Pediatric Eosinophilic Esophagitis Endotypes: Are We Closer to Predicting Treatment Response?

Clin Rev Allergy Immunol. 2018 Aug;55(1):43-55. doi: 10.1007/s12016-017-8658-8.

Abstract

Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven gastrointestinal disease that is characterized by esophageal eosinophilia. Currently, there are no Food and Drug Administration (FDA)-approved treatments for EoE, but the two most commonly prescribed therapies include topical corticosteroids and food elimination diets. Clinical trials have revealed a significant proportion of cases that are resistant to topical corticosteroids, and although we define EoE as a food antigen-driven disease, not all patients with EoE respond to elimination diets or even elemental diets. The varied response to treatments highlights the heterogeneity of EoE and the need for new treatment strategies. Despite the clinical differences in treatment response, predicting the outcome remains difficult since factors including age, histologic severity at diagnosis, atopic history, and anthropometrics are not predictive of treatment response. In our practice at an academic pediatric referral center, we observe distinct clinical EoE phenotypes, including cases with atopy, connective tissue disorders, or responsiveness to a proton pump inhibitor. Similar to the work in progress with asthma, stratification of patients with EoE by clinical phenotypes and/or molecular endotypes will likely assist with therapy selection and prediction of natural history. Molecular analysis with gene expression panels also shows promise in helping us classify patients based on molecular endotypes. In additional to the clinical and molecular classifications, more accurate histologic diagnostic criteria for EoE may help us tease out small differences between patient cohorts. Despite the leaps in knowledge over the past decade regarding EoE pathogenesis, it remains a challenge to predict the response to treatment. Future studies focused on molecular, genetic, and immunologic analyses of larger patient cohorts are needed to assist in identifying EoE phenotypes and endotypes as we attempt to improve patient outcomes in pediatric EoE.

Keywords: Biomarker; Dietary elimination therapy; EoE Diagnostic Panel; Fibrostenotic; Patient outcome; Phenotype; Proton pump inhibitor-responsive esophageal eosinophilia; Stratification; Topical corticosteroids.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Biomarkers, Pharmacological / metabolism
  • Child
  • Diet Therapy
  • Eosinophilic Esophagitis / classification
  • Eosinophilic Esophagitis / diagnosis*
  • Eosinophilic Esophagitis / drug therapy
  • Genetic Testing*
  • Humans
  • Immunologic Tests*
  • Pathology, Molecular*
  • Phenotype
  • Prognosis
  • Proton Pump Inhibitors / therapeutic use
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Biomarkers, Pharmacological
  • Proton Pump Inhibitors