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免疫检查点抑制剂引发的肌无力:新病例及文献综述

Myasthenia triggered by immune checkpoint inhibitors: New case and literature review.

作者信息

Gonzalez Natalia L, Puwanant Araya, Lu Angela, Marks Stanley M, Živković Saša A

机构信息

Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.

出版信息

Neuromuscul Disord. 2017 Mar;27(3):266-268. doi: 10.1016/j.nmd.2017.01.002. Epub 2017 Jan 6.

Abstract

Immune checkpoint molecules are potent regulators of immunologic homeostasis that prevent the development of autoimmunity while maintaining self-tolerance. Inhibitors of immune checkpoint molecules are used as immunotherapy in the treatment of melanoma and different types of refractory cancer, and can trigger various autoimmune complications including myositis and myasthenia gravis. We describe a case of generalized myasthenia gravis induced by pembrolizumab and review 11 other cases. Five patients also had elevated serum CK levels ranging from 1200 to 8729 IU/L, and biopsy showed myositis in one. Severity was highly variable as symptoms normalized spontaneously in one patient, but three others developed myasthenic crisis (including two with fatal outcomes). Steroids have been recommended as a preferred treatment of autoimmune complications of immune-checkpoint inhibitors. Myasthenia gravis should be considered when weakness, diplopia or bulbar symptoms are seen after treatment with immune checkpoint inhibitors, and additional studies are needed to characterize association with hyperCKemia.

摘要

免疫检查点分子是免疫稳态的强效调节因子,可防止自身免疫性疾病的发生,同时维持自身耐受性。免疫检查点分子抑制剂被用作免疫疗法,用于治疗黑色素瘤和不同类型的难治性癌症,并可引发各种自身免疫并发症,包括肌炎和重症肌无力。我们描述了一例由派姆单抗诱发的全身型重症肌无力病例,并回顾了其他11例病例。5例患者血清肌酸激酶(CK)水平也升高,范围为1200至8729 IU/L,其中1例活检显示有肌炎。严重程度差异很大,1例患者症状自发缓解,但另外3例发生了重症肌无力危象(包括2例死亡)。类固醇已被推荐作为免疫检查点抑制剂自身免疫并发症的首选治疗方法。在用免疫检查点抑制剂治疗后出现肌无力、复视或延髓症状时,应考虑重症肌无力,还需要进一步研究以明确其与高CK血症的关联。

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