Pulmonary Alveolar Proteinosis
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Direct answer
Pulmonary alveolar proteinosis is a rare disorder in which surfactant-derived lipoproteinaceous material accumulates within the alveoli, and most adult cases are autoimmune, caused by neutralising antibodies against granulocyte-macrophage colony-stimulating factor. HRCT typically shows bilateral ground-glass opacities with superimposed interlobular septal thickening, the crazy-paving pattern. Whole-lung lavage is the definitive treatment for symptomatic patients, while inhaled GM-CSF is an emerging option in selected cases.
What you must remember
- Autoimmune disease: anti-GM-CSF autoantibodies impair alveolar macrophage clearance of surfactant and account for most adult cases.
- Secondary forms: haematological malignancy, silica or aluminium dust exposure and severe infections, notably Nocardia and mycobacterial disease, can produce the same picture.
- Crazy-paving pattern: ground-glass opacities with septal thickening; the differential includes Pneumocystis pneumonia, pulmonary oedema and alveolar haemorrhage.
- BAL fluid: milky appearance with periodic acid-Schiff positive granular material, which is both diagnostic and therapeutic.
- Whole-lung lavage: performed under general anaesthesia with a double-lumen tube, one lung at a time, with warm saline.
- Infection risk: nocardiosis, aspergillosis and mycobacterial disease are common complications and should be excluded before lavage or immunosuppression.
- Steroids: corticosteroids are not effective in alveolar proteinosis and may increase opportunistic infection.
A diagnostic route for a breathless adult
A 38-year-old man with eight months of progressive exertional breathlessness and a saturation of 91 percent on room air shows the workup in order.
- Image the chest: HRCT shows bilateral crazy-paving, which is suggestive but not specific.
- Sample the alveoli: Bronchoscopy with lavage returns milky fluid rich in periodic acid-Schiff positive material.
- Screen for secondary causes: Before accepting the diagnosis, a full blood count and LDH exclude haematological malignancy, a detailed occupational history checks for silica exposure, and immunosuppression that might explain opportunistic infection is looked for.
- Confirm autoimmunity: Serum anti-GM-CSF testing, available in specialist centres, confirms an autoimmune basis.
- Plan lavage safely: Because he is symptomatic and hypoxic, whole-lung lavage is planned after infection screening, and corticosteroids are withheld.
- Track the response: Follow-up tracks saturation and symptoms, and repeat lavage is considered if breathlessness or the oxygen requirement worsens again. Inhaled granulocyte-macrophage colony-stimulating factor is discussed in specialist centres where it is available.
Where the exam tries to catch you
Examiners return to a few traps in alveolar proteinosis questions.
- Trap: Treating crazy-paving on HRCT as the diagnosis. Correct: Crazy-paving is a pattern, not a diagnosis, and bronchoalveolar lavage or biopsy is what confirms alveolar proteinosis.
- Trap: Giving steroids because the picture resembles interstitial disease. Correct: Steroids seem logical for interstitial disease but are wrong here and risk opportunistic infection.
- Trap: Stopping at an autoimmune label in a stem with lymphoma or silica exposure. Correct: The answer turns to the underlying cause rather than an autoantibody.
In an Indian context, stone quarrying and silica exposure are common occupational settings, so a silica history should prompt a search for both silicosis and secondary proteinosis.
Frequently asked questions
What HRCT pattern is characteristic of pulmonary alveolar proteinosis?
The crazy-paving pattern on HRCT is characteristic of pulmonary alveolar proteinosis, showing ground-glass opacities with superimposed interlobular septal thickening. The pattern is not specific, so bronchoalveolar lavage or biopsy is needed to confirm the diagnosis.
What is the autoantibody in autoimmune pulmonary alveolar proteinosis?
Neutralising autoantibodies against granulocyte-macrophage colony-stimulating factor, abbreviated anti-GM-CSF, cause most adult pulmonary alveolar proteinosis. They impair alveolar macrophage clearance of surfactant, leading to progressive alveolar filling.
Why is whole-lung lavage used in pulmonary alveolar proteinosis?
Whole-lung lavage physically removes the accumulated proteinaceous material from the alveoli and is the definitive treatment for symptomatic disease. It is performed under general anaesthesia with a double-lumen tube, treating one lung at a time.
Why should corticosteroids be avoided in pulmonary alveolar proteinosis?
Corticosteroids are not effective in alveolar proteinosis and may increase the risk of opportunistic infections, which are already a major complication. Infection, including nocardiosis and mycobacterial disease, should be excluded before any immunosuppression.