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A 47-Year Old Woman With Rapidly Progressive Hypoxemic Respiratory Failure. CASE PRESENTATION: A 47-year-old Hispanic woman presented to a pulmonology clinic with 2 weeks of cough productive of white sputum and worsening dyspnea on exertion, requiring increasing supplemental oxygen. In addition, she reported fatigue, night sweats, diffuse myalgias, and extremity weakness. She denied hemoptysis, fevers, chills, weight loss, or rash. Her medical history is significant for undifferentiated rapidly progressive hypoxemic respiratory failure 2 years before her current presentation. At that time, she presented to the ED with 3 weeks of progressive shortness of breath and cough. Chest CT imaging showed bilateral infiltrates concerning for infection, and she was treated empirically for community-acquired pneumonia. She developed worsening hypoxemic respiratory failure despite broadening of her antibiotics and subsequently required intubation. Her course was further complicated by pulseless electrical activity arrest with return of spontaneous circulation and development of shock requiring multiple vasopressors. Because of difficulty with oxygenation, she was referred to our center for extracorporeal membrane oxygenation evaluation and was ultimately started on venous-arterial extracorporeal membrane oxygenation. Bronchoscopy with BAL was negative for bacterial, viral, and fungal origins, and initial autoimmune evaluation (antinuclear antibody and rheumatoid factor) was negative, except an elevated creatine kinase (CK) to 3,000. Her course was complicated by heparin-induced thrombocytopenia, and as a result she suffered limb ischemia requiring amputation of her left lower extremity. Elevated CK at that time was attributed to compartment syndrome before amputation. The patient recovered clinically with supportive care and was ultimately discharged on 2 L supplemental oxygen, with a diagnosis of acute respiratory failure of unclear origin. The patient had stability in her clinical symptoms until this current presentation.