Eosinophilic Gastroenteritis

An Update

Alfredo J Lucendo; Angel Arias


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

In This Article

Clinical Manifestations

From descriptions of EGE, the authors can infer that it is a heterogeneous disease with respect to its clinical presentation. Clinical findings may reflect the extent, location and depth of the eosinophil infiltration in the digestive organs.[3] Following the proposals of Klein et al. in 1970,[2] several studies have established a classification of EGE into three different arbitrary patterns based on clinical manifestations and depth of inflammation into the GI tract wall (Table 2).

Mucosal form: the most common presentation (45% of cases, although in a recent series it reached over 80%),[14] characterized by mucosal and submucosal involvement. Symptoms include abdominal pain, diarrhea, weight loss and malabsorption-related findings, including iron deficiency and losing protein enteropathy.[56] It has been suggested that EGE in the mucosal layer has become predominant in recent years.[10]

Muscular form: appearing in 12–30% of cases.[3,13] In these patients, the inflammation extends deeper into the muscle layers, leading to digestive wall thickening and typical obstructive symptoms. Although any section of the digestive tract can be involved, the stomach and duodenum are the most commonly affected segments.[46,47,57]

Serosal form or eosinophilic ascitis: the rarest presentation of EGE (but reaching up to 12.5–39% of cases in certain series)[3,13] is the serosal manifestation of the disease, in which eosinophil-rich inflammatory infiltrate permeates all layers of the digestive wall, reaching the serosal cover and causing the appearance of eosinophilic ascitis. A white blood cell count of at least 10% characterizes eosinophilic ascitis,[58] but it can reach up to more than 80%.[59] Interestingly, eosinophilic ascitis and the underlying transmural EGE form has been predominantly described in women, occasionally trigger during pregnancy or after delivery.[60–62]

There are reports of some EGE patients presenting with intestinal perforation.[63–67] This complication usually requires surgical repair and represents a transmural involvement of the disease different from that eosinophilic ascitis, but not recognized in the Klein classification. The cytotoxic effector function exerted by eosinophilic granule proteins may be the underlying cause of tissue damage in these patients.[30] It can affect any small bowel segment, from the duodenum to the ileum.

Several aspects of EGE are intriguing, although the lack of large case series prevents us from establishing these assertions with certainty. For example, peripheral blood eosinophilia is a frequent finding, being found in up to 90% of patients.[15] It is more intense and frequent in patients exhibiting mucosal and serosal (with ascitis) types than in those affected only up to the muscle layers.[3,13,57] At same time, 80% of cases have a personal background of allergies, with 50–62% of these being food allergies.[10] By contrast, only 27% of adult patients reported a family history of allergy; this was limited to those with mucosal involvement.[14] Furthermore, 16% of patients had or currently have a relative also suffering EGE.[10]

More than a half of patients had increased IgE serum levels.[15] All these atopic manifestations seem to be more common in mucosal and serosal forms,[12,13] but are also present in a high proportion of muscular EGE forms.[14]

Regarding the topographical distribution of EGE, the stomach and duodenum have been proposed as the most frequently involved digestive organs. However, it should be noted that these are also the most prevalent examined digestive segments by means of endoscopy, so it remains uncertain whether this represents a bias. Nevertheless, virtually any segment of the GI tract may be affected. In fact, 50% of patients present concomitant involvement of the rectum and/or colon,[15] while simultaneous esophageal eosinophilic infiltration is present in between 30 and 50% of patients with EGE. Large bowel-derived symptoms including bloody diarrhea (which can mimic inflammatory bowel disease) and symptoms of esophageal dysfunction (e.g., dysphagia) may coexist together with stomach and small bowel-derived symptoms. Interestingly, infiltration of the lamina propria by eosinophils and their presence in the crypts of rectal mucosal biopsies of young children with constipation due to intolerance to cow's milk has been described,[68] as an alternative to EGE-associated diarrhea.

Biliopancreatic involvement has also been described for EGE.[13,69–71] These patients present with cholecystopancreatitis with bile duct dilation, obstruction or jaundice, together with symptoms derived from gut inflammation.

Together with EGE, hypereosinophilic syndrome and immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome are two additional systemic disorders that can also include eosinophilic inflammation in the digestive tract walls between its components. Hypereosinophilic syndrome are a heterogeneous group of rare systemic diseases of idiopathic origin, characterized by marked blood eosinophilia (at least 1500 cells/mm3) persisting for more than 6 months. Signs or symptoms of organic affectation[72] with eosinophils in the GI tract can be found. Patients show high levels of mast cell tryptase in serum and bone marrow analyzes show a high number of dysplastic mast cells which decrease after treatment with the tyrosine kinase inhibitor imatinib mesylate.[73] IPEX syndrome constitutes an autoimmune-allergic disorder caused by germ-line mutations in the FOXP3 gene, a master transcriptional regulator for the development of CD4 regulatory T cells.[74,75] IPEX syndrome includes enteropathy among its clinical picture, but digestive affection is only one more manifestation of this multisystemic disorder, together with immune dysregulation, polyendocrinopathy and other organ-specific diseases such as anemia, thrombocytopenia, hepatitis and nephritis. In both syndromes, EGE would only be a manifestation of the general disease and a differential diagnosis should be warranted.