Clinical and Allergy Profiles of Eosinophilic Esophagitis Differ From GERD

The 2020 American Gastroenterological Association and Joint Task Force on Allergy–Immunology guidelines on managing eosinophilic esophagitis (EoE) reclassified what was previously known as “proton pump inhibitor (PPI)–responsive EoE” as a “subtype of EoE with PPI response.” A trial of PPI is no longer a diagnostic criterion, and PPI monotherapy is now considered a treatment option for EoE.

However, few studies have compared the clinical and allergy profiles of patients with PPI-responsive EoE (PPI-r-EoE) or PPI-nonresponsive EoE (PPI-nr-EoE) against those of patients who have erosive esophagitis (EE) that can develop secondary to gastroesophageal reflux disease (GERD).

Walter W. Chan, MD, MPH, director of the Center for Esophageal/Gastrointestinal Disorders at Brigham and Women’s Hospital, Mayssan Muftah, MD, senior GI fellow, and colleagues have reported supporting evidence that PPI-r-EoE is clinically similar to PPI-nr-EoE and significantly different from EE. Their report appears in Diseases of the Esophagus.


The team retrospectively studied the following:

  • 104 patients diagnosed with EoE on esophageal biopsies from esophagogastroduodenoscopy (EGD) between May 2006 and September 2015
  • 80 control subjects with confirmed EE without eosinophils on esophageal biopsies

The patients with EoE were treatment-naïve at the time of diagnosis. They underwent a trial of high-dose omeprazole, 40 mg twice daily for at least eight weeks, followed by repeat endoscopy with biopsies. Fifty-seven were classified as having responsive disease and 47 as having non-responsive disease.

Presenting Symptoms

The indication for EGD differed between groups:

  • More PPI-r-EoE patients than EE patients complained of dysphagia (77% vs. 43%, P<0.001)
  • There were no statistically significant differences between PPI-r-EoE and PPI-nr-EoE patients in presenting symptoms; most patients complained of dysphagia, followed by reflux and abdominal pain

Endoscopic Findings

Findings on endoscopy were significantly different among all three groups in pairwise comparisons:

Esophageal rings

  • PPI-nr-EoE: 75%
  • PPI-r-EoE: 52% (P=0.02 vs. PPI-nr-EoE)
  • EE: 2.5% (P<0.001 vs. PPI-r-EoE)

Esophageal furrows

  • PPI-nr-EoE: 49%
  • PPI-r-EoE: 29% (P=0.03 vs. PPI-nr-EoE)
  • EE: 1.3% (P<0.001 vs. PPI-r-EoE)


  • PPI-nr-EoE: 9%
  • PPI-r-EoE: 7% (Statistically similar to PPI-nr-EoE)
  • EE: 71% (P<0.001 vs. PPI-r-EoE)


  • PPI-nr-EoE: 11%
  • PPI-r-EoE: 16% (Statistically similar to PPI-nr-EoE)
  • EE: 39% (P=0.004 vs. PPI-r-EoE)

PPI-r-EoE and PPI-nr-EoE patients were similar concerning other endoscopic findings, including ulcer, stricture, narrowing, plaques, and exudate.

Allergy Findings

More PPI-r-EoE patients than EE patients had a history of an allergic condition (75% vs. 19%, P<0.001). There was no significant difference between PPI-r-EoE and PPI-nr-EoE patients.

Similarly, when allergic conditions were assessed individually, the prevalences were significantly higher in PPI-r-EoE versus EE and not different between PPI-r-EoE and PPI-nr-EoE.

Multivariable Analyses

On multivariable analysis, independent positive predictors were:

  • PPI-nr-EoE vs. EE—History of allergic conditions (OR, 4.8; P=0.03), rings on endoscopy (OR, 27.5; P=0.002), and furrows on endoscopy (OR, 17.1; P=0.04)
  • PPI-r-EoE vs. EE—History of allergic conditions (OR, 20.1; P<0.0001) and rings on endoscopy (OR, 108.3, P=0.001)
  • PPI-nr-EoE vs. PPI-r-EoE—Rings on endoscopy (OR, 2.5; P=0.03)

Implications for Diagnosis and Therapy

These findings support the concept that PPI-r-EoE and PPI-nr-EoE share similar inflammatory pathways. A better understanding of the distinct clinical and allergy profile of patients with PPI-r-EoE should help improve initial diagnosis, guide therapy, and identify novel therapeutic targets.

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