Clinical Reviews in Allergy & Immunology

, Volume 57, Issue 1, pp 111–127 | Cite as

Allergic Comorbidity in Eosinophilic Esophagitis: Mechanistic Relevance and Clinical Implications

  • Peter Capucilli
  • David A. HillEmail author


Allergic eosinophilic esophagitis (EoE) is a chronic, allergen-mediated inflammatory disease of the esophagus, and the most common cause of prolonged dysphagia in children and young adults in the developed world. While initially undistinguished from gastroesophageal reflux disease-associated esophageal eosinophilia, EoE is now recognized as a clinically distinct entity that shares fundamental inflammatory features of other allergic conditions and is similarly increasing in incidence and prevalence. The clinical and epidemiologic associations between EoE and other allergic manifestations are well established. In addition to exaggerated rates of atopic dermatitis, IgE-mediated food allergy, asthma, and allergic rhinitis in EoE patients, each of these allergic manifestations imparts individual and cumulative risk for subsequent EoE diagnosis. As such, EoE may be a member of the “allergic march”—the natural history of allergic manifestations during childhood. Several determinants likely contribute to the relationship between these conditions, including shared genetic, environmental, and immunologic factors. Herein, we present a comprehensive review of allergic comorbidity in EoE. We discuss areas of the genome associated with both EoE and other allergic diseases, including the well-studied variants encoding thymic stromal lymphopoietin and calpain 14, among other “atopic” regions. We summarize ways that environmental factors (such as microbiome-altering pressures and aeroallergen exposure) may predispose to multiple allergic conditions including EoE. Finally, we touch on some fundamental features of type 2 inflammation, and the resulting implications for the development of multiple allergic manifestations. We conclude with an analysis of the “type 2” biologics, and how mechanistic similarities between EoE and the other allergic manifestations have important implications for screening and treatment of the allergic patient.


Eosinophilic esophagitis Atopic dermatitis Food allergy Allergic rhinitis Asthma 



Eosinophilic esophagitis


Atopic dermatitis


IgE-mediated food allergy


Allergic rhinitis




Thymic stromal lymphopoietin


Calpain 14


Oral immunotherapy


Randomized, double-blind placebo-controlled trial

H. pylori

Helicobacter pylori


T helper





We thank Jonathan Spergel and Neil Romberg for their helpful suggestions.


DAH is supported by the NIH (K08 DK116668) and a Children’s Hospital of Philadelphia Junior Faculty grant.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Allergy and Immunology, Department of Pediatrics, Children’s Hospital of PhiladelphiaPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Institute for ImmunologyPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA

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