Background and Aims: Some eosinophilic esophagitis (EoE) patients can have a decline in eosinophil count after proton pump inhibitor (PPI) treatment without achieving histologic response, but little is known about this group. We aimed to determine the effect of PPIs on reducing esophageal eosinophilia in patients deemed non-responsive to PPI therapy.

Methods: We analyzed prospectively collected cohort data from newly diagnosed adults with EoE who were histologic non-responders (≥15 eos/hpf) to PPI-only therapy. Symptoms, endoscopic histologic features were assessed before and after PPI. Pre- and post-PPI treatment esophageal biopsies were read by pathologists to determine peak eosinophil counts and other histologic findings.

Results: Of 125 patients, peak eosinophil counts were 102.1 ± 69.8 and 102.9 ± 101.1 (p=0.93) before and after PPI treatment, respectively, but lamina propria fibrosis decreased from 97% to 41% (p<0.001). Heartburn frequency also decreased (19% to 11%; p=0.006), though endoscopic findings did not change. There were 75 patients (60%) who had some decrease in eosinophil counts, with 30 patients (24%) having ≥50% decrease in counts. When comparing the ≥50% and <50% decrease groups, differences in endoscopic features were identified, but the ≥50% group had improvement in eosinophil degranulation, microabscesses, spongiosis, and basal cell hyperplasia.

Conclusion: Peak eosinophil counts did not decrease overall after PPI treatment, but symptoms of heartburn improved. Approximately a quarter had ≥50% decrease in eosinophil counts, with associated decreases in other histologic findings. Further research may consider what role PPIs have in this subset of non-responders or in combination therapies.


proton pump inhibitor, outcomes, histology, treatment, eosinophilic esophagitis