Eosinophilic Gastroenteritis

An Update

Alfredo J Lucendo; Angel Arias

Disclosures

Expert Rev Gastroenterol Hepatol. 2012;6(5):591-601. 

In This Article

Pathophysiology of EGE

Eosinophil tissue accumulation above normal levels along with infiltration of the epithelium[19] is a common finding in several digestive disturbances, including IgE-mediated food allergy, EGID,[5] gastroesophageal reflux[20,21] and inflammatory bowel disease, in which both findings may constitute a bad prognostic factor.[22,23] However, studies continue to debate what constitutes 'normal' and 'abnormal' numbers of eosinophils in the different sections of the GI tract, and how they vary with patient's age: since the esophageal epithelium lacks eosinophils under normal conditions, these form part of the resident cells in the remaining digestive tract organs, with an increasing gradient from the stomach to the right colon (Table 1).[24] Thus, the histopathological diagnosis of some cases of EGID are based on finding 'more eosinophils than expected' in the gastrointestinal tissues.[25]

It must be taken into account that resident eosinophils are integrated in the mucosal immune system, and have a specific role in the GI tract of healthy individuals.[26] The physiological functions of eosinophils include protection against parasites[27] and allergic-type reactions.[28,29] When their number increases in EGID, eosinophils contribute to tissue damage through their proinflammatory functions. Despite being widely considered as multifunctional proinflammatory cells, the biology of these functionally complex cells is not yet fully known. The effector function, which was the first recognized function of eosinophils, is exerted through cytotoxic proteins contained in their cytoplasm granules, which are capable of causing cell damage.[30] Eosinophils also release preformed proinflammatory mediators, which activate endothelial cells and may stimulate T lymphocytes, acting as antigen-presenting cells.[19]

The physiopathological mechanism of EGID seems to be comprised of mixed disturbances, sharing characteristics of IgE-mediated disorders (e.g., oral allergy syndrome and food-triggered anaphylaxis) and exclusively cell-mediated disorders (e.g. celiac disease or food protein-induced colitis). EGE has been related to food allergies in that it originates from the interplay of environmental and individual genetic factors. Approximately three out of four EGE patients present various atopic manifestations (personal or familiar background of bronchial asthma, allergic rhinitis, dermatitis, hypersensitivity to food, inhalants or drugs, blood hypereosinophilia, elevated total and specific IgE serum levels and positive skin allergic test results), which reinforces the idea that eosinophils accumulate in the stomach and small bowel in response to exposure to food[12,31] or environmental[32] antigens. Clinical and histological responses to therapies used in other allergic diseases and dietary modifications are also observed in most EGE cases.

Limited research has been developed on the molecular basis of EGE and its pathophysiology is poorly known, with most of the available information coming form extrapolations of studies on EoE, the high prevalence of which has allowed more specific research. However, it should be adverted that extrapolating information from other EGIDs may not be adequate.

A Th2-type immune response seems to be involved in both EoE and EGE.[33–36] In fact, IL-5 and IL-13, together with granulocyte–macrophage colony-stimulating factor and especially eotaxins, may play a central role in the recruitment of eosinophils from circulating blood into tissues.[37] The frequent family association of EGID cases (~10% of patients have affected relatives)[5] points to the role of immune response regulatory genes in these diseases, which in the particular case of EoE show a preserved transcriptome among patients.[38,39] The genes involved include eotaxin-3/CCL26, mast cell carboxipeptidase-A3 (CPA3) and tryptase (TPSAB1) and high-affinity IgE receptor (FCɛRI). Timic stromal lymhopoyetine, a master regulating factor of Th2 responses,[40] is also upregulated in these patients.

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