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Brief Report
October 2018

Association Between Autoantibody Phenotype and Cutaneous Adverse Reactions to Hydroxychloroquine in Dermatomyositis

Author Affiliations
  • 1Department of Dermatology, Stanford University School of Medicine, Redwood City, California
  • 2Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
JAMA Dermatol. 2018;154(10):1199-1203. doi:10.1001/jamadermatol.2018.2549
Key Points

Question  Is a skin eruption that develops during hydroxychloroquine sulfate use associated with autoantibodies in dermatomyositis?

Findings  In this cohort study of 111 patients with dermatomyositis treated with hydroxychloroquine, 23 experienced an associated adverse cutaneous event. Of those with a skin eruption, 7 had anti–small ubiquitinlike modifier 1 activating enzyme autoantibodies vs 7 of 88 patients without a skin eruption; in contrast, none of those with a skin eruption had anti–melanoma differentiation-associated gene 5 autoantibodies vs 15 of those without a skin eruption, and associations were significant in multivariable models.

Meaning  Patients with dermatomyositis with anti-small ubiquitinlike modifier 1 activating enzyme autoantibodies appear to be at increased risk of developing a hydroxychloroquine-associated skin eruption, and this may be the result of differences in disease mechanism among autoantibody subsets.

Abstract

Importance  Hydroxychloroquine sulfate is a commonly used medication for patients with dermatomyositis and has been associated with a uniquely elevated risk of adverse cutaneous reactions in this population. No studies to date have examined whether certain subsets of patients with dermatomyositis are at increased risk of experiencing a hydroxychloroquine-associated skin eruption.

Objective  To identify disease features that increase the risk of hydroxychloroquine-associated skin eruption in adults with dermatomyositis.

Design, Setting, and Participants  A retrospective cohort study was conducted in the outpatient dermatology clinic at a tertiary academic referral center. All adults with dermatomyositis (age >18 years) who started receiving hydroxychloroquine between July 1, 1990, and September 13, 2016, were eligible for the analysis. Patients were considered to have a hydroxychloroquine-associated skin eruption if a skin eruption had developed within their first 4 weeks of treatment and resolved with discontinuation of hydroxychloroquine therapy.

Exposures  One or more doses of hydroxychloroquine.

Main Outcomes and Measures  The associations between autoantibodies (against transcription intermediary factor 1γ [TIF-1γ], nucleosome-remodeling deacetylase complex [Mi-2], nuclear matrix protein [NXP-2], small ubiquitinlike modifier 1 activating enzyme [SAE-1/2], melanoma differentiation-associated gene 5 [MDA-5], histidyl–transfer RNA synthetase [Jo-1], Ku, and signal recognition particles) and cutaneous adverse reactions to hydroxychloroquine in patients with dermatomyositis.

Results  A total of 111 patients met the inclusion criteria, and 23 (20.7%) developed a hydroxychloroquine-associated skin eruption (20 [87.0%] were women with a mean [SD] age of 49 [14] years at diagnosis). Skin eruptions were approximately 3 times more common in patients with anti–SAE-1/2 autoantibodies (7 of 14 [50.0%]) compared with those without the autoantibody (16 of 97 [16.5%]). In contrast, none of 15 patients with anti–MDA-5 autoantibodies had a skin eruption vs 23 of 96 (24.0%) of those without the autoantibody. In exact logistic regressions adjusted for age, race/ethnicity, sex, amyopathic status, anti–Ro52 status, and dermatomyositis-associated cancer, the presence of anti–SAE-1/2 autoantibodies was significantly associated with a hydroxychloroquine-associated skin eruption (odds ratio [OR], 8.43; 95% CI, 1.98-49.19; P = .003) and presence of anti–MDA-5 autoantibodies was significantly negatively associated with a hydroxychloroquine-associated skin eruption (OR, 0.06; 95% CI, 0.0004-0.52; P = .006). No other autoantibodies were significantly positively or negatively associated with a hydroxychloroquine-associated skin eruption.

Conclusions and Relevance  Adverse skin reactions to hydroxychloroquine are relatively common in a US cohort of patients with dermatomyositis. Our data suggest that pathophysiologic differences exist between autoantibody subsets in dermatomyositis.

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