To investigate the prevalence, clinical characteristics, and prognostic impact of early-onset infections strictly occurring prior to immunosuppressive therapy in patients with anti–melanoma differentiation–associated gene 5 antibody–positive dermatomyositis (anti-MDA5⁺ DM), and to identify baseline risk factors to guide early management.

From a total cohort of 177 anti-MDA5⁺ DM patients, we retrospectively analyzed a rigorously selected cohort of 43 patients defined as immunosuppression-naïve (disease duration ≤3 months, no prior immunosuppressants, and minimal glucocorticoids ≤5 days and ≤200 mg prednisone-equivalent). Early-onset infection was defined as a microbiologically confirmed or highly suspected active infection documented within this timeframe. We used logistic regression to identify infection risk factors and multivariate logistic proportional hazards models to assess the prognostic impact on one-year overall survival, adjusting for known clinical confounders.

Within this strictly immunosuppression‑naïve cohort, 18 of 43 patients (41.9%) had microbiologically confirmed infections at the time of diagnosis, revealing a strikingly high infection burden even before any immunosuppressive therapy was initiated .The infection was predominantly located in the respiratory tract (94.4%) and, critically, polymicrobial infection was identified in 44.4% of cases, frequently involving non-viral pathogens such as Gram-negative bacteria and fungi. Infection was independently predicted by baseline hypoalbuminemia  (HR = 0.746, 95% CI: 0.561–0.992, p = 0.044). Notably, early infection was not associated with the incidence of rapidly progressive interstitial lung disease (RP-ILD). However, early infection had a profound impact on overall survival. The 1-year all-cause mortality rate was significantly higher in the infected group compared to the non-infected group (66.67% vs. 24.00%, p = 0.011, Table 1). Kaplan–Meier analysis further confirmed the prognostic impact of infection, showing a significantly lower 1-year survival rate in infected patients (HR=0.274, 95% CI: 0.104–0.720, p = 0.0031) .

Early-onset infection is common in immunosuppression-naïve anti-MDA5⁺ DM, suggesting that the underlying disease process itself creates a state of high infectious susceptibility. These findings underscore the need for systematic infection screening, aggressive pathogen surveillance, nutritional optimization, and timely anti-infective interventions as integral components of initial management.