Acid Reflux and EoE: A Complex Relationship

Often caused by acid reflux, eosinophilic esophagitis is an emerging inflammatory disease that is generally unresponsive to proton pump inhibitor therapy.

Often caused by acid reflux, eosinophilic esophagitis (EoE) is an emerging inflammatory disease that is generally unresponsive to proton pump inhibitor (PPI) therapy.

EoE is so new that the First International Gastrointestinal Eosinophil Research Symposium Subcommittee only published the first consensus guideline on the condition in 2007.

This guideline made a clear demarcation between EoE and gastroesophageal reflux disease (GERD), indicating that GERD’s hallmark is PPI responsiveness.

A different condition, proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) responds symptomatically and histologically with PPI therapy. It is not considered EoE, but PPI-REE is phenotypically and genotypically indistinguishable from EoE.

PPI-REE may represent the subset of EoE patients responsive to PPIs.

A pair of researchers explored the link between GERD and EoE in the journal Best Practice & Research Clinical Gastroenterology.

PPIs provide benefit in 33% of EoE patients whose esophageal pH monitoring indicates non-pathological disease.

EoE and PPI-REE mucosal disruption is independent of acid exposure, but EoE patients with acid hypersensitivity may benefit when they take PPIs.

Acid damage to the mucosa during acid reflux episodes allows antigens to penetrate tissues thereby setting off eosinophilia. PPIs appear to reverse inflammatory gene expression in PPI-REE as strongly as steroids benefit patients with EoE.

In other words, PPI therapy in PPI-REE significantly downregulates inflammatory markers in the distal and proximal esophagus. In EoE patients, topical steroids do the same thing.

Conversely, EoE may cause acid reflux through stricture formation or acid reflux, and EoE co-existence with GERD may be coincidental.

The researchers suggested that EoE and PPI-REE will soon be considered the same disease.

They predicted that the standard of care for EoE will shift to include PPIs as first-line therapy, while second-line therapy will include restricted diet and steroids.

Still, questions remain unresolved in PPI-REE: is esophageal barrier impairment the cause or the effect of EoE, and do PPIs primarily target barrier integrity or esophageal inflammation?