EVIDENCE-BASED DERMATOLOGY: ORIGINAL CONTRIBUTION Adverse Cutaneous Reactions to Hydroxychloroquine Are More Common in Patients With Dermatomyositis Than in Patients With Cutaneous Lupus Erythematosus Michelle T. Pelle, MD; Jeffrey P. Callen, MD Background: Hydroxychloroquine sulfate and other an- Main Outcome Measures: Presence or absence of docu- timalarial drugs have been used successfully as adjunc- mented drug eruption due to hydroxychloroquine exposure. tive therapy for patients with cutaneous lesions of der- matomyositis over the past 20 years. An increased Results: Of 39 patients, 12 (31%) with dermatomyositis incidence of cutaneous reactions to hydroxychloro- developed a cutaneous reaction to hydroxychloroquine. quine has been postulated to occur in patients with Among age-, sex-, and race-matched patients with cuta- dermatomyositis. neous lupus erythematosus, only 1 developed a cutane- ous reaction to hydroxychloroquine. None of the reac- Objective: To determine if adverse cutaneous erup- tions observed in our patients resulted in serious morbidity tions due to hydroxychloroquine are more common in or mortality. Additionally, 4 patients with dermatomyo- patients with dermatomyositis than in those with cuta- sitis who reacted to hydroxychloroquine were treated with neous lupus erythematosus. oral chloroquine phosphate, 2 of whom also reacted to chlo- roquine phosphate. Design: Retrospective, age-, sex-, and race-matched case- control study. Conclusions: When contemplating antimalarial therapy for dermatomyositis, both the physician and the patient Setting: University-affiliated practice. should recognize that non–life-threatening cutaneous re- actions may occur in approximately one third of patients Patients: The study comprised 42 patients with and that perhaps one half of those who react to hydroxy- dermatomyositis (39 adults) and 39 age-, sex-, and chloroquine will also react to chloroquine. race-matched adult patients with lupus erythema- tosus. Arch Dermatol. 2002;138:1231-1233 ERMATOMYOSITIS (DM) is an increased frequency of cutaneous re- an idiopathic inflamma- actions to hydroxychloroquine occurs in tory myopathy that has patients with DM, we reviewed the re- characteristic cutaneous cords of 68 patients with DM and com- manifestations including pared them with a group of age-, sex-, and Dthe heliotrope rash, Gottron papules, pho- race-matched patients with cutaneous LE. todistributed erythema or poikiloderma, al- teration of the cuticles, and a pruritic scalp PATIENTS AND METHODS dermatitis.1 Treatment with systemic cor- Approval for research using existing data was re- ticosteroids and immunosuppressive medi- ceived from the Human Studies Committee of the cations usually controls the inflammation University of Louisville School of Medicine. A list of the muscles, but often the skin disease of patients with a diagnosis of DM was computer is not fully controlled. Hydroxychloro- generated from billing records of the university- quine sulfate has been reported to im- affiliated practice. Criteria for the diagnosis of DM prove the cutaneous manifestations asso- were as follows: characteristic skin manifestations ciated with DM.2-5 as diagnosed by a dermatologist and skin biopsy From the Department of Cutaneous reactions to antimalarial result consistent with DM, with or without posi- Dermatology, University of agents were commonly observed in the tiveserologicfindings.Physicalexaminationfind- Pennsylvania School of treatment of psoriasis and psoriatic arthri- ings of muscle weakness and/or muscle enzyme Medicine, Philadelphia 6 analysis, electromyogram and/or muscle biopsy (Dr Pelle); and the Department tis. Similar reactions are unusual in pa- results consistent with myositis supported the of Medicine, Division of tients with lupus erythematosus (LE). We diagnosis, but we did not require the demonstra- Dermatology, University of have observed disease-specific cutaneous tion of myositis as a diagnostic criterion. Only Louisville School of Medicine, reactions to hydroxychloroquine in the patients who had been treated with hydroxychlo- Louisville, Ky (Dr Callen). treatment of DM. To determine whether roquine at some time during the course of their (REPRINTED) ARCH DERMATOL / VOL 138, SEP 2002 WWW.ARCHDERMATOL.COM 1231 ©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 disease were eligible. Patients may have been treated by a referring Of the remaining 3 nonmorbilliform eruptions, 1 pa- physician or the therapy may have been initiated upon referral tient developed an erythroderma within 2 weeks of com- or after other therapies had failed or been demonstrated to be mencing hydroxychloroquine therapy. She was later given toxic. A follow-up period of at least 2 months was also required a trial of chloroquine and developed truncal erythema for eligibility. and pruritus. Another patient developed a widespread blis- Similarly, a list of patients with a diagnosis of cutaneous LE was generated from billing records for use as controls. Cri- tering eruption that was diagnosed as Stevens-Johnson teria for the diagnosis of cutaneous LE were as follows: char- syndrome. She was treated successfully with drug with- acteristic lesions of LE on physical examination by a derma- drawal and oral prednisone. The final patient developed tologist and characteristic findings on skin biopsy. Patient records erythema and edema in an unspecified distribution. None were selected for further review if the patient had been treated of the cutaneous eruptions were associated with serious with hydroxychloroquine. Charts of patients with LE were re- morbidity or mortality. The 1 cutaneous reaction in the quested from our files and were reviewed to verify diagnosis, control patient with LE was morbilliform and resolved ascertain exposure to hydroxychloroquine, and obtain the age, on discontinuation of the drug regimen and a short course race, and sex of the hydroxychloroquine-treated patients. We of oral prednisone. then selected 1 such patient to serve as a control for each pa- Dosages of hydroxychloroquine sulfate were either tient treated for DM. The control patient was matched by age (±5 years), sex, and race. Our protocol called for only 1 matched 200 mg daily or 200 mg twice daily in both the patients patient, and although there may have been many other pos- with DM and LE. At the time of the eruption, 7 patients sible matches, these charts were not further reviewed. were receiving no other therapy (6 patients with DM and Documented cutaneous eruptions to hydroxychloroquine 1 with LE), 5 were also receiving methotrexate and pred- and/or chloroquine phosphate in both groups within 1 month of nisone therapy, 1 was receiving an antidepressant, and initiation of therapy were considered positive reactors. We also 1 patient’s concomitant drug use was not recorded. Among reviewed the medical records for information about other drug our 39 adult patients with DM, 8 reported drug allergy allergies as reported by the patient or observed by a physician and to sulfonamides (3 among the 12 patients who had a re- concomitant drug use at the time of the hydroxychloroquine erup- action to hydroxychloroquine and 5 among the group that tion. All patients seen were asked, often repeatedly, about drug did not). Among the LE patients, 12 reported sulfon- allergies. Statistical analysis was performed using the McNemar test on StatXact software (Cytel Software Corp, Cambridge, Mass). amide allergy, but the patient with the hydroxychloro- A 2-sided P value is reported; PϽ.05 was considered significant. quine reaction was not allergic to sulfonamides. COMMENT RESULTS Antimalarial agents were first used for lupus in 1894 when Eight of the 68 patients qualified as having possible amyo- Payne7 treated a case of discoid lupus with quinine. It was pathic DM based on skin findings, biopsy results, and ab- not until 1951 that Page8 reported the benefits of quinacrine sence of muscle weakness and normal test findings of for lupus. The use of hydroxychloroquine for the cutane- muscle-derived enzymes. The other 60 patients had evi- ous manifestations of DM were first described by Woo et dence of both skin and muscle disease consistent with al in 1984.2 They described 7 patients in whom hydroxy- DM. Of the 68 patients, 42 had been treated with hy- chloroquine therapy achieved partial or complete clearance droxychloroquine at some time following diagnosis and of their skin disease and enabled some patients to reduce were therefore eligible for the study. We were unable to their dosage of corticosteroids. No adverse events related match 3 juvenile patients with DM with controls, and thus to hydroxychloroquine were reported in this study. Sub- 39 patients were included in our statistical analysis. Eli- sequent case reports and small case series followed, sup- gible adults with DM ranged in age from 17 to 81 years porting the use of oral hydroxychloroquine for cutaneous (mean, 48.8 years). Of the 39 patients, 36 (92%) were lesions of DM.3-5 women and 37 (95%) were white. The patients with LE Bloom et al9 provided the first report of adverse cu- were matched for sex and race, and their ages ranged from taneous reactions to hydroxychloroquine in patients with 20 to 76 years (mean, 47.5 years). DM. They described 2 children in whom the addition of Twelve (31%) of the 39 adult patients with DM de- hydroxychloroquine caused exacerbation of existing skin veloped a cutaneous reaction to hydroxychloroquine disease and new