title: Proton pump inhibitors partially restore mucosal integrity in patients with proton pump inhibitor-responsive esophageal eosinophilia but not eosinophilic esophagitis.
abstract: OBJECTIVE
  Histologic analysis is used to distinguish patients with proton pump inhibitor-responsive eosinophilia (PPI-REE) from those with eosinophilic esophagitis (EoE). It is not clear whether these entities have different etiologies. Exposure to acid reflux can impair the integrity of the esophageal mucosal. We proposed that patients with EoE and PPI-REE might have reflux-induced esophageal mucosal damage that promotes transepithelial flux of allergens. We therefore assessed the integrity of the esophageal mucosal in these patients at baseline and after PPI.
  
  
  METHODS
  We performed a prospective study of 16 patients with suspected EoE and 11 controls. Patients had dysphagia, endoscopic signs of EoE, and esophageal eosinophilia (>15 eosinophils/high-power field [eos/hpf]). All subjects underwent endoscopy at baseline; endoscopy was performed again on patients after 8 weeks of treatment with high-dose esomeprazole. After PPI treatment, patients were diagnosed with EoE (>10 eos/hpf; n = 8) or PPI-REE (≤10 eos/hpf; n = 8). We evaluated the structure (intercellular spaces) and function (electrical tissue impedance, transepithelial electrical resistance, transepithelial molecule flux) of the esophageal mucosal barrier.
  
  
  RESULTS
  Compared with controls, electrical tissue impedance and transepithelial electrical resistance were reduced in patients with EoE (P < .001 and P < .001, respectively) and PPI-REE (P = .01 and P = .06, respectively), enabling transepithelial small-molecule flux. PPI therapy partially restored these changes in integrity and inflammation in patients with PPI-REE, but not in those with EoE.
  
  
  CONCLUSIONS
  The integrity of the esophageal mucosa is impaired in patients with EoE and PPI-REE, allowing transepithelial transport of small molecules. PPI therapy partially restores mucosal integrity in patients with PPI-REE, but not in those with EoE. Acid reflux might contribute to transepithelial allergen flux in patients with PPI-REE. Trialregister.nl number: NTR3480.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: b.d.vanrhijn@amc.uva.nl.
authors.forename: Bram D
authors.initials: BD
authors.lastname: van Rhijn
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Pim W
authors.initials: PW
authors.lastname: Weijenborg
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marius A
authors.initials: MA
authors.lastname: van den Bergh Weerman
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Verseijden
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: René M J G J
authors.initials: RM
authors.lastname: van den Wijngaard
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: de Jonge
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Andreas J P M
authors.initials: AJ
authors.lastname: Smout
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Bredenoord
mesh_terms: D000328:Adult; D004802:Eosinophilia / Q000188:drug therapy*; D057765:Eosinophilic Esophagitis / Q000188:drug therapy*; D004947:Esophagus / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology* / Q000503:physiopathology*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D054328:Proton Pump Inhibitors
keywords: Epithelial Barrier; Pathophysiology; Transepithelial Resistance; Treatment