Proton Pump Inhibitors Plus Food Elimination Diet Superior to Monotherapy in Refractory EoE


A small retrospective study examined outcomes in patients with eosinophilic esophagitis (EoE) who did respond to solo therapies.

A recently published study found that a combination of proton pump inhibitors (PPIs) and a food elimination diet (FED) works better than either one alone in patients with eosinophilic esophagitis (EoE) who are refractory to monotherapy.

High-dose PPI monotherapy is a current first-line treatment to induce remission in EoE, which is defined as having at least 15 eosinophils per high-power field (eos/hpf).

Combination therapy is understudied, said the researchers, writing in Gastro Hep Advances; what is known focuses on topical corticosteroids and FED, and not PPI and FED.

The current study aimed to answer some questions raised by an earlier study of 64 children, which showed a reduction in eos/hpf with the removal of milk, wheat, soy, and egg from the diet and PPI therapy. There was a greater proportion of patents reaching histological remission with this combination therapy than with PPI monotherapy, but what was not delineated was if some patients are only responsive to combination therapy and not monotherapy or if one subset responds to PPI therapy while another subset responds to a FED.

This retrospective cohort study identified patients with EoE seen at Tufts Medical Center in Boston, Massachusetts. They did not respond to PPI monotherapy and FED monotherapy, but were histologically responsive to PPI and FED combination therapy. A chart review of the patients also identified symptom changes.

Of 405 patients with EoE diagnosed between January 2013 and September 2021, 12 patients were included in the analysis. Eight of the 12 were male (66.7%) and 3 were children. Ages ranged from 7 to 53 years, with a median age of 23.

Of 12 patients, 4 had histologically active EoE while on PPI monotherapy, so baseline information was only available for 8 out the 12. Of these 8, all reported symptoms, with most having dysphagia. Histologic findings showed a median (IQR) peak eosinophil count of 45 (35.5-50) eos/hpf.

Using PPI monotherapy, different types of dosing schedules were attempted, but for 75% of the patients, symtpoms remained after 6 weeks of treatments, including food impaction, heartburn, and abdominal pain.

Results with an elimination diet were similar. The most popular FED removed milk and wheat. Symptoms continued after 6 weeks of the restrictive diet.

Median peak eosinophil counts were similar after both types of monotherapy: 45.5 eos/hpf after PPI, and 47.5 eos/hpf after FED.

After implementing the combination therapy, 11 of the 12 saw their symptoms resolve.

Comparative analysis of peak eosinophil counts showed that patients achieved a median of 4.5 (2.0-6.5) eos/hpf, which was significantly reduced from baseline (median, 45 [35.5-50.0]; Wilcoxon signed-rank test, P < .001); PPI monotherapy (median, 41 [26.0-50.0]; Wilcoxon signed-rank test, P < .001); and FED monotherapy (median, 45 [17.0-67.5]; Wilcoxon signed-rank test, P < .001).

As recently as 2017, the authors said, the combination of FED plus drug therapy was discouraged, “due to the potential for additive side effects, negative impacts of quality of life, and confounding which treatment induces histologic remission.”

In light of their findings, the authors said “combination therapy should be considered in the treatment algorithm for EoE, especially for patients who fail to achieve histologic remission with monotherapy.”

The retrospective nature of the study and small sample size are among the limitations of their work, they said; they were not able to pinpoint the specifics of efficacy since different treatment combinations of PPIs and FED were used. They encouraged additional study, using standardized treatment plans and to take into consideration the increased patient burden with combination therapy.


Leung J, Sia T, Miller M, et al. Combination of proton pump inhibitors and food elimination diet for eosinophilic esophagitis refractory to monotherapy. Gastro Hep Adv. Published online April 14, 2022. doi:10.1016/j.gastha.2022.04.002

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