eMedicine Specialties > Pediatrics: General Medicine > Pulmonology

Alveolar Proteinosis: Differential Diagnoses & Workup

Author: Anne E Stone, MD, Fellow, Division of Pediatric Pulmonary Medicine, Columbia University Medical Center, Children's Hospital of New York-Presbyterian
Coauthor(s): Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; David J Vaughan, MBBCh, Consultant Pediatrician, Department of Pediatrics, Our Lady of Lourdes Hospital, Ireland; Jerry Zimmerman, MD, PhD, Professor, Department of Pediatrics/Anesthesia, University of Washington School of Medicine; Director, Division of Pediatric Critical Care Medicine, Children's Hospital of Seattle
Contributor Information and Disclosures

Updated: Aug 5, 2008

Differential Diagnoses

Respiratory Distress Syndrome

Other Problems to Be Considered

Pneumonia (bacterial, viral, atypical)
Interstitial pneumonitis
Bronchiolitis obliterans organizing pneumonia (BOOP)
Chronic eosinophilic pneumonia
Acute eosinophilic pneumonia
Hypersensitivity pneumonitis
Usual interstitial pneumonitis

Workup

Laboratory Studies

  • Gene mutation analysis
    • Blood of infants with congenital pulmonary alveolar proteinosis (PAP) should be analyzed for mutation analysis of the SP-B and SP-C gene.
    • As an alternative, the child's biologic parents may be analyzed.
  • Surfactant analysis
    • Levels of surfactant B may be determined from bronchoalveolar lavage (BAL) fluid; low levels of SP-B are usually found.
    • Elevated levels of surfactant proteins A and D (SP-A, SP-D) have been observed in patients with PAP.
  • Lactate dehydrogenase (LDH) measurement10
    • The serum LDH level may be elevated. Patients with PAP may have an LDH level of 168% ±66% (mean ± standard deviation), which is the upper limit of the normal range.
    • Individual case reports suggest that serial LDH measurements may be useful to track the severity of disease.
    • Few data are available in the pediatric literature concerning the utility of LDH measurements. Mahut et al (1996) reported that 2 of 3 children with PAP had elevated LDH values.14
  • CBC count: Polycythemia may be found as a consequence of chronic hypoxia
  • ABG analysis
    • In their examination of 410 patients reported in the literature, Seymour et al reported a an arterial partial pressure of oxygen (PaO2) of 58.6 ±15.8 mm Hg.10
    • ABG analysis may reveal a low partial pressure of oxygen and a compensated respiratory alkalosis secondary to hyperventilation.10
  • Latex agglutination test: The finding of autoantibodies (neutralizing IgG antibody against GM-CSF) in patients with acquired PAP has led to the development of a test with 100% sensitivity and 98% specificity for diagnosis.15

Imaging Studies

  • Chest radiography
    • In the neonatal-onset form, radiographic appearances are indistinguishable from those of infantile respiratory distress syndrome; both conditions are characterized by a diffuse ground-glass appearance and air bronchograms.
    • In the acquired and secondary forms, chest radiography typically reveals widespread, bilateral patchy and asymmetric airspace consolidation without central or peripheral distribution.16,10
    • Radiographic findings are typically disproportionately abnormal in comparison to the clinical presentation.2
    • Many radiographic patterns are demonstrated. Goldstein (1998) reported that 62% of patients had an alveolar pattern of involvement, 12% had an interstitial pattern, and 12% had a mixed pattern on chest radiography.4
  • Chest CT
    • Chest CT imaging reveals scattered airspace filling. Air bronchograms are uncommon.
    • High-resolution chest tomography (HRCT) typically demonstrates a ground-glass appearance or consolidation. Interlobular and intralobular septae are thickened and arranged in an irregular manner that has been termed "crazy paving."17
    • Reticular interstitial attenuations may also be noted.
    • HRCT appearances are said to be characteristic enough to strongly suggest the diagnosis in the appropriate clinical setting.
    • HRCT scanning after lung lavage usually reveals resolution of the alveolar filling and correlates with functional improvement. Albafouille et al (1999) confirmed this finding in children.18

Other Tests

  • Pulmonary function testing (PFT) may reveal a mildly restrictive pattern of lung disease and a diminished carbon monoxide diffusing capacity.10,2
  • PAP is said to increase the shunt fraction more than other diffuse infiltrative lung processes.2

Procedures

  • BAL
    • Classic findings in diagnostic BAL include a milky or opalescent aspirate with large alveolar macrophages and increased lymphocytes but few other inflammatory cell types.2,19
    • Cell counts and differential counts are not helpful in the diagnosis. However, elevated levels of inflammatory cells may suggest infection, as either a primary or a secondary process.
    • The aspirated material stains strongly positive for PAS, as is expected.1
    • SP-A and SP-D levels are elevated in BAL fluid from patients with PAP, as compared with healthy volunteers.19
  • Lung biopsy
    • Open lung biopsy is the criterion standard for the diagnosis of PAP.2,19,1
    • Open lung biopsy is not commonly required because the diagnosis can be established in approximately 75% of cases by the classic BAL findings.19,10

Histologic Findings

  • The classic pathologic finding is granular, proteinaceous, fluid-filled alveolar spaces that stain strongly on PAS staining. Cholesterol crystals are sometimes observed. Alveolar structure is generally well preserved, as are intralobular septa, with some thickening of interlobular septae. No airway involvement occurs.19,10
  • Electron microscopy (EM) may reveal lamellar bodies and tubular myelin within the alveolar space in PAP. The EM appearances in congenital PAP differ in that usually no tubular myelin is present. However, EM usually adds little to the diagnostic workup.19,10
  • Immunohistochemistry may provide useful information in congenital PAP. Staining for surfactant proteins A, B, C, and D is possible. Levels of SP-B are reduced, whereas SP-A and SP-D levels are generally elevated.3

More on Alveolar Proteinosis

Overview: Alveolar Proteinosis
Differential Diagnoses & Workup: Alveolar Proteinosis
Treatment & Medication: Alveolar Proteinosis
Follow-up: Alveolar Proteinosis
References
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Further Reading

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Keywords

alveolar proteinosis, pulmonary alveolar proteinosis, PAP, respiratory failure, congenital alveolar proteinosis, CAP, secondary pulmonary alveolar proteinosis, pulmonary macrophage dysfunction, smoking, tobacco use, neonatal respiratory distress, respiratory distress syndrome, pneumonia, sepsis, failure to thrive, dyspnea, pneumothorax, lysinuric protein intolerance, Nocardia species, Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, human immunodeficiency virus, HIV, Pneumocystis species, Cryptococcus species, cytomegalovirus, polycythemia, respiratory alkalosis, hyperventilation

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Contributor Information and Disclosures

Author

Anne E Stone, MD, Fellow, Division of Pediatric Pulmonary Medicine, Columbia University Medical Center, Children's Hospital of New York-Presbyterian
Anne E Stone, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

Coauthor(s)

Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons
Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Merck Honoraria Speaking and teaching

David J Vaughan, MBBCh, Consultant Pediatrician, Department of Pediatrics, Our Lady of Lourdes Hospital, Ireland
David J Vaughan, MBBCh is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Jerry Zimmerman, MD, PhD, Professor, Department of Pediatrics/Anesthesia, University of Washington School of Medicine; Director, Division of Pediatric Critical Care Medicine, Children's Hospital of Seattle
Jerry Zimmerman, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, Society for Pediatric Research, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Medical Editor

Susanna A McColley, MD, Director of Cystic Fibrosis Center; Head, Division of Pulmonary Medicine; Associate Professor, Department of Pediatrics, Children's Memorial Medical Center of Chicago, Northwestern University
Susanna A McColley, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Sleep Disorders Association, and American Thoracic Society
Disclosure: Genentech Honoraria Speaking and teaching; Genentech Consulting fee Consulting; Novartis Consulting fee Consulting; Altus Consulting fee Consulting; Axcan Scandi Consulting fee Consulting; Boston Scientific Consulting fee Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Charles Callahan, DO, Professor, Deputy Chief of Clinical Services, Walter Reed Army Medical Center
Charles Callahan, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American College of Osteopathic Pediatricians, American Thoracic Society, Association of Military Surgeons of the US, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

CME Editor

Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Professor of Clinical Pediatrics, State University of New York at Stony Brook; Director of Children's Sleep Services, Winthrop University Hospital
Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians
Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons
Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Merck Honoraria Speaking and teaching

 
 
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