B35-52 Rapidly Progressive Interstitial Lung Disease in a Young Male With Anti-Melanoma Differentiation-Associated Gene 5 (Anti-MDA5) Antibodies: A Case Report

Abstract Introduction Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies are associated with clinically amyopathic dermatomyositis (CADM), a subtype of dermatomyositis (DM) characterized by cutaneous findings without muscle involvement. CADM is rare; a retrospective study estimates the incidence rate of DM to be 9.63 per 1,000,000 people, CADM representing approximately 20 % of DM cases, with up to 60 % showing anti-MDA5 positivity. Anti-MDA5-positive CADM carries a high risk of rapidly progressive interstitial lung disease (RP-ILD), which has a poor prognosis. Among DM/CADM patients, anti-MDA5 antibodies are detected in 50-80 % of those who develop RP-ILD, with mortality approaching 50 % within six months despite aggressive immunosuppression and corticosteroid therapy. Case Description A previously healthy 32-year-old man presented in November 2024 with extensor skin lesions initially diagnosed as psoriasis and progressive dyspnea leading to hospitalization for presumed pneumonia in February 2025. Computed tomography (CT) revealed bilateral lower-lobe patchy infiltrates. He was discharged on supplemental oxygen, but his dyspnea persisted. In June 2025, rehospitalization CT showed bilateral lower-lobe consolidation and traction bronchiectasis without honeycombing. Autoimmune testing demonstrated an antinuclear antibody titer of 1:320 and a mildly elevated rheumatoid factor. Lung biopsy evaluation was deferred after spontaneous pneumomediastinum was identified. Examination showed dyspnea on speaking, low-flow oxygen requirement, basilar crackles, Gottron papules, and facial poikiloderma. Repeat CT revealed subpleural, peripheral, and basal-predominant reticular and ground-glass opacities with architectural distortion and traction bronchiectasis. Respiratory cultures grew normal flora. Rheumatology was consulted for suspected anti-MDA5-positive CADM-associated RP-ILD. The autoimmune panel was initially negative but later confirmed anti-MDA5 antibody positivity. After infection was excluded, he received pulse methylprednisolone (1 g × 3 days) followed by taper, cyclophosphamide, and tacrolimus (1 mg twice daily). On follow-up, he showed improved exercise tolerance, required oxygen only with exertion, and had stable CT findings. He was subsequently referred for lung-transplant evaluation. Discussion Establishing rare autoimmune diagnoses such as anti-MDA5 CADM is challenging, particularly when early recognition is critical for survival. Our patient developed RP-ILD months before antibody detection and was empirically treated with triple immunosuppressive therapy (high-dose corticosteroids, cyclophosphamide, and a calcineurin inhibitor), resulting in symptomatic and radiographic stabilization. Recent multicenter studies demonstrate that early “triple therapy” significantly improves survival in anti-MDA5-associated RP-ILD compared with conventional regimens. This case underscores the need for a high index of suspicion when clinical phenotype precedes serologic confirmation. Prompt initiation of immunosuppression and early lung-transplant evaluation remain vital given the disease’s high mortality. This abstract is funded by: None