Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China.
Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Immunol. 2024 Jul 12;15:1414136. doi: 10.3389/fimmu.2024.1414136. eCollection 2024.
INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare yet life-threatening adverse events associated with immune checkpoint inhibitors (ICIs). This systematic review synthesizes the current literature to elucidate the clinical characteristics and outcomes of patients with ICI-related SJS/TEN. METHODS: We conducted a thorough search across databases including Embase, Web of Science, Cochrane, MEDLINE, Scopus, and PubMed. Selection criteria focused on reports of SJS/TEN among cancer patients treated with ICIs, analyzing clinical manifestations, therapeutic interventions, and outcomes. RESULTS: Our analysis included 47 articles involving 50 patients with ICI-related SJS/TEN. The cohort had a mean age of 63 years, with a slight male predominance (54%). Most patients had melanoma or non-small cell lung cancer. SJS/TEN typically occurred early, with a median onset of 23 days post-ICI initiation. Treatment primarily involved systemic corticosteroids and intravenous immunoglobulins. The overall mortality rate was 20%, higher for TEN at 32%, with infections and tumor progression as leading causes. Median time from onset to death was 28 days. Survivors experienced a median re-epithelization time of 30 days, positively correlated with the extent of epidermal detachment (r = 0.639, = 0.009). Deceased patients exhibited a significantly higher proportion of TEN (90% vs. 48%, = 0.029) and a larger epidermal detachment area (90% vs. 30% of the body surface area [BSA], = 0.005) compared to survivors. The combination therapy group showed a higher proportion of TEN compared to corticosteroid monotherapy or non-corticosteroid therapy groups (72% vs. 29% and 50%, = 0.01), with no significant differences in mortality or re-epithelization time. Dual ICI therapy resulted in a higher TEN rate than single therapy (100% vs. 50%, = 0.028). Among single ICI therapies, the sintilimab-treated group trended towards a higher TEN rate (75% vs. 40-50%, = 0.417), a larger detachment area (90% vs. 30-48% of BSA, = 0.172), and a longer re-epithelization time (44 vs. 14-28 days, = 0.036) compared to other ICI groups, while mortality rates remained similar. CONCLUSION: ICI-related SJS/TEN substantially impacts patient outcomes. Prospective clinical trials are critically needed to further clarify the pathogenesis and optimize therapeutic regimens.
简介：史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）是与免疫检查点抑制剂（ICI）相关的罕见但危及生命的不良事件。本系统评价综合了目前的文献，阐明了接受 ICI 治疗的癌症患者中 SJS/TEN 的临床特征和结局。
方法：我们全面检索了 Embase、Web of Science、Cochrane、MEDLINE、Scopus 和 PubMed 等数据库，纳入了ICI 相关 SJS/TEN 患者的报告，分析了临床表现、治疗干预和结局。
结果：我们的分析纳入了 47 篇涉及 50 名 ICI 相关 SJS/TEN 患者的文章。队列的平均年龄为 63 岁，略偏向男性（54%）。大多数患者患有黑色素瘤或非小细胞肺癌。SJS/TEN 通常发生较早，ICI 治疗后中位发病时间为 23 天。治疗主要包括全身皮质类固醇和静脉注射免疫球蛋白。总体死亡率为 20%，TEN 为 32%，感染和肿瘤进展是主要原因。从发病到死亡的中位时间为 28 天。幸存者的再上皮化时间中位数为 30 天，与表皮脱落程度呈正相关（r = 0.639， = 0.009）。与幸存者相比，死亡患者的 TEN 比例（90% vs. 48%， = 0.029）和更大的表皮脱落面积（90% vs. 30%的体表面积 [BSA]， = 0.005）明显更高。与皮质类固醇单药治疗或非皮质类固醇治疗组相比，联合治疗组 TEN 的比例更高（72% vs. 29%和 50%， = 0.01），死亡率或再上皮化时间无显著差异。双重 ICI 治疗导致 TEN 发生率高于单一治疗（100% vs. 50%， = 0.028）。在单一 ICI 治疗中，信迪利单抗治疗组的 TEN 发生率（75% vs. 40-50%， = 0.417）、更大的脱落面积（90% vs. 30-48%的 BSA， = 0.172）和更长的再上皮化时间（44 天 vs. 14-28 天， = 0.036）均高于其他 ICI 组，而死亡率相似。
结论：ICI 相关 SJS/TEN 严重影响患者结局。迫切需要前瞻性临床试验进一步阐明发病机制并优化治疗方案。
Cochrane Database Syst Rev. 2022-3-11
Br J Hosp Med (Lond). 2024-9-30
Curr Treat Options Oncol. 2025-8-14
Front Immunol. 2025-5-30
Allergol Int. 2025-7
Front Med (Lausanne). 2024-12-23
Ann Dermatol. 2023-5
Int J Mol Sci. 2023-8-8
J Allergy Clin Immunol Pract. 2023-11
J Allergy Clin Immunol Pract. 2023-9
Zotero 插件