title: Development of microscopic polyangiitis-related pulmonary fibrosis in a patient with autoimmune pulmonary alveolar proteinosis.
abstract: BACKGROUND
  Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease caused by the autoantibody against granulocyte-macrophage colony stimulating factor (GM-CSF). The clinical course of aPAP is variable; in severe cases, patients develop lethal respiratory failure due to pulmonary fibrosis. However, the pathogenesis of pulmonary fibrosis in aPAP has never been delineated.
  
  
  METHODS
  Here, we describe a rare case of aPAP that was subsequently complicated by microscopic polyangiitis-related pulmonary fibrosis. The patient was a 75-year-old Japanese man diagnosed with aPAP based on the crazy-paving appearance on high-resolution computed tomography (HRCT), "milky" appearance of broncho-alveolar lavage fluid (BALF), and elevated serum levels of the anti-GM-CSF antibody. The patient was followed-up without aPAP-specific treatment for 3 years. During this period, both hematuria and proteinuria appeared; in addition, serum myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) turned positive and increased markedly. The second BAL performed one year after the diagnosis, showed that the "milky" appearance had resolved. The HRCT showed that fibrotic changes had developed and that the crazy-paving appearance had disappeared. These data suggest an association between pulmonary fibrosis that developed during the natural course of aPAP and ANCA-related systemic vasculitis.
  
  
  CONCLUSIONS
  This is the first case report that suggests the existence of a pathogenetic relationship between ANCA-associated systemic vasculitis and aPAP-related pulmonary fibrosis. The link between ANCA-associated systemic vasculitis and aPAP-related pulmonary fibrosis requires further investigation.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kinehara
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. hiroshi.kida@imed3.med.osaka-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masaki
authors.initials: M
authors.lastname: Hirose
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nakabayashi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Hayama
authors.forename: Kiyoharu
authors.initials: K
authors.lastname: Fukushima
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Hirata
authors.forename: Koji
authors.initials: K
authors.lastname: Inoue
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Minami
authors.forename: Izumi
authors.initials: I
authors.lastname: Nagatomo
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeda
authors.forename: Toshiki
authors.initials: T
authors.lastname: Funakoshi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kijima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
mesh_terms: D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D001327:Autoimmune Diseases / Q000150:complications*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006801:Humans; D008297:Male; D055953:Microscopic Polyangiitis / Q000097:blood / Q000150:complications*; D011649:Pulmonary Alveolar Proteinosis / Q000150:complications* / Q000000981:diagnostic imaging; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000209:etiology*; D011859:Radiography
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic