Eosinophilic gastrointestinal disorders (EGID)

Primary eosinophilic gastrointestinal disorders are defined as disorders that selectively affect the gastrointestinal tract with eosinophil-rich inflammation in the absence of known causes for eosinophilia (eg, drug reactions, parasitic infections, and malignancy). Primary eosinophilic gastrointestinal disorders are defined as disorders that selectively affect the gastrointestinal tract with eosinophil-rich inflammation in the absence of known causes for eosinophilia (eg, drug reactions, parasitic infections, and malignancy). These disorders include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis and are occurring with increasing frequency. Significant progress has been made in elucidating that eosinophils are integral members of the gastrointestinal mucosal immune system and that eosinophilic gastrointestinal disorders are primarily polygenic allergic disorders that involve mechanisms that fall between pure IgE-mediated and delayed TH2-type responses. 

Primary eosinophilic gastrointestinal disorders (EGIDs; eg, EE, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis) are defined as disorders that primarily affect the gastrointestinal tract with eosinophil-rich inflammation in the absence of known causes for eosinophilia (eg, drug reactions, parasitic infections, and malignancy). Patients with EGIDs have a variety of problems, including failure to thrive, abdominal pain, irritability, gastric dysmotility, vomiting, diarrhea, and dysphagia.

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Evidence in support of the concept that EGIDs arise as a result of the interplay of genetic and environmental factors is accumulating. Notably, a large percentage (approximately 10%) of patients with EGIDs have an immediate family member with an EGID.21 Additionally, several lines of evidence support an allergic cause, including the finding that approximately 75% of patients with EGIDs are atopic, the finding that the severity of disease can sometimes be reversed by institution of an allergen-free diet, and the common finding of mast cell degranulation in tissue specimens. Importantly, our recent models of EGIDs support a potential allergic cause for these disorders. Interestingly, despite the common finding of food-specific IgE in patients with EGIDs, food-induced anaphylactic responses only occur in a minority of patients. Thus EGIDs have properties that fall between pure IgE-mediated food allergy and cellular-mediated hypersensitivity disorders

These disorders include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis and are occurring with increasing frequency. Significant progress has been made in elucidating that eosinophils are integral members of the gastrointestinal mucosal immune system and that eosinophilic gastrointestinal disorders are primarily polygenic allergic disorders that involve mechanisms that fall between pure IgE-mediated and delayed TH2-type responses. Preclinical studies have identified a contributory role for the cytokine IL-5 and the eotaxin chemokines, providing a rationale for specific disease therapy. An essential question is to determine the cellular and molecular basis for each of these clinical problems and the best treatment regimen, which is the main subject of this review.

Although the incidence of primary EGIDs has not been rigorously calculated, a miniepidemic of these diseases (especially EE) has been noted over the last decade.9, 35 One group of investigators has found that 1% of their pediatric patients with GERD have EE. Another group of investigators has reported that 6% of their patients with esophagitis have EE.9 Finally, we have estimated that one type of EGID, EE, occurs in approximately 2 of 10,000 children in the geographic region of our medical center in Cincinnati (Richard Noel, Phil Putnam, and Marc Rothenberg, unpublished findings). Collectively, these epidemiologic results indicate that the EGIDs are not an uncommon group of diseases and might have a combined prevalence even higher than that of IBD.

EGIDs typically occur independent of peripheral blood eosinophilia (>50% of the time), indicating the potential significance of gastrointestinal-specific mechanisms for regulating eosinophil levels; indeed, our work has demonstrated the importance of the eotaxin pathway in this process. However, some patients with EGIDs (typically those with eosinophilic gastritis) can have substantially increased levels of peripheral blood eosinophils and meet the diagnostic criteria for the idiopathic hypereosinophilic syndrome (HES). This syndrome is defined by sustained severe peripheral blood eosinophilia (>1500 cells/mm2) and the presence of end-organ involvement (in the absence of known causes for eosinophilia). Notably, although HES commonly involves the gastrointestinal tract, the other end organs typically associated with HES (eg, heart and skin) are uncommonly involved in EGIDs. Recently, it has been appreciated that a subset of patients with HES have a microdeletion on chromosome that generates an activated tyrosine kinase susceptible to imatinib mesylate therapy39; the possible occurrence of this and other genetic events in patients with EGIDs, especially those with significant circulating eosinophilia, is currently being investigated.

Eosinophil accumulation in the gastrointestinal tract is a common feature of numerous gastrointestinal disorders, including classic IgE-mediated food allergy, eosinophilic gastroenteritis, allergic colitis, eosinophilic esophagitis (EE), inflammatory bowel disease (IBD), and gastroesophageal reflux disease (GERD). In IBD eosinophils usually represent only a small percentage of the infiltrating leukocytes,11, 19 but their level has been proposed to be a negative prognostic indicator. Primary eosinophilic gastrointestinal disorders (EGIDs; eg, EE, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis) are defined as disorders that primarily affect the gastrointestinal tract with eosinophil-rich inflammation in the absence of known causes for eosinophilia (eg, drug reactions, parasitic infections, and malignancy). Patients with EGIDs have a variety of problems, including failure to thrive, abdominal pain, irritability, gastric dysmotility, vomiting, diarrhea, and dysphagia. Evidence in support of the concept that EGIDs arise as a result of the interplay of genetic and environmental factors is accumulating. Notably, a large percentage (approximately 10%) of patients with EGIDs have an immediate family member with an EGID. Additionally, several lines of evidence support an allergic cause, including the finding that approximately 75% of patients with EGIDs are atopic,23, 24, 25, 26, 27, 28, 29, 30 the finding that the severity of disease can sometimes be reversed by institution of an allergen-free diet,29, 30, 31 and the common finding of mast cell degranulation in tissue specimens. Importantly, our recent models of EGIDs support a potential allergic cause for these disorders.18 Interestingly, despite the common finding of food-specific IgE in patients with EGIDs, food-induced anaphylactic responses only occur in a minority of patients. Thus EGIDs have properties that fall between pure IgE-mediated food allergy and cellular-mediated hypersensitivity disorders

Source : jaci

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