Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence

Semin Arthritis Rheum. 2010 Dec;40(3):241-9. doi: 10.1016/j.semarthrit.2010.03.002. Epub 2010 May 21.


Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biopsy
  • Esophagus / diagnostic imaging
  • Esophagus / pathology
  • Esophagus / physiopathology
  • Gastroesophageal Reflux / complications*
  • Gastroesophageal Reflux / drug therapy
  • Humans
  • Lung / diagnostic imaging
  • Lung / pathology
  • Lung / physiopathology
  • Lung Diseases, Interstitial / etiology*
  • Lung Diseases, Interstitial / prevention & control
  • Manometry
  • Radiography
  • Respiratory Function Tests
  • Scleroderma, Systemic / complications*