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Pulmonary Alveolar Proteinosis Clinical Presentation

  • Author: Roger B Olade, MD, MPH; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
 
Updated: Dec 17, 2015
 

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[5, 6, 7]
  • Hematologic malignancies, mostly myeloid disorders
  • Lysinuric protein intolerance (rare)
  • HIV infection (AIDS)
  • Leflunomide - Case report (disease-modifying antirheumatic arthritis therapy)[8]

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.[9, 10]

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Contributor Information and Disclosures
Author

Roger B Olade, MD, MPH Medical Director, Genesis Health Group

Roger B Olade, MD, MPH is a member of the following medical societies: American College of Occupational and Environmental Medicine, 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, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

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, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

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

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

References
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  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. 2010 Feb. 77(2):119-30. [Medline].

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

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  16. Sunadome H, Nohara J, Noguchi T, Matsui C, Kono T, Terada Y. [A case of pulmonary alveolar proteinosis that showed solitary ground-glass opacity in the subpleural area]. Nihon Kokyuki Gakkai Zasshi. 2010 Jul. 48 (7):516-9. [Medline].

  17. 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. 2010 May. 51(4):407-12. [Medline].

  18. 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. 2010 Feb 18. [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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