Acute silicosis (silicotic alveolar proteinosis) may occur after inhalation of high doses of fine silica particles over a short period of time. It resembles usual alveolar proteinosis. Patients present with progressive dyspnea [1-3].

CT shows geographic, ground-glass opacities with an accompanying interlobular septal thickening (A). Accentuation of the interlobular septa is usually caused by presence of the proteinaceous material in the septal interstitium [4]. Note the sharp transition between the normal and abnormal lung.

A

B. Postmortem lungs from untreated patients may weigh up to 2000 g apiece. The cut surface has patchy, yellowish consolidation and may show accentuation of interlobular septa as seen near the apex of the lung in this slice. A milky fluid may exude from the cut surface [1,2].

This section (C) was stained with the periodic acid-Schiff (PAS) stain. Alveoli are filled with granular, pink, PAS-positive, exudate with darker pink clumps and slit-like clefts from which lipoid material has been dissolved in the processing. The upper arrow points to a degenerating macrophage, several of which are present. The lower arrow indicates a type II cell that is representative of the generalized hypertrophy of these cells [1,2]. Scattered lymphocytes are present in the alveolar walls, which are slightly thickened. A lymphocytic alveolitis has been described in these patients [5].

C

D. Therapy consists of washing the abnormal fluid out of the alveoli [2]. The tube at the left contains a suspension of the opaque, milky lavage fluid from a patient. The tube at the right contains water, which simulates lavage fluid at the end of a therapeutic procedure.

Ultrastructure of lavage fluid: Lavage fluid contains many types of particles (E). Membranous vesicles and amorphous material comprise much of what is seen. Large, multilamellated structures (lower right), composed of tubular myelin-like membranes, are the characteristic feature [6]. Diagnosis of alveolar proteinosis does not, however, require electron microscopic confirmation.

E

Diagnosis: Diagnosis of acute silicosis is based on a history of heavy exposure to silica dust and documentation by biopsy or lavage fluid of a diagnosis of alveolar proteinosis. Histologic sections of lung sometimes show typical silicotic nodules. Birefringent particles can sometimes be seen with polarized light, but definite mineralogic diagnosis requires X-ray diffraction analysis [3].

Pathogenesis: Recent reports have suggested the importance of GM-CSF deficiency in the pathogenesis of pulmonary alveolar proteinosis (PAP). GM-CSF knockout mice developed PAP [7]. Subcutaneous injections of GM-CSF produced clinical improvement in a patient with PAP [8]. In vitro studies showed that GM-CSF production was absent in BAL cells from a patient with PAP, but that its production could be restored by abrogating the effects of an inhibitor (IL-10) by anti-IL-10 [9]. In regard to silica, it has been shown that an oxidant (ferric ion), which normally becomes complexed to the surface of the dust, causes production of more surfactant material after intratracheal instillation than silica free of the oxidant [10]. The relationship of this oxidant injury to the GM-CSF story remains to be described.

References

1. Rosen S, Castleman B, Liebow A. Pulmonary alveolar proteinosis. N Engl J Med 1958; 258:1123-1142.

2. Prakash U, Barham S, Carpenter H, Dines D, Marsh H. Pulmonary alveolar phospholipoproteinosis: experience with 34 cases and a review. Mayo Clin Proc 1987; 62:499-518.

3. Silicosis and Silicate Disease Committee. Diseases associated with exposure to silica and nonfibrous silicate minerals. Arch Pathol Lab Med 1988; 112:673-720.

4. Godwin J, Müller N, Takasugi J. Pulmonary alveolar proteinosis: CT findings. Radiology 1988; 169:609-613.

5. Milleron B, Costabel U, Teschler H, Ziesche R, Cadranel J, Matthys H, Akoun G. Bronchoalveolar lavage cell data in alveolar proteinosis. Am Rev Respir Dis 1991; 144:1330-1332.

6. Gilmore L, Talley F, Hook G. Classification and morphometric quantitation of insoluble materials from the lungs of patients with alveolar proteinosis. Am J Pathol 1988; 133:252-264.

7. Dranoff G, Crawford A, Sadelain M, Ream B, Rashid A, Bronson R, Dickersin G, et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science 1994; 264:713-716.

8. Seymour J, Dunn A, Vincent J, Presneill J, Pain M. Efficacy of granulocyte-macrophage colony-stimulating factor in acquired alveolar proteinosis. N Engl J Med 1996; 335:1924-1925.

9. Tchou-Wong K, Harkin T, Chi C, Bodkin M, Rom W. GM-CSF gene expression is normal but protein release is absent in a patient with pulmonary alveolar proteinosis. Am J Respir Crit Care Med 1997; 156:1999-2002.

10. Ghio A, Hatch G. Lavage phospholipid concentration after silica instillation in the rat is associated with complexed [Fe3+] on the dust surface. Am J Respir Cell Mol Biol 1993; 8:403-407.

Clinical summaryDiscussion

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