Eosinophilic Esophagitis: A Review

Abstract

Importance: Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disease of the esophagus that affects an estimated 34.4/100 000 people in Europe and North America. EoE affects both children and adults, and causes dysphagia, food impaction of the esophagus, and esophageal strictures.

Observations: EoE is defined by symptoms of esophageal dysfunction, such as vomiting, dysphagia, or feeding difficulties, in a patient with an esophageal biopsy demonstrating at least 15 eosinophils per high-power field in the absence of other conditions associated with esophageal eosinophilia such as gastroesophageal reflux disease or achalasia. Genetic factors and environmental factors, such as exposure to antibiotics early in life, are associated with EoE. Current therapies include proton pump inhibitors; topical steroid preparations, such as fluticasone and budesonide; dietary therapy with amino acid formula or empirical food elimination; and endoscopic dilation. In a systematic review of observational studies that included 1051 patients with EoE, proton pump inhibitor therapy was associated with a histologic response, defined as less than 15 eosinophils per high-power field on endoscopic biopsy, in 41.7% of patients, while placebo was associated with a 13.3% response rate. In a systematic review of 8 randomized trials of 437 patients with EoE, topical corticosteroid treatment was associated with histologic remission in 64.9% of patients compared with 13.3% for placebo. Patients with esophageal narrowing may require dilation. Objective assessment of therapeutic response typically requires endoscopy with biopsy.

Conclusions and relevance: EoE has a prevalence of approximately 34.4/100 000 worldwide. Treatments consist of proton pump inhibitors, topical steroids, elemental diet, and empirical food elimination, with esophageal dilation reserved for patients with symptomatic esophageal narrowing.

Figure 1.

Pathophysiology of Eosinophilic Esophagitis Early-life exposures, genetic factors, and an atopic state likely increase disease susceptibility in eosinophilic esophagitis. Exposure to antigens causes the esophageal epithelium to release alarmins, IL-33, and thymic stromal lymphopoietin (TSLP). These cytokines in turn stimulate T-helper type 2 (Th2) cells’ secretion of IL-13, IL-4, and IL-5. IL-13 and IL-4 stimulate the changes seen in the esophageal epithelium, including basal cell hyperplasia and dilated intracellular spaces. Chemotaxins, eotaxin-3 and IL-5, lead to granulocyte infiltration. The mixed cytokine milieu also contributes to the activation of fibroblasts in the lamina propria, collagen deposition, and tissue stiffness.

Figure 2.

Endoscopic and Histologic Appearance of the Eosinophilic Esophagitis (EoE) Esophagus Endoscopy of EoE: normal esophagus (A); linear furrows (B); mucosal pallor representing edema, decreased vascular pattern, and concentric rings or trachealization (C); small white plaques (D); and esophageal narrowing and rent due to endoscope passage (E). Histology (hematoxylin and eosin) of EoE: F, Normal esophageal squamous epithelium with inconspicuous basal layer, luminal squamous differentiation, and absence of inflammation. G, EoE mucosa demonstrating elongated papilla (yellow arrowheads), basal cell hyperplasia (blue line), infiltrating eosinophils (white arrowheads), eosinophil microabscess (black arrowhead), and epithelial spongiosis (pink arrowheads). Images courtesy of Benjamin Wilkins, MD, PhD, Children’s Hospital of Philadelphia.