免疫检查点抑制剂所致免疫相关性肌炎2例及文献复习

Immune-related myositis induced by immune checkpoint inhibitors: two case reports and literature review

目的探讨免疫检查点抑制剂(ICIs)所致免疫相关性肌炎(IRM)的临床特征及治疗现状, 以提高该病的诊治率。方法结合2例IRM临床病例的诊断及治疗过程, 复习近10年来有关IRM的文献资料, 共收集59例患者的临床资料。计数资料使用率或构成比进行统计学描述。结果 IRM多见于男性, 共47例(79.7%), IRM通常发生在用药45 d或2次给药后出现, 临床表现以肌痛、肌无力为主, 多见于四肢, 部分患者以眼部为首发症状, 常见的为上睑下垂、复视。50例患者(84.7%)的血清肌酸激酶水平超过正常上限2倍以上。免疫学检查中18例患者检测出了抗横纹肌抗体阳性, 肌炎特异性抗体、肌炎相关抗体检查多为阴性。34例患者(75.6%)肌电图有异常, 多数患者肌电图提示肌源性损伤。8例患者肌肉MRI提示肌肉水肿及炎症。18例(45.0%)患者肌肉活检显示出不同程度的坏死肌纤维。57例患者(96.6%)出现IRM后停用了ICIs, 54例(91.5%)患者使用了激素, 20例患者(33.9%)进行了其他治疗, 包括静脉注射免疫球蛋白(IVIG)、血浆置换等。结论 IRM可在ICIs治疗早期发生, 对可疑病例肌电图、肌肉MRI及肌肉活检以提高该病的诊断率, 尽早使用激素、IVIG等免疫治疗可有效缓解病情。

ObjectiveTo investigate the clinical features and treatment status of immune-related myositis (IRM) caused by immune checkpoint inhibitors (ICIs) in order to improve the diagnosis and treatment rate of the disease.MethodsTwo cases of IRM combined with the diagnosis and treatment were described and the literature about IRM in the past 10 years was reviewed, and the clinical data of 59 patients were analyzed.ResultsIRM was more common in males, with a total of 47 (79.7%). IRM usually occurred after 45 days of medication or after two doses. The clinical manifestations were mainly myalgia and muscle weakness, which were more common in the limbs. The initial symptoms were ptosis and diplopia. Fifty patients (84.7%) had serum creatine kinase (CK) levels higher than twice the upper limit of normal (UNL). In immunological examinations, 18 patients were found to be positive for anti-rhabdoid muscle antibody (AsM-Ab), while most of the myositisspecific antibodies (MSAs) and myositis-associated antibodies (MAAs) were negative. Thirty-four patients (75.6%) had abnormal EMG, and most patients showed myogenic injury. Muscle magnetic resonance imaging (MRI) showed muscle edema and inflammation in 8 patients. Muscle biopsies from 18 (45.0%) patients showed varying degrees of necrotic myofibers. Fifty-seven patients (96.6%) discontinued ICIs after developing IRM, 54(91.5%) received cortico-steroids, and 20(33.9%) received other treatments including intravenous immuno-globulin (IVIG), plasma exchange.ConclusionIRM can occur in the early stage of ICIs treatment. Electro-myography, muscle MRI and muscle biopsy in suspicious cases can improve the diagnosis rate of the disease. Early use of corticoteroid, IVIG and other immunotherapy can effectively alleviate the disease.