Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy.
Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy.
Int J Mol Sci. 2023 Jun 30;24(13):10919. doi: 10.3390/ijms241310919.
Immune checkpoint inhibitors (ICIs) represent a major advance in cancer treatment. The lowered immune tolerance induced by ICIs brought to light a series of immune-related adverse events (irAEs). Pembrolizumab belongs to the ICI class and is a humanized IgG4 anti-PD-1 antibody that blocks the interaction between PD-1 and PD-L1. The ICI-related irAEs involving various organ systems and myocarditis are uncommon (incidence of 0.04% to 1.14%), but they are associated with a high reported mortality. Unlike idiopathic inflammatory myositis, ICI-related myositis has been reported to frequently co-occur with myocarditis. The triad of myasthenia, myositis, and myocarditis must not be underestimated as they can rapidly deteriorate, leading to death. Herein we report a case of a patient with metastatic melanoma who fatally developed myasthenia gravis, myocarditis, and myositis, after a single cycle of pembrolizumab. Considering evidence from the literature review, autopsy, histological, and immunohistochemical investigations on heart and skeletal muscle are presented and discussed, also from a medical-legal perspective.
免疫检查点抑制剂 (ICIs) 代表了癌症治疗的重大进展。ICI 降低的免疫耐受性揭示了一系列与免疫相关的不良反应 (irAEs)。Pembrolizumab 属于 ICI 类，是一种人源化 IgG4 抗 PD-1 抗体，可阻断 PD-1 和 PD-L1 之间的相互作用。涉及各种器官系统和心肌炎的 ICI 相关 irAEs 并不常见（发生率为 0.04%至 1.14%），但与高报告死亡率相关。与特发性炎性肌病不同，ICI 相关的肌炎常与心肌炎同时发生。肌无力、肌炎和心肌炎三联征不容忽视，因为它们可能迅速恶化，导致死亡。在此，我们报告了一例转移性黑色素瘤患者，在接受单次 Pembrolizumab 治疗后，致命性地发展为重症肌无力、心肌炎和肌炎。考虑到文献复习、尸检、心脏和骨骼肌组织学和免疫组织化学检查的证据，我们还从医学法律的角度进行了讨论。
