Anti-melanoma differentiation-associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) is a subtype of dermatomyositis, which characterized by a remarkably elevated risk of rapidly progressive interstitial lung disease (RP-ILD), resulting in poor prognosis. Whereas, the etiology and pathology remain unclear.

Anti-MDA5+DM is a systemic disease, which can affect various organs throughout the body, clinical manifestations are skin ulceration, rash, alopecia, mechanic’s hands, joint pain, arthritis, muscle weakness, ILD, cardiac involvement and spontaneous pneumomediastinum. ILD is one of the most common clinical manifestations of anti-MDA5+DM, RP-ILD responds poorly to currently available treatment options and is the main cause of death.

Anti-MDA5+DM patients with ILD are detectable by high-resolution computed tomography (HRCT) to detect morphological and pathological patterns of ILD, although the diagnosis of ILD patterns relies on histopathological examination. Spontaneous pneumomediastinum, ground-glass opacity, and consolidation were demonstrated to be the most significant features in HRCT findings of MDA5+DM patients with ILD. ILD patterns commonly include organizing pneumonia, non-specific interstitial pneumonia and non-specific interstitial pneumonia–organizing pneumonia overlap. A variety of prognostic factors have been found. Baseline forced vital capacity (FVC) %-based staging could be used as a simplified risk stratification system. Serum biomarkers including MDA5 antibody titers, ferritin, KL-6 levels, and peripheral lymphocyte count could evaluate the ILD severity and treatment response, as well as potential predictive value for survival. The current treatment of this disease is still largely empirical, however, patients with RP-ILD respond poorly to conventional treatments (glucocorticoids in combination with immunosuppressants) and have high mortality rates. Recent studies have shown JAK inhibitors could be beneficial for the treatment of RP-ILD in patients with anti-MDA5+DM. In addition, the prevention of infection is of great significance to improve the prognosis.

Therefore, there is an urgent need to explore the pathogenic mechanisms of anti-MDA5+DM patients with ILD and develop novel therapeutic targets and options. This Review discusses recent clinical progress and pathogenic findings of MDA5+DM-ILD.