Distinct Phenotypes Observed in Anti-MDA5 Positive Dermatomyositis

Patients with antimelanoma differentiation-associated gene 5 antibody (anti-MDA5) dermatomyositis have a systemic syndrome that is distinct from patients without the anti-MDA5 antibody, according to study results published in Neurology.

Dermatomyositis associated with the anti-MDA5 antibody is typically characterized by a skin rash, polyarthralgia, and interstitial lung disease (ILD), but clinical signs of myositis are commonly absent. In this study, researchers aimed to explore the characteristics of patients with anti-MDA5 antibody dermatomyositis and identify subgroups with different prognoses.

The multicenter observational study included data from 37 medical centers in France between 2011 and 2017. The study cohort included 121 patients with anti-MDA5 antibody (mean age, 49 years) and 201 patients without anti-MDA5 antibody myositis.

Researchers identified 3 groups of patients with positive anti-MDA5 antibody with different prognoses. Cluster 1 included 15 patients (18.1%) who had rapidly progressive ILD. In this group, 86.7% of patients were admitted to the intensive care unit and had a high early mortality rate (80%; P <.001).

Cluster 2 included 46 patients (55.4%), a majority of whom were women and had dermato-rheumatologic symptoms, including arthralgia (82.6%; P <.01); however, skin lesions, digital necrosis, and rapidly progressive lung disease were less common. Patients in this subgroup had the best prognosis, with no early deaths documented.

Cluster 3 included 22 patients (26.5%), a majority of whom were men and had severe skin vasculopathy, Raynaud phenomenon, skin ulcers, and digital necrosis and calcinosis, along with high rates of proximal weakness. Approximately one-fifth of patients had rapidly progressive ILD. This subgroup had an intermediate prognosis, with an early mortality rate of 4.5%.

An unsupervised analysis of data from the study cohort revealed that the presence of the anti-MDA5 antibody can identify patients with myositis with distinct clinical features and prognosis.

Results indicated that dermatomyositis skin rash, skin ulcers, calcinosis, ILD, and arthralgia/arthritis were more common among patients with the anti-MDA5 antibody, and myositis was more severe among those without the anti-MDA5 antibody. Furthermore, mortality rates were higher among patients with vs without the anti-MDA5 antibody (27.3% vs 6.8%; P <.0001).

Limitations included the retrospective design of the study and potential detection bias.

“[T]hese data show that patients [with the] anti-MDA5 [antibody] are a distinct group from patients with myositis and have a systemic syndrome composed of 3 different entities with different prognoses,” concluded the researchers.

Reference

Allenbach Y, Uzunhan Y, Toquet S, et al. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases [published online, Jun 2, 2020]. Neurology. doi:10.1212/WNL.0000000000009727