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
- 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.
Elevated levels of lactate dehydrogenase (LDH) and GM-CSF antibodies (in idiopathic forms) are also encountered 4.
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.
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
- reminiscent of a miliary pattern
- more common in children
- extensive diffuse consolidation
- reticulonodular opacities
Pleural effusions, cardiomegaly and lymphadenopathy usually not features of uncomplicated PAP.
Two main features characterise the appearance of pulmonary alveolar proteinosis on HRCT:
- smooth thickening of interlobular and intralobular septal lines, and
- 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.
Treatment and prognosis
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 sp. 1
- pulmonary fibrosis (occurs in ≈30%)
Imaging differential considerations for specific patterns include:
- 1. Godwin JD, Müller NL, Takasugi JE. Pulmonary alveolar proteinosis: CT findings. Radiology. 1988;169 (3): 609-13. Radiology (abstract) - Pubmed citation
- 2. Holbert JM, Costello P, Li W et-al. CT features of pulmonary alveolar proteinosis. AJR Am J Roentgenol. 2001;176 (5): 1287-94. AJR Am J Roentgenol (full text) - Pubmed citation
- 3. Zimmer WE, Chew FS. Pulmonary alveolar proteinosis. AJR Am J Roentgenol. 1993;161 (1): 26. AJR Am J Roentgenol (citation) - Pubmed citation
- 4. Frazier AA, Franks TJ, Cooke EO et-al. From the archives of the AFIP: pulmonary alveolar proteinosis. Radiographics. 28 (3): 883-99. doi:10.1148/rg.283075219 - Pubmed citation
- 5. Miller PA, Ravin CE, Smith GJ et-al. Pulmonary alveolar proteinosis with interstitial involvement. AJR Am J Roentgenol. 1981;137 (5): 1069-71. AJR Am J Roentgenol (citation) - Pubmed citation
- 6. McCook TA, Kirks DR, Merten DF et-al. Pulmonary alveolar proteinosis in children. AJR Am J Roentgenol. 1981;137 (5): 1023-7. AJR Am J Roentgenol (abstract) - Pubmed citation
- 7. Naidich DP, Srichai MB, Krinsky GA. Computed tomography and magnetic resonance of the thorax. Lippincott Williams & Wilkins. (2007) ISBN:0781757657. Read it at Google Books - Find it at Amazon
- 8. Webb WR, Higgins CB. Thoracic Imaging. Lippincott Williams & Wilkins. (2010) ISBN:1605479764. Read it at Google Books - Find it at Amazon
- 9. Aster JC. Robbins Basic Pathology: with STUDENT CONSULT Online Access, 9e. Saunders. ISBN:1437717810. Read it at Google Books - Find it at Amazon
- 10. Webb WR, Muller NL, Naidich DP. High-resolution CT of the lung. Lippincott Williams & Wilkins. ISBN:0781769094. Read it at Google Books - Find it at Amazon