免疫介导坏死性肌病诊治进展

Advances in study on diagnosis and treatment of immune-mediated necrotizing myopathy

免疫介导坏死性肌病(immune-mediated necrotizing myopathy,IMNM)是一种特发性炎性肌病(Idiopathic Inflammatory Myopathy,IIM)的重要亚型。IMNM的典型临床表现包括对称性四肢近端肌无力,伴随血清肌酸激酶(creatine kinase,CK)等肌酶谱的显著升高。此外,部分患者还可能出现皮疹、间质性肺病和心肌受累等骨骼肌外表现。自2003年首次被国际医学界命名以来,IMNM逐渐被研究者和临床医师所认识。IMNM的发病率和患病率在不同地域和种族间可能有所不同,如在美国的小样本调查中,IMNM的发病率为0.83/10万,患病率为1.85/10万;而在欧洲西班牙北部地区,抗HMGCR抗体阳性患者的IMNM发病率为0.6/10万,患病率为3/10万,目前中国尚缺乏相关数据。IMNM的患病风险因素包括易感等位基因如HLA-DRB1*11,以及使用他汀类药物、免疫检查点抑制剂和感染病毒感染等。诊断IMNM需要综合考虑肌肉受累症状、肌炎特异性自身抗体、肌酶谱水平和肌活检病理等检查结果。目前,IMNM的治疗主要基于临床经验,包括使用糖皮质激素和传统免疫抑制剂。对于难治性患者,可能采用利妥昔单抗和静脉注射人免疫球蛋白等治疗方案。针对B细胞及其致病性自身抗体的产生过程,未来的研究可能揭示新的治疗靶点。本文旨在系统介绍IMNM的临床特征、诊断方法及相关辅助检查,并探讨当前的治疗策略,以期为临床医师提供诊治IMNM的参考和借鉴。

Immune-mediated necrotizing myopathy(IMNM)is a significant,subtype of idiopathic inflammatory myopathy(IIM),characterized by symmetrical proximal limb muscle weakness and markedly elevated serum creatine kinase levels.Some patients may also exhibit extra-skeletal muscle manifestations,including rashes,interstitial lung disease,and myocardial involvement.Since its international nomenclature in 2003,IMNM has gained increasing recognition among researchers and clinicians,leading to numerous scientific investigations and clinical applications.The incidence and prevalence of IMNM can vary across different geographic regions and ethnic groups.A small sample survey conducted in the United States reported an incidence of 0.83 per 100,000 and a prevalence of 1.85 per 100,000.In northern Spain,among patients positive for anti-HMGCR antibodies,the incidence was found to be 0.6 per 100,000,with a prevalence of 3 per 100,000.However,there is a notable paucity of relevant data regarding IMNM in China.Identified risk factors for IMNM include susceptibility alleles(e.g.,HLA-DRB1*11),the use of statins or immune checkpoint inhibitors,and viral infections.Diagnosing IMNM requires a comprehensive evaluation that includes assessing muscle involvement symptoms,identifying myositis-specific autoantibodies,measuring creatine kinase levels,analyzing muscle biopsy pathology,and conducting related examinations.Currently,there is a lack of prospective randomized controlled studies on the treatment of IMNM.In clinical practice,glucocorticoids and traditional immunosuppressants are primarily employed on an empirical basis.For refractory cases,treatment regimens may involve rituximab and intravenous human immunoglobulin.Therapeutic strategies targeting B cells and the mechanisms underlying pathogenic autoantibody production may offer promising avenues for future treatment.This article systematically reviews the clinical characteristics,diagnostic criteria,relevant auxiliary examinations,and treatment strategies for IMNM,aiming to provide a comprehensive reference for clinicians in understanding,diagnosing,and managing this condition.