Fujita Kana, Ohashi Yoshitaka, Nagasawa Yoshinori, Otani Tomoyuki, Hatakeyama Kinta
Department of Cardiology, Ako City Hospital, 1090, Nakahiro, Ako, Hyogo 678-0232, Japan.
Department of Cardiology, Konan Medical Center, 1-5-16, Kamokogahara, Higashinada-ku, Kobe 658-0064, Japan.
Eur Heart J Case Rep. 2024 Jul 24;8(8):ytae370. doi: 10.1093/ehjcr/ytae370. eCollection 2024 Aug.
Immunotherapy with immune checkpoint inhibitors (ICIs) enhances the host immune reaction against tumour cells by inhibiting intrinsic down-regulators of the T cell-mediated immune response. Although the advent of ICIs has dramatically changed oncology, ICIs may also trigger an overactivation of T cells against non-cancerous tissues, leading to off-target immune-related adverse events (irAEs).
A 64-year-old man with a history of seven courses of atezolizumab, an ICI, for small-cell lung cancer and coronavirus disease 2019 (COVID-19) was admitted to the hospital complaining of acute chest pain. Transthoracic echocardiography showed preserved ejection fraction (EF), but electrocardiography indicated precordial ST-elevations and marked increases in biomarkers for myocardial injury were observed. Emergent cardiac catheterization showed no significant coronary stenosis. On the fifth hospital day, EF decreased to 25% and pericardial effusion occurred. Endomyocardial biopsy was immediately performed, and prednisolone (60 mg/day) was administered. Troponin I level rapidly reduced, ST changed, and EF improved. Histological examinations demonstrated CD8-predominant T lymphocytic infiltration with myocardial cell injury, consistent with irAE-myocarditis.
In irAEs, myocarditis is the most common and severe cardiac manifestation with a high mortality. Even at 20 weeks after the initial ICI treatment, irAE-myocarditis occurs and the clinical presentation may mimic ST-elevation myocardial infarction. The histopathological findings suggested the high possibility of irAE-myocarditis rather than COVID-19-induced myocarditis, but COVID-19 has possibly played a role in the development of late-onset irAE-myocarditis. This educational case implies the importance of immediate recognition of irAE even after stable ICI treatment.
免疫检查点抑制剂（ICI）免疫疗法通过抑制T细胞介导的免疫反应的内在下调因子来增强宿主对肿瘤细胞的免疫反应。尽管ICI的出现极大地改变了肿瘤学，但ICI也可能引发T细胞对非癌组织的过度激活，导致脱靶免疫相关不良事件（irAE）。
一名64岁男性，有因小细胞肺癌接受过7个疗程的阿替利珠单抗（一种ICI）治疗及2019冠状病毒病（COVID-19）病史，因急性胸痛入院。经胸超声心动图显示射血分数（EF）正常，但心电图显示胸前导联ST段抬高，且观察到心肌损伤生物标志物显著升高。紧急心脏导管检查显示无明显冠状动脉狭窄。住院第5天，EF降至25%，出现心包积液。立即进行心内膜活检，并给予泼尼松龙（60mg/天）。肌钙蛋白I水平迅速下降，ST段改变，EF改善。组织学检查显示以CD8为主的T淋巴细胞浸润伴心肌细胞损伤，符合irAE-心肌炎。
在irAE中，心肌炎是最常见且严重的心脏表现，死亡率高。即使在初始ICI治疗20周后，仍会发生irAE-心肌炎，其临床表现可能类似于ST段抬高型心肌梗死。组织病理学结果提示irAE-心肌炎而非COVID-19诱导的心肌炎的可能性很大，但COVID-19可能在迟发性irAE-心肌炎的发生中起了作用。这个教学病例提示即使在ICI治疗稳定后，立即识别irAE也很重要。
