抗PD-1治疗引起无症状心肌炎合并重症肌无力、肝损伤及肌炎1例报道

A case of asymptomatic myositis with myasthenia gravis,liver injury and myositis complicating anti-PD-1 therapy

免疫检查点抑制剂(ICI)相关心肌炎合并重症肌无力是一种罕见且致命的免疫相关不良事件(irAE)。我们报告1例74岁女性晚期直肠癌患者PD-1单药治疗第18天出现无症状ICI相关心肌炎、肝损伤及肌炎、重症肌无力(MG)。临床表现为全身乏力、食欲不振及双侧上眼睑下垂,实验室检查示肌钙蛋白I(TnI)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)升高,谷草转氨酶(AST)及谷丙转氨酶(ALT)升高,诊断ICI相关心肌炎、肝损伤,大剂量强的松龙(2 mg/kg)治疗后,心肌酶、转氨酶明显下降,乏力及眼睑下垂改善。激素减量后,患者出现MG危象,给予激素、丙种球蛋白及利妥昔单抗(美罗华)治疗后,肌无力危象症状缓解,但在疾病恢复期患者因误吸胃内容物死亡。激素治疗对ICI相关心肌炎有效,但大剂量激素可能加重MG。ICI相关心肌炎易合并MG、肌炎,早期识别和谨慎制定治疗策略有助于改善预后。

Immune checkpoint inhibitor(ICI)-associated myocarditis with myasthenia gravis is a rare and fatal immune-related adverse event(irAE).We reported a 74-year-old woman with advanced rectal cancer who developed asymptomatic ICI-associated myocarditis,liver injury,myositis,and myasthenia gravis(MG)on day 18 of initial PD-1 monotherapy.The patient first complained of general fatigue,anorexia and bilateral upper eyelid ptosis,and laboratory tests showed elevated levels of troponin I(TnI),creatine kinase(CK),creatine kinase-myocardial band fraction(CK-MB),and elevated aspartate aminotransferase(AST),alanine aminotransferase(ALT).ICI related myocarditis with liver injury was diagnosed.High-dose prednisolone therapy resulted in the decrease of TnI,CK,CK-MB and relief of fatigue and eyelid ptosis.After hormone reduction,the patient was diagnosed as MG and MG crisis.After treatment with hormone,gamma globulin and Rituximab,myasthenia crisis was improved but the patient died due to aspiration of gastric contents.Steroid corticosteroid therapy is effective for ICI related myocarditis,but high dose-steroid therapy may result in MG exacerbation.ICI-associated myocarditis easily complicates MG/myositis as an immune-related adverse event.Early recognition and prompt treatment are crucial for improving clinical outcomes.