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