Eosinophilic gastroenteritis: A state-of-the-art review : Eosinophilic gastroenteritis

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 T(H)2-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.

Functional abnormalities of the duodenum have been observed in non-ulcer dyspepsia. We aimed to identify whether eosinophils in the upper gastrointestinal tract are a biomarker for non-ulcer dyspepsia. A random sample of an adult Swedish population (n = 1001; mean age, 54 y; 51% female) underwent upper endoscopy. Non-ulcer dyspepsia cases (n = 51, Rome II) and randomly selected controls (n = 48) were identified. Two blinded independent observers assessed the gastroduodenal eosinophil counts. Eosinophils were quantified by counting the number per 5 high-power fields at each of 5 sites (cardia, body, antrum, D1 duodenal bulb, and D2 second portion of duodenum), and total counts were summed over the 5 fields at each site. The odds ratio for non-ulcer dyspepsia (vs asymptomatic controls) in subjects with high duodenal bulb eosinophil counts (median, >/=22, relative to <22) was 11.7 (95% confidence interval, 3.9-34.9), adjusting for age, sex, and H pylori; similar results were observed in D2 (odds ratio = 7.3; 95% confidence interval, 2.9-18.1). A significant association with the number of eosinophil clusters was detected in the duodenum, with higher values in non-ulcer dyspepsia (P < .01). By immunostaining with major basic protein antibody in a subset of duodenal biopsy specimens, eosinophil degranulation was observed in non-ulcer dyspepsia (7 of 15 vs 0 of 5 controls; P = .11). Gastric eosinophil counts were overall not significantly increased in non-ulcer dyspepsia vs controls. Early satiety was associated with eosinophilia in D1 (P = .01) and D2 (P = .02), adjusting for age, sex, and H pylori. Duodenal eosinophilia may characterize a subset of adults with non-ulcer dyspepsia.

Eosinophil infiltration into the esophagus is observed in diverse diseases including gastroesophageal reflux and allergic gastroenteritis, but the processes involved are largely unknown. We now report an original model of experimental esophagitis induced by exposure of mice to respiratory allergen. Allergen-challenged mice develop marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, features that mimic the human disorders. Interestingly, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. Furthermore, in the absence of eotaxin, eosinophil recruitment is attenuated, whereas in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia are ablated. These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation.