Abstract / Summary
Background/Objectives: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody is associated with dermatomyositis/clinically amyopathic dermatomyositis and a high risk of rapidly progressive interstitial lung disease (RP-ILD). Methods: We retrospectively analyzed 34 consecutive anti-MDA5-positive patients evaluated at a tertiary Advanced Lung Disease and Lung Transplant center between 1 January 2018 and 31 December 2024. Results: Of 1720 interstitial lung disease (ILD) evaluations, 34 (2.0%) were anti-MDA5 positive (median age 51 years; 56% female). ILD was present in 85%; RP-ILD developed in 13 patients (38%). Overall mortality was 32%, with 11 of 13 deaths occurring in the RP-ILD subgroup (85% mortality). Six patients were listed for lung transplantation and three underwent transplantation; all three remained alive at last follow-up (24–49 months). Right-heart catheterization performed in 11 patients demonstrated pulmonary hypertension (PH) in the majority (64%). Inpatient presentation and elevated ferritin were associated with RP-ILD; elevated CRP and RP-ILD predicted mortality. Conclusions: We conclude that anti-MDA-5-associated ILD carries high mortality when RP-ILD develops. Early recognition, aggressive immunosuppression, systematic consideration of PH, and timely referral for lung transplantation can improve outcomes in selected patients. Routine screening for anti-MDA-5 antibodies should be considered in younger patients with new or progressive ILD.