Original article
Alimentary tract
Proton Pump Inhibitors Partially Restore Mucosal Integrity in Patients With Proton Pump Inhibitor–Responsive Esophageal Eosinophilia but Not Eosinophilic Esophagitis

https://doi.org/10.1016/j.cgh.2014.02.037Get rights and content

Background & Aims

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.

Section snippets

Study Subjects

In this prospective study, we included 16 adult patients with suspected EoE (>15 eosinophils/high-power field [eos/hpf], predominant symptoms of dysphagia and/or food impaction, and endoscopic signs of EoE), and 11 healthy controls. Based on peak eosinophil counts after PPI, patients were divided into 2 subgroups: responders (PPI-REE, ≤10 eos/hpf) and nonresponders (EoE, >10 eos/hpf) (Figure 1). Patients were recruited consecutively from the outpatient clinic of our hospital. Healthy controls

Subject characteristics

We consecutively included 16 patients (13 men) with suspected EoE, and 11 controls (7 men). No patients were excluded or dropped out after enrolment in the study. The median age at first endoscopy was 42 years (IQR, 32–46 y) for patients and 35 years (IQR, 29–53 y) for controls (P = .6). None of the controls had abnormalities on endoscopy. Based on peak eosinophil counts after PPI, 8 patients (6 men) were classified as PPI-REE (range, 0–10 eos/hpf), and 8 patients (7 men) were classified as EoE

Discussion

This study investigated the esophageal mucosal integrity in patients with PPI-REE and EoE. By using structural and functional measurements we found that the esophageal mucosal integrity was impaired, to a similar extent, in patients with PPI-REE and EoE. Furthermore, acid suppression with PPIs partially restored mucosal integrity parameters and decreased inflammation in patients with PPI-REE, but not in patients with EoE.

In this study, we showed passage of molecules that were 40,000 daltons

References (19)

There are more references available in the full text version of this article.

Cited by (160)

  • Eosinophilic Esophagitis: What the Otolaryngologist Needs to Know

    2024, Otolaryngologic Clinics of North America
  • Dietary Management of Eosinophilic Esophagitis

    2024, Immunology and Allergy Clinics of North America
  • Pharmacologic Management of Eosinophilic Esophagitis

    2024, Immunology and Allergy Clinics of North America
View all citing articles on Scopus

Conflicts of interest These authors disclose the following: Albert Bredenoord has received research funding from AstraZeneca, Endostim, Medical Measurement Systems, and Shire, and has received speaker fees from Medical Measurement Systems and Shire; and Wouter de Jonge has received funding from Glaxo Smith Kline. The remaining authors disclose no conflicts.

Funding A.J.B. and W.J.d.J. are supported by The Netherlands Organization for Scientific Research (Nederlandse Organisatie voor Wetenschappelijk Onderzoek).

View full text