Pulmonary alveolar proteinosis

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic "crazy paving" pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.

Figure 1.

Chest radiograph of a patient with auto-immune pulmonary alveolar proteinosis showing diffuse alveolar opacities with a peri-hilar and basal distribution.

Figure 2.

Chest computed tomography scan of a patient with auto-immune pulmonary alveolar proteinosis. Reticulations are superimposed on ground-glass opacities forming a “crazy paving” pattern with a geographic distribution: juxtaposition of healthy and sick zones. a) A horizontal section and b) a coronal section.

Figure 3.

Bronchoalveolar lavage fluid with a milky appearance in a) normal saline compared to b) pulmonary alveolar proteinosis.

Figure 4.

Periodic acid-Schiff (PAS) staining of bronchoalveolar lavage fluid with pulmonary alveolar proteinosis showing extracellular globular hyaline material homogeneously PAS positive with large, foamy macrophages containing eosinophilic granules. Magnification 400x.

Figure 5.

Ultrastructural analysis of bronchoalveolar lavage fluid with pulmonary alveolar proteinosis showing numerous lamellar bodies.

Figure 6.

Chest computed tomography (CT) scan of a patient with pulmonary alveolar proteinosis secondary to myelodysplastic syndrome. The CT scan shows ground-glass opacities and reticulations mainly in the lower zone with patchy, slightly peripheral distribution. a) A horizontal section and b) coronal section.