Background/Purpose: The classification of autoimmune myopathies (AIM) is evolving. Pure dermatomyositis (DM) and overlap myositis are dominant AIM subsets, while pure polymyositis (pPM) is uncommon and confused with myositis mimickers. Our objective was to evaluate the disease spectrum in patients presenting with a pPM phenotype and to evaluate clinical features, autoantibodies (aAbs) and membrane attack complex (MAC) in muscle biopsies of patients with treatment-responsive, statin-exposed necrotizing AIM. 

Methods: Our study included all patients from the CHUM AIM Cohort with a pPM phenotype (i.e absence of DM rash, overlap features and overlap aAbs), a documented response to immunosuppression and a follow-up of at least three years. We selected statin-exposed necrotizing AIM, thus excluding patients with significant inflammatory infiltrates on muscle biopsy or no previous statin-exposure.

Results: Of 17 consecutive patients with pPM, 14 patients had a necrotizing AIM, of whom 12 were previously exposed to atorvastatin (mean duration: 38.8 months). These 12 patients were therefore suspected of atorvastatin-induced AIM (atorAIM) and selected for study. None had overlap aAbs, anti-SRP or cancer. Anti-HMGCR aAbs were present in sera of these 12 patients using addressable laser bead immunoassay.

Three clinical stages of myopathy were recognized: stage 1 (serum CK elevation, normal muscle strength, normal EMG), stage 2 (CK elevation, normal strength, abnormal EMG) and stage 3 (CK elevation, proximal weakness, abnormal EMG). At diagnosis, 10/12 patients (83%) had stage 3 myopathy (mean CK elevation: 7,247 U/L). However the presenting feature was stage 1 myopathy in 6 patients (50%) (mean CK elevation: 1,540 U/L), all of whom later progressed to stage 3 myopathy (mean delay: 37 months) despite atorvastatin discontinuation. 

MAC deposition was observed in all tested muscle biopsies (n=13). Three patterns were seen: isolated sarcolemmal deposition on non-necrotic fibers, isolated granular deposition on endomysial capillaries and a mixed pattern.

Oral corticosteroids alone were unable to normalize CKs and induce remission (n=9). Ten patients (83%) received intravenous immune globulin (IVIG) as part of an induction regimen. Of 10 patients with evaluable maintenance therapy (≥ 1-year remission on stable maintenance therapy), IVIG was needed in 5 patients (50%), either with MTX monotherapy (n=3) or with combination immunosuppression (n=2). In the remaining 5 patients, MTX monotherapy (n=3) and combination therapy (n=2) maintained remission without IVIg.

Conclusion: atorAIM emerged as the dominant entity in patients with a pPM phenotype and treatment-responsive myopathy. Isolated CK elevation, i.e. stage 1 myopathy, was the initial mode of presentation of atorAIM. Thus, the new onset of isolated CK elevation on atorvastatin and persistent CK elevation on statin discontinuation should raise early suspicion for atorAIM. Three patterns of MAC deposition were seen and, while non pathognomonic, were pathological clues to atorAIM. AtorAIM was uniformly corticosteroid resistant but responsive to IVIG as induction and maintenance therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/atorvastatin-induced-autoimmune-myopathy-an-emerging-dominant-entity-in-patients-with-autoimmune-myopathy-presenting-with-a-pure-polymyositis-phenotype/