Pulmonary Alveolar Proteinosis

Abstract

Pulmonary alveolar proteinosis is a rare clinical syndrome that was first described in 1958. Subsequently, over 240 case reports and small series have described at least 410 cases in the literature. Characterized by the alveolar accumulation of surfactant components with minimal interstitial inflammation or fibrosis, pulmonary alveolar proteinosis has a variable clinical course ranging from spontaneous resolution to death with pneumonia or respiratory failure. The most effective proven treatment--whole lung lavage--was described soon after the first recognition of this disease. In the last 8 years, there has been rapid progress toward elucidation of the molecular mechanisms underlying both the congenital and acquired forms of pulmonary alveolar proteinosis, following serendipitous discoveries in gene-targeted mice lacking granulocyte-macrophage colony-stimulating factor (GM-CSF). Impairment of surfactant clearance by alveolar macrophages as a result of inhibition of the action of GM-CSF by blocking autoantibodies may underlie many acquired cases, whereas congenital disease is most commonly attributable to mutations in surfactant protein genes but may also be caused by GM-CSF receptor defects. Therapy with GM-CSF has shown promise in approximately half of those acquired cases treated, but it is unsuccessful in congenital forms of the disease, consistent with the known differences in disease pathogenesis.

Hemophagocytic lymphohistiocytosis and pulmonary alveolar proteinosis in a 13-month-old boy with lysinuric protein intolerance

“…These findings were consistent with a diagnosis of PAP, which is a syndrome characterized by defective macrophages and the accumulation of surfactant leading to impaired oxygenation, and respiratory distress. [12] The patient's clinical presentation, in addition to the histopathological findings, were consistent with a primary cause of HLH and genetic testing was ordered. Next Generation Sequencing of an HLH panel of genes identified compound heterozygote frameshift and splice site mutations in the SLC7A7 gene, which occur in patients with LPI.…”

Pulmonary alveolar proteinosis - a crazy presentation of dyspnea

“…Depending on the severity, gas exchange is impaired resulting in a reduced diffusion capacity leading to dyspnea, cough, fatigue and weight loss, and subsequently respiratory failure. The median age at presentation is 39 years with a male predomination (male:female ratio 2.7:1.0) [2]. Approximately 90% of the PAP cases are associated with an autoimmune production of antibodies against GM-CSF [3].…”

“…The symptoms are often vague and the onset is often slowly developing, and thereby delaying the diagnosis. The clinical presentation of dyspnea, cough, and weight loss is similar to other respiratory diseases, but symptoms and clinical presentation are variable [2,3]. One third of PAP patients are asymptomatic, while others unfortunately suffer from fatal respiratory failure.…”

“…Both symptoms and prognosis are variable ranging from spontaneous remission to terminal respiratory2 failure [2]. The majority of cases are of autoimmune origin, but PAP also occurs as a congenital disease or secondary to inhalational exposures e.g.…”

Pulmonary alveolar proteinosis in a marble worker

“…In 10-50% of cases of patients suffering from this disease they recover spontaneously [1,14,15], and sometimes the disease progresses with relapses and remissions. The treatment varies depending on the subgroup and the severity of the disease.…”