title: Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence.
abstract: OBJECTIVE
  Interstitial lung disease (ILD) is currently the main cause of death in systemic sclerosis (SSc) and has an unknown pathogenesis. Gastroesophageal reflux (GER) has been strongly implicated as a cause of ILD in several lung diseases, including SSc-ILD. This review summarizes clinical, radiologic, histopathologic, and treatment aspects of GER in SSc-ILD.
  
  
  METHODS
  The PubMed database was searched using the following keywords: "systemic sclerosis, scleroderma, interstitial lung disease, and gastroesophageal reflux." The research was limited to English-language studies that included SSc patients with ILD.
  
  
  RESULTS
  Pulmonary function tests were related with the presence of GER in several esophageal functional tests (esophageal endoscopy, pH monitoring, and manometric analysis). Regarding the histopathologic data, a pattern called centrilobular fibrosis was described in 21% of 28 lung biopsies, with a bronchocentric distribution and with an intraluminal content resembling gastric fluid. Radiologic evidence of esophageal dilation is very frequent in SSc patients, and consolidation with a patchy distribution was almost exclusively found in SSc patients with centrilobular fibrosis lung pattern. Furthermore, high levels of serum KL-6, a marker of epithelial injury, are indicative of active ILD in SSc disease.
  
  
  CONCLUSIONS
  The association of GER with SSc-ILD is strongly supported by several studies. An aggressive treatment for reflux is recommended in all SSc patients with ILD; however, future studies need to be performed to prove a long-term benefit.
authors.affiliation: Rheumatology Division, University of São Paulo, São Paulo, Brazil.
authors.forename: Romy B
authors.initials: RB
authors.lastname: Christmann
authors.forename: Athol U
authors.initials: AU
authors.lastname: Wells
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Richard M
authors.initials: RM
authors.lastname: Silver
mesh_terms: D001706:Biopsy; D004947:Esophagus / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000209:etiology* / Q000517:prevention & control; D008365:Manometry; D011859:Radiography; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000150:complications*