eMedicine Specialties > Pulmonology > Idiopathic Lung Disorders

Pulmonary Alveolar Proteinosis: Differential Diagnoses & Workup

Author: Roger B Olade, MD, MPH, Medical Director, Providence Health Group
Coauthor(s): Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital; Ali Hmidi, MD, Staff Physician, Department of Internal Medicine, Brooklyn Hospital Center, Cornell University; Oluwatoyin E Ijitola, MD, PhD, Adjunct Professor, International University for Graduate Studies (IUGS)
Contributor Information and Disclosures

Updated: Nov 19, 2008

Differential Diagnoses

Hypersensitivity Pneumonitis
Lung Cancer, Non-Small Cell
Lung Cancer, Oat Cell (Small Cell)
Pneumocystis Carinii Pneumonia
Pulmonary Edema, Cardiogenic
Sarcoidosis

Other Problems to Be Considered

Bronchoalveolar cell carcinoma
Desquamative interstitial pneumonitis
Alveolar microlithiasis
Alveolar hemorrhage
Lipoid pneumonia

Workup

Laboratory Studies

  • Serologic studies are generally not useful for pulmonary alveolar proteinosis (PAP). Flexible bronchoscopy with bronchoalveolar lavage (BAL) remains the criterion standard.
    • Elevated levels of the proteins SP-A and SP-D in serum and BAL fluid may be useful.
    • Elevated titer of neutralizing autoantibody against GM-CSF (immunoglobulin G [IgG] isotype) in serum and BAL fluid may be useful. Recent studies have proposed that deficiency of GM-CSF causes pulmonary alveolar proteinosis (PAP); all patients studied had the antibody to GM-CSF.4,5
    • Serum lactate dehydrogenase (LDH) level is usually elevated, but this finding is nonspecific.
  • The diagnosis can be made by BAL only if PAS staining is requested. Therefore, PAP is probably underdiagnosed.
  • Lung biopsies are classic for PAP: Alveoli are filled with nonfoamy material. Transbronchial biopsies are adequate, and open lung biopsy is not required.

Imaging Studies

  • CXR in pulmonary alveolar proteinosis (PAP) shows bilateral perihilar infiltrates with consolidation in a "bat-wing" configuration, which may mimic pulmonary edema, although with a typical absence of cardiomegaly or pleural effusion. Unilateral involvement occurs occasionally, and lymphadenopathy is rarely present. Typically, changes progress over weeks to months into a diffuse reticulogranular pattern.
  • High-resolution computed tomography (HRCT) scan of the chest demonstrates areas of patchy ground-glass opacification with smooth interlobular septal thickening and intralobular interstitial thickening, which produces a polygonal pattern referred to as "crazy paving." The crazy-paving pattern also can be observed in lipoid pneumonia, sarcoidosis, mucinous bronchoalveolar cell carcinoma, and acute respiratory distress syndrome (ARDS).6,7

Procedures

  • Bronchoscopy with transbronchial biopsy and BAL: Transbronchial biopsies of affected lung segments, coupled with findings on BAL, are sufficient to make the diagnosis.
    • Use PAS reagent for BAL. Bronchoalveolar lavage fluid appears "milky."
    • Papanicolaou staining may reveal green and orange globules that are diagnostic for PAP.
    • Electron microscopy of BAL may reveal characteristic multilamellar structures.
  • Transbronchial biopsies may increase the yield.
  • Surgical lung biopsy rarely is necessary for definitive diagnosis.

Histologic Findings

Light microscopy of the lung parenchymal tissue shows alveoli filled with a granular PAS base-reactive and diastase-resistant eosinophilic material. Electron microscopy of the material in the alveoli shows multilamellated structures and membranous vesicles.

More on Pulmonary Alveolar Proteinosis

Overview: Pulmonary Alveolar Proteinosis
Differential Diagnoses & Workup: Pulmonary Alveolar Proteinosis
Treatment & Medication: Pulmonary Alveolar Proteinosis
Follow-up: Pulmonary Alveolar Proteinosis
Multimedia: Pulmonary Alveolar Proteinosis
References
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References

  1. Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. N Engl J Med. Jun 5 1958;258(23):1123-42. [Medline].

  2. Bonfield TL, Farver CF, Barna BP, Malur A, Abraham S, Raychaudhuri B, et al. Peroxisome proliferator-activated receptor-gamma is deficient in alveolar macrophages from patients with alveolar proteinosis. Am J Respir Cell Mol Biol. Dec 2003;29(6):677-82. [Medline].

  3. Wardwell NR Jr, Miller R, Ware LB. Pulmonary alveolar proteinosis associated with a disease-modifying antirheumatoid arthritis drug. Respirology. Sep 2006;11(5):663-5. [Medline].

  4. Bonfield TL, John N, Barna BP, Kavuru MS, Thomassen MJ, Yen-Lieberman B. Multiplexed particle-based anti-granulocyte macrophage colony stimulating factor assay used as pulmonary diagnostic test. Clin Diagn Lab Immunol. Jul 2005;12(7):821-4. [Medline].

  5. Carraway MS, Ghio AJ, Carter JD, Piantadosi CA. Detection of granulocyte-macrophage colony-stimulating factor in patients with pulmonary alveolar proteinosis. Am J Respir Crit Care Med. Apr 2000;161(4 Pt 1):1294-9. [Medline].

  6. Godwin JD, Müller NL, Takasugi JE. Pulmonary alveolar proteinosis: CT findings. Radiology. Dec 1988;169(3):609-13. [Medline].

  7. Murayama S, Murakami J, Yabuuchi H, Soeda H, Masuda K. "Crazy paving appearance" on high resolution CT in various diseases. J Comput Assist Tomogr. Sep-Oct 1999;23(5):749-52. [Medline].

  8. Abdul Rahman JA, Moodley YP, Phillips MJ. Pulmonary alveolar proteinosis associated with psoriasis and complicated by mycobacterial infection: successful treatment with granulocyte-macrophage colony stimulating factor after a partial response to whole lung lavage. Respirology. Aug 2004;9(3):419-22. [Medline].

  9. Anders P. Pulmonary Alveolar Proteinosis. In: Fishman AP, Elia JA, Fishman JA, Grippi MA, Kaiser LR, Senior RM, eds. Fishman's Pulmonary Diseases and Disorders. 3rd ed. New York, NY: McGraw-Hill; 1998:1223-9.

  10. Crocker HL, Pfitzner J, Doyle IR, Hague WM, Smith BJ, Ruffin RE. Pulmonary alveolar proteinosis: two contrasting cases. Eur Respir J. Feb 2000;15(2):426-9. [Medline].

  11. Ioachimescu OC, Kavuru MS. Pulmonary alveolar proteinosis. Chron Respir Dis. 2006;3(3):149-59. [Medline].

  12. Kitamura T, Uchida K, Tanaka N, Tsuchiya T, Watanabe J, Yamada Y, et al. Serological diagnosis of idiopathic pulmonary alveolar proteinosis. Am J Respir Crit Care Med. Aug 2000;162(2 Pt 1):658-62. [Medline].

  13. Presneill JJ, Nakata K, Inoue Y, Seymour JF. Pulmonary alveolar proteinosis. Clin Chest Med. Sep 2004;25(3):593-613, viii. [Medline].

  14. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med. Jul 15 2002;166(2):215-35. [Medline].

  15. Venkateshiah SB, Thomassen MJ, Kavuru MS. Pulmonary alveolar proteinosis. Clinical manifestations and optimal treatment strategies. Treat Respir Med. 2004;3(4):217-27. [Medline].

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Further Reading

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Keywords

pulmonary alveolar proteinosis, PAP, alveolar filling with floccular material, periodic acid-Schiff, PAS, surfactant-associated protein B deficiency, SP-B deficiency, GM-CSF antibodies, GM-CSF deficiency, inhalation of silica dust, acute silicoproteinosis, insecticide exposure, aluminum dust exposure, titanium dioxide exposure, inorganic dust exposure, hematologic malignancy, myeloid disorder, lysinuric protein intolerance, HIV infection, AIDS

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Contributor Information and Disclosures

Author

Roger B Olade, MD, MPH, Medical Director, Providence Health Group
Roger B Olade, MD, MPH is a member of the following medical societies: American College of Occupational and Environmental Medicine and American College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: sepracor Ownership interest None

Ali Hmidi, MD, Staff Physician, Department of Internal Medicine, Brooklyn Hospital Center, Cornell University
Disclosure: Nothing to disclose.

Oluwatoyin E Ijitola, MD, PhD, Adjunct Professor, International University for Graduate Studies (IUGS)
Oluwatoyin E Ijitola, MD, PhD is a member of the following medical societies: American Academy of Tropical Medicine, American College of Healthcare Executives, American Society of Tropical Medicine and Hygiene, HIV Medicine Association of America, and International AIDS Society
Disclosure: Nothing to disclose.

Medical Editor

Gregory Tino, MD, Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital
Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Gregg T Anders, DO, Medical Director, Great Plains Regional Medical Command , Brook Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio
Gregg T Anders, DO is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

 
 
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