title: Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy.
abstract: OBJECTIVE
  Necrotizing autoimmune myopathy (NAM) is characterized pathologically by necrotic muscle fibers with absent or minimal inflammation. It is often accompanied by statin therapy, connective tissue diseases, cancer, and autoantibodies specific for signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Data are limited concerning differences among etiologic subgroups and treatment outcomes in NAM.
  
  
  OBJECTIVE
  To describe the clinical, serologic, and electrophysiologic characteristics of NAM, compare patient subgroups, and determine clinical outcome predictors.
  
  
  METHODS
  We conducted a retrospective review of medical records for 63 adult Mayo Clinic patients assigned the clinical and histopathologic diagnosis of NAM from January 1, 2004, through December 31, 2013. Patients were stratified by presumed cause and autoantibody status.
  
  
  METHODS
  Clinical, electrophysiologic, and pathologic characteristics were collected and compared among patient subgroups. Predictors of response to treatment were identified by univariate logistic regression.
  
  
  RESULTS
  Lower extremity weakness predominated (46 [73%]). Distal weakness (26 [41%]), dysphagia (22 [35%]), and dyspnea (23 [37%]) were common. Twenty-two patients (35%) were receiving a statin medication at onset, 6 had cancer, and 3 had a connective tissue disease. The median creatine kinase level was 5326 U/L. In 13 patients (24%), SRP-IgG was detected, and in 17 patients (34%), HMGCR-IgG was detected (one-third of whom had not received statin medication). One patient was dual seropositive. Facial weakness was more common in SRP-IgG-positive patients. Myotonic discharges were more common in statin-associated NAM. Prednisone monotherapy was insufficient to control disease in most patients; 30 (90%) of 32 patients required 2 or more immunotherapeutic agents. Relapse occurred in 16 (55%) of 29 patients during immunosuppressant taper or discontinuation. Predictors of favorable outcome were male sex and use of 2 or more immunotherapeutic agents within 3 months of onset.
  
  
  CONCLUSIONS
  Necrotizing autoimmune myopathy was idiopathic in half of this cohort with clinical and histopathologically defined disease. In the remainder, NAM was associated with statin medication, cancer, or connective tissue disease. One in 4 patients was SRP-IgG positive, and 1 in 3 was HMGCR-IgG positive. The disease was usually not controlled by corticosteroid monotherapy. Presentation, course, and outcomes did not differ significantly in seropositive, seronegative, and statin-associated cases. Early aggressive immunosuppressant therapy improved outcomes, and risk of relapse was high during medication dose reduction or withdrawal.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester Minnesota.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Kassardjian
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester Minnesota2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota3Department of Immunology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Nora B
authors.initials: NB
authors.lastname: Alfugham
authors.affiliation: Inova Diagnostics, San Diego, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Mahler
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester Minnesota.
authors.forename: Margherita
authors.initials: M
authors.lastname: Milone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D003346:Corticotropin-Releasing Hormone / Q000276:immunology; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000209:etiology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy / Q000379:methods*; D008171:Lung Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D009135:Muscular Diseases / Q000097:blood / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D009336:Necrosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D054832:Urocortins / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; C426705:UCN2 protein, human; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases