Reflux plays a part in the pathogenesis of eosinophilic esophagitis (EoE), and is more relevant in cases responsive to proton pump inhibitor (PPI) therapy, according to a study published in The American Journal of Gastroenterology. The study also found that PPI refractoriness may be predicted by a low impedance gradient between the mid and distal esophagus.

The role of reflux in EoE and the mechanisms of response to PPI therapy in EoE have not been fully elucidated in prior studies. This prospective, multicenter study was designed to examine these questions through a comprehensive assessment using impedance-pH monitoring, comparing 60 consecutive EoE patients with 60 patients with gastroesophageal reflux disease and 60 age- and sex-matched healthy controls. EoE patients were evaluated on- and off-PPIs, and histology was used to assess responsiveness. Impedance-pH appraisal included mucosal integrity, measured with mean nocturnal baseline impedance (MNBI), and chemical clearance, assessed with the post-reflux swallow-induced peristaltic wave (PSPW) index.

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Compared with healthy controls, the number of refluxes was higher in participants with EoE, while the PSPW index was lower (P <.0167 for all pairwise comparisons). Off PPI therapy, 20 patients with PPI-refractory EoE were distinguished from 40 patients with PPI-responsive EoE by a lower gradient of MNBI between the mid and distal esophagus, which was a predictor of PPI failure. On PPI, the sole reflux parameter that distinguished PPI-refractory from PPI-responsive EoE was a lower PSPW index. In PPI-responsive patients, all reflux parameters improved, while in PPI-refractory cases, the PSPW index was not modified and was independently associated with PPI-responsiveness (OR, 1.143; 95% CI, 1.049-1.247, P =.002). Compared with PPI-refractory EoE, MNBI in the mid and distal esophagus improved much more in PPI-responsive EoE.

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Study investigators concluded that the study, “shows that EoE is characterized by abnormal reflux burden. Low impedance gradient between the mid and distal esophagus may predict PPI refractoriness, in turn characterized by lack of on-therapy improvement of impaired chemical clearance and marginal recovery of mucosal integrity. Conversely, in PPI-responsive EoE, less-extensive mucosal damage is associated with on-therapy improvement of chemical clearance and foremost recovery of mucosal integrity. Our findings indicate that reflux plays a role in the pathogenesis of EoE, more relevant in PPI-responsive cases, and that PPIs mainly act by antireflux mechanisms, supporting long-term prescription in PPI-responsive EoE.”


Frazzoni M, Penagini R, Frazzoni L, et al. Role of reflux in the pathogenesis of eosinophilic esophagitis: Comprehensive appraisal with off- and on PPI impedance-pH monitoring. Am J Gastroenterol. 2019;114(10):1606-1613.