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

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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.

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Abbreviations

ACG:

American College of Gastroenterology

EoE:

Eosinophilic esophagitis

EDP:

EoE Diagnostic Panel

FP:

Fluticasone proprionate

FDA:

Food and Drug Administration

GERD:

Gastroesophageal reflux disease

HPF:

High-power microscopic field

Ig:

Immunoglobulin

IL:

Interleukin

NASPGHAN:

North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition

OBS:

Oral budesonide suspension

PPI:

Proton pump inhibitor

PPI-REE:

Proton pump inhibitor-responsive esophageal eosinophilia

SFED:

Six-food elimination diet

SPT:

Skin prick test

Th2:

T-helper cell

TSLP:

Thymic stroma lymphopoietin

TGF-β:

Transforming growth factor beta

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Acknowledgements

The authors wish to thank Dr. Phil Putnam for valuable input and Shawna Hottinger for editorial assistance.

Funding

This work was supported by the NIH Grant U54 AI117804. The Consortium for Eosinophilic Gastrointestinal Disease Researchers (CEGIR, U54 AI117804) is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS, and is funded through collaboration between NIAID, NIDDK, and NCATS. CEGIR is also supported by patient advocacy groups including the American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Diseases (CURED), and Eosinophilic Family Coalition (EFC).

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Authors and Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA

    Anna E. Ferguson & Vince A. Mukkada

  2. Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, ML7028, Cincinnati, OH, 45229, USA

    Patricia C. Fulkerson

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  1. Anna E. Ferguson
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  2. Vince A. Mukkada
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  3. Patricia C. Fulkerson
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Correspondence to Patricia C. Fulkerson.

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Conflicts of Interest

A. E. Ferguson does not declare any conflicts of interest. P.C. Fulkerson has served as a consultant for Genentech, Inc., and has received research funding from Knopp Biosciences, LLC. V. A. Mukkada has served as a consultant for Shire Pharmaceuticals.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Ferguson, A.E., Mukkada, V.A. & Fulkerson, P.C. Pediatric Eosinophilic Esophagitis Endotypes: Are We Closer to Predicting Treatment Response?. Clinic Rev Allerg Immunol 55, 43–55 (2018). https://doi.org/10.1007/s12016-017-8658-8

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