Advances in clinical management of eosinophilic esophagitis

Abstract

Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsy specimens, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia. We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histological features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and proton pump inhibitor-responsive esophageal eosinophilia. It is also important to consider the epidemiology of EoE (with a current incidence of 1 new case per 10,000 per year and prevalence of 0.5 to 1 case per 1000 per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids, such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and nondirected empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenotic complications of EoE. There are a number of unresolved issues in EoE, including phenotypes, optimal treatment end points, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines; EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians.

Keywords: Diagnosis; Endoscopy; Management Algorithm; Treatment.

Figure 1

Endoscopic findings in EoE. (A) Fixed esophageal rings, previously called trachealization. Rings can vary in severity from subtle ridges to tight fibrotic bands, and full insufflation of the esophagus is required to appreciate their extent. (B) Transient esophageal rings, also called felinization. (C) Linear furrows, which are fissures that run parallel to the axis of the esophagus and have a train track appearance. (D) White plaques/exudates, which are eosinophilic micro-abscesses that can be confused with candidal esophagitis; brushings from this patient were negative for candida. (E) Esophageal narrowing with mucosa edema and decreased vascularity. Of note, decreased vascularity and mucosal edema are also visible in images C, D, G, H, and I, and can be a subtle finding in EoE. (F) A more focal stricture in the distal esophagus. Strictures can be located at any location in the esophagus, however. (G) Crêpe-paper mucosa, in which there is a mucosal tear with passage of the endoscope in a narrowed esophagus. (H) A combination of multiple findings including rings, furrows, plaques, narrowing, and decreased vascularity. (I) A combination of several findings including rings, deep furrows, plaques, and mucosa edema.

Figure 2

Histologic findings in EoE (40x images). (A) Mucosal biopsy of the esophagus showing a marked eosinophilic infiltrate. Additional findings of note include eosinophil degranulation (white asteric), which often indicates eosinophil activation; eosinophil microabscesses, defined as clusters of at least 4 eosinophils and superficial layering with sloughing of the apical epithelial cells (arrow); and basal cell hyperplasia, frequently occupying 50% or more of the epithelium, with spongiosis, a result of dilated intracellular spaces reflecting leaky mucosal barrier (black bar). (B) In addition to the eosinophilic infiltrate and degranulation (white asterisk), this specimen shows lamina propria fibrosis (black bracket).

Figure 3

Overview of response rates and treatment outcomes in clinical trials of topical corticosteroids for EoE. The histologic response rate for the active (blue bars) and comparator (green bars) treatments are shown, for the most stringent outcome measure reported for each trial. MDI indicates use of a multi-dose inhaler in all three of the placebo-controlled fluticasone trials, and in one of the comparative trials.^,, Budesonide indicates use of a viscous budesonide suspension or slurry,^,, NEB indicates use of swallowed nebulized budesonide,^, and BET indicates use of a budesonide effervescent The studies listed under the fluticasone RCTs and budesonide RCTs headers are all placebo controlled.

Figure 4

Dietary reintroduction of food allergens (Modified with permission from Dr. Spergel and colleagues).

Figure 5

Examples of esophageal dilation to treat EoE. (A) A guidewire, which was placed with the neonatal scope, is seen coursing through a very tight proximal esophageal stricture prior to passing the wire-guided bougie. (B) The desired post-dilation effect with a mucosal tear. (C) View through an inflated through-the-scope balloon during a dilation at the gastro-esophageal junction. The developing mucosal tear is seen in the 7–8 o’clock area. (D) The desired post-dilation effect with a mucosal tear.

Figure 6

Algorithm for diagnosis and treatment of EoE.