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Pulmonary alveolar proteinosis in children

Manuel Silva Carmona, MD
Section Editor
George B Mallory, MD
Deputy Editor
Alison G Hoppin, MD


Pulmonary alveolar proteinosis (PAP) was first described in 1958 as an uncommon disorder in adults characterized by the accumulation of lipoproteinaceous material within alveoli [1]. The prognosis was highly variable, and for over three decades the pathophysiology and treatment of this disease remained a mystery. With developments in molecular genetics, our understanding of the pathogenesis of PAP has improved significantly. At the same time, there were case reports of atypical forms of PAP arising in neonates, infants, and children. Today there is mounting evidence that most cases of pediatric PAP result from a genetic or acquired defect in surfactant metabolism, leading to excessive accumulation of this material in air spaces [2].

The pathogenesis, clinical features, and treatment of pulmonary alveolar proteinosis in infants and children are discussed in this topic review. PAP in adults has different causes and clinical manifestations, and is discussed in separate topic reviews. (See "Causes, clinical manifestations, and diagnosis of pulmonary alveolar proteinosis in adults" and "Treatment and prognosis of pulmonary alveolar proteinosis in adults".)


Four forms of pulmonary alveolar proteinosis (PAP) are recognized in children: congenital, acquired, secondary, and idiopathic (table 1). The common characteristic is the accumulation of pulmonary surfactants in the alveolar space, which can be due to altered surfactant production, removal, or both [3]. In infants and young children, PAP is most likely to be caused by inborn errors of surfactant metabolism or immune deficiencies, whereas the vast majority of cases in adults are autoimmune.

Congenital form — The congenital form of PAP, also known as congenital alveolar proteinosis (CAP), includes inborn errors of surfactant metabolism, lysinuric protein intolerance, and mutations in the components of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor.

It is now recognized that the histopathologic manifestations of the congenital form are primarily interstitial changes, often with a relatively minor component of alveolar proteinosis, in contrast with the autoimmune (classic) form of PAP in which the alveolar proteinosis is prominent. (See 'Histopathology' below.)

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Literature review current through: Nov 2017. | This topic last updated: Dec 04, 2017.
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