Journal of Gastroenterology

, Volume 48, Issue 4, pp 473–482 | Cite as

Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn

  • Edoardo SavarinoEmail author
  • Patrizia Zentilin
  • Luca Mastracci
  • Pietro Dulbecco
  • Elisa Marabotto
  • Lorenzo Gemignani
  • Luca Bruzzone
  • Nicola de Bortoli
  • Anna Chiara Frigo
  • Roberto Fiocca
  • Vincenzo Savarino
Original Article—Alimentary Tract



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).


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.


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).


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.


Dilated intercellular spaces Gastroesophageal reflux Functional heartburn NERD 



Microscopic esophagitis


Dilation of intercellular spaces


Non-erosive reflux disease


Erosive esophagitis


Healthy volunteers


Functional heartburn


Hypersensitive esophagus


Symptom association probability


Symptom index


Proton pump inhibitor


Gastroesophageal reflux disease


Transmission electron microscopy


Light microscopy


Squamocolumnar junction


Basal cell hyperplasia


Papillae elongation


Global score


Acid exposure time


Generalized estimating equations


Lower esophageal sphincter


Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer 2012

Authors and Affiliations

  • Edoardo Savarino
    • 1
    Email author
  • Patrizia Zentilin
    • 2
  • Luca Mastracci
    • 3
  • Pietro Dulbecco
    • 2
  • Elisa Marabotto
    • 2
  • Lorenzo Gemignani
    • 2
  • Luca Bruzzone
    • 2
  • Nicola de Bortoli
    • 4
  • Anna Chiara Frigo
    • 5
  • Roberto Fiocca
    • 3
  • Vincenzo Savarino
    • 2
  1. 1.Gastroenterology Unit, Department of Surgical, Oncological and Gastroenterological SciencesUniversity of PaduaPaduaItaly
  2. 2.Division of Gastroenterology, Department of Internal MedicineIRCCS AOU San Martino, ISTGenoaItaly
  3. 3.Dipartimento di Discipline ChirurgicheMorfologiche E Metodologie Integrate, University of GenoaGenoaItaly
  4. 4.Gastroenterology Unit, Department of Internal MedicineUniversity of PisaPisaItaly
  5. 5.Department of Cardiac, Thoracic and Vascular SciencesUniversity of PaduaPaduaItaly

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