Researchers outlined the clinical and histopathologic manifestations of dermatomyositis (DM) by melanoma-differentiation antigen 5 (MDA5) seropositivity status, in a study published in Clinical and Experimental Dermatology. Patients with MDA5-positive DM were more likely to present with Raynaud syndrome, dysphagia, and joint and pulmonary involvement.
Previous research suggested that MDA5 autoantibodies are associated with distinct clinical manifestations of DM. However, these studies used research laboratory-based testing, which may not be accessible to patients in a clinical setting.
Researchers sought to confirm the association between certain DM manifestations and MDA5 seropositivity, as determined by commercially available tests. The retrospective medical record review enrolled patients with DM who received care at the Mayo Clinic Department of Dermatology in Rochester, Minnesota. Eligible patients were tested for the presence of MDA5 autoantibodies with commercial tests between January 2010 and December 2019. Descriptive statistics were used to compare the rates of certain DM manifestations between the MDA5-positive and -negative groups.
The study cohort included 73 patients with DM, among whom 33 (45%) had MDA5 autoantibodies and 40 (55%) did not. Approximately half of patients with MDA5 autoantibodies and 20% of patients without MDA5 autoantibodies were men. MDA5 was “weakly positive” in 19 patients, “moderately positive” in 9 patients, and “strongly positive” in 4 patients. Patients with MDA5-positive DM were more likely to present with myriad cutaneous manifestations, including Raynaud syndrome (P <.0001), cutaneous ulcerations (P =.013), mechanic hands (P =.0164), palmar papules (P =.004), oral ulcers (P =.024), and alopecia (P =.027).
Regarding systemic manifestations, the MDA5-positive group was more likely to experience joint and pulmonary involvement. Specifically, patients with MDA5 autoantibodies were more likely to report shortness of breath and to present with interstitial lung disease on pulmonary imaging (both P <.0001). Pulmonary function and diffusion capacity for carbon monoxide were significantly reduced in patients with MDA5-positive DM (P <.0001). Dysphagia was also significantly more common in the MDA5-positive group compared with the MDA5-negative group (P =.0029).
A total of 42 skin biopsies were available for 22 patients, primarily taken from the chest and back. Patients with MDA5-positive DM were more likely to present with vasculopathy on biopsy (P =.005). No other significant histopathologic differences were observed between groups.
Results from this study confirmed certain clinical and histopathologic features associated with MDA5 seropositivity. In addition, new associations were identified, including the association between MDA5 autoantibodies and Raynaud syndrome. The use of commercial testing to determine MDA5 status may be as effective as using research-based assays.
Study limitations included the small study cohort and retrospective design. The authors also noted the inherent accuracy limitations in MDA-5 autoantibody assays, and advised that clinicians should not depend on them for patient management.
“We…found that clinical features classically associated with MDA-5 positive DM, as determined by research-based testing, tend to hold true when MDA-5 seropositivity status is determined by commercially available testing,” the researchers concluded.
Shakshouk H, Deschaine MA, Wetter DA, Drage LA, Ernste FC, Lehman JS. Clinical and histopathological features of adult patients with dermatomyositis and MDA5 autoantibody seropositivity status, as determined by commercial-based testing: a retrospective, single-institution comparative cohort study. Clin Exp Dermatol. Published online August 3, 2021. doi:10.1111/ced.14870