Di Palma-Grisi James C, Vijayagopal Kesav, Muslimani Muhammad A
Università degli Studi di Pavia Facoltà di Medicina e Chirurgia, Piazza Volontari del Sangue Pal. Avis, Pavia (PV), 27100, Italy.
Autoimmune Dis. 2019 Jun 9;2019:7595706. doi: 10.1155/2019/7595706. eCollection 2019.
Monoclonal antibodies constitute a potent and broadly tolerable drug class, representing for some conditions the first newly approved treatment in years. As such, many are afforded "fast-track" or "breakthrough therapy" designations by the U.S. Food and Drug Administration, leading to provisional approval before Phase III clinical trials are reported. Although these drugs are usually safe, some patients experience life-threatening complications-myositis and encephalitis have led to permanent or temporary recalls. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity condition easily missed due to its long incubation period and nonspecific presentation. This minireview is primarily intended as an abbreviated guide for practitioners who may be using these powerful treatments.
We searched PubMed using a string of symptoms consistent with DRESS syndrome and monoclonal antibodies approved by the FDA since 2015. Then, we excluded studies reporting dermatological complications of reactivation of nonherpetic infection, immunodeficiency-related infection, or reactions to the injection site or infusion. We searched for and accessed prior reviews and background studies via PubMed, Mendeley, and Google Scholar.
Two cases of DRESS syndrome were identified in the literature, both the result of treatment with daclizumab. There was one additional case of encephalitis without cutaneous symptoms caused by daclizumab. Drug-induced hypersensitivity dermatitis was reported following treatment with nivolumab and two cases of combination treatment with ipilimumab and either nivolumab or durvalumab produced maculopapular rash and bullae in the first patient and lichenoid dermatitis and blisters in the second patient.
Daclizumab was the only recently approved monoclonal antibody associated with DRESS syndrome as such. Limitations in the diagnostic reliability of DRESS syndrome as a clinical entity and the lack of negative clinical trial reporting suggest enhanced vigilance on the part of clinicians and regulators may be warranted.
单克隆抗体是一类强效且耐受性广泛的药物,在某些情况下代表了多年来首个新获批的治疗方法。因此,许多单克隆抗体被美国食品药品监督管理局授予“快速通道”或“突破性疗法”称号,从而在III期临床试验结果报告之前获得临时批准。尽管这些药物通常是安全的,但一些患者会出现危及生命的并发症——肌炎和脑炎已导致药物被永久或临时召回。药物性嗜酸性粒细胞增多和系统症状(DRESS)综合征是一种超敏反应性疾病,由于其潜伏期长且表现不具特异性,很容易被漏诊。本综述主要旨在为可能正在使用这些强效治疗方法的从业者提供一份简要指南。
我们在PubMed上使用与DRESS综合征一致的症状字符串以及自2015年以来美国食品药品监督管理局批准的单克隆抗体进行搜索。然后,我们排除了报告非疱疹性感染再激活、免疫缺陷相关感染的皮肤并发症,或对注射部位或输液反应的研究。我们通过PubMed、Mendeley和谷歌学术搜索并查阅了先前的综述和背景研究。
文献中确定了2例DRESS综合征病例,均为使用达利珠单抗治疗的结果。还有1例由达利珠单抗引起的无皮肤症状的脑炎病例。使用纳武单抗治疗后报告了药物性过敏性皮炎,1例使用伊匹木单抗与纳武单抗或度伐鲁单抗联合治疗的患者出现了斑丘疹和大疱,另1例患者出现了苔藓样皮炎和水疱。
达利珠单抗是近期唯一获批的与DRESS综合征相关的单克隆抗体。DRESS综合征作为一种临床实体的诊断可靠性存在局限性,且缺乏阴性临床试验报告,这表明临床医生和监管机构可能需要提高警惕。