Successful treatment of alveolar proteinosis by inhaled GM-CSF and intravenous rituximab

We report a case of successful treatment of alveolar proteinosis by a combination of inhaled GM-CSF and intravenous administration of rituximab, a monoclonal antibody directed against the B-lymphocyte antigen CD20. Pulmonary alveolar proteinosis is a chronic disorder of surfactant clearance from the alveoli due to an impaired phagocytosis of alveolar macrophages. A 49-year-old woman referred with progressive shortness of breath. Typical computed tomography of the chest visualizes geographic ground-glass opacity combined with interlobular septal thickening (crazy paving). Pulmonary function test showed severe impairment of diffusion capacity and apparent respiratory insufficiency. Therapeutic whole-lung lavage was performed several times without clinical benefit. Because of the presence of anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies, a combination of inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF 250 µg/day; every second week ), with 4 courses of intravenous infusions of rituximab (1,000 mg day 1 and 15) was given every 3 months within one year. Twelve months after the initiation of the treatment, dyspnea improved from NYHA III to NYHA I; in parallel, the DLCO, CT scan and P(A-a)O2 and alveolar-arterial oxygen tension difference in room air improved dramatically. Lung function and X-rays also improved. This case shows that the combination of inhaled GM-CSF and Rituximab could be a treatment for pulmonary alveolar proteinosis.