Pulmonary alveolar proteinosis is a rare condition  and patients with this disease usually present with insidious dyspnoea that has progressed over months, sometimes with mild systemic symptoms such as low grade fever and weight loss. Image Link (NEJM)

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Usually, it has a benign course with eventual resolution. Rarely, rapid progression to respiratory failure  is seen.

Death occurs due to progressive filling of alveoli or superimposed infection.

Clinical signs are few, and minor in comparison to the radiological opacification which commences as bilateral peri-hilar feathery and nodular shadowing.     Image Link

Computarised tomography may show a ‘mosaic’ of involved and spared lobules.

The disease is characterized histologically by eosinophilic material filling the alveoli.

The material has a dense, finely granular appearance and is PAS- positive and diastase resistant.

There is relative preservation of the parenchymal architecture and no inflammatory response.

Cholesterol crystal clefts and foamy macrophages are present, the latter frequently degenerating. Image Link

Interstitial changes are initially minimal, although type-II pneumocyte hyperplasia may be present.

Pulmonary alveolar proteinosis may be heralded by a phase of endogenous lipid pneumonia ( indicated by the foamy macrophages ).

The differential diagnosis includes pneumocystis pneumonia and protein-rich edema.

The former is foamy with tiny haematoxyphil dots, the latter much more homogenous.

Both lack of granularity, acinar clefts, foamy macrophages and strong PAS positivity of alveolar proteinosis.

In case of doubt, immunohistochemistry (for pneumocystis and for surfactant apoprotein), a Gomori-Grocott stain (for pneumocystis) or electron microscopy may assist.

Electron microscopy demonstrates that the granular material is composed of large numbers of osmiophilic lamellar bodies up to 5 microns in diameter.

It resembles surfactant and stains for surfactant apoprotein.

This disease is often idiopathic. It may occurs after exposure to irritating dusts, chemicals and in immunosuppressed individuals.

Pulmonary alveolar proteinosis may be associated with dusty occupations (particularly acute high dose silica exposure) and immunosuppression (leukemia, lymphomas, their treatment and related opportunistic infections).

Animal models employing heavy dust exposure implicate overproduction of surfactant, compounded by inadequate clearance.

Cases associated with immunosuppression stain poorly for surfactant and here the material may represent cell debris.

 In children the disease may reflect compensatory oversecretion in the face of surfactant apoprotein B deficiency.

The alveolar material promotes the growth in vitro of organisms such as Nocardia asteroides and secondary nocardiosis  is a recognized complication.

Treatment is by high volume alveolar lavage.

Pulmonary alveolar proteinosis is a rare syndrome characterized by intra-alveolar accumulation of surfactant components and cellular debris, with minimal interstitial inflammation or fibrosis. The condition has a variable clinical course, from spontaneous resolution to respiratory failure and death due to disease progression or superimposed infections. The standard of care for alveolor proteinosis therapy is represented by whole lung lavage. Important discoveries have been made in the last decade with respect to disease pathogenesis and therapy of both congenital and acquired forms of the disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway has been shown to be involved in the disease pathogenesis of both acquired and congenital disease. Furthermore, anti-GM-CSF blocking autoantibodies have been found in the serum and bronchoalveolar lavage fluid and seem to interfere with the surfactant clearance by alveolar macrophages in many acquired cases. In the congenital form, the most common defects identified to date are several mutations of the genes encoding GM-CSF receptor subunits or surfactant proteins. Using GM-CSF as a therapeutic tool has also been shown to be effective in at least half of the acquired cases treated, while the importance of quantitative determination of anti-GM-CSF antibodies before and during the course of the therapy, as well as the autoantibody titer-GM-CSF dose relationship are to be elucidated. The congenital form of the disease does not respond to therapy with GM-CSF, consistent with the known primary defects and differences in disease pathogenesis.

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