫缺陷有关。尽管有人推测具有明显遗传倾向的患者的免疫系统失调可能是导致 PG 发病的原因之一,但 PG 的发病机制尚未阐明。我们在系统综述和荟萃分析首选报告项目(PRISMA)指导下进行了一次系统综述,目的是确定存在 PG 的先天性免疫错误及其严重程度的临床特征,包括 PG 病变的数量和受影响的解剖区域,以及治疗结果:方法:使用 PubMed/MEDLINE、Embase、Cochrane Library 和 Web of Science 对截至 2023 年 8 月 24 日以英文发表的研究进行文献检索,检索词包括"脓皮病"、"先天性免疫错误"、"免疫缺陷*"以及可能与 PG 相关的基因突变列表:结果:共发现 74 例与先天性免疫错误有关的脓疱疮病例。结果表明,PG 与多种先天性免疫错误有关,其中包括与该病症不相关的基因突变。在特发性或综合征 PG 中发现了 BTK、IL1RN、ITGB2、LPIN2、MEFV、NFkB1、NLRP3、NLRP12、NOD2、PSMB8、PLCG2、PSTPIP1、RAG1、TTC37 和 WDR1 等基因突变,以及补体成分 2/补体成分 4(C2/C4)和补体成分 7(C7)缺陷。值得注意的是,PSMB8、NLRP3 和 IL1RN 等基因的突变与 PG 更严重和不典型的病程有关,而 RAG1 基因突变以及导致 C2/C4 缺乏症的基因突变与 PG 最轻微的临床表现有关。NFkB1、ITGB2和PSTPIP1的突变与最异质性的临床表现有关:人类先天性免疫错误可能与 PG 的遗传易感性有关,并可能影响临床表现。结论:人类先天性免疫错误可能与 PG 的遗传易感性有关,并可能影响临床表现。由于此类疾病的罕见性,必须进一步研究先天性免疫错误与 PG 之间的关联。找出可能导致 PG 发病的先天性免疫错误可能有助于进一步阐明 PG 的发病机制、指导有针对性的治疗并改善这些患者的临床预后。
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引用次数: 0
Association Between Biologic Exposure and the Risk of Depression in Patients with Psoriasis: A Retrospective Analysis of Large US Administrative Claims Data 生物制剂暴露与银屑病患者抑郁风险之间的关系:美国大型行政索赔数据的回顾性分析。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-06-27 DOI: 10.1007/s40257-024-00877-w
Bruce Strober, Ahmed M. Soliman, Bang Truong, Manish B. Patel, Yazan K. Barqawi, Paolo Gisondi
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引用次数: 0
The Current State of Systemic Therapy of Metastatic Uveal Melanoma 转移性葡萄膜黑色素瘤的系统治疗现状。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-06-22 DOI: 10.1007/s40257-024-00872-1
Elias A. T. Koch, Markus V. Heppt, Carola Berking

Uveal melanoma (UM) is genetically a distinct tumor compared to cutaneous melanoma (CM), and due to its low mutational burden, it is far less perceptible to the immune system. Thus, treatments that have revolutionized the treatment of CM remain widely inefficient in metastatic UM or only demonstrate effectiveness in a small subpopulation of patients. To this end, the therapeutic benefit of immune checkpoint blockade is very limited and may come at the expense of severe immune-related adverse events that could potentially affect all organ systems. Notably, tebentafusp, an entirely novel class of anti-cancer drugs, has received official authorization for the treatment of metastatic UM. It is the first agent that demonstrated a survival advantage in a randomized controlled trial of metastatic UM patients. Despite the survival benefit and approval, the restriction of tebentafusp to HLA-A*02:01-positive patients and the low objective response rate indicate the persistent need for additional therapies. Thus, liver-directed therapies are commonly used for tumor control of hepatic metastases and represent a central pillar of the daily management of liver-dominant disease. Further, promising data from targeted therapies independent of MEK-inhibitors, such as the combination of darovasertib and crizotinib, raise hope for additional options in metastatic UM in the future. This narrative review provides a timely and comprehensive overview of the current treatment landscape for metastatic UM.

葡萄膜黑色素瘤(UM)与皮肤黑色素瘤(CM)相比,在基因上是一种独特的肿瘤,而且由于其突变负荷低,免疫系统对它的感知能力要差得多。因此,已经彻底改变了皮肤黑色素瘤治疗方法的治疗方法在转移性皮肤黑色素瘤中仍然普遍无效,或者只在一小部分患者中有效。为此,免疫检查点阻断疗法的治疗效果非常有限,而且可能以可能影响所有器官系统的严重免疫相关不良事件为代价。值得注意的是,作为一种全新的抗癌药物,特本伐普已获得治疗转移性 UM 的正式授权。这是第一种在转移性 UM 患者随机对照试验中显示出生存优势的药物。尽管获得了生存优势和批准,但特本伐斯普仅限于 HLA-A*02:01 阳性患者使用,而且客观反应率较低,这表明仍然需要其他疗法。因此,肝脏靶向疗法通常用于控制肝转移瘤,是肝脏占位性疾病日常治疗的核心支柱。此外,独立于MEK抑制剂的靶向疗法(如darovasertib和crizotinib的联合疗法)也取得了令人鼓舞的数据,为未来转移性UM的更多选择带来了希望。这篇叙述性综述及时、全面地概述了目前转移性 UM 的治疗情况。
{"title":"The Current State of Systemic Therapy of Metastatic Uveal Melanoma","authors":"Elias A. T. Koch,&nbsp;Markus V. Heppt,&nbsp;Carola Berking","doi":"10.1007/s40257-024-00872-1","DOIUrl":"10.1007/s40257-024-00872-1","url":null,"abstract":"<div><p>Uveal melanoma (UM) is genetically a distinct tumor compared to cutaneous melanoma (CM), and due to its low mutational burden, it is far less perceptible to the immune system. Thus, treatments that have revolutionized the treatment of CM remain widely inefficient in metastatic UM or only demonstrate effectiveness in a small subpopulation of patients. To this end, the therapeutic benefit of immune checkpoint blockade is very limited and may come at the expense of severe immune-related adverse events that could potentially affect all organ systems. Notably, tebentafusp, an entirely novel class of anti-cancer drugs, has received official authorization for the treatment of metastatic UM. It is the first agent that demonstrated a survival advantage in a randomized controlled trial of metastatic UM patients. Despite the survival benefit and approval, the restriction of tebentafusp to HLA-A*02:01-positive patients and the low objective response rate indicate the persistent need for additional therapies. Thus, liver-directed therapies are commonly used for tumor control of hepatic metastases and represent a central pillar of the daily management of liver-dominant disease. Further, promising data from targeted therapies independent of MEK-inhibitors, such as the combination of darovasertib and crizotinib, raise hope for additional options in metastatic UM in the future. This narrative review provides a timely and comprehensive overview of the current treatment landscape for metastatic UM.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 5","pages":"691 - 700"},"PeriodicalIF":8.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436584","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}
引用次数: 0
An Update on New and Existing Treatments for the Management of Melasma 关于治疗黄褐斑的新疗法和现有疗法的最新进展。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-06-19 DOI: 10.1007/s40257-024-00863-2
Christian Gan, Michelle Rodrigues

Melasma is a chronic, acquired disorder of focal hypermelanosis that carries significant psychosocial impact and is challenging for both the patient and the treating practitioner to manage in the medium to long term. Multiple treatments have been explored, often in combination given the many aetiological factors involved in its pathogenesis. Therapeutic discoveries to treat melasma are a focal topic in the literature and include a range of modalities, with recent developments including updates on visible light photoprotection, non-hydroquinone depigmenting agents, oral tranexamic acid, chemical peels, and laser and energy-based device therapy for melasma. It is increasingly important yet challenging to remain up-to-date on the arsenal of treatments available for melasma to find an efficacious and well-tolerated option for our patients.

黄褐斑是一种慢性、后天性的局灶性黑素沉着症,对社会心理有重大影响,患者和治疗医生在中长期管理上都面临挑战。鉴于其发病机制涉及多种致病因素,人们探索了多种治疗方法,而且通常是综合治疗。治疗黄褐斑的新发现是文献中的一个焦点话题,包括一系列治疗方法,最近的发展包括更新可见光光保护、非氢醌脱色剂、口服氨甲环酸、化学换肤以及激光和能量设备治疗黄褐斑。了解黄褐斑治疗方法的最新进展,以便为患者找到疗效好、耐受性好的治疗方法,这一点越来越重要,但也越来越具有挑战性。
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引用次数: 0
期刊
American Journal of Clinical Dermatology
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