Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy
Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy
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DOI：
10.1001/jamaneurol.2015.1207
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发表时间：
2015-09-01
期刊：
影响因子：
29
通讯作者：
Milone, Margherita
中科院分区：
文献类型：
--
作者：
Kassardjian, Charles D.;Lennon, Vanda A.;Milone, Margherita
重要性坏死性自身免疫性肌病（NAM）的病理特征是肌纤维坏死，炎症消失或轻微。它通常伴随着他汀类药物治疗、结缔组织疾病、癌症和对信号识别颗粒（SRP）或3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）具有特异性的自身抗体。关于NAM的病因亚组和治疗结果之间的差异的数据是有限的。结论为了描述NAM的临床、血清学和电生理学特征，比较患者亚组，并确定临床结果预测因子。设计、设置和参与者我们对63名成人马约诊所患者的病历进行了回顾性分析，这些患者从2010年1月1日起被分配到NAM的临床和组织病理学诊断。2004年至2013年12月31日。患者分层的假定原因和自身抗体status.Main结果和措施临床，电生理和病理特征进行了收集和患者亚组之间的比较。通过单变量logistic回归确定治疗反应的预测因子。结果下肢无力占优势（46 [73%]）。远端无力（26例[41%]）、吞咽困难（22例[35%]）和呼吸困难（23例[37%]）较为常见。22例患者（35%）在发病时接受他汀类药物治疗，6例患有癌症，3例患有结缔组织病。中位肌酸激酶水平为5326 U/L。在13例患者（24%）中，检测到SRP-IgG，在17例患者（34%）中，检测到HMGCR-IgG（其中三分之一未接受他汀类药物治疗）。一名患者呈双重血清阳性。面部无力在SRP-IgG阳性患者中更常见。肌强直放电在他汀类药物相关NAM中更常见。在大多数患者中，泼尼松单药治疗不足以控制疾病; 32例患者中有30例（90%）需要2种或更多种免疫抑制剂。29例患者中有16例（55%）在免疫抑制剂减量或停药期间复发。预测有利的结果是男性性别和使用2个或更多的immunodeficiency agents在3个月内onset.CONCLUSIONS和RELEVANCE坏死性自身免疫性肌病是特发性的一半，这个队列的临床和组织病理学定义的疾病。在其余患者中，NAM与他汀类药物、癌症或结缔组织疾病相关。4例患者中1例SRP-IgG阳性，3例患者中1例HMGCR-IgG阳性。皮质类固醇单药治疗通常不能控制疾病。血清阳性、血清阴性和他汀类药物相关病例的临床表现、病程和结局无显著差异。早期积极的免疫抑制剂治疗改善了预后，在药物剂量减少或停药期间复发的风险很高。
IMPORTANCE Necrotizing autoimmunemyopathy (NAM) is characterized pathologically by necrotic muscle fibers with absent or minimal inflammation. It is often accompanied by statin therapy, connective tissue diseases, cancer, and autoantibodies specific for signal recognition particle (SRP) or 3- hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Data are limited concerning differences among etiologic subgroups and treatment outcomes in NAM.OBJECTIVES To describe the clinical, serologic, and electrophysiologic characteristics of NAM, compare patient subgroups, and determine clinical outcome predictors.DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective review of medical records for 63 adult Mayo Clinic patients assigned the clinical and histopathologic diagnosis of NAM from January 1, 2004, through December 31, 2013. Patients were stratified by presumed cause and autoantibody status.MAIN OUTCOMES AND MEASURES Clinical, electrophysiologic, and pathologic characteristics were collected and compared among patient subgroups. Predictors of response to treatment were identified by univariate logistic regression. RESULTS Lower extremity weakness predominated (46 [73%]). Distal weakness (26 [41%]), dysphagia (22 [35%]), and dyspnea (23 [37%]) were common. Twenty-two patients (35%) were receiving a statin medication at onset, 6 had cancer, and 3 had a connective tissue disease. The median creatine kinase level was 5326 U/L. In 13 patients (24%), SRP-IgG was detected, and in 17 patients (34%), HMGCR-IgG was detected (one-third of whom had not received statin medication). One patient was dual seropositive. Facial weakness was more common in SRP-IgG-positive patients. Myotonic discharges were more common in statin-associated NAM. Prednisone monotherapy was insufficient to control disease in most patients; 30 (90%) of 32 patients required 2 or more immunotherapeutic agents. Relapse occurred in 16 (55%) of 29 patients during immunosuppressant taper or discontinuation. Predictors of favorable outcome were male sex and use of 2 or more immunotherapeutic agents within 3 months of onset.CONCLUSIONS AND RELEVANCE Necrotizing autoimmunemyopathy was idiopathic in half of this cohort with clinical and histopathologically defined disease. In the remainder, NAM was associated with statin medication, cancer, or connective tissue disease. One in 4 patients was SRP-IgG positive, and 1 in 3 was HMGCR - IgG positive. The disease was usually not controlled by corticosteroid monotherapy. Presentation, course, and outcomes did not differ significantly in seropositive, seronegative, and statin-associated cases. Early aggressive immunosuppressant therapy improved outcomes, and risk of relapse was high during medication dose reduction or withdrawal.