Title: Rutin: A Double-Edged Sword in Statin-Induced Necrotizing Autoimmune Myopathy
Author(s): Kwabena Owusu-Ansah, MD; Arman Hemmat, MD; Gregory Polcha, DO; David Regule, MD
Email: KOwusuAnsah@mercy.com
Introduction: Statins effectively reach target cholesterol levels through inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [1]. Statins are well-known to cause myopathies that are not tolerated by some patients. In rare instances they can lead to Statin-induced necrotizing autoimmune myopathy (SINAM), with an incidence of 2-3 per 100,000 people [2]. SINAM is caused by immune-mediated direct or indirect damage to muscle fibers, and it can develop in patients who previously tolerated statins [1]. Patients experience proximal muscle weakness associated with myalgias and extra-muscular symptoms such as dysphagia and pulmonary dyspnea. Serum CK levels greater than 2 times the upper limits of normal should raise suspicion for SINAM. The gold standard for diagnosis is the presence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme, which one review found to be positive in 93.8% of patients with SINAM. Current data suggests a genetic susceptibility to SINAM, as a result of HMG-CoA reductase overexpression combined with a direct enzymatic effect by HMG-CoA reductase inhibitors [1, 3]. With the rise in popularity of supplements and herbal medicine, we also need to consider potential interactions with these supplements. Rutin is a natural flavonoid glycoside, attractive due to its potential neuroprotective effects and metabolic benefits [4]. In rat models, rutin has was found to improve lipid profiles; yet was inferior to atorvastatin [5]. Rutin specifically inhibits the CYP3A4 cytochrome P450 in rats and human hepatic cancer cells (75.3 %, p < 0.0001) [4, 6]. Since CYP3A4 is responsible for the metabolism of lipophilic statins [7], this inhibition is a potential route for statin toxicity and complications.
Case: A 48-year-old male with a medical history notable for hypertension, hyperlipidemia, and diabetes mellitus was admitted to the emergency department presenting with cramping pain and weakness in the bilateral lower and upper extremities persisting for 2-3 months. There was no reported history of trauma or substance abuse. The initial examination revealed elevated blood pressure and a Creatine Kinase (CK) level that was exceeding 22,000 U/L. Further laboratory testing showed: AST 300 U/L, and ALT 500 U/L, negative hepatitis viral panel. C-reactive protein (CRP) and other inflammatory markers were found to be within normal ranges. The patient’s LDL cholesterol levels were well-managed on Lipitor 40 mg daily, having decreased from 190 mg/dL in 2014 to 76 mg/dL in 2023. A comprehensive autoimmune myositis panel, including JO-1 antibodies, returned negative results. Despite discontinuation of statin therapy and the initiation of intravenous hydration, CK levels remained elevated throughout hospitalization; however, the patient reported a improvement in symptoms. Ultimately, the patient tested positive for anti-hydroxymethylglutaryl-coenzyme A reductase (HMGCR) antibodies and was diagnosed with SINAM. The patient ultimately revealed he had been consuming a supplement containing rutin before the onset of symptoms. The use of statins was ultimately discontinued, and the patient was advised to cease the consumption of the implicated supplement.
Discussion: This case report delves into an intricate and relatively underexplored area of pharmacology and medical science, examining the nuanced role of rutin—a flavonoid glycoside known for its potential health benefits—in the context of statin-induced necrotizing autoimmune myopathy (SINAM). This condition is a serious and rare side effect of statin therapy characterized by muscle weakness; elevated serum creatine kinase (CK) levels; and, in severe cases, significant muscle damage.
