免疫检查点抑制剂相关结肠炎八例临床特征分析  

Clinical characteristics of eight cases of immune checkpoint inhibitor-related colitis

作　　者：谭蓓[1] 王汉萍[2] 李玥[1] 张晓彤[2] 斯晓燕[2] 周炜洵[3] 张力[2] 钱家鸣[1] Tan Bei;Wang Hanping;Li Yue;Zhang Xiaotong;Si Xiaoyan;Zhou Weixun;Zhang Li;Qian Jiaming(Department of Gastroenterology,Peking Union Medical College Hospital,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100730,China;Department of Respiratory and Critical Care Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100730,China;Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院消化内科,100730 [2]中国医学科学院北京协和医学院北京协和医院呼吸与危重症医学科,100730 [3]中国医学科学院北京协和医学院北京协和医院病理科,100730

出　　处：《中华消化杂志》2021年第5期330-335,共6页Chinese Journal of Digestion

基　　金：国家自然科学基金(82000526);北京市自然科学基金(7192172);中国医学科学院医学与健康科技创新工程项目协同创新团队"人体微生物组平台建设与应用研究"(2017-I2M-3-017);。

摘　　要：目的:总结、分析免疫检查点抑制剂(ICI)相关结肠炎的临床特征。方法:回顾性收集和分析2019年1月至2020年9月于北京协和医院诊治的8例ICI相关结肠炎患者的临床资料,包括ICI相关结肠炎的起病情况、临床症状、内镜和病理表现,ICI相关结肠炎的治疗、合并症、重启ICI情况等。采用独立样本t检验进行统计学分析。结果:8例患者均为男性,中位年龄(范围)为66岁(55~74岁);其中7例为肺癌Ⅳ期患者,1例为肾盂癌Ⅲc期;4例ICI相关结肠炎发生在抗程序性死亡1(PD-1)联合化学治疗过程中,2例发生在抗PD-1联合化学治疗后予以抗PD-1单药维持治疗过程中,2例发生在抗PD-1单药治疗过程中;首次抗PD-1治疗至ICI相关结肠炎起病的中位时间(范围)为44 d(27~198 d),末次抗PD-1治疗至ICI相关结肠炎起病的中位时间(范围)为8 d(6~35 d);4例患者经肿瘤免疫治疗后病情部分缓解,2例病情稳定,1例病情进展,1例未评估肿瘤疗效。8例ICI相关结肠炎均为中、重度,以广泛结肠型(5/8)为主,临床表现均有腹泻,3例伴有腹痛;内镜下表现为弥漫性黏膜糜烂,其中2例伴有溃疡;病理表现以隐窝炎或隐窝脓肿为主,其中2例伴有凋亡改变。8例患者均接受糖皮质激素治疗,其中2例患者因糖皮质激素治疗效果不佳而接受生物制剂治疗,4例患者发生机会性感染。发生和未发生机会性感染患者的起始糖皮质激素剂量分别为(85.00±52.60)、(60.00±23.09)mg,糖皮质激素疗程分别为(8.75±4.03)、(7.50±3.11)周,差异均无统计学意义(P均>0.05)。3例患者重启ICI治疗,但均复发结肠炎。结论:ICI相关结肠炎具有相应ICI治疗史和临床、内镜、组织病理特征,以糖皮质激素治疗为主,重启ICI治疗易复发。Objective Summarize and analyze the clinical features of immune checkpoint inhibitor(ICI)-related colitis.Methods From January 2019 to September 2020,the clinical data of 8 patients with ICI-related colitis from Peking Union Medical College Hospital were retrospectively collected and including the onset of ICI-related colitis,clinical symptoms,endoscopic and pathological findings,treatment,comorbidities and resuming of ICI.Independent sample t test was used for statistical analysis.Results Eight patients were all male,and the median age(range)was 66 years old(55 to 74 years old),7 cases were diagnosed with stageⅣlung cancer and 1 case was diagnosed with stageⅢc pyelo-carcinoma.Among 8 patients,4 cases of ICI-related colitis occurred during combination of anti-programmed death-1(PD-1)treatment and chemotherapy,2 cases occurred during anti-PD-1 monotherapy after combination of anti-PD-1 treatment and chemotherapy,and 2 cases occurred after anti-PD-1 monotherapy.The median time(range)was 44 d(27 to 128 d)from initial anti-PD-1 treatment to the onset of ICI-related colitis and the median time(range)was 8 d(6 to 35 d)from last anti-PD-1 treatment to onset of ICI-related colitis.The ICI efficacy of 4 patients had partial response,2 patients had stable disease,1 patient had disease progression,and 1 patient′s condition was not assessed.All 8 patients had moderate to severe extensive colitis.The main clinical manifestation was diarrhea(5/8),3 patients accompanied by abdominal pain.The endoscopic findings were diffuse mucosal erosion,accompanied by ulcer in 2 patients.The main pathologic findings were cryptitis or crypt abscess,accompanied by apoptosis in 2 patients.Eight patients were all treated with glucocorticoids,among them 2 patients were further treated with biologics,due to the insufficient efficacy of glucocorticoid treatment,4 patients had opportunistic infections.The initial prednisone dose for patients with opportunistic infections and patients without opportunistic infections was(85.00±52.60)and(60.00�

关 键 词：免疫检查点抑制剂 免疫治疗相关不良反应 结肠炎 临床特征 抗程序性死亡1 

分 类 号：R574.62[医药卫生—消化系统]