Matsui Hotaka, Kawai Taketo, Sato Yusuke, Ishida Junichi, Kadowaki Hiroshi, Akiyama Yoshiyuki, Yamada Yuta, Nakamura Masaki, Yamada Daisuke, Akazawa Hiroshi, Suzuki Motofumi, Komuro Issei, Kume Haruki
Department of Urology, Graduate School of Medicine, The University of Tokyo.
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.
Int Heart J. 2020 Sep 29;61(5):1070-1074. doi: 10.1536/ihj.20-162. Epub 2020 Sep 12.
We report a case of lethal myocarditis and myositis after pembrolizumab treatment for advanced upper urinary tract urothelial carcinoma. A 69-year-old man underwent pembrolizumab therapy as a second-line treatment. He had myalgia and a slightly elevated creatinine kinase (CK) on the day of the second administration of pembrolizumab. Five days later, the patient was admitted with severe fatigue and an abnormal gait. Physical examination revealed reduced muscle reflexes and proximal muscle weakness. An electrocardiogram (ECG) demonstrated a wide QRS complex ventricular rhythm. A marked elevation of cardiac enzymes, including CK, myoglobin, and cardiac troponin I, was detected. Myocardial biopsy revealed inflammatory cell infiltration and the partial impairment of myocardial tissue. The electromyogram was normal, but inflammation in myofibers was noted in a muscle biopsy. Myocarditis and myositis as immune-related adverse events (irAEs) were suspected, and the patient began intravenous steroid therapy and plasma exchange. However, the patient underwent cardiac arrest three days after admission and began extracorporeal membrane oxygenation and intra-aortic balloon pumping therapy. Despite steroid pulse therapy, the patient demonstrated no sign of improvement and subsequently died 17 days after admission. Immune-mediated myocarditis is a rare but fatal irAE of an immune checkpoint inhibitor (ICI). The present case suggests that myositis precedes myocarditis. Therefore, if myositis is suspected, subsequent myocarditis may need attention. In conclusion, we found that myositis and myocarditis developed in a patient with advanced urothelial carcinoma after pembrolizumab treatment. A routine follow-up of CK and cardiac troponin I, as well as an ECG, should be performed to identify any possible ICI-induced myocarditis and myositis quickly.
我们报告了一例在使用帕博利珠单抗治疗晚期上尿路尿路上皮癌后发生致死性心肌炎和肌炎的病例。一名69岁男性接受帕博利珠单抗治疗作为二线治疗。在第二次使用帕博利珠单抗当天，他出现肌痛且肌酐激酶（CK）略有升高。五天后，患者因严重疲劳和步态异常入院。体格检查发现肌肉反射减弱和近端肌肉无力。心电图（ECG）显示宽QRS波群室性心律。检测到包括CK、肌红蛋白和心肌肌钙蛋白I在内的心脏酶显著升高。心肌活检显示有炎性细胞浸润和心肌组织部分受损。肌电图正常，但肌肉活检中发现肌纤维有炎症。怀疑心肌炎和肌炎是免疫相关不良事件（irAE），患者开始接受静脉类固醇治疗和血浆置换。然而，患者在入院三天后发生心脏骤停，开始接受体外膜肺氧合和主动脉内球囊反搏治疗。尽管进行了类固醇冲击治疗，患者仍无改善迹象，随后在入院17天后死亡。免疫介导的心肌炎是免疫检查点抑制剂（ICI）罕见但致命的irAE。本病例表明肌炎先于心肌炎出现。因此，如果怀疑有肌炎，后续可能需要关注心肌炎。总之，我们发现一名晚期尿路上皮癌患者在接受帕博利珠单抗治疗后发生了肌炎和心肌炎。应常规随访CK和心肌肌钙蛋白I以及进行心电图检查，以便快速识别任何可能由ICI引起的心肌炎和肌炎。
