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

Abstract

IMPORTANCEHydroxychloroquine 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 hydroxychloroquineassociated skin eruption.OBJECTIVE To identify disease features that increase the risk of hydroxychloroquineassociated skin eruption in adults with dermatomyositis. DESIGN, SETTING, AND PARTICIPANTSA 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 MEASURESThe 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.

Mechanic's Hands and Drug Eruption to Hydroxychloroquine: Precious Diagnostic Tools

“…Regarding this latter aspect, adverse skin reactions to HCQ have been previously reported as common in patients with DM, particularly when associated with anti-SAE-1/2 antibodies -approximately 4-fold increase in risk compared to those without this antibody. 7 In DM it is important to timely install appropriate treatment and most patients do not respond to isolated skin directed therapies and will require systemic therapies. 9 Antimalarials have been the preferred initial treatment for cutaneous DM due to their photoprotective and Revista SPDV 78(2) 2020; Mãos de mecânico e toxidermia à hidroxicloroquina; Maria Mendonça Sanches, Rita Pimenta, Inês Cordeiro, Bernardo Baptista.…”

“…[4][5][6] Adverse skin reactions to hydroxychloroquine (HCQ), a standard first-line treatment in DM, have been reported and a strong association with anti-small ubiquitin-like modifier activating enzyme (SAE-1/2) antibodies was recently described. 7…”

Dermatomyositis autoantibodies: how can we maximize utility?

“…MSAs may be associated with differential response to treatments. As examples, anti-Mi-2 patients experience greater and more rapid benefit from rituximab, patients with anti-MDA-5 antibodies have lower chance of achieving cutaneous clinical remission even after aggressive systemic therapies, and patients with anti-SAE-1/2 antibodies are more likely to have hydroxychloroquine-related skin eruptions whereas anti-MDA-5 antibodies appear to be protective for this (16,(80)(81)(82)(83)(84)(85).…”

The sunburn sign and the suntan sign‐ two novel findings in Hispanic patients with dermatomyositis

“…This results in a worsening of the cutaneous eruption and the appearance of non-specific erythematous, and pruritic cutaneous eruptions. 6 A yellow-brown to slate grey or black hyperpigmentation can be seen after a few months of use. 7,8 This pigmentation can arise on the face, forearms, lower limbs, mouth, mucosa and nail beds.…”