免疫检查点抑制剂治疗恶性肿瘤导致神经肌肉和心肌损害2例报告

Immune checkpoint inhibitors induced neuromuscular and myocardial damage: a case report of two cases

目的 总结免疫检查点抑制剂(immune checkpoint inhibitors,IGIs)导致的神经肌肉和心肌损害的病例特征,以提高对ICIs治疗恶性肿瘤时出现神经系统并发症的认识。方法 报告2例由ICIs治疗恶性肿瘤时产生神经肌肉和心肌损害的病例,并结合文献分析其临床特征。结果2例患者用单种或联合两种ICIs治疗后出现急性起病、进展快、范围广的神经肌肉损害症状,主要表现为重症肌无力,合并肌炎和心肌炎,其中1例同时有多发性周围神经损害。肌无力主要累及咽喉肌及呼吸肌,症状无明显波动性,血乙酰胆碱受体抗体阳性,对胆碱酯酶抑制剂治疗反应差,其中1例血浆置换治疗后症状缓解,并逐渐痊愈,另1例死于多器官功能衰竭。联合使用两种ICIs者,发病快,病情进展更为迅速。结论 本文在国内首次报告使用ICIs治疗恶性肿瘤时,可产生重症肌无力等神经肌肉损害和心脏损害并发症,临床上应高度警惕,早期诊断和治疗可能获得良好疗效。

Objective To summarize the clinical features and improve the understanding of the cases of neuromuscular and myocardial damage caused by immune checkpoint inhibitors(ICIs)in malignant tumors patients to increase the awareness in China.Methods We reported two cases of neuromuscular and myocardial damage induced by ICIs,and summarize their clinical features with literature.Results Two patients had acute onset,rapid progress and wide range of neuromuscular damage,showing myasthenia gravis complicated with myositis and myocarditis following treatment with single or combined ICIs.One case was also accompanied by multiple peripheral nerve damage.Muscle weakness mainly involved bulbar muscles and respiratory muscles.There was no obvious fluctuation of symptoms and serum acetylcholine receptor antibody was positive.Patients had poor response to cholinesterase inhibitor.One patient was relieved after plasma exchange and gradually recovered.The other one died of multiple organ failure.Combination therapy with two ICIs led to much faster onset of disease and progression.Conclusion Special attention should be pay to the occurrence of neuromuscular and myocardial damage in tumor patients treated with ICIs.Early diagnosis and treatment may result in a good prognosis.