Systemic Treatment for Clinically Amyopathic Dermatomyositis at 4 Tertiary Care Centers

Clinically amyopathic dermatomyositis (CADM), characterized by pathognomonic cutaneous findings without muscle weakness, is an important subset and accounts for 20% of patients with dermatomyositis (DM).^1,2 In patients with CADM, limited literature exists regarding treatment specifically for cutaneous disease because many studies involve patients treated for pulmonary disease.^3,4 Furthermore, no consensus exists on treatment for CADM. Given that there is often a discordance between the response of systemic and skin disease to therapy in DM and that cutaneous manifestations frequently represent a therapeutic challenge,^3,4 studies focusing on treatment of skin disease in CADM remain an unmet need.

To investigate the use of systemic treatment for skin disease in CADM at 4 tertiary care centers, an institutional review board–approved (Brigham and Women’s and New York University Hospitals) search of Partners HealthCare (Research Patient Data Registry, encompassing more than 2 billion patient data points) and New York University electronic medical record systems was performed between January 1, 2000, and December 31, 2016. The search was conducted using natural language queries and International Classification of Diseases codes for amyopathic and hypomyopathic DM. A total of 115 patients diagnosed and managed by a board-certified dermatologist or rheumatologist were included. All patients for whom treatment was not specifically prescribed for skin manifestations of CADM were excluded.

Data collected included demographics, referral types, laboratory test results, medications, and adverse effects. Patient demographics and treatment characteristics were compared by diagnosis and clinic type (dermatology vs rheumatology). Differences in age by group were assessed with 2-sample t tests. Wilcoxon rank sum tests were used to compare number of treatments, and χ² or Fisher exact tests were applied as appropriate for group comparisons of all other nominal variables. Two-sided tests were performed, and P < .05 was considered statistically significant.

Of 115 patients, 93 were amyopathic and 22 were hypomyopathic. The mean (SD) age at diagnosis was 51.1 (14.6) years. Patient demographics did not significantly differ by diagnosis or clinic type (Table 1). Most patients were referred from dermatology (45.9% [51 of 115]) and rheumatology (29.7% [33 of 115]) providers. Antimalarial agents were the most commonly used systemic treatment (76.5% [88 of 115] of patients), but they achieved adequate control of skin disease in only 11.4% (10 of 88) of cases. Consistent with the existing literature,⁵ a total of 30.7% (27 of 88) of patients herein developed a cutaneous hypersensitivity reaction to hydroxychloroquine sulfate. Of the entire cohort, 80.0% (92 of 115) required at least 1 immunosuppressive therapy to control their cutaneous disease. Furthermore, a median of 3 (interquartile range, 3-5) treatments were prescribed before achieving skin disease control. Methotrexate (51.3% [59 of 115]) and mycophenolate mofetil or mycophenolic acid (40.0% [46 of 115]) were the most common nonantimalarial medications used, followed closely by intravenous immunoglobulin (28.7% [33 of 115]). Thirteen patients were followed exclusively by a rheumatology provider, and none of these patients received intravenous immunoglobulin compared with 32.4% (33 of 102) of patients followed exclusively by a dermatology provider (P = .02) (Table 2). Because existing data support the efficacy of intravenous immunoglobulin for skin disease in DM, this difference in treatment approach may alter patient outcomes.^3,6

This study emphasizes the recalcitrant nature of DM skin disease. Antimalarial agents have often been reported as first-line treatment for cutaneous DM. However, in this study, patients rarely responded sufficiently to antimalarial agents, and 30.7% (27 of 88) developed a morbilliform eruption in response to antimalarial therapy, which can subsequently aggravate cutaneous DM. At our institutions, patients with DM who are prescribed hydroxychloroquine are given a pretreatment warning regarding the risk of a drug-related eruption. Furthermore, in patients with moderate or severe skin disease, given the low response rate to antimalarial therapy alone, a more aggressive therapy (eg, methotrexate or mycophenolate mofetil) is typically started as initial therapy alone or in conjunction with hydroxychloroquine. This study highlights that aggressive therapy is often warranted on the basis of cutaneous involvement alone, especially given that CADM is typically a chronic condition that negatively influences quality of life and in which full remission may take years.² Although this is the largest reported cohort of patients with CADM to date, our study is limited by small sample size, lack of an available skin severity measure given its retrospective nature, and potential increased disease severity among patients in tertiary care centers. Further studies are warranted to better characterize therapeutic response in CADM.

Accepted for Publication: November 17, 2018.

Corresponding Author: Ruth Ann Vleugels, MD, MPH, Department of Dermatology, Brigham and Women’s Hospital and Harvard Medical School, 221 Longwood Ave, Boston, MA 02115 (rvleugels@partners.org).

Published Online: January 23, 2019. doi:10.1001/jamadermatol.2018.5215

Author Contributions: Drs Pinard and Vleugels had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Pinard and Femia are co–first authors. Drs Lin and Vleugels are co–last authors.

Concept and design: Pinard, Femia, Lin, Vleugels.

Acquisition, analysis, or interpretation of data: Pinard, Femia, Roman, Alsarheed, Joyce, Lin, Vleugels.

Drafting of the manuscript: Pinard, Femia, Lin, Vleugels.

Critical revision of the manuscript for important intellectual content: Femia, Roman, Alsarheed, Joyce, Vleugels.

Statistical analysis: Joyce, Lin.

Administrative, technical, or material support: Pinard, Vleugels.

Supervision: Femia.

Conflict of Interest Disclosures: Dr Pinard reported serving as consultant/advisor for Celgene, Actelion, Janssen, Eli Lilly, and Novartis Canada. No other disclosures were reported.