- • Symptoms are nonspecific and include dyspnea,
cough, fatigue, and malaise.
- • Chest radiograph demonstrates diffuse alveolar
- • Computed tomography of the chest demonstrates an
alveolar filling process with a characteristic “crazy paving” pattern.
- • Diagnosis confirmed by detection of periodic acid–Schiff-positive
material in bronchoalveolar lavage or lung biopsy.
Pulmonary alveolar proteinosis (PAP) was identified in 1958,
based on experience with 27 patients in whom the major histological
finding was filling of alveolar spaces by a lipid-rich, insoluble,
periodic acid–Schiff-positive lipoproteinaceous material.
The first case dated to 1953; the pathology was sufficiently distinctive
that it was unlikely to have escaped previous notice. Subsequent
studies of the abnormal alveolar contents revealed that the major
biochemical components of this substance were phospholipids with
small amounts of protein. Prakash suggested that the term “pulmonary
alveolar phospholipoproteinosis” more appropriately characterized
the disorder. However, this term is rarely used today.
The amorphous, insoluble, proteinaceous material is deposited
in alveoli and can exude into bronchioles. This material is unique
in that it does not appear to stimulate an inflammatory response, although
fibrosis is noted in some biopsies, particularly in late stages
PAP is an uncommon, idiopathic disease. It is difficult to determine
its exact frequency because of the absence of a national registry.
The disease has been reported throughout the United States and in
virtually all industrialized countries. In 1969, only 139 cases
of PAP had been reported worldwide; by 1980, approximately 260 cases
were recognized. Even now fewer that 500 cases have been reported.
The ratio of male to female patients in most series is about 4 to
1, with most being 30 to 50 years of age. Many of the patients in
published reports had been exposed to various dusts and chemicals
such as silica and aluminum dust, but existence of the disease in
unexposed siblings also suggests a genetic predisposition. Superimposed
infections by unusual pathogens may occur. Infection by Nocardia asteroides is most commonly
reported, followed by fungal and atypical mycobacterial infections.
Amiodarone lung toxicity in humans has some features of a lung phospholipidosis.
Experimental animals exposed to a variety of chemicals demonstrate
pathological features identical to those in human PAP, and reports
describe morphological findings identical to those in PAP following exposure
to silica, fiberglass, volcanic ash, and aluminum dust. PAP is also
associated with malignant diseases, especially acute or chronic
myeloid leukemias. These forms are termed secondary PAP. Initial
reports were in patients with chronic myeloid leukemias, but the
disease also occurs in acute leukemia, multiple myeloma, Waldenstrom’s
disease, and lymphoma. Primary and secondary PAP are indistinguishable
from a morphological perspective as they share the same microscopic
and ultrastructural pattern. However, their clinical response to
lavage therapy is different. Secondary PAP is a rare cause of respiratory
failure in patients with cancer and probably results from concomitant
events, including exposure to pulmonary irritants as well as functional
defects of alveolar macrophages. Recent data suggest that ...