Statin-induced Myopathy Beyond the Surface: Immune-mediated Necrotizing Myopathy Triggered by CYP3A4 Interaction
Akash Rawat1, Drishtdeum Malik1, Reshma Kaushik1
1Himalayan Institute of Medical Sciences
Objective:

To highlight the role of CYP3A4-mediated drug interaction and renal dysfunction in precipitating severe statin-associated IMNM.

Background:

Statins can rarely induce immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy often associated with anti-HMGCR antibodies. Drug interactions and comorbidities may significantly amplify this risk.

Design/Methods:

Single-patient observational report with clinical, biochemical, radiologic, electrodiagnostic, and histopathological correlation.

Results:

A 72-year-old male with aplastic anemia (post-ATG) and prior PTCA presented with rapidly progressive proximal weakness, dysarthria, and bulbar dysfunction. He was receiving high-dose Atorvastatin (80 mg) and Cyclosporine.

 

Examination showed quadriceps weakness (MRC 3/5) and absent gag reflex. Creatine kinase peaked at 51,586 IU/L with concurrent acute kidney injury (creatinine 3 mg/dL) and transaminitis. Nerve conduction studies revealed mixed polyneuropathy. MRI demonstrated diffuse edema of thigh musculature.

 

Muscle biopsy revealed myofiber necrosis with minimal inflammatory infiltrate, consistent with necrotizing myopathy. Anti-HMGCR antibody testing was unavailable.

 

Cyclosporine-mediated inhibition of the Cytochrome P450 3A4 pathway likely increased statin exposure, precipitating severe myotoxicity in the setting of renal dysfunction.

 

Atorvastatin was discontinued. Despite corticosteroid therapy, progression necessitated escalation to immunosuppression, after which stabilization was achieved.

Conclusions:

Statin-associated IMNM is a severe autoimmune myopathy that may present with rapid progression and bulbar involvement. Advanced age, renal dysfunction, and CYP3A4-mediated drug interactions significantly increase risk. In resource-limited settings, clinicopathologic correlation can support diagnosis in the absence of antibody testing. Early recognition is essential, as immunosuppressive therapy may be required beyond statin withdrawal.

Generative AI Usage
Yes, used generative AI in the drafting or editing in this abstract.

Tool, version, and prompt(s) used, as well as area of the abstract affected
The authors used ChatGPT for language editing and formatting. Prompts focused on improving the clarity and structure of the abstract. Edits were applied to all sections. The authors are responsible for all content.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.