Eosinophilic oesophagitis (EoE) and Gastroesophageal reflux disease (GERD) are the most prevalent chronic esophageal inflammatory
conditions in children and adults in the Western world. Whereas the first is an allergen-driven disease, the latter develops as a consequence of pathological exposure of the oesophageal mucosa to
acid-predominant gastric contents. Distinguishing both disorders is important because of their different aetiopathogenesis, natural history and monitoring. However, a rigid distinction between EoE and GERD is difficult due to overlapping clinical and histological features, not to mention their frequent coexistence and potential partially shared pathogenic pathways. The presence of heartburn and marked esophageal eosinophilia, for instance, might be fairly common in both entities.
In order to solve this diagnostic conundrum, the first consensus recommendations for diagnosis and management of EoE were published in 2007. These guidelines advocated a diagnosis of EoE in
patients with symptomatic oesophageal eosinophilia (>15 eosinophils per high power field (eos/HPF)) showing either lack of response to proton pump inhibitor (PPI) therapy or a normal acid exposure
on esophageal pH monitoring. Accordingly, a diagnosis of GERD was recommended for those patients who were either responders to PPI therapy or had objective evidence of pathological esophageal acid exposure. This distinction was based on the assumption that only GERD, as an acid-related disorder, could respond to the acid-suppressive effect of PPIs. As such, these guidelines equated
GERD with symptomatic and histological response to PPI therapy. Far from fulfilling the expectation of distinguishing GERD from EoE, the recommended PPI trial unexpectedly uncovered a third intriguing category of patients apparently sharing features of EoE and GORD. Updated consensus recommendations in 2011 included changes to these findings: (1) the description of a novel phenotype, PPI-responsive oesophageal eosinophilia (PPI-REE), referring to patients with features of EoE who achieve clinical and histological
remission on PPI therapy (2) response to PPI therapy in patients with PPI-REE was not necessarily considered a manifestation of GERD and (3) the retraction of recommending esophageal
pH monitoring as a diagnostic criterion, due to its low accuracy to predict response to PPI. Nonetheless, support for a PPI trial was maintained as a diagnostic criterion, since PPI-REE and EoE
were still considered separate clinical entities as they showed a different response to the PPI trial.
The PPI-REE Task Force of the European Society of Eosinophilic Esophagitis (EUREOS), integrated by an international group of EoE experts, has recently release a consensus document that provides a new definition for PPI-responsive esophageal eosinophilia (PPI-REE).
The accurate location of PPI-REE within the spectrum between
EoE and GERD, the therapeutic mechanisms leading to responsiveness to PPI therapy in patients with suspected
EoE and whether the response to a PPI trial has any validity
as a means of excluding EoE has been ascertained by an EUREOS task force integrated by European and American gastroenterologists, allergists and pediatricians. In a new document published in GUT, the differences and similarities beetwen EoE, PPI-REE and GERD are discussed, including symptoms, endoscopic and histological findings, and the mollecular and genetic features in these conditions. The efficacy of PPIs to induce and maintain remission in EoE and the potential mode of action of PPIs in EoE are also summarized in this paper.
The EUREOS task force provides a reapraisal of the PPIs as a diagnostic tool and position of PPIs in the treatment of EoE, and most importantly, a proposal for updated diagnostic criteria for EoE, which should be now characterized by:
1. Symptoms of oesophageal dysfunction (dysphagia/food impaction in adults; abdominal pain, nausea, reflux-like symptoms, feeding difficulties, growth failure, dysphagia in children)
2. Baseline oesophageal eosinophil-predominant inflammation (characteristically consisting of a peak value of ≥15 eos/HPF) limited to the oesophagus
▸ Baseline endoscopy should be preferably performed off proton pump inhibitor (PPI) therapy to better understand the patient profile in case of further response to PPI therapy
▸ Other local and systemic causes of oesophageal eosinophilia should be ruled out: eosinophilic gastroenteritis, Crohn’s disease, hypereosinophilic syndrome, parasites, drug hypersensitivity, achalasia, vasculitis, pemphigoid, connective tissue disorders and
▸ Biopsies from the antrum and/or duodenum should be obtained in all children and in adults with GI symptoms or endoscopic abnormalities
▸ A diagnosis of EoE in patients based solely on histology, without clinical and endoscopic features compatible with EoE, might be questionable
▸ Routine oesophageal pH monitoring is not recommended in the diagnostic work-up of EoE
▸ A majority of patients with EoE will achieve symptom response and histological remission (<15 eos/HPF) on PPI, topical steroid or dietary intervention
The new consensus document on PPI-R-EoE also includes a section of unsolved issues, that includes specific consideration in pediatric EoE patients, the mechanisms underlying the response to PPIs, how to define response to PPI therapy, the adequate doses, intervals and duration of therapy, as well as the effect of PPIs on the natural history of EoE. The new option on combining PPIs and steroids in particular cases is also discussed.