Eosinophilic gastroenteritis: Pathogenesis, diagnosis, and treatment

Abstract

Eosinophilic gastroenteritis (EGE) is a gastrointestinal disorder of unclear etiology that is characterized by eosinophilic infiltration of the stomach and small intestine, and consists of mucosal, muscular, and serosal subtypes. Eosinophilic infiltration of the gastrointestinal tract is a fundamental histopathological characteristic of EGE and is driven by several T-helper type 2 (Th2)-dependent cytokines and induced by food allergy. Due to the lack of a diagnostic gold standard, EGE has a high rate of delayed diagnosis or misdiagnosis. However, several new diagnostic strategies have been developed, such as novel genetic biomarkers and imaging tests. Although dietary therapy and corticosteroids remain the common choices for EGE treatment, recent decades have seen the emergence of novel treatment alternatives, such as biologics that target particular molecules involved in the pathogenic process. Preliminary investigations and clinical trials have demonstrated the efficacy of biologics and provided additional insights for the era of refractory or corticosteroid-dependent EGE biologics.

Figure 1

A schematic diagram showing the pathogenesis and potential targets of EGE. Exposure to food allergens in the gastrointestinal tract activates T and B cells in blood and tissue. Th2-mediated cytokines (IL-4, IL-5, IL-13, etc.) play important roles in the release, migration, and degranulation of eosinophils. In the bone marrow compartment, IL-3, IL-5, and GM-CSF stimulate the maturation of eosinophils. Further, IL-5 regulates the release of eosinophils from the bone marrow, while eotaxin promotes chemotaxis and migration toward tissue. After being recruited in the gut, eosinophils undergo a degranulation process, releasing four major cationic proteins (MBP, EPO, EDN, and ECP) that are cytotoxic to the epithelium and secrete cytokines that enhance the inflammatory responses. Activated B cells produce IgE, which binds to the FcεRI receptor on eosinophils and mast cells, inducing mast cell degranulation. Recently, it has been found that epithelial cells can secrete TSLP, the long isoform of which has pro-inflammatory functions. CRTH2 locates to the surface of eosinophils, mast cells, and basophils and mediates chemotaxis. Siglec-8 is an inhibitory receptor expressed on the surface of eosinophils and mast cells. Binding of Siglec-8 by its antibody can regulate cell death in vitro. CRTH2: Chemoattractant receptor expressed on Th2 cells; ECP: Eosinophil cationic protein; EDN: Eosinophil-derived neurotoxin; EGE: Eosinophilic gastroenteritis; EPO: Eosinophil peroxidase; FcεRIFc: Fc epsilon receptor I; GI tract: Gastrointestinal tract; GM-CSF: Granulocyte-macrophage colony-stimulating factor; IgE: Immunoglobulin E; IL: Interleukin; MBP: Major basic protein; PGD2: Prostaglandin D2; Siglec: Sialic acid-binding immunoglobin-like lectin; TGF-β: Transforming growth factor beta; Th2: T-helper type 2; TSLP: Thymic stromal lymphopoietin.

Figure 2

Diagnostic flowchart of EGE. 18F-FDG: ¹⁸F-fluorodeoxyglucose; ^99mTc-HMPAO: ^99mTc-hexamethylpropyleneamineoxime; CT: Computed tomography; ECP: Eosinophil cationic protein; EGE: Eosinophilic gastroenteritis; HES: Hypereosinophilic syndrome; EGPA: Eosinophilic granulomatous vasculitis; GI: Gastrointestinal; HPFs: High-power fields;IBD: Inflammatory bowel disease; IgE: Immunoglobulin E; PFAS: Pollen-food allergy syndrome; RAST: Radioallergosorbent testing.