Pulmonary Alveolar Proteinosis Clinical Presentation

  • Author: Roger B Olade, MD, MPH; Chief Editor: Zab Mosenifar, MD   more...
 
Updated: Mar 16, 2011
 

History

Patients with pulmonary alveolar proteinosis (PAP) typically present with a gradual onset of symptoms. As many as 30% of patients are asymptomatic, even with diffuse chest radiograph (CXR) abnormalities. Symptoms include the following:

  • Persistent dry cough (or scant sputum production)
  • Progressive dyspnea
  • Fatigue and malaise
  • Weight loss
  • Intermittent low-grade fever and/or night sweats
  • Pleuritic chest pain
  • Cyanosis (rare)
  • Hemoptysis (rare)
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Physical

Physical findings are usually nonspecific. Symptoms include the following:

  • Fine end-inspiratory crackles
  • Clubbing (25%)
  • Cyanosis (20%)
  • Pulmonary hypertension and cor pulmonale (rare)
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Causes

The etiology of pulmonary alveolar proteinosis (PAP) is unknown, but it has been associated with a number of other processes, implying a causal relationship. Causes may include the following:

  • Inhalation of silica dust (acute silicoproteinosis)
  • Exposure to insecticides, aluminum dust, titanium dioxide, indium-tin oxide and other inorganic dusts
  • Hematologic malignancies, mostly myeloid disorders
  • Lysinuric protein intolerance (rare)
  • HIV infection (AIDS)
  • Leflunomide - Case report (disease-modifying antirheumatic arthritis therapy)[5]

Recessive CSF2RA mutations may cause a rare, hereditary form of PAP. GM-CSF signaling may be absent or severely reduced, and the GM-CSF receptor alpha chain may be absent or abnormal, paralleling the GM-CSF signaling defects. This is unlike secondary PAP, in which a deficiency of GM-CSF and increased autoantibodies are noted. Genetic analysis may reveal multiple distinct CSF2RA abnormalities, including missense, duplication, frameshift, and nonsense mutations; exon and gene deletion; and cryptic alternative splicing.[6]

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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 Thoracic Society, and Society of Critical Care Medicine

Disclosure: Sepracor None None

Ali Hmidi, MD  Staff Physician, Department of Internal Medicine, Brooklyn Hospital Center, Cornell University

Disclosure: Nothing to disclose.

Oluwatoyin E Ijitola, MD, PhD, RN  Dean and Professor, International University for Graduate Studies (IUGS)

Oluwatoyin E Ijitola, MD, PhD, RN is a member of the following medical societies: American Academy of Tropical Medicine, American College of Healthcare Executives, American Medical Association, American Society of Tropical Medicine and Hygiene, HIV Medicine Association of America, and International AIDS Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Gregg T Anders, DO  Medical Director, Great Plains Regional Medical Command , Brooke 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.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St 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, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

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.

References

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

  2. Griese M, Brasch F, Aldana VR, Cabrera MM, Goelnitz U, Ikonen E, et al. Respiratory disease in Niemann-Pick type C2 is caused by pulmonary alveolar proteinosis. Clin Genet. Feb 2010;77(2):119-30. [Medline].

  3. Xue Y, Han Y, Li T, Chen S, Zhang J, Pan J, et al. Pulmonary alveolar proteinosis as a terminal complication in a case of myelodysplastic syndrome with idic(20q-). Acta Haematol. 2010;123(1):55-8. [Medline].

  4. 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].

  5. 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].

  6. Suzuki T, Sakagami T, Young LR, et al. Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med. Nov 15 2010;182(10):1292-304. [Medline]. [Full Text].

  7. 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].

  8. 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].

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

  10. 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].

  11. Choi HK, Park CM, Goo JM, Lee HJ. Pulmonary alveolar proteinosis versus exogenous lipoid pneumonia showing crazy-paving pattern: Comparison of their clinical features and high-resolution CT findings. Acta Radiol. May 2010;51(4):407-12. [Medline].

  12. Tazawa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, et al. Inhaled Granulocyte/Macrophage-Colony Stimulating Factor as Therapy of Pulmonary Alveolar Proteinosis. Am J Respir Crit Care Med. Feb 18 2010;[Medline].

  13. 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].

  14. 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.

  15. Carey B, Trapnell BC. The molecular basis of pulmonary alveolar proteinosis. Clin Immunol. Mar 24 2010;[Medline].

  16. 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].

  17. Cummings KJ, Donat WE, Ettensohn DB, Roggli VL, Ingram P, Kreiss K. Pulmonary alveolar proteinosis in workers at an indium processing facility. Am J Respir Crit Care Med. Mar 1 2010;181(5):458-64. [Medline].

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

  19. 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].

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

  21. 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].

  22. 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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A periodic acid-Schiff histochemical stain of transbronchial biopsy: Alveolar spaces contain considerable amounts of granular material.
 
 
 
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