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alveolar proteinosis

Monday 7 March 2005

Digital cases

- Case 87 (HPC:87)

Definition: Pulmonary alveolar proteinosis (PAP) is a rare cause of chronic interstitial lung disease in children characterised by accumulation of a lipoproteinaceous material in the alveoli.

Acquired pulmonary alveolar proteinosis (PAP) is a syndrome characterized by pulmonary surfactant accumulation occurring in association with granulocyte/macrophage colony-stimulating factor autoantibodies (autoimmune PAP) or as a consequence of another disease (secondary PAP).

Synopsis

- Bronchoalveolar lavage

  • milky appearance of the return fluid
  • periodic acid-Schiff staining material in the alveolar macrophages
  • homogeneous, granular material typical of PAP.

Ultrastructure

The material is composed of extracellular, multilamellated bodies when viewed by electron microscopy.

Etiology

- genetic primary PAP

  • SFTPB mutations with SP-B deficiency (early-onset PAP) (#8163685#)
  • SFTPC mutations with SP-C deficiency (MIM.178620) at 8p21
  • ABCA3 mutations with neonatal surfactant deficiency
  • CSF2RB mutations (GM-CSF receptor ß subunit) (MIM.138981)
  • TTF1 (TITF-1) gene mutation (MIM.600635) (#15517377#)
  • CSF2RB mutations (GM-CSF/IL-3/IL-5 receptor common beta chain) (#9694696#)

- acquired pulmonary alveolar proteinosis (PAP)

  • adult idiopathic PAP
  • autoimmune alveolar proteinosis (autoimmune PAP) (#18202348#)
    • autoantibody anti-GM-SCF (#16423275#, #15618581#)

- secondary PAP (associated PAP)

  • immunodeficiency
    • constitutional immunodeficiency
    • acquired immunodeficiency
      • AIDS and HIV infection
      • bone marrow allograft (#16162733#)
      • umbilical cord blood transplantation (#12111790#, #12562244#)
      • lung allograft recipients (#9416695#)
  • immunosuppression
    • corticosteroids
    • antirheumatoid arthritis drug leflunomide (#16916345#)
  • leukemias and blood diseases (#7429503#)
    • chronic myeloid leukemia (chronic myelogenous leukemia or CML) (#9568140 #)
    • acute myeloid leukemia (#16173954#, #16432866#)
    • acute lymphoblastic leukemia
    • sideroblastic anemia
    • myelodysplastic syndrome (#10407875#, #12547151#)
    • Fanconi anemia (Fanconi disease) (#515542#)
    • myelofibrosis after essential thrombocythemia (#12854908#)
  • pulmonary infections
    • Pneumocystis carinii
    • Nocardia asteroides
    • Histoplasma sp.
  • systemic infections
    • nocardiosis (#9517865#)
  • lysinuric protein intolerance (#8163273#)
  • dermatomyositis
  • Imatinib treatment (#14656624#)
  • dusts
    • silicosis (silicoproteinosis of the lung)
    • cotton and linen dust (#15757263#)
    • fibrous insulation material (#10858425#)
    • Orasol Navy Blue dust (#7530021#)
    • cement dust (#2918407#)
    • aluminum dust exposure (#6465685#)
    • glass fiber (#372672#)
  • NO2 exposure (?) (#1870017#)

Associations

- busulfan lung (#2316373#)
- end-stage pulmonary fibrosis
- malignant mesothelioma (#15838000#)
- disseminated atypical mycobacteriosis (#2316373#)

  • disseminated Mycobacterium kansasii infection (#14587059#)

- cytomegalovirus infection (#218518#)
- human parainfluenza virus giant cell pneumonia (#12562244#)
- sporadic associations

  • renal tubular acidosis (#7742818#)
  • Fanconi disease (#7742818#)
  • glioblastoma multiforme (#7742818#)
  • atrioventricular septal defect (#7742818#)

Animal model

- development of PAP in

  • GM-CSF knock-out mice / (GM-CSF)(-/-) mice
  • GM-CSF receptor knock-out mice

References

- de Blic J. Pulmonary alveolar proteinosis in children. Paediatr Respir Rev. 2004 Dec;5(4):316-22. PMID: #15531257#

- Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med. 2003 Dec 25;349(26):2527-39. PMID: #14695413#

- Yousem SA. Alveolar lipoproteinosis in lung allograft recipients. Hum Pathol. 1997 Dec;28(12):1383-6. PMID: #9416695#

- Bedrossian CW, Luna MA, Conklin RH, Miller WC. Alveolar proteinosis as a consequence of immunosuppression. A hypothesis based on clinical and pathologic observations. Hum Pathol. 1980 Sep;11(5 Suppl):527-35. PMID: #7429503#

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