title: Atorvastatin-induced necrotizing autoimmune myositis: An emerging dominant entity in patients with autoimmune myositis presenting with a pure polymyositis phenotype.
abstract: The general aim of this study was to evaluate the disease spectrum in patients presenting with a pure polymyositis (pPM) phenotype. Specific objectives were to characterize clinical features, autoantibodies (aAbs), and membrane attack complex (MAC) in muscle biopsies of patients with treatment-responsive, statin-exposed necrotizing autoimmune myositis (NAM). Patients from the Centre hospitalier de l'Université de Montréal autoimmune myositis (AIM) Cohort with a pPM phenotype, response to immunosuppression, and follow-up ≥3 years were included. Of 17 consecutive patients with pPM, 14 patients had a NAM, of whom 12 were previously exposed to atorvastatin (mean 38.8 months). These 12 patients were therefore suspected of atorvastatin-induced AIM (atorAIM) and selected for study. All had aAbs to 3-hydroxy-3-methylglutaryl coenzyme A reductase, and none had overlap aAbs, aAbs to signal recognition particle, or cancer. Three stages of myopathy were recognized: stage 1 (isolated serum creatine kinase [CK] elevation), stage 2 (CK elevation, normal strength, and abnormal electromyogram [EMG]), and stage 3 (CK elevation, proximal weakness, and abnormal EMG). At diagnosis, 10/12 (83%) patients had stage 3 myopathy (mean CK elevation: 7247 U/L). The presenting mode was stage 1 in 6 patients (50%) (mean CK elevation: 1540 U/L), all of whom progressed to stage 3 (mean delay: 37 months) despite atorvastatin discontinuation. MAC deposition was observed in all muscle biopsies (isolated sarcolemmal deposition on non-necrotic fibers, isolated granular deposition on endomysial capillaries, or mixed pattern). Oral corticosteroids alone failed to normalize CKs and induce remission. Ten patients (83%) received intravenous immune globulin (IVIG) as part of an induction regimen. Of 10 patients with ≥1 year remission on stable maintenance therapy, IVIG was needed in 50%, either with methotrexate (MTX) monotherapy or combination immunosuppression. In the remaining patients, MTX monotherapy or combination therapy maintained remission without IVIG. AtorAIM emerged as the dominant entity in patients with a pPM phenotype and treatment-responsive myopathy. Isolated CK elevation was the mode of presentation of atorAIM. The new onset of isolated CK elevation on atorvastatin and persistent CK elevation on statin discontinuation should raise early suspicion for atorAIM. Statin-induced AIM should be included in the differential diagnosis of asymptomatic hyperCKemia. Three patterns of MAC deposition, while nonpathognomonic, were pathological clues to atorAIM. AtorAIM was uniformly corticosteroid resistant but responsive to IVIG as induction and maintenance therapy.
authors.affiliation: Divisions of Rheumatology, Department of Medicine Internal Medicine, Hôpital du Sacré-Coeur Division of Rheumatology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, University of Montreal Faculty of Medicine, Montreal, QC Mitogen Advanced Diagnostics Laboratory, Cumming School of Medicine, University of Calgary, Calgary, AB Department of Pathology, Hôpital Maisonneuve-Rosemont, University of Montreal Faculty of Medicine, Montreal, QC, Canada Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center Oklahoma Medical Research Foundation, Oklahoma City, OK Department of Pathology, Hôpital Sainte-Justine Department of Pathology and Cell Biology, University of Montreal Faculty of Medicine Division of Rheumatology, Department of Medicine, Centre hospitalier affilié universitaire régional de Trois-Rivières, University of Montreal Faculty of Medicine, Montreal Division of Rheumatology, Centre Hospitalier de l'Université Laval, Laval University Faculty of Medicine, Québec, QC, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Troyanov
authors.forename: Océane
authors.initials: O
authors.lastname: Landon-Cardinal
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
authors.forename: José
authors.initials: J
authors.lastname: Ferreira
authors.forename: Ira N
authors.initials: IN
authors.lastname: Targoff
authors.forename: Eric
authors.initials: E
authors.lastname: Rich
authors.forename: Michelle
authors.initials: M
authors.lastname: Goulet
authors.forename: Jean-Richard
authors.initials: JR
authors.lastname: Goulet
authors.forename: Josiane
authors.initials: J
authors.lastname: Bourré-Tessier
authors.forename: Yves
authors.initials: Y
authors.lastname: Robitaille
authors.forename: Julie
authors.initials: J
authors.lastname: Drouin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Albert
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Senécal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069059:Atorvastatin / Q000009:adverse effects*; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000276:immunology; D060828:Induction Chemotherapy; D008137:Longitudinal Studies; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D017285:Polymyositis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D001323:Autoantibodies; D015938:Complement Membrane Attack Complex; D005938:Glucocorticoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin; D008775:Methylprednisolone