Common and disparate clinical presentations and mechanisms in different eosinophilic gastrointestinal diseases.

Eosinophilic gastrointestinal diseases (EGIDs) are a group of diseases characterized by selective eosinophil infiltration of the gastrointestinal (GI) tract in the absence of other causes of eosinophilia. These diseases are generally driven by type 2 inflammation, often in response to food allergen exposure. Among all EGIDs, the clinical presentation often includes a history of atopic disease with a variety of GI symptoms. EGIDs are traditionally separated into eosinophilic esophagitis (EoE) and non-EoE EGIDs. EoE is relatively better understood and now associated with clinical guidelines and 2 US Food and Drug Administration-approved treatments, whereas non-EoE EGIDs are rarer and less well-understood diseases without US Food and Drug Administration-approved treatments. Non-EoE EGIDs are further subclassified by the area of the GI tract that is involved; they comprise eosinophilic gastritis, eosinophilic enteritis (including eosinophilic duodenitis), and eosinophilic colitis. As with other GI disorders, the disease presentations and mechanisms differ depending on the involved segment of the GI tract; however, the differences between EoE and non-EoE EGIDs extend beyond which GI tract segment is involved. The aim of this article is to summarize the commonalities and differences between the clinical presentations and disease mechanisms for EoE and non-EoE EGIDs.

Eosinophil Involvement Outside the Esophagus in Eosinophilic Esophagitis.

Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune-mediated disorders, characterized clinically by gastrointestinal (GI) symptoms and histologically by eosinophil-predominant infiltration in ≥1 GI tract segment.1 A recent, international consensus by 91 experts proposed a new framework for EGID nomenclature to establish updated terms, designations, and conventions.2 Although this framework offers a standardized starting point for the field, debate is ongoing regarding the appropriate terminology for cases involving multiple areas, such as "non-eosinophilic esophagitis (EoE) EGID and EoE" or "non-EoE EGID with esophageal involvement (EI)." Notably, in a survey of these experts, 61% agreed with the later term "non-EoE EGID with EI," because EoE is isolated to the esophagus by current diagnostic criteria.3 However, limited molecular and pathogenic data exist to support the distinction. Furthermore, disease burden of symptoms and comorbidities generally is higher in non-EoE EGIDs than EoE.4 Presently, there is no screen to predict non-EoE EGID concomitance in EoE; therefore, decision-making to further explore other GI segment involvement is clinically challenging. We aimed to answer 2 fundamental questions in the field (Figure 1A): Is there a shared or distinct pathogenesis between patients with isolated EoE and non-EoE EGIDs with EI as assessed by patient characteristics and molecular profiles? Can we predict concomitant non-EoE EGIDs when EoE exists? Herein, we report a similar molecular signature between EoE and EI and a potential predictive model to identify concomitant non-EoE EGIDs in patients with EoE.