Anti- Melanoma Differentiation-Associated Gene 5 Antibody Positive Dermatomyositis: Recent Progress in Pathophysiology and Treatment

Abstract Purpose of Review Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a rare systemic autoimmune disease characterized by a clinically amyopathic presentation and a high-risk association with rapidly progressive interstitial lung disease. Although frequently fatal, the underlying mechanisms remain incompletely understood. This review provides a comprehensive summary of recent advances in research on MDA5-DM, aiming to deepen our understanding of its pathogenic mechanisms and to accelerate future basic research that will contribute to the development of novel therapeutic strategies. Recent Findings Recent advancements have shed light on various aspects of this disease, including genetic and environmental factors contributing to disease susceptibility and the immunopathological processes and cytokine networks. Furthermore, significant progress has been made in understanding the pathogenicity, epitope recognition, and production mechanisms of anti-MDA5 antibodies, which have long been subjects of debate. On the therapeutic front, in addition to the conventional triple-combination regimen, emerging efficacy of JAK inhibitors and rituximab has been recognized. The development of biologics targeting lymphocytes offers additional hope for advancing therapeutic options. Summary Advancing our understanding of the latest pathophysiological mechanisms of MDA5-DM is expected to pave the way for the development of safer and more effective therapeutic strategies.