Pediatric Alveolar Proteinosis

Updated: Dec 21, 2015
  • Author: Danielle M Goetz, MD; Chief Editor: Girish D Sharma, MD, FCCP, FAAP  more...
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Overview

Background

Pulmonary alveolar proteinosis (PAP) is an extremely rare cause of respiratory failure in the pediatric age group. PAP is characterized by intra-alveolar accumulation of surfactant, namely lipid and proteinaceous material that is periodic acid-Schiff (PAS) positive when visualized on light microscopy. [1, 2] The disease is not associated with inflammation, and lung architecture is typically preserved. The clinical course of PAP varies and ranges from respiratory failure and death to spontaneous resolution. [2]

Three clinically distinct forms of PAP have been described: autoimmune (primary or idiopathic), secondary, and genetic (congenital). [3, 4, 5] Genetic PAP is seen more commonly in children, while adult forms are usually autoimmune. [1, 3, 6, 7, 8] The 3 distinct types of PAP differ in respect to etiology, clinical course, therapy, and outcome. [1, 9, 10]

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Pathophysiology

The alveolar airspaces are filled with a dense proteinaceous-lipid fluid mix, which is thought to occur secondary to impaired clearance of surfactant by alveolar macrophages. [7, 11, 12] Surfactant production, secretion, and reuptake are normal, while surfactant catabolism in alveolar macrophages is impaired. [13] This surfactant-derived alveolar fluid may cause increased work of breathing, a diminished surface area for gas diffusion, and, ultimately, respiratory failure. [11] The pulmonary interstitium and airways are relatively spared.

Secondary iatrogenic lung damage may occur in the congenital form as a consequence of the required high levels of ventilator support and high-inspired oxygen concentrations. [14, 15] Pulmonary macrophage dysfunction occurs, resulting in increased risk of superinfection [13, 16, 17]

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Epidemiology

Frequency

International

PAP is extremely rare. In a 2002 report, at least 410 cases in the literature were identified. [18] The estimated annual incidence was 0.36, and the prevalence was 3.76 cases per million population worldwide.

A 2002 French retrospective study reported 41 patients, while a 2008 Japanese study reported 248 patients. [19]

Mortality/Morbidity

In neonates with congenital alveolar proteinosis (CAP), the mortality rate associated with conventional therapy is 100%. [11, 14] Lung transplantation improves survival.

In a retrospective analysis of 343 cases of acquired pulmonary alveolar proteinosis, the 5-year survival rate was 75%. [18] The same retrospective analysis estimated the 5-year survival rate for children younger than 5 years to be 14% ±13%, with only one of 7 young children surviving beyond 10 months. Children with late-onset disease appear to have the best likelihood for survival, but they generally require treatment with repeated lung lavage. [18]

Many children have prolonged oxygen dependence and other symptoms of respiratory compromise, including dyspnea, chronic cough, and failure to gain weight in the absence of recurrent PAP. [18]

Race

No race predilection is reported in children or adults.

Sex

Most patients with acquired PAP are men (male-to-female ratio of 2.65:1), and 56-72% have a history of smoking. [1, 12, 18]

No male predominance is observed among nonsmokers with PAP; this observation suggests that the overall male predominance is secondary to a more common use of tobacco by men than by women. [18]

Age

More than 90% of all cases of PAP are the autoimmune type. The median age at the time of diagnosis is between 39 and 51 years. [1, 12, 18]

The age distribution of PAP in children is unknown.

The congenital form occurs shortly after birth. [11, 14, 20]

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