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Statin-induced Necrotizing Autoimmune Myopathy


Authors: T. Horák 1;  S. Voháňka 1;  E. Tvrdíková 2;  M. Horáková 1;  J. Bednařík 1
Authors place of work: Neurologická klinika LF MU a FN Brno 1;  Ústav patologie, LF MU a FN Brno 2
Published in the journal: Cesk Slov Neurol N 2017; 80/113(5): 569-577
Category: Původní práce
doi: https://doi.org/10.14735/amcsnn2017569

Summary

Aim:
Statin therapy might be rarely associated with production of specific autoantibodies against 3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR), proximal muscle weakness, high creatine kinase (CK) levels and myofibril necrosis in muscle biopsy. Presence of these symptoms established the main criteria of a new clinical unit called Statin Induced Necrotizing Autoimmune Myopathy (SINAM). Assumed autoimmune etiopathogenesis justifies the use of combined immunosuppressive therapy. Clinical course, diagnostic criteria and therapeutic efficacy of immunosuppressive treatment are similar to that of Immune Mediated Necrotizing Myopathy (IMNM) without association with statin therapy.

Methods:
The group of 7 SINAM patients was classified by reassessment of the diagnostic group of 30 patients diagnosed with autoimmune myopathies based on determination of anti-HMGCR antibodies, structured quantitative revision of muscle biopsies and detailed medical history (confirming chronic statin therapy).

Results:
In total 30 subjects with the original diagnosis dermatomyositis, polymyositis or IMNM were tested for HMGCR antibodies. Twelve patients out of them were anti-HMGCR positive (IMNM 5×, 7× PM) and 7 of them had been on statin therapy before the symptoms developed. These 7 patients were reclassified as SINAM. Myofibrillar necrosis was found in their muscle biopsies in all cases and 5 patients also had inflammatory cell infiltration. All these patients had significantly elevated CK levels (> 10 fold) at early stage of the disease. Combined immunosuppression led to remission of clinical symptoms and normalization or significant CK level drop in all patients.

Key words:
myopathy – statins – autoimmunity – necrosis – autoantibodies – anti-HMGCR

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.


Chinese summary - 摘要

他汀类药物诱导的坏死性自身免疫性肌病

目标:

在肌肉活检中,他汀治疗可能很少与特异性自身抗体3-羟基-3-甲基戊二酰辅酶A还原酶(抗HMGCR)生成量、近端肌肉无力、高肌酸激酶(CK)水平和肌原纤维坏死有关。这些症状的存在确立了被称为他汀诱导的坏死性自身免疫性肌病的新临床单位的主要标准(SINAM)。假定自身免疫发病机理适合使用联合免疫抑制疗法。免疫抑制治疗的临床过程,诊断标准和治疗效果与免疫介导的坏死性肌病(IMNM)相似,而与他汀治疗无关。

方法:

基于抗HMGCR抗体检测、肌肉活检结构化定量修正和详细病史(确认的慢性他汀治疗),对一组30名被诊断为自身免疫性肌病的患者进行重新评估,分出了7名SINAM患者。

结果:

在30名最初被诊断为皮肌炎的被试中,测试了多发性肌炎或IMNM的HMGCR抗体。其中12例患者抗HMGCR结果呈阳性(IMNM5×,7×PM),7例在症状出现前已接受他汀类药物治疗,这7名患者被重新分为SINAM类。所有病例均发现了肌纤维坏死,并且5例患者患有炎性细胞浸润。 所有这些患者在疾病早期CK水平显著升高(> 10倍)。 联合免疫抑制疗法可以缓解所有患者的临床症状和CK水平显著降低。

关键词:

肌病 - 他汀类药物 - 自身免疫 - 坏死 - 自身抗体 - 抗HMGCR


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Štítky
Dětská neurologie Neurochirurgie Neurologie

Článek vyšel v časopise

Česká a slovenská neurologie a neurochirurgie

Číslo 5

2017 Číslo 5

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