Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis

Abstract

Treatment of eosinophilic esophagitis has progressed from elemental formula for children and esophageal dilation for adults to selective exclusion of food triggers and swallowed topical corticosteroids. Management guidelines are available from the American Gastroenterological Association and the Joint Task Force on Allergy Immunology Practice Parameters. We cannot, however, evaluate the efficacy of treatments without a definition of response. We propose a treat-to-target approach, based on symptoms and findings from endoscopy and histology. This approach addresses dissociations between outcomes, such as symptom persistence despite normalization of histologic features and symptom resolution after esophageal dilation despite histologic features of active disease. Eosinophilic esophagitis can now be treated with biologic agents that target specific immune pathways, and findings from prospective trials have indicated that less-restrictive, empiric, elimination diets can be effective and reduce the need for repeated endoscopic assessment of disease activity during food reintroduction. We also discuss eosinophilic esophagitis subtypes, factors associated with disease, and advances in management.

Keywords: Dysphagia; Eosinophilic Esophagitis; Eosinophilic Gastroenteritis; Eosinophilic Gastrointestinal Disease; Gastroesophageal Reflux Disease.

Figure 1.

Pathogenesis and therapeutic targets for EoE. Pathogenesis of EoE involves presentation of dietary and environmental antigens to T cells leading to an inflammatory response mediated by T-helper 2 cells and IL13. In the esophageal mucosa, IL5 and eotaxin-3 recruit eosinophils from the bone marrow. Eosinophils and mast cells secrete proteases, cytokines, and histamines to promote inflammation and tissue remodeling. Phase 2 trials of patients with eosinophilic gastrointestinal disorders have studied the efficacy of monoclonal antibodies against IgE, IL4 receptor–α, IL5, IL5 receptor, IL13, and sialic acid binding Ig-like lectin 8 (Siglec8), as well as an oral antagonist of prostaglandin D2 receptor 2. Other targets for treatment could include IL9, IL15, thymic stromal lymphopoietin (TSLP), transforming growth factor–β (TGF-β), and eotaxin 3.

Figure 2.

Goals of management. Goals of treatment are to minimize symptoms and endoscopic histopathologic features of EoE. Maximal symptoms are dysphagia with every meal, despite a modified, soft-solid diet, whereas minimal symptoms are complete absence of dysphagia without any dietary avoidance based on food texture. Minimal histologic activity is defined as 0 eos/hpf. Minimal endoscopy activity is defined as an absence of endoscopic features of inflammation (furrows, exudate, or edema) and an esophageal diameter >20 mm. Effective treatment would normalize all of these disease features (white center); whereas ineffective therapy would result in maximal activity of these features (black outer circle). The composite approach identifies clinically relevant issues with dissociation among outcomes. For example, anti-inflammatory therapies often normalize histologic features of EoE, but have small effects on symptoms generated by fibrostenotic esophageal strictures (yellow circle 1). Esophageal dilation, however, is effective at relieving symptoms of dysphagia and endoscopic stricture, but does not reduce mucosal inflammation (yellow circle 2).