Autoimmune myopathy due to statin treatment in an elderly woman.

We report a case of statin-related autoimmune myopathy with positive anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibodies in an elderly woman. An 84-year-old woman was hospitalized for muscle pain. Her medical history included hypertension, type 2 diabetes mellitus, Hashimoto thyroiditis, and dyslipidemia. She had been treated with atorvastatin for a decade, nebivolol, perindopril, L-thyroxin, metformin, and gliclazide. She reported gait disorders with instability that had started 18 months earlier and progressive weakness, especially in the lower limbs. The initial biological screening found a high creatine kinase (CK) level (1,442 UI/L), leading to the cessation of atorvastatin before her hospitalization. Clinical examination revealed low strength, particularly in the shoulder and hip (Gowers' sign). There was neither myalgia nor sensory deficit, and the rest of the examination, including the neurological examination, was normal. Biological screening confirmed the high CK level (2,130 UI/L) and showed a high level of aspartate aminotransferase (155 UI/L) and alanine aminotransferase (246 UI/L); the troponin level was normal. There was no inflammatory syndrome or renal insufficiency. Serological analyses were negative for hepatitis A, B, and C and positive in immunoglobulin G for cytomegalovirus and Epstein-Barr virus. Autoimmune markers were positive for antithyroid peroxidase antibodies (677 UI/mL) and anti-HMGCR-antibodies and negative for antinuclear antibodies, antimyositis antibodies, antiliver antibodies, and antipolynuclear cytoplasm. Electromyogram showed no evidence of myopathic or neuropathic impairment. Quadriceps magnetic resonance imaging was normal. Histopathologic analysis of a muscle biopsy of the quadriceps showed moderately inflammatory necrotizing vacuolar myopathy with a slight overexpression of major histocompatibility complex class 1 (Figure 1). The diagnosis of autoimmune myopathy due to statins was made. The woman received an intravenous bolus of corticosteroids each day for 3 days, which reduced the CK level (450 UI/L), followed by oral corticosteroid therapy associated with azathioprine. Nevertheless, after 1 month of treatment, there was no clinical improvement, and the strength in her legs and arms continued to decline. Intravenous immunoglobulin therapy was started in addition to the oral corticosteroid therapy pending the effect of azathioprine. This led to an increase in strength in the upper limbs. The discovery of anti-HMGCR antibodies in the context of autoimmune myopathy whether due to statins or not is rare.1 Autoimmune diseases are classically found in younger people, but this patient was elderly. Statin tolerance is often excellent, but adverse effects have been found.2, 3 The risk of myopathy depends on the dose of the statin and on drug interactions. A meta-analysis showed that intensive high-dose statin therapy was associated with a significantly higher risk of CK levels greater than 10 times the upper limit of normal than low to moderate doses.4 Cytochrome P450 3A4 metabolizes simvastatin and atorvastatin, which can increase statin serum concentrations.5 The time between the start of statin therapy and the onset of myopathy symptoms is not well known, but median time varies from 1 to 6 months.2 The same applies to the time to resolution after discontinuing the treatment. Incompletely understood pathophysiological mechanisms cause the condition. Several hypotheses have been suggested. First, coenzyme Q10 depletion in the mitochondria could induce oxidative stress.6 Second, statins could inhibit mevalonate synthesis through HMGCR inhibition. Mevalonate is a precursor of geranyl pyrophosphate and farnesyl pyrophosphate, which are necessary for the prenylation of some proteins (e.g., guanosine triphosphatase) essential for cell survival.7 In addition, the presence of a specific polymorphism of the gene of the solute carrier organic anion transporter family member-1B1 (which encodes the organic anion transporting polypeptide-1B1, a peptide that regulates statin capture in the liver) is significantly associated with the appearance of statin-induced myopathy.8 Anti-HMGCR antibodies have recently been discovered in the context of the follow-up of a cohort of patients with autoimmune necrotizing myopathy with no specific diagnosis.9 The authors showed that exposure to statins was significantly more frequent in the group with positive antibodies. The time to the appearance of myopathy symptoms after the start of the statin was 31.3 months, and immunosuppressive therapy was required to obtain partial to complete remission; discontinuation of the statin was not enough.10 Anti-HMGCR antibodies can be found in persons not exposed to a statin1 and in subjects without hyperlipidemia, as shown in a previous study, which included 1,966 individuals with hyperlipidemia in whom the prevalence of anti-HMGCR-antibodies was 0.7%.1 In this study, the antibody was screened for in individuals with familial hyperlipidemia and in individuals with symptoms of intolerance to statins. None of these individuals were anti-HMGCR positive.1 The authors are grateful to Mr. Philip Bastable. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Nicolas, Manckoundia: study concept, acquisition of subject and data, interpretation of data, preparation of manuscript. Berthier: acquisition of subject and data, interpretation of data, preparation of manuscript. Sordet-Guépet and Aubriot-Lorton: interpretation of data, preparation of manuscript. Sponsor's Role: There was no sponsor in this study.