From its initial description [6], EGE has been recognized as an extremely heterogeneous disease with respect to its clinical presentation. In 1970, Klein et al. proposed a classification of EGE into three different arbitrary patterns based on clinical manifestations and the depth of the eosinophilic infiltrate into the GI tract wall [99]. This classification has been used by many subsequent authors because, when combined with the topographical location of the eosinophilic inflammation, it helps to predict clinical symptoms. (Table 27.3)

Although it is a fairly accurate tool, Klein’s “classic” classification should be broadened to include two important EGE-related conditions that have been described repeatedly in literature.

While primary EGE has been described in patients of all ages, the majority of cases are diagnosed between the third and fifth decades of life [82]. In contrast to EoE, which is clearly predominant in males [78], no definitive data are available on gender predominance in EGE in general, although eosinophilic ascitis and the underlying transmural EGE form have been described predominantly in women, occasionally triggered during pregnancy and/or after delivery [34, 103, 110–112].

Several clinical aspects of EGE are intriguing, but the lack of large case series makes it difficult to propose definitive conclusions. Still, studies conducted to date indicate that peripheral blood eosinophilia is frequent among sufferers of EGE, being found in up to 90 % of patients [113]. This condition is more intense and frequent in patients with mucosal and serosal (with ascitis) EGE than in those affected only up to the muscle layers [43, 53, 79]. In addition, 80 % of cases have a personal background of allergies, 50–62 % of which are food allergies [3]. In contrast, only 27 % of adult patients reported a family history of allergy; interestingly, this was limited to patients with mucosal involvement [44]. Finally, 16 % of patients had or currently have a relative also suffering from EGE [3].

More than half of the patients also exhibited increased IgE serum levels [113]. While all these atopic manifestations seem to be more common in mucosal and serosal forms [79, 86], they are also present in a high proportion of patients with muscular forms of EGE [44].

With regard to the topographical distribution of EGE, the stomach and duodenum have been proposed as the most frequently involved digestive organs. However, these are also the digestive segments most commonly examined by means of endoscopy, which may lead to bias. Indeed, virtually any segment of the GI tract may be affected, with 50 % of patients presenting concomitant involvement of the rectum and/or colon [112] and 30–50 % of patients exhibiting simultaneous esophageal eosinophilic infiltration [4]. Thus, 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 cow’s milk intolerance has been described [86] as an alternative to EGE-associated diarrhea.

Although EGE and eosinophilic colitis were both described decades ago, data on the typical radiological or endoscopic appearance of lesions in patients come mostly from more recent reports.

Most of the endoscopic findings described in EGE tend to be nonspecific, with mucosal hyperemia and thickened gastric folds [44] being the most common. Areas of rough or nodular appearance, erosions, aphthae, and ulcers have also been described in the disorder while in some cases, the endoscopic results have been normal [79]. Findings from capsule endoscopy include multiple erythematous lesions, loss of villi [113], incomplete strictures with ulcerated mucosa alternating with preserved areas [114], and a mimicking of mucosal diaphragms with complete retention of the capsule [115]. One patient with eosinophilic ascitis showed a bluish discoloration of the deep layers of the intestinal wall without mucosal changes; the authors hypothesized that in this case, eosinophilic infiltration had respected the mucosa [116].

Radiological findings in EGE are equally nonspecific in two thirds of patients [44, 117]; double contrast radiology findings are usually normal [44], but may occasionally show thickened folds, irregular or serrated edges in the walls of the small intestine, nodular contrast defects, or slow contrast progression indicative of GI hypomotility.

The findings in the colonoscopies of patients with eosinophilic colitis tend to be modest and nonspecific, sometimes showing patchy erythematous changes, loss of vascular pattern, and superficial ulceration. In other cases, the mucosa appears to be normal. A biopsy diagnosis is thus essential for demonstrating eosinophilic involvement of the colon [118].

In spite of the approximately 500 EGE cases described in the literature to date, very little research has focused on elucidating the natural history of the disease . A recently published French study analyzed the clinical characteristics and evolution of 43 adult patients with EGE who were followed for a mean period of 13 years [79]. The authors described three different evolutionary patterns (Fig. 27.1). (a) 42 % of patients suffered a single outbreak of EGE lasting < 3 months, a pattern confirmed in a recent population-based study which also describes this self-limited course as being present in a majority of middle-aged adult patients suffering from eosinophilic colitis [119], (b) 37 % of patients exhibited a recurrent pattern of disease, with an average of 5.2 flare-ups at extremely variable intervals, and finally (c) 21 % of patients had a continuous disease course with persistent symptoms. No other studies have determined the global relapse rate after the first flare-up, although high eosinophil blood counts at the time of diagnosis have been associated with an increased risk of disease recurrence [79]. No tumoral or myeloproliferative transformation was observed in any patient during follow-up. In fact, an association between EGE and malignancy has only been described once in the literature in a case study of a 69-year-old Japanese man with multiple gastric cancer and EGE who responded well to a total gastrectomy and prednisolone treatment [120] .

Nevertheless, many questions regarding the natural history of EGE remain unanswered. For example, it has yet to be determined whether the disease in children and adults is the same or whether pediatric forms of EGE persist into adulthood. There is also a shortage of data concerning the ability of different therapeutic modalities to change the natural history of the disease, especially regarding the response to dietary-based therapeutic interventions [7].

With regard to AEPC in infants, the disorder is characterized by a benign course in which dietary elimination of the aggressor often resolves the symptoms within days [118].

Heterogeneity in the clinical presentation, severity, and evolution of EGE, together with its low prevalence, has made it difficult to establish ideal treatment strategies for these patients. As in the case of other EGIDs, including EoE, no drugs have been approved specifically for the treatment of EGE and comparative studies of different therapeutic modalities are lacking. To make matters more confusing, both patient age (children or adults) and the medical specialty area in which they are attended tend to determine which treatments are administered. Basically, three major therapeutic modalities for managing these patients have been described in the literature; these include several dietary modifications to reduce the antigenic capacity of the diet, administration of drugs with anti-inflammatory and immunosuppressant effects, and finally, surgical intervention when complications arise.