Autoimmune pulmonary alveolar proteinosis: clinical course and diagnostic criteria

Pulmonary alveolar proteinosis (PAP) is caused by accumulation of surfactant components in the alveoli and terminal airways. All forms of PAP are caused by insufficient surfactant clearance by alveolar macrophages. Autoimmune PAP, a rare, antibody-mediated disease, that compromises 90% of cases of PAP, is causes by IgG autoantibodies that block GM-CSF effect, a crucial step for macrophage maturation. Alveolar filling may progress to respiratory insufficiency, but the course of the disease is variable. Patients usually complain of dyspnea, mainly with exertion, and cough. Chest CT shows highly suggestive ground grass opacification crossed by heavy septal lines, leading to the typical "crazy paving" appearance. Bronchoalveolar lavage reveals "milky" fluid, containing semisolid remnants of surfactant components, packed as lamellar bodies. The surfactant appears granular and pink on PAS staining, and lung architecture is preserved. These cytological and pathological characteristics are diagnostic for PAP. In addition, a high titer of IgG anti GM-CSF autoantibodies is highly sensitive and specific for the diagnosis. The trigger for antibodies formation and their role (if any) in regulation GM-CSF activity in the normal state are unknown. Based on the specificity of these characteristics we suggest a structured framework for the diagnosis of Autoimmune PAP. Lung lavage with a large volume of saline is the standard therapy, and is effective in most patients. However, immune-modulatory therapy, by either supplying exogenous GM-CSF, or by inhibiting the CD20+ antibody forming cells, with Rituximab, is also effective in many patients. The precise role of each therapy, alone or in combination, should be systematically studied.