摘要
目的探讨免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)所致的严重免疫相关皮肤不良反应(immunerelated cutaneous adverse effect,irCAE)的临床特点及其诊疗策略。方法选取2019—2022年北京大学肿瘤医院消化肿瘤内科收治的4例接受ICIs治疗并产生irCAE的肿瘤患者。在中国知网、万方、维普、PubMed和Web of Science等数据库中检索2018年以来中英文数据库,收集ICIs治疗所致irCAE的相关文献。整理汇总患者的临床信息和治疗及转归。结果4例患者均为免疫治疗联合化疗的肿瘤患者,治疗期间分别出现免疫相关皮肤损伤、史蒂文斯-约翰逊综合征(Stevens-Johnson syndrome,SJS)、中毒性表皮坏死松解症(toxic epidermal necrolysis,TEN),前驱皮疹出现时间为2~28 d,应用激素治疗后皮肤症状完全缓解;4例患者的总生存时间分别为21.7、13.7、47.5、19.4个月。文献检索共纳入50例患者,最终诊断为SJS 23例(46%)、TEN 17例(34%)、重叠型SJS/TEN 8例(16%)、其他2例(4%),经激素治疗后好转38例(76%)、死亡9例(18%)、未知3例(6%)。死因为感染性休克、多器官功能衰竭、十二指肠溃疡穿孔所致严重脓毒症、吸入性肺炎、原发肿瘤进展及转移、全身皮肤糜烂合并多重细菌感染。结论ICIs所致irCAE患者在合理应用激素治疗后大部分症状缓解,但仍有与继发性感染相关的死亡病例,因此在ICIs治疗肿瘤患者的过程中要密切关注irCAE的早期诊断及早期治疗。
Objective To investigate the clinical characteristics and diagnosis and treatment strategies of severe immune-related cutaneous adverse effect(irCAE)caused by immune checkpoint inhibitors(ICIs).Method Four patients from the Department of Gastrointestinal Oncology of Peking University Cancer Hospital during 2019 to 2022 who received ICIs treatment and developed irCAE were enrolled.Chinese and English databases such as CNKI,Wanfang,VIP,PubMed and Web of Science since 2018 years searched to collect reports of severe irCAE caused by ICIs.Organize and summarize clinical information,treatment and outcome of patients.Result The 4 cases enrolled in our department were patients with gastrointestinal tumors treated with immunotherapy combined with chemotherapy.During the treatment,they developed immune-related skin injury,Stevens-Johnson syndrome(SJS),and toxic epidermal necrolysis(TEN),respectively.All the 4 patients developed prodromal rash for 2-28 days,and their skin symptoms completely faded away after hormone application.The overall survival time were 21.7,13.7,47.5,and 19.4 months in 4 patients,respectively.As for the literature search,we included 50 patients,with a final diagnosis of SJS in 23 patients(46%),TEN in 17 patients(34%),overlapping SJS/TEN in 8 patients(16%),and other in 2 patients(4%).After hormonal treatment,38 patients(76%)improved,9 patients(18%)died,and 3 patients(6%)were unknown.The causes of death in 9 patients were:septic shock,multiple organ dysfunction syndrome,severe sepsis due to perforated duodenal ulcer,aspiration pneumonia,primary tumor progression and metastasis,generalized skin erosion combined with multiple bacterial infections.Conclusion Most of the patients with irCAE caused by ICIs have their symptoms relieved after reasonable application of hormone therapy,but there are still cases of death associated with secondary infections.Therefore,in the process of ICIs treatment for oncology patients,clinicians should pay close attention to the early diagnosis and treatment of irCAE.
作者
高梦婷
焦曦
董凤晓
鲁智豪
Gao Mengting;Jiao Xi;Dong Fengxiao;Lu Zhihao(Department of Gastrointestinal Oncology,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Peking University Cancer Hospital&Institute,Beijing 100142,China)
出处
《肿瘤综合治疗电子杂志》
2023年第4期66-77,共12页
Journal of Multidisciplinary Cancer Management(Electronic Version)
