Pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a lung disease characterised by an abnormal intra-alveolar accumulation of surfactant-like lipoproteinaceous material.

On imaging, although not pathognomonic, it is classically described by the presence of a crazy paving pattern on CT.

Pulmonary alveolar proteinosis is rare and usually presents in young and middle-aged adults (20-50 years of age) 6-7. Smoking is strongly associated with the condition, and in smokers, there is a recognised male predilection (M:F of  ~2:1) 6, which is absent in non-smoking patients 4.

When the disease presents before the age of 1 year, there is an association with thymic alymphoplasia 6.

Clinical presentation is usually with nonspecific respiratory symptoms such as dyspnoea or minimally productive cough. Approximately one-third of patients may be asymptomatic. In children, the presentation is often less clearly respiratory in nature, with diarrhoea, vomiting, failure to thrive and even cyanosis being more common 6. The presentation may also be due to superimposing opportunistic infections (see below). Signs include crackles on auscultation, clubbing or cyanosis.

There is deposition of PAS +ve lipoproteinacous material in alveoli as a result of impaired turnover of surfactant. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been implicated in the pathogenesis 4. The disease can be divided into three broad categories:

  • idiopathic: 90% of cases
    • also termed adult or acquired
    • autoimmune with IgG antibodies to GM-CSF
  • secondary: 5-10% presents in individuals with other precipitating illness
  • congenital: 2%
    • presents in the neonatal period in term babies
    • poor prognosis if left untreated (lung transplantation)
    • may be distinct entity also know as chronic pneumonitis of infancy
    • due to a mutation in genes encoding SP-B, SP-C, or GM-CSF receptor 8,9

Although imaging, bronchial lavage and sputum examination can strongly suggest the diagnosis, lung biopsy is sometimes required 4,6.

Markers

Elevated levels of lactate dehydrogenase (LDH) and GM-CSF antibodies (in idiopathic forms) are also encountered 4.

Complications

A number of opportunistic pathogens may cause superimposed pneumonia in patients with PAP. Offending agents include 4

  • Aspergillus spp
  • Candida spp
  • Cryptococcus neoformans
  • cytomegalovirus (CMV)
  • Histoplasma capsulatum
  • Mycobacterium (tuberculous and nontuberculous)
  • Nocardia spp
  • Pneumocystis spp
  • Streptococcus pneumoniae

As a general rule, radiographic features are often much more severe than the clinical presentation would suggest 6.

Plain radiograph

Initial plain chest radiographs can be inconclusive 2. Later findings can be variable including 4,6:

  • bat wing pulmonary opacities:
    • bilateral central symmetrical lung opacities with relative apical and costophrenic angle sparing
    • reminiscent of pulmonary oedema
    • most common appearance in adults
  • diffuse small pulmonary opacities
  • extensive diffuse consolidation
  • reticulonodular opacities

Pleural effusions, cardiomegaly and lymphadenopathy usually not features of uncomplicated PAP.

HRCT

Two main features characterise the appearance of pulmonary alveolar proteinosis on HRCT: 

  1. smooth thickening of interlobular and intralobular septal lines, and
  2. ground glass opacities

The combination of these two features results in what is termed crazy paving pattern, which although a highly characteristic feature is unfortunately not pathognomonic. Additionally, pulmonary consolidation or later in the disease pulmonary fibrosis may be evident.

Lung changes are of either patchy or geographic distribution and may have a slight lower lobe predilection 2.

Ground glass opacity typically resolves after therapeutic bronchoalveolar lavage, although septal thickening may persist10.

Bronchoalveolar (whole lung) lavage is used therapeutically to remove alveolar material, although its role in children is less certain 6.

Prognosis is variable ranging from improvement (with treatment) to a chronic and terminal course. A 30% 2-year mortality has been reported in adults prior to routine use of bronchoalveolar lavage 6. The 5-year mortality has now been reduced to approximately 5% 4. In children, that figure is much higher due to the reduced efficacy of bronchoalveolar lavage 6.

Although double lung transplants have been performed PAP may still recur 4.

  • superimposed infection: especially with Nocardia asteriodes sp1
  • pulmonary fibrosis (occurs in ≈30%)

Imaging differential considerations for specific patterns include:

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Article Information

rID: 8206
System: Chest
Section: Pathology
Synonyms or Alternate Spellings:
  • Alveolar proteinosis
  • Pulmonary alveolar proteinosis (PAP)
  • PAP

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Cases and Figures

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    Alveolar Proteino...
    Case 1: acinar opacities mimicking a miliary pattern
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    Alveolar Proteino...
    Case 1: HRCT with crazy paving
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