Background

Statins, widely prescribed for cardiovascular disease, effectively reduce cardiovascular risk in primary and secondary prevention. However, muscle pain is a common side effect, affecting 2% to 11% of users. It is crucial to differentiate between benign muscle pain and serious myopathies, as severe myopathy (characterized by a creatine kinase (CK) level greater than 10 times the reference value) occurs in approximately 0.5% of patients. Immune-mediated necrotizing myopathy (IMNM), associated with anti-HMGCR antibodies, anti-SRP auto-antibodies, HIV, hepatitis C virus (HCV), connective tissue disorders, paraneoplastic disease, or idiopathic causes, is one such severe condition. IMNM presents with acute or subacute mild to moderate symmetrical muscle weakness, and discontinuing statins does not halt muscle weakness and elevated CK levels in HMGCR antibody-associated IMNM.

Case Presentation

A 67-year-old female presented with muscle weakness and elevated creatine phosphokinase (CPK) levels. Initially active, she began experiencing muscle weakness, particularly with overhead movements, in October 2023. She consulted her primary care doctor and was referred to a rheumatologist, who discontinued her statin medication in March 2024. Her symptoms temporarily improved but then worsened, with leg weakness and difficulty swallowing. By April 2024, her CPK level rose to 4806.

Laboratory findings revealed anemia of inflammatory condition, elevated AST (175 U/L) and ALT (195 U/L) levels, a low A/G ratio, and low serum potassium. CT scans of the chest, abdomen, and pelvis with contrast did not indicate malignancy. Immunological testing revealed an elevated HMGCR Antibody IgG at 95 and SSA-52 (RO52) at 43. A muscle biopsy indicated skeletal muscle necrosis and regeneration.

The patient received 1 gram of Solu-Medrol (Methylprednisolone sodium succinate), significantly improving her muscle strength and mobility, with CPK levels decreasing to 2779 and then to 855. The treatment plan included IV Solu-Medrol for three days, followed by oral Prednisone, Vitamin D, a proton pump inhibitor (PPI), and scheduled IVIG therapy for 2 days. Follow-up showed symptom relief and normalization of CPK levels.

Discussion

This case underscores the importance of recognizing statin-induced myopathy, particularly HMGCR antibody-mediated IMNM. Before diagnosing statin-induced myopathy, various differential diagnoses, including dermatomyositis, myopathy/myositis with significant CK elevation, polymyalgia rheumatica, and HMGCR antibody-mediated IMNM, must be considered. Understanding its natural course, particularly in cases of HMGCR antibody-mediated IMNM, is essential for informed patient consent and effective management. This case highlights the need for thorough differential diagnosis and appropriate treatment to ensure optimal patient outcomes.