Objective

Anti-3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) positive immune-mediated necrotizing myopathy (IMNM) is a rare disease. It is induced by exogenous substances, most often by statins. Little is known about cutaneous manifestations of HMGCR positive IMNM and about HMGCR antibody positivity in other diseases.

Methods

The characteristics of patients with anti-HMGCR autoantibodies measured at our laboratory between January 2012 and September 2020 were studied. Characteristics of patients with IMNM were compared to those patients with positive antibodies but without muscle involvement. Associations of IMNM with other organ involvements were searched for.

Results

Of the 32 patients studied, 23 showed characteristics of IMNM, 9 did not fulfill current classification criteria but most showed signs of connective tissue diseases. Patients with IMNM were older (66 and 35 years, respectively; 0.92 (0.73–0.98); p < 0.001), had more frequent statin exposure (87% and 33%, respectively; 0.84 (0.61–0.94); p = 0.005) and higher mean peak CK (8717U/l and 329U/l, respectively; 1.0 (0.85–1.0); p < 0.001). 13/23 (56%) of IMNM patients showed cutaneous lesions; none of the patients suffered from cancer; only three IMNM patients showed drug-free complete remission. Incidence of IMNM in the catchment area of our center is at least 2.7/Mio/year.

Conclusion

Cutaneous lesions were found to be more frequent in anti-HMRCR positive IMNM than previously reported. Titer of anti-HMGCR antibodies and CK levels were significantly higher in IMNM than in other autoimmune connective tissue diseases. The data support the hypothesis of an antigen-driven response in IMNM, and suggests an activation of autoreactive B-lymphocytes in non-IMNM patients.

中文翻译：

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抗 HMGCR 阳性坏死性肌病的皮肤受累

客观的

抗 3-羟基-3-甲基戊二酰辅酶 A 还原酶 (HMGCR) 阳性免疫介导的坏死性肌病 (IMNM) 是一种罕见疾病。它是由外源性物质引起的，最常见的是他汀类药物。关于 HMGCR 阳性 IMNM 的皮肤表现和其他疾病中 HMGCR 抗体阳性的情况知之甚少。

方法

研究了 2012 年 1 月至 2020 年 9 月在我们实验室测量的抗 HMGCR 自身抗体患者的特征。将 IMNM 患者的特征与抗体阳性但没有肌肉受累的患者进行比较。搜索了 IMNM 与其他器官受累的关联。

结果

在研究的 32 名患者中，23 名表现出 IMNM 的特征，9 名不符合当前的分类标准，但大多数表现出结缔组织疾病的迹象。IMNM 患者年龄较大（分别为 66 岁和 35 岁；0.92（0.73-0.98）；p < 0.001），他汀类药物暴露的频率更高（分别为 87% 和 33%；0.84（0.61-0.94）；p = 0.005）和更高的平均峰值 CK（分别为 8717U/l 和 329U/l；1​​.0 (0.85–1.0)；p < 0.001）。13/23 (56%) 的 IMNM 患者出现皮肤病变；没有患者患有癌症；只有三名 IMNM 患者表现出无药物完全缓解。我们中心集水区的 IMNM 发病率至少为 2.7/Mio/年。

结论

发现抗 HMRCR 阳性 IMNM 中的皮肤损伤比以前报道的更常见。IMNM 中的抗 HMGCR 抗体滴度和 CK 水平显着高于其他自身免疫性结缔组织疾病。数据支持 IMNM 中抗原驱动反应的假设，并表明非 IMNM 患者中自身反应性 B 淋巴细胞的激活。