Simmons Duncan, Lang Eddy
Faculty of Medicine and Dentistry, University of Alberta.
Emergency Medicine, University of Calgary.
Cureus. 2017 Oct 13;9(10):e1774. doi: 10.7759/cureus.1774.
Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmable cell death protein 1 (PD-1)/PD-L1 have shown antitumor activity in cancers such as melanoma, non-small cell lung cancer, renal cell carcinoma, and urothelial cancer. Certain checkpoint inhibitors have been approved for use in Canada, and are becoming a mainstay in the treatment of melanoma and other malignancies. These drugs have a unique side effect profile and are known to cause immune-related adverse events (irAEs). These adverse events often appear to originate from an infectious etiology, when in fact they result from the enhanced immune response caused by immune checkpoint therapy. IrAEs are primarily treated with corticosteroids, which suppress the overactive immune response that is secondary to the treatment. IrAEs can occur in any organ system, but adverse events in the skin, gastrointestinal, endocrine, and pulmonary systems are among the most common. As an emergency physician, one must be familiar with these drugs and their adverse events in order to identify patients presenting with irAE and treat them accordingly. This paper provides a brief introduction to immune checkpoint inhibitors, discusses the most common irAEs relevant to emergency physicians, and gives suggestions on how to manage patients presenting to the emergency department (ED) suffering from irAEs.
靶向细胞毒性T淋巴细胞相关蛋白4(CTLA-4)和程序性细胞死亡蛋白1(PD-1)/PD-L1的免疫检查点抑制剂已在黑色素瘤、非小细胞肺癌、肾细胞癌和尿路上皮癌等癌症中显示出抗肿瘤活性。某些检查点抑制剂已在加拿大获批使用,并正成为黑色素瘤和其他恶性肿瘤治疗的主要手段。这些药物具有独特的副作用特征,已知会引起免疫相关不良事件(irAE)。这些不良事件往往看似源于感染性病因,而实际上它们是由免疫检查点治疗引起的免疫反应增强所致。IrAE主要用皮质类固醇治疗,皮质类固醇可抑制继发于该治疗的过度活跃的免疫反应。IrAE可发生于任何器官系统,但皮肤、胃肠道、内分泌和肺部系统的不良事件最为常见。作为一名急诊医生,必须熟悉这些药物及其不良事件,以便识别出现irAE的患者并进行相应治疗。本文简要介绍免疫检查点抑制剂,讨论与急诊医生相关的最常见irAE,并就如何处理到急诊科就诊的irAE患者给出建议。