Pulmonary alveolar proteinosis (PAP) was first described in 1958 as an uncommon disorder in adults characterized by the accumulation of lipoproteinaceous material within alveoli . The prognosis was highly variable, and for over three decades the pathophysiology and treatment of this disease remained a mystery. With recent 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 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 .
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 "Clinical manifestations and etiology of pulmonary alveolar proteinosis in adults" and "Diagnosis and treatment of pulmonary alveolar proteinosis in adults".)
ETIOLOGY AND PATHOGENESIS
Four forms of pulmonary alveolar proteinosis (PAP) are recognized in children: congenital, acquired, secondary, and idiopathic.
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 different from the autoimmune (classic) form of PAP. (See 'Histopathology' below.)