What are the gastrointestinal diseases characterized by the presence of increased eosinophils? What causes the eosinophil accumulation in the gastrointestinal tract?
Many conditions have an increased number of eosinophils in the gastrointestinal (GI) tract. The finding of eosinophils in the esophagus is a pathologic condition because this segment of the GI tract is normally devoid of eosinophils. Pathologic eosinophil accumulation in various segments of the GI tract occurs in a variety of processes including diseases limited to specific segments of the GI tract such as eosinophilic esophagitis (EoE) and eosinophilic colitis (EC) and gastroesophageal reflux; GI disorders that affect multiple segments of the gut include eosinophilic gastroenteritis (EGE) and systemic diseases such as the idiopathic hypereosinophilic syndrome, inflammatory bowel disease, parasitic infections, and drug reactions.
The exact incidence and prevalence of the primary eosinophil disorders of the GI tract (EoE, EGE, EC) is variable for each type of GI disorder. For example, the incidence of EoE may be as high as 1:1000 individuals. These diseases are occurring or being diagnosed with increasing frequency in both pediatric and adult populations and are especially prominent in pediatric populations. The underlying causes of the primary eosinophil-associated GI disorders are not yet understood; however, several investigations have demonstrated an association with allergies. For example, nearly half of the patients with eosinophilic GI disorders are allergic as defined by elevated levels of total immunoglobulin E (IgE) or food-specific IgE. IgE-mediated mast cell degranulation has been demonstrated in patients with EGE, but the occurrence of anaphylactic food-induced IgE-mediated reactions occurs in only a minority of patients. In at least some of these disorders, such as those in which eosinophils are the predominant cellular infiltrate (e.g. EoE, EGE, EC), eosinophils are believed to be critical effector cells involved in the pathological manifestations of the disease.
Why are eosinophils believed to be critical effector cells for eosinophilic gastrointestinal disorders?
In vitro studies have shown that eosinophil granule constituents are toxic to a variety of tissues including the intestinal epithelium. Clinical investigations have demonstrated extracellular deposition of eosinophil-derived major basic protein and eosinophilic cationic protein in the small bowel of patients with EGE and a correlation between the number of eosinophils and disease severity. Electron microscopy studies have revealed ultrastructural changes in the secondary granules (indicative of eosinophil degranulation and mediator release) in duodenal samples from patients with EGE. Furthermore, Charcot-Leyden crystals, remnants of eosinophil degranulation, are commonly found on microscopic examination of stools obtained from patients with EGE.
In addition, in experimental models of eosinophilic GI disorders, eosinophils have been shown to have a critical role in the development of the disease. It is currently thought that eosinophils may augment and sustain gastrointestinal inflammatory responses through the release of proinflammatory mediators and/or granule cationic proteins that are toxic to the mucosa.