A35-10 Autoimmune Pulmonary Alveolar Proteinosis: An Elusive Cause of Steroid-refractory Interstitial Lung Disease

Abstract Background Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease (ILD) characterized by intra-alveolar accumulation of surfactant due to impaired clearance by dysfunctional macrophages. The clinical and radiographic overlap with other ILDs often leads to delayed or inappropriate corticosteroid therapy, which may worsen infection risk without benefit. We present an intriguing case of steroid-refractory ILD, highlighting the diagnostic challenges and the dramatic response to disease-specific therapies, including whole-lung lavage and inhaled GM-CSF. Case-presentation A 48-year-old woman with morbid obesity, pre-diabetes, and vitamin D deficiency presented with six months of progressive exertional dyspnea and resting hypoxemia (SpO2 87% on room air). Chest CT angiography demonstrated diffuse bilateral ground-glass opacities with interlobular septal thickening. Infectious and autoimmune serologies, including ANA, ANCA and RF were unrevealing. Bronchoscopy with BAL demonstrated elevated lymphocytes but was non-diagnostic. Empiric doxycycline and high-dose prednisone 60 mg daily were initiated for presumed Hypersensitivity Pneumonitis, yet the patient showed no clinical or radiographic improvement, requiring 5-6 L/min supplemental oxygen for persistent hypoxemia. A repeat bronchoscopy was pursued due to steroid-refractory disease. BAL cytology revealed granular, eosinophilic, periodic acid-Schiff (PAS)-positive material with foamy macrophages. Transbronchial biopsy confirmed alveolar filling with PAS-positive proteinaceous material, consistent with PAP. Subsequent serum testing revealed high-titer neutralizing anti-granulocyte-macrophage colony-stimulating-factor (GM-CSF) antibodies, establishing the diagnosis of autoimmune PAP (aPAP). The patient underwent therapeutic whole-lung lavage (WLL) resulting in marked improvement in oxygenation and radiographic clearing, allowing weaning off supplemental oxygen and tapering off steroids. Maintenance therapy with inhaled GM-CSF (sargramostim; Nivemyst) was initiated, resulting in sustained clinical and functional stability at six-month follow-up. Discussion This case underscores the importance of considering aPAP in patients with diffuse ground-glass opacities, septal thickening, and crazy paving patterns unresponsive to corticosteroids. Autoimmune PAP (aPAP), driven by neutralizing anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies, accounts for 90% of primary PAP. The pathognomonic BAL and biopsy findings, coupled with anti-GM-CSF antibody positivity, confirm the diagnosis. Corticosteroid monotherapy is ineffective and may increase infection risk. WLL effectively removes accumulated surfactant and improves gas exchange, while inhaled GM-CSF therapy restores macrophage function and sustains remission. Early recognition of this steroid-refractory ILD mimic prevents unnecessary immunosuppression and allows prompt initiation of disease-specific therapy, transforming a potentially progressive and disabling condition into a treatable, remission-capable disease. This abstract is funded by: none