Abstract Introduction Antisynthetase syndrome (ASS) is a rare autoimmune disorder defined by myositis-specific antibodies and commonly associated with severe interstitial lung disease (ILD). Rapidly progressive ILD poses significant diagnostic and therapeutic challenges, especially when clinical features overlap with infection, drug-induced pneumonitis, and other pulmonary pathologies. Timely differentiation is crucial, as immunosuppression may worsen occult infection. Case Description A woman in her mid-30s with no significant prior lung disease presented with a multi-week history of progressive dyspnea and was admitted for hypoxemic respiratory failure. She had multiple recent hospitalizations for pneumonia and required high-flow oxygen and empiric antibiotics. Imaging revealed patchy bilateral infiltrates and CT showed progressive organizing pneumonia. Her clinical differential included recurrent bacterial pneumonia, aspiration, vasculitis, drug- or eosinophilic pneumonitis, and connective tissue disease-associated ILD.Extensive serological and microbiological work-up disclosed a positive antisynthetase antibody (Jo-1), PR3, and ANA, with elevated inflammatory markers; blood and sputum cultures were negative for pathogens. Initial bronchoscopy was non-diagnostic, showing only inflammatory cells, and post-bronchoscopy, worsening hypoxemia necessitated ICU transfer and pulse-dose methylprednisolone. Progressively severe ILD was suspected, and multidisciplinary input led to an open lung biopsy. Peri-biopsy, the patient suffered transient hemodynamic collapse due to hyperkalemia and required pressor support and mechanical ventilation. Further management in the ICU involved high-dose corticosteroids, plasma exchange (PLEX), and intravenous immunoglobulin for presumed ASS-related ILD, with infectious disease consultants guiding judicious antimicrobial stewardship and ruling out pneumonia or CMV pneumonitis by molecular testing.Despite two weeks of escalating immunosuppression—including rituximab—the patient’s course was marked by persistent ventilator dependence, myopathy, and recurrent infections. Tracheostomy was performed, and after stabilization, the patient was discharged to long-term acute care. The working diagnosis was antisynthetase syndrome with organizing pneumonia pattern, meeting Connors criteria for ASS and rapid ILD. Discussion This case highlights the diagnostic complexity of rapidly progressive ILD in the context of autoimmune myopathy, underscoring the essential role of early multidisciplinary collaboration. It also illustrates the critical interplay between controlling immune-mediated lung injury and mitigating infectious complications. The patient’s outcome demonstrates that in ASS, integrating rheumatology, pulmonology, infectious disease, and critical care can guide clinical reasoning and optimize management strategies. Timely exclusion of infection before initiating immunosuppression remains paramount in improving morbidity and mortality in severe autoimmune lung disease. This abstract is funded by: None
A Onyemeh (Fri,) studied this question.