Williams Barbara, Horn Michael P, Banz Yara, Feldmeyer Laurence, Villiger Peter M
Department of Rheumatology and Immunology, University Hospital and, University of Bern, CH-3010, Bern, Switzerland.
Department of Clinical Chemistry, University Hospital and, University of Bern, CH-3010, Bern, Switzerland.
J Autoimmun. 2021 Sep;123:102691. doi: 10.1016/j.jaut.2021.102691. Epub 2021 Jul 28.
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.
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.
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.
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.
抗3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）阳性免疫介导性坏死性肌病（IMNM）是一种罕见疾病。它由外源性物质诱发，最常见的是他汀类药物。关于HMGCR阳性IMNM的皮肤表现以及其他疾病中HMGCR抗体阳性情况，人们了解甚少。
对2012年1月至2020年9月在我们实验室检测抗HMGCR自身抗体的患者特征进行研究。将IMNM患者的特征与抗体阳性但无肌肉受累的患者进行比较。寻找IMNM与其他器官受累的关联。
在研究的32例患者中，23例表现出IMNM的特征，9例不符合当前分类标准，但大多数表现出结缔组织病的迹象。IMNM患者年龄较大（分别为66岁和35岁；0.92（0.73 - 0.98）；p < 0.001），他汀类药物暴露更频繁（分别为87%和33%；0.84（0.61 - 0.94）；p = 0.005），平均肌酸激酶峰值更高（分别为8717U/l和329U/l；1.0（0.85 - 1.0）；p < 0.001）。23例IMNM患者中有13例（56%）出现皮肤病变；所有患者均未患癌症；只有3例IMNM患者实现无药完全缓解。我们中心服务区域内IMNM的发病率至少为每年2.7/百万。
发现抗HMRCR阳性IMNM中的皮肤病变比先前报道的更常见。IMNM患者中抗HMGCR抗体滴度和肌酸激酶水平显著高于其他自身免疫性结缔组织病。这些数据支持IMNM中抗原驱动反应的假说，并提示非IMNM患者中自身反应性B淋巴细胞的激活。
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