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免疫检查点抑制剂相关的皮肤不良反应。

Immune checkpoint inhibitor-related dermatologic adverse events.

机构信息

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

State University of New York Downstate Health Sciences University, Brooklyn, New York.

出版信息

J Am Acad Dermatol. 2020 Nov;83(5):1255-1268. doi: 10.1016/j.jaad.2020.03.132. Epub 2020 May 23.

Abstract

Immune checkpoint inhibitors have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related adverse events, wherein the skin and its appendages are the most frequent targets. Cutaneous immune-related adverse events include a diverse group of inflammatory reactions, with maculopapular rash, pruritus, psoriasiform and lichenoid eruptions being the most prevalent subtypes. Cutaneous immune-related adverse events occur early, with maculopapular rash presenting within the first 6 weeks after the initial immune checkpoint inhibitor dose. Management involves the use of topical corticosteroids for mild to moderate (grades 1-2) rash, addition of systemic corticosteroids for severe (grade 3) rash, and discontinuation of immunotherapy with grade 4 rash. Bullous pemphigoid eruptions, vitiligo-like skin hypopigmentation/depigmentation, and psoriasiform rash are more often attributed to programmed cell death-1/programmed cell death ligand-1 inhibitors. The treatment of bullous pemphigoid eruptions is similar to the treatment of maculopapular rash and lichenoid eruptions, with the addition of rituximab in grade 3-4 rash. Skin hypopigmentation/depigmentation does not require specific dermatologic treatment aside from photoprotective measures. In addition to topical corticosteroids, psoriasiform rash may be managed with vitamin D analogues, narrowband ultraviolet B light phototherapy, retinoids, or immunomodulatory biologic agents. Stevens-Johnson syndrome and other severe cutaneous immune-related adverse events, although rare, have also been associated with checkpoint blockade and require inpatient care as well as urgent dermatology consultation.

摘要

免疫检查点抑制剂已成为治疗晚期恶性肿瘤的重要手段。然而,非特异性免疫激活可能导致免疫相关不良反应,其中皮肤及其附属物是最常见的靶器官。皮肤免疫相关不良反应包括一组不同的炎症反应,其中斑丘疹、瘙痒、银屑病样和苔藓样发疹是最常见的亚型。皮肤免疫相关不良反应发生较早,斑丘疹在首次免疫检查点抑制剂剂量后 6 周内出现。治疗包括轻度至中度(1-2 级)皮疹使用局部皮质类固醇,严重(3 级)皮疹加用全身皮质类固醇,以及 4 级皮疹停用免疫治疗。大疱性类天疱疮样发疹、白癜风样皮肤色素减退/脱失和银屑病样皮疹更常归因于程序性细胞死亡-1/程序性细胞死亡配体-1 抑制剂。大疱性类天疱疮样发疹的治疗与斑丘疹和苔藓样发疹相似,3-4 级皮疹加用利妥昔单抗。皮肤色素减退/脱失除了光保护措施外,无需特殊皮肤科治疗。除了局部皮质类固醇外,银屑病样皮疹还可以用维生素 D 类似物、窄带紫外线 B 光疗、类视黄醇或免疫调节生物制剂治疗。史蒂文斯-约翰逊综合征和其他严重的皮肤免疫相关不良反应虽然罕见,但也与检查点阻断有关,需要住院治疗,并紧急皮肤科咨询。

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