Plachouri Kerasia-Maria, Vryzaki Eleftheria, Georgiou Sophia
Dermatology Department, University General Hospital of Patras, Patras, Greece.
Curr Drug Saf. 2019;14(1):14-20. doi: 10.2174/1574886313666180730114309.
The introduction of Immune Checkpoint Inhibitors in the recent years has resulted in high response rates and extended survival in patients with metastatic/advanced malignancies. Their mechanism of action is the indirect activation of cytotoxic T-cells through the blockade of inhibitory receptors of immunomodulatory pathways, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Despite their impressive therapeutic results, they can also induce immune-related toxicity, affecting various organs, including the skin.
To provide an updated summarized overview of the most common immune-mediated cutaneous side effects and their management.
English articles derived from the databases PubMed and SCOPUS and published between 2009 and 2018, were analyzed for this narrative review.
The most common adverse cutaneous reactions include maculopapular rash, lichenoid reactions, vitiligo and pruritus, with severity Grade 1 or 2. Less frequent but eventually life-threatening skin side effects, including Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal necrolysis, have also been reported.
Basic knowledge of the Immune-Checkpoint-Inhibitors-induced skin toxicity is necessary in order to recognize these treatment-related complications. The most frequent skin side effects, such as maculopapular rash, vitiligo and pruritus, tend to subside under symptomatic treatment so that permanent discontinuation of therapy is not commonly necessary. In the case of life-threatening side effects, apart from the necessary symptomatic treatment, the immunotherapy should be permanently stopped. Information concerning the management of ICIs-mediated skin toxicity can be obtained from the literature as well as from the Summary of Product Characteristics of each agent.
近年来,免疫检查点抑制剂的引入使转移性/晚期恶性肿瘤患者获得了高缓解率并延长了生存期。其作用机制是通过阻断免疫调节途径的抑制性受体,如细胞毒性T淋巴细胞相关抗原4(CTLA-4)、程序性细胞死亡蛋白1(PD-1)及其配体(PD-L1),间接激活细胞毒性T细胞。尽管它们取得了令人瞩目的治疗效果,但也会诱发免疫相关毒性,影响包括皮肤在内的各种器官。
提供最常见的免疫介导皮肤副作用及其管理的最新综述。
对2009年至2018年间发表在PubMed和SCOPUS数据库中的英文文章进行分析,以进行本叙述性综述。
最常见的皮肤不良反应包括斑丘疹、苔藓样反应、白癜风和瘙痒,严重程度为1级或2级。也有报道称,虽不常见但最终可能危及生命的皮肤副作用,包括史蒂文斯-约翰逊综合征、伴有嗜酸性粒细胞增多和全身症状的药物反应以及中毒性表皮坏死松解症。
了解免疫检查点抑制剂引起的皮肤毒性的基本知识对于识别这些与治疗相关的并发症是必要的。最常见的皮肤副作用,如斑丘疹、白癜风和瘙痒,在对症治疗下往往会消退,因此通常无需永久停药。对于危及生命的副作用,除了必要的对症治疗外,应永久停止免疫治疗。有关免疫检查点抑制剂介导的皮肤毒性管理的信息可从文献以及每种药物的产品特性摘要中获得。