The dark side of pulmonary alveolar proteinosis

Abstract

Background: Pulmonary alveolar proteinosis (PAP) has an unpredictable clinical course. Although usually benign, an association with pulmonary fibrosis is described in literature, with troubling therapeutic and prognostic implications.

Clinical case: We report the case of a patient affected by autoimmune PAP who developed pleuro-parenchymal fibroelastosis (PPFE) after 6 years of disease and underwent bilateral lung transplantation due to end stage respiratory failure.

Conclusion: Punctual descriptions of pulmonary fibrosis in PAP are still lacking and no predictors of fibrotic evolution of PAP are known. It is necessary to ensure a strict follow up in order to promptly recognize signs of fibrotic evolution and early refer patients with evolutive disease to lung transplant center. Moreover, an extended genetic analysis by targeted next-generation sequencing could provide high-resolution information that may allow the identification of susceptible patients in a pre-fibrotic stage of disease.

Figure 1

Axial high resolution computerized tomography scans of the chest at different time-points. A, B and C) images show the typical PAP appearance characterized by bilateral ground glass opacities with patchy distribution and thickened interlobar septa creating a “crazy paving” pattern. D, E and F) images show the reduced extent of the ground glass opacities after treatment with rGM-CSF; early signs of possible fibrotic evolution can be appreciated at the apical region of the left lung. G, H, and I) images correspond to the late phases of the disease, and show the features of PPFE, characterized by fibrotic subpleural thickening involving lung apices, upper lobes and apical segments of the lower lobes, a subsequent hypoexpansion of the involved pulmonary parenchyma and traction bronchiectasis and bronchiolectasis with distortion of the affected bronchial branches.

Figure 2

EE x 2. Prominent subpleural fibrosis (ARROW) with an abrupt transition to adjacent normal lung parenchyma (ARROWHEAD). A classic thickened visceral pleural feature. No fibroblastic foci were observed and only scanty inflammation is present. An area of giant cell reaction (blue circle) with cholesterol needles is present in the transition area between fibro-elastosis and normal parenchyma.

Figure 3

High-resolution axial computed tomography scans of the chest after lung transplantation. A, B, and C) images show the relapse of circumscribed areas of ground glass opacities, sharply demarcated by areas of unaffected parenchyma, one year after double lung transplant. D, E, and F) images refer to one year after the introduction of statins. They exhibit the overall reduction in extent of the multiple ground-glass opacities, especially in the basal segments of the right lower lobe.