title: Antimalarials as a risk factor for elevated muscle enzymes in systemic lupus erythematosus.
abstract: OBJECTIVE
  To investigate the relationship between antimalarials (AM) and elevated muscle enzymes in systemic lupus erythematosus (SLE).
  
  
  METHODS
  325 lupus patients with abnormal creatine phosphokinase (CPK) for at least two consecutive clinic visits were enrolled; 54 patients on statins/fibrates (n = 43) and/or active myositis (n = 14) were excluded. The control group consisted of 1453 lupus patients with no CPK elevation during follow-up. Descriptive statistics and Cox regression analyses were performed, p < 0.05 was considered significant.
  
  
  RESULTS
  Cases and controls did not differ regarding age at SLE diagnosis, gender ratio, or disease duration. AM use was more frequent in cases, which had more prolonged AM use. Total frequency of elevated CPK in AM users was 216/1322 (16.3%). Chloroquine was associated with a 3.3-fold, and hydroxychloroquine with a 3.1-fold, increased risk for CPK elevation. Black race was associated with higher CPK (HR = 2.941), whereas female gender was protective (HR = 0.697). 203 patients were followed for 7.3 ± 5.6 years; 49.8% had persistent and 14.8% intermittent CPK elevation, while in 35.4% CPK was normalized. Clinical proximal muscle weakness developed in 5/203 patients.
  
  
  CONCLUSIONS
  Chronic AM use is a potential risk factor for muscle enzyme elevation in SLE patients. CPK abnormalities persist in almost two thirds of the patients, but this remains mainly a biochemical finding, evolving to clinical myopathy in about 2.5%.
authors.affiliation: University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Tselios
authors.affiliation: University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Canada.
authors.forename: D D
authors.initials: DD
authors.lastname: Gladman
authors.affiliation: University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Canada.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Su
authors.affiliation: University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Canada m.urowitz@utoronto.ca.
authors.forename: M B
authors.initials: MB
authors.lastname: Urowitz
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003402:Creatine Kinase / Q000097:blood*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D009135:Muscular Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000201:enzymology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000962:Antimalarials; D015415:Biomarkers; D003402:Creatine Kinase
keywords: Antimalarials; chloroquine; hydroxychloroquine; muscle enzymes; systemic lupus erythematosus