Abstract Introduction Interstitial lung disease (ILD) has been increasingly associated with melanoma differentiation-associated gene 5 (MDA-5) autoantibodies. Although classically linked to dermatomyositis, pulmonary manifestations can precede or occur without muscular involvement. MDA-5-positive ILD is often rapidly progressive and carries a poor prognosis. We report a case of MDA-5-associated ILD presenting with fulminant respiratory decline. Case A 72-year-old man presented with generalized weakness and unintentional weight loss following a trip to the Philippines, where he developed a gastrointestinal illness. On admission, he was febrile, tachycardic, and tachypneic. Laboratory studies were unremarkable, and chest X-ray showed a left basilar opacity. A respiratory pathogen panel was negative, and he was treated empirically for community-acquired pneumonia. Despite antibiotic therapy, his respiratory status worsened. Chest CT revealed patchy bilateral opacities consistent with multifocal pneumonia. With continued antimicrobials, he improved and was discharged home on supplemental oxygen. One week later, he returned with worsening dyspnea and hypoxemia refractory to oxygen therapy, requiring a non-rebreather mask. Repeat CT demonstrated progression of bilateral, multilobar consolidations. Broad-spectrum antibiotics were restarted, but infectious workup again remained negative. The hospital’s standardized autoimmune panel was unrevealing; however, Rheumatology ordered an extended myositis panel. Due to ongoing respiratory decline, pulse-dose corticosteroids were initiated. Despite aggressive immunosuppression, the patient’s respiratory failure worsened, necessitating intubation and ICU admission. The extended myositis panel subsequently returned positive for MDA-5 antibodies. Unfortunately, his condition continued to deteriorate, and he died from progressive respiratory failure. Discussion Following multidisciplinary review, it was postulated that his prior viral infection may have triggered an autoimmune response, resulting in MDA-5-associated ILD. This case highlights the diagnostic challenge of MDA-5-associated ILD, which can occur without dermatologic or myopathic findings. Clinicians should maintain high suspicion for autoimmune etiologies in patients with rapidly progressive hypoxemia unresponsive to antibiotics. When imaging suggests ILD, early involvement of Pulmonology, Rheumatology, and Infectious Disease is critical. A comprehensive workup—including autoimmune, bacterial, and fungal studies—should be initiated promptly. If clinical suspicion is high, early immunosuppressive therapy may be warranted even before confirmatory results. Bronchoscopy may aid diagnosis but is often precluded by patient instability. Despite early recognition, outcomes remain poor. Emerging evidence suggests that patients with lower MDA-5 antibody titers may benefit from lung transplantation, warranting early evaluation to optimize long-term survival. This abstract is funded by: None
Weit et al. (Fri,) studied this question.