title: Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn.
abstract: BACKGROUND
  Microscopic esophagitis (ME) is common in patients with non-erosive reflux disease (NERD), and dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. We aimed to compare these histological abnormalities in healthy volunteers (HVs) and patients with erosive esophagitis (EE), NERD, and functional heartburn (FH).
  
  
  METHODS
  Consecutive patients with heartburn prospectively underwent upper endoscopy and impedance-pH off-therapy. Twenty EE patients and fifty-seven endoscopy-negative patients (NERD), subclassified as 22 with pH-POS (positive for abnormal acid exposure), 20 with hypersensitive esophagus (HE; normal acid/symptom association probability [SAP]+ or symptom index [SI]+), and 15 with FH (normal acid/SAP-/SI-/ proton pump inhibitor [PPI] test-), were enrolled. Twenty HVs were also included. In each patient/control, multiple specimens (n = 5) were taken from the distal esophagus and histological alterations were evaluated. ME was diagnosed when the global histological score was >0.35.
  
  
  RESULTS
  The prevalence of ME was higher (p < 0.0001) in EE (95 %), pH-POS (77 %), and HE (65 %) NERD patients than in FH patients (13 %) and HVs (15 %). Also, basal cell hyperplasia (p < 0.0023), DIS (p < 0.0001), and papillae elongation (p < 0.0002) showed similar rates of prevalence in the above populations (p < 0.0001). ME, including each histological lesion, had similar low frequencies in FH and HVs (p = 0.9990). Considering the histological abnormalities together, they permitted us to clearly differentiate EE and NERD from FH and HVs (p < 0.0001 and p < 0.0001, respectively).
  
  
  CONCLUSIONS
  The lack of ME in the esophageal distal biopsies of FH patients indicates a limited role of these histological abnormalities in symptom generation in them. ME can be considered as an accurate and reliable diagnostic marker for distinguishing FH patients from GERD patients and has the potential to be used to guide the correct therapy.
authors.affiliation: Gastroenterology Unit, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Via Giustiniani, 2, 35121, Padua, Italy. esavarino@libero.it
authors.forename: Edoardo
authors.initials: E
authors.lastname: Savarino
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zentilin
authors.forename: Luca
authors.initials: L
authors.lastname: Mastracci
authors.forename: Pietro
authors.initials: P
authors.lastname: Dulbecco
authors.forename: Elisa
authors.initials: E
authors.lastname: Marabotto
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Gemignani
authors.forename: Luca
authors.initials: L
authors.lastname: Bruzzone
authors.forename: Nicola
authors.initials: N
authors.lastname: de Bortoli
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Frigo
authors.forename: Roberto
authors.initials: R
authors.lastname: Fiocca
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Savarino
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D017097:Electric Impedance; D016099:Endoscopy, Gastrointestinal / Q000379:methods; D050782:Esophageal pH Monitoring; D004941:Esophagitis / Q000209:etiology* / Q000473:pathology; D004942:Esophagitis, Peptic / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D004947:Esophagus / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D006356:Heartburn / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult