Pulmonary Interstitial Fibrosis Following Alveolar Proteinosis

doi:10.1378/chest.65.6.700

Chest

Volume 65, Issue 6, June 1974, Pages 700-702

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Whether permanent structural lung changes follow pulmonary alveolar proteinosis (PAP) is not known. A patient with PAP, but with no evidence of lung fibrosis, became asymptomatic spontaneously. However, 13 years after the onset of his illness he died from pulmonary insufficiency due to lung fibrosis. This suggests that the typical histologic picture of PAP is only a stage of a disease in which the end stage is fibrosis.

Section snippets

Case Report

A black construction worker was well until 1959, when at 45 years of age he experienced an acute illness characterized by cough, shortness of breath, fever and generalized arthralgias. He was hospitalized and treated for “pneumonia.” On a subsequent admission in 1960 an open biopsy of the right lung was interpreted as alveolar proteinosis. From 1961 to 1967 the patient resided in southern California and was asymptomatic without therapy. During the interval he did not visit a doctor,

Discussion

In the original description of PAP by Rosen et al,¹² an increase in the number of alveolar septal inflammatory cells was noted in cases 11 and 18. Case 2 from that series, reported in more detail elsewhere, demonstrated mild fibrosis on initial lung biopsy followed by more extensive fibrosis 9½ months later at postmortem.⁷ The initial lung biopsy from case 7 showed typical PAP and was free from inflammatory reaction or fibrosis.¹² Two and one-half years later when the patient was asymptomatic a

ACKNOWLEDGMENT

We thank Dr. Robin T. Vollmer for performing the postmortem examination.

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Cited by (33)

Pulmonary alveolar proteinosis-like change: A fairly common reaction associated with the severity of idiopathic pulmonary fibrosis
2016, Respiratory Investigation
Citation Excerpt :
In contrast, secondary PAP occurs as a consequence of various underlying clinical conditions including hematological malignancies, inhalation of toxic dust, and infectious or pharmacological immunosuppression that impairs alveolar macrophage function, resulting in surfactant accumulation [4]. Some reports have indicated an association between PAP and severe pulmonary fibrosis mimicking idiopathic pulmonary fibrosis (IPF) [6–8]. Most of these are case reports that conclude that the fibrosis is a part of PAP [7,8]. However, Hudson et al. [6] have suggested that in some cases, PAP may be a stage of fibrotic disease.
We have seen cases of chronic interstitial pneumonia (IP) with pulmonary alveolar proteinosis (PAP)-like changes that are focal histological features similar to PAP. To our knowledge, the association between PAP-like changes and chronic IP has not been investigated. We aimed to evaluate the incidence of PAP-like changes in chronic IP cases, and the association between the existence of PAP-like changes and the clinical features seen in patients with idiopathic pulmonary fibrosis (IPF).
We selected 144 cases of chronic IP that had a video-assisted thoracoscopic surgery biopsy between 2008 and 2011. Clinical records and hematoxylin and eosin-stained slides were reviewed, and clinicopathological findings, including the cumulative survival probability, were compared between IPF cases with and without a PAP-like change.
A PAP-like change was identified in 20 of 144 cases (13.9%) of chronic IP and 14 of 61 IPF cases (23.0%). When comparing IPF cases with and without a PAP-like change, histological findings of honeycomb cysts and fibroblastic foci were associated with PAP-like changes (p=0.022 and 0.036, respectively). The percent-predicted values for forced vital capacity and diffusion capacity of carbon monoxide were lower (p=0.006 and 0.015, respectively), and concentrations of serum Krebs von den Lungen-6 and lactate dehydrogenase were higher (p=0.007 and 0.037, respectively) in cases of IPF with a PAP-like change than in those without one.
The presence of a PAP-like change in IPF cases was fairly common in our study, and may be a secondary reaction associated with IPF severity.
A novel immunodeficiency syndrome as a rare cause of secondary pulmonary alveolar proteinosis: A diagnosis after 5 decades
2014, Revista Portuguesa de Pneumologia
Case report of a male patient with a five-decade follow-up history in a tertiary care hospital distinguished for malabsorption syndrome, failure-to-thrive, meningitis and recurrent bacterial, fungal and mycobacterial pulmonary infections. Additionally, he developed epidermodysplasia verruciformis, several in situ spinocellular carcinomas and an uncharacteristic parenchymal lung disease. Surgical lung biopsy suggested pulmonary alveolar proteinosis with fibrotic change. Retrospectively, severe monocytopenia had been overlooked in the past, as well as low B and NK cell blood counts. Flow cytometry confirmed the absence of the previous cell subsets along with an undetectable population of dendritic blood cells.
Dendritic cell, monocyte, B and NK lymphoid Human Deficiency Syndrome (DCMLS) is a novel rare immunodeficiency described in 2010, linked to GATA-2 mutation. This syndrome should be highlighted as a rare cause of acquired PAP, with a radiological pattern encompassing potential fibrotic change. Failure to recognize monocytopenia may impede the chance to diagnose.
Relato de um caso clínico de um doente do sexo masculino com um historial de acompanhamento de cinco décadas, num hospital de cuidados terciários, caracterizado por um síndrome de malabsorção, insuficiência de crescimento, meningite e infecções pulmonares bacterianas, fúngicas e micobacterianas recorrentes. Além disso, desenvolveu epidermodisplasia verruciforme, diversos carcinomas espinocelulares in situ e uma doença pulmonar parenquimatosa não definida. Uma biópsia pulmonar cirúrgica sugeriu uma Proteinose Alveolar Pulmonar com alterações fibróticas. Em retrospectiva, uma monocitopenia grave negligenciada no passado, bem como uma baixa contagem de células B (linfócitos B) e NK (células ‘natural killer’). Uma citometria de fluxo confirmou a ausência dos subconjuntos de células anteriores, juntamente com uma população indetectável de células dendríticas sanguíneas.
A Síndrome de Deficiência Humana de células dendríticas, monócitos, linfóides B e NK é uma rara imunodeficiência descrita recentemente em 2010 e relacionada com a mutação do gene GATA-2. Esta síndrome deverá ser referida como uma causa rara de PAP (proteinose alveolar pulmonar) adquirida, com um padrão radiológico que poderá apresentar uma potencial alteração fibriótica. A ausência de reconhecimento da monocitopenia pode impedir a oportunidade de chegar a este diagnóstico.
Elevated monocyte chemotactic proteins 1, 2, and 3 in pulmonary alveolar proteinosis are associated with chemokine receptor suppression
2005, Clinical Immunology
Pulmonary alveolar proteinosis (PAP) is a rare autoimmune lung disease characterized by abnormal surfactant accumulation within alveolar macrophages, and circulating auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) resulting in functional GM-CSF deficiency. Monocyte/macrophage chemotactic protein-1 (MCP-1) is elevated in PAP, suggesting association with the pathophysiology. Because PAP has been associated with inflammatory pulmonary changes, we hypothesized that other MCP family chemokines would be present and that Chemokine Chemotaxis Receptor 2 (CCR2) would be elevated on PAP mononuclear cells. Here we show for the first time that MCP-2 and MCP-3, like MCP-1, are highly elevated in PAP. We also confirm that PAP alveolar macrophages and not epithelial cells produce MCP-1, and that MCP-1 from PAP lung has functional chemoattractant activity. Surprisingly, CCR2 expression is diminished in PAP lymphocytes and alveolar macrophages compared to controls. Further, MCP-1 from PAP lung suppresses CCR2 expression in vitro, suggesting that in PAP, MCP-1 participates in an autocrine regulatory network in vivo.
Pulmonary alveolar proteinosis mimicking idiopathic pulmonary fibrosis
2003, Annals of Diagnostic Pathology
Pulmonary alveolar proteinosis (PAP) is a rare disorder of unknown etiology. While most biopsies from patients with PAP disclose a prominent positive periodic acid-Schiff, diastase-resistant intra-alveolar exudate, and minimal interstitial thickening, interstitial fibrosis and honeycombing can be the predominant histologic findings. We recently identified two patients with PAP who initially were thought to have idiopathic pulmonary fibrosis, but whose biopsies ultimately disclosed PAP with considerable interstitial fibrosis. Because the clinical and radiographic presentation of PAP can overlap with other interstitial lung disorders, it should be considered in the differential diagnosis of unexplained idiopathic interstitial pneumonias in young patients. Ann Diagn Pathol 7: 82-86, 2003.
Pulmonary Alveolar Phospholipoproteinosis: Experience With 34 Cases and a Review
1987, Mayo Clinic Proceedings
A retrospective review of Mayo Clinic records through 1983 revealed 34 patients (24 male and 10 female; mean age, 41 years) with the diagnosis of pulmonary alveolar phospholipoproteinosis. The major clinical features were dyspnea, cough, fever, and chest pain. Chest roentgenograms usually showed bilateral symmetric alveolar infiltrates, but asymmetric, unilateral, and chronic patchy patterns were also noted. Diagnosis was established by thoracotomy-lung biopsy in 26 patients. Histologic analysis revealed uniform filling of the alveoli by periodic acid-Schiff-positive material and maintenance of normal alveolar architecture. Electron microscopy showed enlarged alveolar macrophages with lamellar osmiophilic inclusions, dense granules, and myeloid bodies. Of the 21 patients who underwent therapeutic bronchoalveolar lavage, 13 had no recurrence of the disease during a mean follow-up of 8.8 years. In patients who underwent pulmonary function testing both before and after lavage, significant restrictive dysfunctions present before the procedure were alleviated afterward. Three deaths occurred among the 34 patients. Pulmonary alveolar phospholipoproteinosis may result from defective clearance of phospholipids by the alveolar macrophages, excessive production of phospholipids by type II pneumocytes, or both. It is likely a nonspecific response to a variety of injuries to the alveolar macrophage or type II pneumocyte or both, including exposure to certain dusts and chemicals and occurrence of hematologic diseases or infections. The uncommon occurrence of this disorder suggests individual susceptibility.
A case of autoimmune pulmonary alveolar proteinosis with pulmonary fibrosis and asbestosis-like features
2019, Kurume Medical Journal

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Chest

SELECTED REPORTSPulmonary Interstitial Fibrosis Following Alveolar Proteinosis

Section snippets

Case Report

Discussion

ACKNOWLEDGMENT

Br J Dis Chest

Am J Med

Am J Med

Lancet

Dis Chest

Dis Chest

Blood

SELECTED REPORTS
Pulmonary Interstitial Fibrosis Following Alveolar Proteinosis