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Review
. 2022 Jan 12:12:815842.
doi: 10.3389/fphys.2021.815842. eCollection 2021.

Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

Francesca Racca  1   2 , Gaia Pellegatta  3 , Giuseppe Cataldo  1 , Edoardo Vespa  2   3 , Elisa Carlani  3 , Corrado Pelaia  4 , Giovanni Paoletti  1   2 , Maria Rita Messina  1   2 , Emanuele Nappi  1   2 , Giorgio Walter Canonica  1   2 , Alessandro Repici  2   3 , Enrico Heffler  1   2
Affiliations
Review

Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

Francesca Racca et al. Front Physiol. .

Abstract

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients' quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.

Keywords: eosinophilic esophagitis; pathophysiology; precision medicine; therapeutic targets; type 2 inflammation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with several of the authors GWC and EH.

Figures

FIGURE 1
FIGURE 1
Main endoscopic features of eosinophilic esophagitis. From top left: (A) Normal appearance of esophageal mucosa; (B) Edema. Pale mucosa with attenuation of the normal vascular pattern; (C) Rings. Trachealized esophagus with multiple concentric rings (arrow); (D) Exudates. Whitish small plaques not washable through water jet (arrow); (E) Furrows. Typical longitudinal furrows (arrows); (F) Stricture. Narrowing of esophageal lumen not passable by a standard scope (diameter around 9 mm).
FIGURE 2
FIGURE 2
First-line therapies with the range of reported remission rates and therapeutic targets.
FIGURE 3
FIGURE 3
Main pathogenetic mechanisms of EoE.
FIGURE 4
FIGURE 4
Type 2 inflammation in EoE. The figure represents the involved cells and mediators and the therapeutic approaches described in the review. The drugs are colored as follows: Red tag: first-line therapy, Plum tag: orphan drugs, Lilac tag: drugs with reported results on human patients, Green tag: drugs without reported results on human patients, Gray tag: drugs that failed to obtain significant results on human patients.
See this image and copyright information in PMC

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