Pach J, Leventhal J S
Yale University School of Medicine, New Haven, CT, USA.
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510, USA.
Crit Rev Immunol. 2022;42(4):1-20. doi: 10.1615/CritRevImmunol.2023046895.
Immune checkpoint inhibitors (CPIs) are highly effective in the treatment of various cancers. Immunotherapy enhances antitumor activity by relieving inhibition of T cells responsible for immune surveillance. However, overactivation of T cells leads to immune-related adverse events (irAE), of which cutaneous adverse events are the most common. Examples include pruritus and maculopapular eruption most commonly, psoriasis and bullous dermatoses less commonly, and, rarely, severe, life-threatening eruptions such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. Many of these are autoimmune in nature, and these may present de novo or as recurrence of pre-existing disease. In order to maximize the therapeutic potential of CPIs, it is essential to recognize and effectively manage cutaneous irAE, which can otherwise lead to treatment interruption or discontinuation. This review summarizes the presentation and management of dermatologic adverse events secondary to immune dysregulation as a result of immune checkpoint inhibitor therapy, including the most common (maculopapular eruption, pruritus, lichenoid dermatitis, and vitiligo), less common (psoriasis, bullous pemphigoid, erythema multiforme, eczematous dermatitis, alopecia areata, and granulo-matous and neutrophilic dermatoses), and severe (acute generalized exanthematous pustulosis [AGEP], drug reaction with eosinophilia and systemic symptoms [DRESS], and Stevens-Johnson syndrome or toxic epidermal necrolysis [SJS/TEN]), as well as exacerbation of pre-existing cutaneous autoimmune disease (subacute cutaneous lupus erythematosus, dermatomyositis, eosinophilic fasciitis, leukocytoclastic vasculitis, and scleroderma-like reaction).
免疫检查点抑制剂（CPI）在多种癌症的治疗中具有高度有效性。免疫疗法通过解除对负责免疫监视的T细胞的抑制来增强抗肿瘤活性。然而，T细胞的过度激活会导致免疫相关不良事件（irAE），其中皮肤不良事件最为常见。常见的例子包括瘙痒和斑丘疹，较少见的有银屑病和大疱性皮肤病，罕见的有严重的、危及生命的皮疹，如史蒂文斯 - 约翰逊综合征或中毒性表皮坏死松解症。其中许多本质上是自身免疫性的，可能新发或表现为既往疾病的复发。为了最大限度地发挥CPI的治疗潜力，识别并有效管理皮肤irAE至关重要，否则可能导致治疗中断或停药。本综述总结了免疫检查点抑制剂治疗导致免疫失调继发的皮肤不良事件的表现和管理，包括最常见的（斑丘疹、瘙痒、苔藓样皮炎和白癜风）、较不常见的（银屑病、大疱性类天疱疮、多形红斑、湿疹性皮炎、斑秃以及肉芽肿性和嗜中性皮肤病）、严重的（急性泛发性脓疱病[AGEP]、伴有嗜酸性粒细胞增多和全身症状的药物反应[DRESS]以及史蒂文斯 - 约翰逊综合征或中毒性表皮坏死松解症[SJS/TEN]），以及既往皮肤自身免疫性疾病的加重（亚急性皮肤型红斑狼疮、皮肌炎、嗜酸性筋膜炎、白细胞破碎性血管炎和硬皮病样反应）。
