帕博利珠单抗致严重免疫相关皮肤不良反应的文献分析  

Literature analysis of severe immuned-related skin adverse reactions induced by pembrolizumab

作　　者：吴迪 WU Di(Anhui Provincial Centre for ADR Monitoring,Anhui Hefei 230031,China)

机构地区：[1]安徽省药品不良反应监测中心,安徽合肥230031

出　　处：《中国医院药学杂志》2022年第21期2282-2287,共6页Chinese Journal of Hospital Pharmacy

摘　　要：目的:探讨帕博利珠单抗致Stevens-Johnson综合征(SJS)、中毒性表皮坏死松懈症(TEN)严重皮肤反应的临床特点,旨在为临床合理使用帕博利珠单抗提供参考。方法:检索中国知网、维普、万方、PubMed、Web of Science和Medline等数据库,收集整理自数据库建库至2022年2月关于帕博利珠单抗致SJS/TEN的个案报道,分析该药致SJS/TEN的临床特点。结果:共收集25例病例,其中帕博利珠单抗致SJS病例13例,TEN7例,SJS/TEN重叠征5例。3种类型SJS/TEN反应中TEN发生最早,中位发生时间为16(3,39)d;其次为SJS/TEN重叠征,发生时间为30(22.5,115)d;SJS反应最晚为55(7,106.5)d。25例中有22例(88.0%)伴随着黏膜受累,17例(68.0%)在黏膜受累或皮肤脱落之前出现前驱性皮疹。25例患者24例(96.0%)接受了全身性糖皮质激素治疗,9例(36.0%)接受静脉注射免疫球蛋白,4例(16.0%)接受免疫抑制剂。最终,25例患者中17例(68.0%)好转或痊愈,5例(20.0%)死亡,3例(12.0%)预后未知。结论:帕博利珠单抗可诱发SJS/TEN,应注意黏膜损伤,异常皮疹等可能为SJS/TEN发生信号,除了全身性糖皮质激素治疗以外,静脉注射免疫球蛋白和环孢素治疗证实是有益补充。OBJECTIVE To analyze the incidence of Stevens-Johnson symptom(SJS)and toxic epidermal necrolysis(TEN)adverse reactions induced by pembrolizumab,so as to provide reference for clinical rational use.METHODS Retrieving the databases[Pubmed,Web of Science,Medline,China National Knowledge Infrastructure(CKNI),VIP Journal Database,Wan-Fang Journal Articles Database,etc],case reports on pembrolizumab-induced SJS/TEN were searched and statistically analyzed.RESULTS A total of 25 patients were enrolled in this study.In the 25 cases,there were 13 cases with SJS,7 cases with TEN,and 5 cases with SJS/TEN.The median occurrence time of TEN was 16(3,39)d,and that of SJS/TEN and TEN was 30(22.5,115)d and 55(7,106.5)d,respectively.Of the 25 patients who developed SJS/TEN reactions,22 cases(88.0%)accompanied by mucosal injury,17 cases(68.0%)described as prodromal rash before the onset of mucosal/conjunctival involvement and skin sloughing.Among the patients,24 received systemic steroid therapy,7 received IVIG,and 4 received immunosuppression.Of the 25 patients,17 had improved symptoms,5 died,and 3 were with unknown prognosis.CONCLUSION Pembrolizumab can induce SJS/TEN,and attention should be paid to mucosal injury and prodromal rash,which may be the signals of SIS/TEN Except systemic steroid therapy,IVIG and immunosuppression have certain positive effects.

关 键 词：帕博利珠单抗 不良反应 STEVENS-JOHNSON综合征 中毒性表皮坏死松懈症 

分 类 号：R751[医药卫生—皮肤病学与性病学]