Rare case of autoimmune pulmonary alveolar proteinosis with ANCA positivity

Pulmonary alveolar proteinosis (PAP) with concurrent anti-neutrophil cytoplasmic antibody (ANCA) positivity represents an exceptionally rare clinical phenomenon, the pathogenesis and management implications of which remain poorly understood. A 49-year-old woman was referred to our institution for evaluation of progressive respiratory symptoms. Two months prior to admission, she developed an intermittent cough productive of whitish sputum, followed by exertional dyspnea limiting ambulation to 400–500 m on level ground. Initial investigations revealed hypoxemic respiratory failure (PaO₂/FiO₂ 277 mmHg) and the characteristic “crazy-paving” pattern on chest computed tomography. Bronchoalveolar lavage yielded milky-white fluid with periodic acid-Schiff (PAS)-positive material, confirming the diagnosis of PAP. Notably, immunological evaluation demonstrated positive myeloperoxidase (MPO)-ANCA (20.03 RU/mL) (reference < 5 RU/mL), with perinuclear ANCA (p-ANCA) positive at a titer of 1:10 by indirect immunofluorescence, and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies, establishing a rare coexistence of autoimmune PAP with ANCA positivity. A comprehensive vasculitis workup—including serial urinalysis with microscopy, and otorhinolaryngological evaluation—revealed no evidence of subclinical vasculitis. The patient underwent successful bilateral whole lung lavage without the need for immunosuppressive therapy. At 3-month follow-up, p-ANCA remained positive (1:10) with MPO-ANCA at 14.15 RU/mL (reference < 5 RU/mL), while urinalysis and renal function remained within normal limits. At 12-month follow-up, the patient reported no dyspnea during daily activities and maintained oxygen saturation above 95% without supplemental oxygen. This case illustrates the rare association between autoimmune PAP and ANCA positivity, underscoring the importance of comprehensive immunological evaluation and individualized therapeutic approaches. Long-term surveillance is imperative, as vasculitic manifestations may emerge years after the initial PAP diagnosis.