(1130) Drug Versus Disease: A Unique Case of Pulmonary Alveolar Proteinosis

Introduction: Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease caused by surfactant accumulation in alveoli. PAP can be autoimmune, hereditary, or secondary to hematologic malignancies and medications. We present a 59-year-old male diagnosed with PAP with underlying polycythemia vera treated with ruxolitinib.

Description: A 59-year-old male with polycythemia vera (PV) initially presented to an outpatient pulmonology clinic for evaluation of progressive exertional dyspnea over nine months. Symptoms began after initiating hydroxyurea, but his dyspnea resolved after this was switched to ruxolitinib. Unfortunately, his symptoms returned following escalating doses, so this medication was subsequently weaned. Cardiac evaluation, chest X-ray (CXR), ventilation/perfusion scan, and pulmonary function testing (PFT) were unremarkable at that time. He was restarted on ruxolitinib, which he continued for 1.5 years without acute issues. However, he subsequently began to experience worsening dyspnea and rib pain. CXR showed diffuse bronchial thickening, and PFT revealed mildly reduced diffusion capacity. Computed tomography (CT) chest showed diffuse bilateral patchy ground glass opacities with a “crazy paving appearance.” Bronchoscopy with transbronchial biopsy showed strongly positive periodic acid-Schiff (PAS) staining, suggesting PAP. Ruxolitinib was discontinued following the diagnosis, but he continued to have dyspnea.

Discussion: In our case, the possible underlying etiologies for PAP are ruxolitinib use, PV, and autoimmune. Although his symptoms appeared to correlate within several months of ruxolitinib initiation, which typically is the course, we did not find any significant improvement in his symptoms following discontinuation of the drug (1). PV has been described in the literature as associated with PAP (2). Autoimmune etiology is to be ruled out; anti-GM-CSF is still pending. He has no family history which likely excludes the hereditary form. It is hypothesized that PV and ruxolitinib have a synergistic effect in developing PAP or can aggravate underlying autoimmune pathology. To our knowledge, we have not seen any reported cases so far with our suspected hypothesis. We need further studies to identify this combination as a possible etiology and its effect on the disease course.