Background: Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5⁺ DM) is significantly associated with interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD) due to poor prognosis, resulting in high mortality rates. However, the pathogenic mechanism of MDA5⁺ DM-RPILD is unclear. Although some MDA5⁺ DM patients have a chronic course of ILD, many do not develop RPILD. Therefore, the related biomarkers for the early diagnosis, disease activity monitoring, and prediction of the outcome of RPILD in MDA5⁺ DM patients should be identified. Blood-based biomarkers are minimally invasive and can be easily detected.

Methods: Recent relative studies related to blood biomarkers in PubMed were reviewed.

Results: An increasing number of studies have demonstrated that dysregulated expression of blood biomarkers related to ILD such as ferritin, Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and cytokines, and some tumor markers in MDA5⁺ DM may provide information in disease presence, activity, treatment response, and prognosis. These studies have highlighted the great potentials of blood biomarker values for MDA5⁺ DM-ILD and MDA5⁺ DM-RPILD. This review provides an overview of recent studies related to blood biomarkers, besides highlighted protein biomarkers, including antibody (anti-MDA5 IgG subclasses and anti-Ro52 antibody), genetic (exosomal microRNAs and neutrophil extracellular traps related to cell-free DNA), and immune cellular biomarkers in MDA5⁺ DM, MDA5⁺ DM-ILD, and MDA5⁺ DM-RPILD patients, hopefully elucidating the pathogenesis of MDA5⁺ DM-ILD and providing information on the early diagnosis, disease activity monitoring, and prediction of the outcome of the ILD, especially RPILD.

Conclusions: Therefore, this review may provide insight to guide treatment decisions for MDA5⁺ DM-RPILD patients and improve outcomes.