Riesco-Eizaguirre G, Arpa-Gutiérrez F J, Gutiérrez M, Toribio E
Hospital Universitario La Paz, Madrid, España.
Rev Neurol. 2003;37(10):934-6.
Myotoxicity is the most common adverse reaction of statins, being its frequency less than 0.5%. Mild myopathy reversible after statin withdrawal is the most common event. We present a case of severe polymyositis which was likely to be induced by simvastatin.
75 years old man with hypercholesterolemia treated with simvastatin 20 mg/day for 6 months started previous 2 months with proximal limb weakness, dysphagia and myalgias during exercise that did not release after simvastatin withdrawal. Laboratory findings showed increased creatinin kinase (6,010 UI/L), raised aldolase (51 UI/L) and lactic acid dehydrogenase (1,406 UI/L). Muscular biopsy showed abundant inflammatory cell infiltration in perivascular areas, muscle fibre necrosis with miofagocitosis and considerable variation in fibre size, some of them reaching 210 mm. Treatment with cortico esteroids was started and 4 months later clinical remission and nomalization of creatinin kinase was observed.
Mechanisms of statins induced myotoxicity are not well known. Studies in rats suggest a muscle membrane defect (increased membrane fluidity) and abundant signs of damage (fiber necrosis, hipercontraction) but no cellular infiltrates were seen, pointing to a non inflammatory myopathy which was dose dependent. In our case, and Giordano s et al, the remission of the disease with cortico esteroid therapy and the finding of abundant inflammatory cell infiltration suggest the implication of immunological mechanism and not only a muscle membrane defect.
肌毒性是他汀类药物最常见的不良反应,其发生率低于0.5%。他汀类药物停药后可逆转的轻度肌病是最常见的情况。我们报告一例可能由辛伐他汀诱发的严重多发性肌炎病例。
一名75岁高胆固醇血症男性,服用辛伐他汀20毫克/天,持续6个月,在之前2个月开始出现近端肢体无力、吞咽困难以及运动时肌痛,停用辛伐他汀后症状未缓解。实验室检查结果显示肌酐激酶升高(6010国际单位/升)、醛缩酶升高(51国际单位/升)和乳酸脱氢酶升高(1406国际单位/升)。肌肉活检显示血管周围区域有大量炎性细胞浸润、伴有肌纤维吞噬现象的肌纤维坏死以及纤维大小存在显著差异,其中一些纤维直径达210微米。开始使用皮质类固醇治疗,4个月后观察到临床缓解且肌酐激酶恢复正常。
他汀类药物诱发肌毒性的机制尚不清楚。对大鼠的研究表明存在肌肉膜缺陷(膜流动性增加)和大量损伤迹象(纤维坏死、过度收缩),但未见细胞浸润,提示为非炎性肌病,且呈剂量依赖性。在我们的病例以及乔达诺等人的病例中,疾病通过皮质类固醇治疗得以缓解,且发现大量炎性细胞浸润,这表明免疫机制参与其中,而非仅仅存在肌肉膜缺陷。