Eosinophilic Gastroenteritis: A Review

Dig Dis Sci (2007) 52:2904–2911 DOI 10.1007/s10620-005-9011-2

ORIGINAL PAPER

Eosinophilic Gastroenteritis: A Review Nahum M´endez-S´anchez · Norberto C. Ch´avez-Tapia · Genaro Vazquez-Elizondo · Misael Uribe

Received: 26 June 2005 / Accepted: 11 August 2005 / Published online: 11 April 2007 C Springer Science+Business Media, Inc. 2007


Abstract Eosinophilic gastroenteritis is a rare benign disease characterized by tissue eosinophilic infiltration that may involve several digestive tract layers. Also known as allergic, or eosinophilic allergic, gastroenteropathy, it usually involves the stomach and small intestine: rarely the colon. It may or may not be accompanied by higher counts of eosinophils in the peripheral blood. The main clinical manifestations depend on the site affected. It has been classified according to clinical and pathological features, and the symptoms depend on the patient’s immunological response to several cytokines released by eosinophils. Because of lack of understanding of the etiology and triggering factors, treatment is based mainly on corticosteroids; although other drugs acting on the immune system have been tested, the results are not always satisfactory. This review focuses on the epidemiology, pathophysiology, clinical features, and treatment of this hitherto under-diagnosed disease. Keywords Eosinophilic gastroenteritis . Eosinophils . Abdominal pain . Corticosteroids

Introduction Eosinophils are present at low levels in many tissues. However, eosinophil infiltrations in the gastrointestinal tract are associated with degranulation [1]. Eosinophilic gastroenteritis (EG) is a rare, benign disease, characterized by the presence of eosinophilic infiltration that can involve distinct digestive tract (DT) layers [2]. EG is classified according to the DT layer that is affected: the mucosa, muscular tunic, subserosal layer, or transmural layers [3]. Eosinophilic infiltration of the DT is associated with a characteristic clinical picture first described by Kaijser in 1937 [4]. The disease has been reviewed many times [5–14], but it is still difficult to estimate its real incidence because many patients are undiagnosed or not reported [15]. It is also known as allergic gastroenteropathy or eosinophilic allergic gastroenteropathy [12]. The main clinical manifestations depend on the site affected. Infiltration of the DT by eosinophils can involve the whole digestive tract, but it usually affects the stomach and small intestine [16]. Definition and epidemiology

N. M´endez-S´anchez · N. C. Ch´avez-Tapia · G. Vazquez-Elizondo · M. Uribe Departments of Internal Medicine, Gastroenterlogy & Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico N. M´endez-S´anchez (
) Departments of Internal Medicine, Gastroenterology & Liver Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Col. Toriello Guerra, Mexico City, Mexico e-mail: [email protected]

Springer

Eosinophilic gastroenteritis is a rare, benign condition of the DT, pathologically characterized by an important eosinophilic infiltration of the wall of the DT that usually involve the stomach and small intestine and, rarely, the colon. It may or may not be accompanied by elevated numbers of eosinophils in the peripheral blood [3, 16, 17]. EG is observed in 1–20 individuals in 100,000 (1, 16). Its real incidence is difficult to estimate, because many cases are not diagnosed or reported. The peak incidence of presentation is classically during the third to fifth decade of life [17], but it can be seen in any age group [15]. There are reports

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2905 Table 1 Classification of eosinophilic gastroenteritis according to clinical and pathological features Type

Characteristics

Class I Group A (polyenteric type)

Diffuse eosinophilic gastroenteritis Involves the prepyloric region and can affect the small intestine in an anterograde manner. Microscopically, eosinophils are observed from the submucosa through the muscular fibers of the tunica muscularis and the serosa. The mucosa is free of alterations Involves the prepyloric region and affects the stomach in a retrograde way without affecting the small intestine. Microscopically, it is similar to the polyenteric type Inflammation is confined and might be limited to the prepyloric and pyloric regions. Microscopically, the process is acute and edges are badly defined Well-circumscribed granulomata infiltrated by eosinophils Circumscribed pseudotumor characteristics; lesions are observed throughout the digestive tract Circumscribed pseudotumor characteristics; lesions are confined to the pyloric antrum

Group B (mono-enteric type)

Fig. 1 The mononuclear cells are predominantly eosinophils, with foci of transepithelial migration to the superficial epithelium (arrows). Other mononuclear cells such as lymphocytes and plasma cells are present

of cases in patients from 25 days of age to 77 years [12], with a small predominance of males [15]. The diagnostic criteria for the EG are well defined [15]. They include gastrointestinal symptoms, eosinophilic infiltration in at least one area of the DT demonstrated by biopsy (Fig. 1), absence of eosinophilic infiltration in other organs outside the DT and absence of parasitic infections. Although the last two criteria are sometimes mentioned as common diagnostic factors, they are not always accepted as necessary [12]. Because eosinophilia might be absent in about 20% (and sometimes nearly 40%) of patients, it is not considered a diagnostic criterion [3]. Importantly, there is no relation between the magnitude of peripheral eosinophilia and the degree of tissue infiltration by eosinophils or of epithelial damage [3]. Tolerance or allergy to a particular food is not required to make the diagnosis [15], as elevated immunoglobulin (Ig) E levels are not observed [3]. Etiology EG is often associated with other diseases, as is allergy to milk and dairy products [18], infection with Strongyloides stercoralis [19], Dientamoeba fragilis [20], or Ascaris suum [21], and gluten-related enteropathy [22]. EG may be associated with the use of certain medications, such as enalapril [23], rifampicin [24], gemfibrozil [25], naproxen [26], and bromazepam. However, the trigger is not clear in most cases [7]. Classification Originally described in 1937 by Kaijser [4], the disease has been revisited many times. Ureles et al. [13] were the first

Group C (regional type)

Class II Group A (regional type) Group B (polyploid type)

to classify it into two main types based on clinical presentation: Class I is diffuse EG and Class II comprises well-circumscribed eosinophilic infiltrations forming granulomata, which can be subdivided further by their distribution patterns (Table 1). Later, Klein et al. [7] described three patterns based on the affected layer determining particular clinical characteristics: mucosal-predominant, muscularispredominant, and subserosal-predominant. The mucosal and submucosal patterns are the most common [27]. Patients with the mucosal-predominant disease present with low serum protein levels caused by protein-losing enteropathy, anemia caused by bleeding in the gastrointestinal tract, and weight loss caused by chronic intestinal malabsorption [27]. Patients with muscularis-predominant disease present with symptoms of intestinal obstruction [28]. In those with subserosalpredominant disease, the cardinal manifestation is the presence of ascites fluid with large numbers of eosinophils [29, 30]. Patients with EG have also been divided into two groups based on allergic responses. First, there are those with atopia, asthma, elevated serum IgE levels, and positive responses to allergy tests; in these patients, relapses of the disease have been observed, with increases in serum IgE levels and peripheral eosinophilia in response to specific food tests. Patients with the second type have no history of atopia, usually show Springer

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normal serum IgE levels, and do not respond to tests for allergies [31]. Finally, EG can be classified therapeutically as a proteinsensitive form or as idiopathic [32].

Pathophysiology In 1970, Klein et al. [7] concluded that EG is not a process mediated solely by allergic factors and speculated that this disease might be a self-perpetuating process aggravated by the ingestion of different foods. Cello et al. [9] were among the first to postulate that altered immune reactions might form part of the pathogenesis. They revised the existing theories to explain the process of chemotaxis by eosinophils to the DT. First, an immediate Arthus-type hypersensitivity might cause migration of the eosinophils to regions of antibody– antigen complexes; second, activation of complement could attract eosinophils because they express surface complement C3 receptors; and third, activation of sensitized T cells by their respective antigens to liberate lymphokines and thereby attract eosinophils from the peripheral blood. They also supported the hypothesis that alimentary antigens react with IgE specific antigens that bind Fc receptors on mast cells; these are increased in the DT of patients with EG, particularly in the esophagus and duodenum [33]. Others have reported the same observations and supported this theory [10]. Recently, this theory has been questioned, as eosinophils show down-regulation during immediate immune hypersensitivity. Thus, Min et al. [6] reported that the cytoplasmic granules of the eosinophils contain cytotoxic substances that induce tissue damage; these include major basic proteins, cationic eosinophilic proteins, and neurotoxins. Other factors involved in the disease include leukotrienes and prostaglandins [34], platelet activator factor [5], and tumor necrosis factor α [35]. There are also increases in the serum levels of interleukin IL-3 [36], IL-4 [37], IL-5 [38], IL2 soluble receptor [39], and macrophage colony-stimulating factor. Moreover, there is activation and degranulation of eosinophils in delayed allergic responses, which respond to histamine, IgE, and possibly cytokines, but not directly to allergens. Immunological dysfunction in patients with EG is also shown by the downregulation of cytokines controlling the development of oral tolerance, such as growthtransformation factor ß and IL-10 (Fig. 2) [40]. The eotaxin (CCL11) pathway also plays an important role in the pathophysiology of digestive inflammatory disease, probably via eosinophil recruitment and activation [41]. The activity of eotaxins 1 and 2 has been investigated by injection of these chemokines in human epithelial cells; both induce an immediate wheal-and-flare response associated with mast cell degranulation and subsequent infiltrations by eosinophils, basophils, and neutrophils [42]. Springer

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Clinical presentation The presentation of the symptoms varies, depending on the extension and the layer of the DT affected. Most frequently, patients complain of abdominal pain, nausea, vomiting, weight loss, abdominal distension, diarrhea [17, 23], anorexia, ascites [29, 30, 43, 44], dysphagia [45–47], edema, intestinal malabsorption [48, 49], melena [12], acute abdomen [50, 51] pyloric stenosis [28], jaundice [52], or intestinal perforation [3]. In patients with eosinophilic colitis affecting the left colon, intussusception could cause obstructive symptoms [53], and might even simulate the presence of a tumor that could confuse the clinician, leading to an unnecessary surgical approach [54, 55]. Recent reports indicate that esophagitis may represent another form of eosinophilic gastroenteritis, causing dysphagia, and that this should be considered during the differential diagnosis of gastric reflux disease [47, 56–60]. There are a few reports of cases involving biliary or pancreato-biliary obstruction and even acute pancreatitis [44, 55, 61, 62]. EG may even manifest in an extra-intestinal nature, presenting in synchrony with bronchial asthma attacks [17].

Laboratory and radiology studies Blood eosinophilia (absolute eosinophil count [AEC], ≥ 600 cells/µL) is the usual initial clue for the presence of an eosinophilic disorder. The degree of blood eosinophilia, in the absence of active treatment, can be categorized into mild (AEC, 600–1500 cells/µL), moderate (AEC, 1500– 5000 cells/µL), or severe (AEC, (5000 cells/µL). Target organ damage is unusual with mild eosinophilia, but its occurrence in association with moderate to severe eosinophilia does not appear to depend on the specific cause [63]. Complete blood cell counts might show eosinophilia in about 80% of cases, with higher levels in patients with the mucosapredominant pattern [17]. In such cases, other causes of peripheral eosinophilia with gastrointestinal symptoms should be eliminated. These include medication abuse (aspirin, sulfonamides, penicillin, and cephalosporins) parasites, vasculitis, and lymphoma. Ferropenic anemia can be observed, probably as the result of gastrointestinal blood loss (mainly in patients with the mucosa-predominant pattern), and manifests as hypoalbuminemia (20%–30% of cases). Proteinlosing enteropathy has been documented using radiolabeled albumin or with α-1 antitrypsin depuration. Elevated IgE levels have been observed and the erythrocyte sedimentation rate can be slightly elevated [15]. The radiological changes found in patients with EG are variable and nonspecific and are found in only about 40% of patients. Thickening of gastric folds with or without filling

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Fig. 2 Pathophysiological factors involved in eosinophilic gastroenteritis. The presence of mast cells might precede eosinophil infiltration into the tract. Both cell types produce cytokines, which mediate tissue

defects of a nodular type and thinning of the small intestine can be observed during the course of the disease [15]. Ultrasonographic findings that can support the diagnosis of EG are based on the thinning of all the layers of the DT or by the finding of a pseudo-kidney image (a targethighlighting sign), first described as a sign of intussusception and characterized by the presence of an echogenic center surrounded by a hypoechogenic ring. This sign is considered nonspecific and is observed in other disorders such as lymphoma, Crohn’s disease [64], intestinal ischemia, tuberculosis, lymphangiectasia, intramural hematoma, acute appendicitis, and other inflammatory diseases [3]. Although nonspecific, it could be used as a follow-up strategy in selected cases [65]. On computer tomography (CT) scans, thinning of the intestinal walls can be observed (Fig. 3) and sometimes mesenteric lymphadenopathy may be observed, especially during the course of serosa-predominant pattern disease [15]. Scintigraphy scanning with radiolabeled leukocytes has been useful in the evaluation of intestinal inflammatory diseases and sepsis. Labeling granulocytes selectively using tecnetium-99 with hexamethyl-propylenamine oxime (HMPAO) has been used with single-photon emission CT scanning for the study of intestinal inflammatory disease [66]. Its

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damage. Such tissue damage, plus eosinophil and mast cell activity, increase the production of immunoregulatory substances with chemotactic activity, which leads to immunological tolerance

Fig. 3 Computed tomography scan showing an irregular wall in the terminal ileum

utility has also been proved in patients with EG, being more accurate than biopsy by endoscopy (Fig. 4) or with barium contrast studies (Fig. 5). It is also useful for follow-up study [67]. The most common findings in eosinophilic esophagitis diagnosed by endoscopy are loss of the capillary pattern and white exudates of different intensities, shapes, and sizes (fine reticular lines, pinhead-like nodules, scales, or patches) [68]. In some cases, the diagnosis was so difficult that the Springer

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Dig Dis Sci (2007) 52:2904–2911 Table 2

Differential diagnosis of eosinophilic gastroenteritis

Pathologies Intestinal effects Pseudomembranous colitis Chronic mucosal prolapse Colonopathy secondary to portal hypertension Ampullar adenoma Parasitic infections Intestinal perforation Acute abdomen Crohn’s disease Celiac disease Lymphangiectasia Intramural hematoma Acute appendicitis

Fig. 4 Colonoscopy showing erosions on the left side in a woman with eosinophilic colitis caused by bromazepam consumption

Fig. 5 Barium contrast x-ray study of a subject with eosinophilic duodenitis

patient required diagnostic laparoscopy [32]. There are isolated reports of successful outcomes with capsule endoscopy [69, 70]. Differential diagnosis Because of the nonspecificity of the symptomatology and because other diseases can induce tissue eosinophilia, EG should be differentiated from other processes compatible with the clinical picture; these are listed in Table 2 [3, 15, 17, 23, 24, 26, 51, 55, 71, 72]. Treatment With the generally poor understanding of the etiology and pathogenesis of EG, there is no definitive treatment, and to Springer

Systemic effects Graft-versus-host disease Drug-mediated reactions Vasculitis Systemic mastocytosis Hyper-eosinophilic syndrome Lymphoma Cancer Tuberculosis Connective tissue diseases

date the use of glucocorticoids is the main standard for management. However, as it is difficult to maintain a sustained therapy with such medications, other therapies have been used, with diverse results. Dietary modification, such as low-calorie and low-fat diets [32], gluten-free diets [22], and diets free of previously identified allergens, could be useful, especially for patients with the mucosa-predominant pattern disease [15]. The use of elemental diets has been effective in reducing the need for corticosteroids and has improved the poor growth associated with the disease [31]. The treatment of EG is based principally on the use of glucocorticoids [11]; thus, ketotifen [16, 73, 74], montelukast [75–77], and sodium chromoglycate [22, 78] have yet to be tested. Good responses are reported with the use of prednisone for 8 weeks at daily doses of 20– 40 mg [32]. Budesonide is a corticosteroid that acts locally, with an efficacy similar to that of prednisone. Its main advantage is a high first-step metabolism; this carries a lower risk for adrenal suppression, and its efficacy looks promising for treating EG [72]. Immunotherapy has been applied in small clinical trials, especially using the newer antiallergic agents that suppress the action of the cytokines IL-4 and IL-5, such as suplatast tosilate [79] and anti-IL-5 monoclonal antibodies [38].

Prognosis Reports on patients with EG have not shown any changes in survival rate, even if growth alterations have been seen in children and adolescents [80] that must be reversed with the use of steroids and—in selected cases—immunotherapy. The use of corticosteroids can help resolve the symptoms, but they can reappear if the treatment is stopped. Therefore, dietary management and the use of corticosteroid-saving

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medications are necessary to lower the collateral effects of steroid use and maintain an adequate quality of life. Followup studies in small series demonstrate that EG is not associated with malignancy [81].

Conclusions EG is a benign disease requiring a broad knowledge from the gastroenterologist. However, because it is commonly underdiagnosed (or underreported), it lacks high-quality studies to determine its natural history, and the absence of controlled clinical trials to evaluate the best treatment available impedes the adequate management of these patients.

References 1. Rothenberg ME (2004) Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol 113:11–28, quiz 29 2. Talley NJ (2002) Eosinophilic gastroenteritis. In Feldman M, Tschumy Jr. WO, Friedman LS, Sleisenger MH (eds) Sleisenger & Fordtran’s gastrointestinal and liver disease. Pathophysiology/diagnosis/management. Saunders, Philadelphia, pp 1972– 1980 3. Huang FC, Ko SF, Huang SC, Lee SY (2001) Eosinophilic gastroenteritis with perforation mimicking intussusception. J Pediatr Gastroenterol Nutr 33:613–615 4. Kaijser R (1937) Zur kenntnis der allergischen affektionen des verdaugskanal von standpunkt des chirurgen aus. Arch Klin Chir 188:36–64 5. Bischoff SC (1996) Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut. Baillieres Clin Gastroenterol 10:443–459 6. Min K, Metcalfe D (1991) Eosinophilic gastroenteritis. Immunol Allergy Clin North Am 11:799–813 7. Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH (1970) Eosinophilic gastroenteritis. Medicine (Baltimore) 49:299–319 8. Leinbach GE, Rubin CE (1970) Eosinophilic gastroenteritis: a simple reaction to food allergens? Gastroenterology 59:874–889 9. Cello JP (1979) Eosinophilic gastroenteritis—a complex disease entity. Am J Med 67:1097–1104 10. Oyaizu N, Uemura Y, Izumi H, Morii S, Nishi M, Hioki K (1985) Eosinophilic gastroenteritis. Immunohistochemical evidence for IgE mast cell-mediated allergy. Acta Pathol Jpn 35:759–766 11. Talley NJ, Shorter RG, Phillips SF, Zinsmeister AR (1990) Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues. Gut 31:54–58 12. Kelly KJ (2000) Eosinophilic gastroenteritis. J Pediatr Gastroenterol Nutr 30(Suppl):S28–S35 13. Ureles A, Alschibaja T, Lodico D, Stabins S (1961) Idiopathic eosinophilic infiltration of the gastrointestinal tract, diffuse and circumscribed. Am J Med 30:899–909 14. Khan S (2005) Eosinophilic gastroenteritis. Best Pract Res Clin Gastroenterol 19:177–198 15. Sleisenger MH, Fordtran JS (1993) Gastrointestinal disease: pathophysiology, diagnosis, management. Saunders, Philadelphia, p 2 v (xxx, 2136, cxiii, 2120] 16. Persic M, Stimac T, Stimac D, Kovac D (2001) Eosinophilic colitis:a rare entity. J Pediatr Gastroenterol Nutr 32:325–326

2909 17. von Wattenwyl F, Zimmermann A, Netzer P (2001) Synchronous first manifestation of an idiopathic eosinophilic gastroenteritis and bronchial asthma. Eur J Gastroenterol Hepatol 13:721–725 18. Rossel M, Ceresa S, Las Heras J, Araya M (2000) [Eosinophilic colitis caused by allergy to cow’s milk protein]. Rev Med Chil 128:167–175 19. Corsetti M, Basilisco G, Pometta R, Allocca M, Conte D (1999) Mistaken diagnosis of eosinophilic colitis. Ital J Gastroenterol Hepatol 31:607–609 20. Cuffari C, Oligny L, Seidman EG (1998) Dientamoeba fragilis masquerading as allergic colitis. J Pediatr Gastroenterol Nutr 26:16–20 21. Takeyama Y, Kamimura S, Suzumiya J, Oh K, Okumura M, Akahane H, Maruyama H, Nawa Y, Ohkawara T, Kikuchi M (1997) Case report: eosinophilic colitis with high antibody titre against Ascaris suum. J Gastroenterol Hepatol 12:204–206 22. Butterfield JH, Murray JA (2002) Eosinophilic gastroenteritis and gluten-sensitive enteropathy in the same patient. J Clin Gastroenterol 34:552–553 23. Barak N, Hart J, Sitrin MD (2001) Enalapril–induced eosinophilic gastroenteritis. J Clin Gastroenterol 33:157–158 24. Lange P, Oun H, Fuller S, Turney JH (1994) Eosinophilic colitis due to rifampicin. Lancet 344:1296–1297 25. Lee JY, Medellin MV, Tumpkin C (2000) Allergic reaction to gemfibrozil manifesting as eosinophilic gastroenteritis. South Med J 93:807–808 26. Bridges AJ, Marshall JB, Diaz-Arias AA (1990) Acute eosinophilic colitis and hypersensitivity reaction associated with naproxen therapy. Am J Med 89:526–527 27. Mason T, Andablo A (2003) Eosinophilic gastroenteritis. J Gen Intern Med 18:73 28. Khan S, Orenstein SR (2000) Eosinophilic gastroenteritis masquerading as pyloric stenosis. Clin Pediatr (Phila) 39:55–57 29. Khalil M, Granieri R (2003) An unusual cause of ascites:a case of eosinophilic gastroenteritis. J Gen Intern Med 18:66–67 30. Kuri K, Lee M (1994) Eosinophilic gastroenteritis manifesting with ascites. South Med J 87:956–957 31. Justinich C, Katz A, Gurbindo C, Lepage G, Chad Z, Bouthillier L, Seidman E (1996) Elemental diet improves steroid-dependent eosinophilic gastroenteritis and reverses growth failure. J Pediatr Gastroenterol Nutr 23:81–85 32. Vara-Thorbeck C, Toscano-Mendez R, Osorio D (1997) Eosinophilic gastroenteritis: diagnostic laparoscopy. Surg Laparosc Endosc 7:66–69 33. Al-Herz W, Barone C, Mehta D, Justinich C, Morales CM, Akhilesh M, Stephen J (2002) Mast cell number in the upper gastrointestinal tract of patients with idiopathic eosinophilic gastroenteritis. J Allergy Clin Immunol 109:S248 34. Ngo P, Furuta G, Burks W (2004) The pathobiology of eosinophilic gastroenteritis of childhood:is it really the eosinophil, allergic mediated, or something else? Curr Gastroenterol Rep 6:436–440 35. Beil WJ, Weller PF, Tzizik DM, Galli SJ, Dvorak AM (1993) Ultrastructural immunogold localization of tumor necrosis factor-alpha to the matrix compartment of eosinophil secondary granules in patients with idiopathic hypereosinophilic syndrome. J Histochem Cytochem 41:1611–1615 36. Desreumaux P, Bloget F, Seguy D, Capron M, Cortot A, Colombel JF, Janin A (1996) Interleukin 3, granulocyte-macrophage colonystimulating factor, and interleukin 5 in eosinophilic gastroenteritis. Gastroenterology 110:768–774 37. Hogan SP, Mishra A, Brandt EB, Royalty MP, Zimmermann N, Foster PS, Rothenberg ME (2001) Molecular dissection of experimental oral antigen–induced eosinophilic gastroenteritis reveals a pathological role for eotaxin and eosinophils. J Allergy Clin Immunol 107:S34 Springer

2910 38. Prussin C, James SP, Huber MM, Klion AD, Metcalfe DD. Pilot study of anti-IL-5 in eosinophilic gastroenteritis. J Allergy Clin Immunol 111:S275 39. Tajima K, Katagiri T (1996) Deposits of eosinophil granule proteins in eosinophilic cholecystitis and eosinophilic colitis associated with hypereosinophilic syndrome. Dig Dis Sci 41:282–288 40. Chehade M, Qin L, Magid M, Castro R, Sampson H, Beyer K (2003) Expression of TGF-[beta] and IL-10 in patients with allergic eosinophilic gastroenteritis and esophagitis. J Allergy Clin Immunol 111:S291 41. Forbes E, Murase T, Yang M, Matthaei KI, Lee JJ, Lee NA, Foster PS, Hogan SP (2004) Immunopathogenesis of experimental ulcerative colitis is mediated by eosinophil peroxidase. J Immunol 172:5664–5675 42. Menzies-Gow A, Ying S, Sabroe I, Stubbs VL, Soler D, Williams TJ, Kay AB (2002) Eotaxin (CCL11) and eotaxin-2 (CCL24) induce recruitment of eosinophils, basophils, neutrophils, and macrophages as well as features of early- and late-phase allergic reactions following cutaneous injection in human atopic and nonatopic volunteers. J Immunol 169:2712–2718 43. Kinderman AL, Shim TL (2003) Eosinophilic gastroenteritis:an unusual cause of chronic diarrhea and ascites. J Gen Intern Med 18:68 44. Le Connie D, Nguyen H (2004) Eosinophilic gastroenteritis, ascites, and pancreatitis: a case report and review of the literature. South Med J 97:905–906 45. Lucendo AJ, Carrion G, Navarro M, Pascual JM, Gonzalez P, Castillo P, Erdozain JC (2004) Eosinophilic esophagitis in adults: an emerging disease. Dig Dis Sci 49:1884–1888 46. Noel RJ, Putnam PE, Collins MH, Assa’ad AH, Guajardo JR, Jameson SC, Rothenberg ME (2004) Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis. Clin Gastroenterol Hepatol 2:568–575 47. Croese J, Fairley SK, Masson JW, Chong AK, Whitaker DA, Kanowski PA, Walker NI (2003) Clinical and endoscopic features of eosinophilic esophagitis in adults. Gastrointest Endosc 58:516– 522 48. Thomas E, Lev R, McCahan JF, Pitchumoni CS (1975) Eosinophilic gastroenteritis with malabsorption, extensive villous atrophy, recurrent hemorrhage and chronic pulmonary fibrosis. Am J Med Sci 269:259–265 49. Kaplan SM, Goldstein F, Kowlessar OD (1970) Eosinophilic gastroenteritis. Report of a case with malabsorption and protein-losing enteropathy. Gastroenterology 58:540–545 50. Garcia-Sancho T, Rodriguez-Montes J, Sastre A, Jimenez P, Suarez-Miguelez J, Garcia-Sancho M (1995) Gastroduodenal: acute abdomen due to eosinophilic gastroenteritis: review of 11 cases. Br J Surg 82:46 51. Tran D, Salloum L, Tshibaka C, Moser R (2000) Eosinophilic gastroenteritis mimicking acute appendicitis. Am Surg 66:990– 992 52. Whitaker IS, Gulati A, McDaid JO, Bugajska-Carr U, Arends MJ (2004) Eosinophilic gastroenteritis presenting as obstructive jaundice. Eur J Gastroenterol Hepatol 16:407–409 53. Box JC, Tucker J, Watne AL, Lucas G (1997) Eosinophilic colitis presenting as a left-sided colocolonic intussusception with secondary large bowel obstruction: an uncommon entity with a rare presentation. Am Surg 63:741–743 54. Garcia-Sancho T, Garcia-Sancho M, Rodriguez-Montes J, Sastre A, Asenio P (1995) Gastroduodenal:pseudotumoural eosinophilic colitis. Br J Surg 82:46–47 55. Madhotra R, Eloubeidi MA, Cunningham JT, Lewin D, Hoffman B (2002) Eosinophilic gastroenteritis masquerading as ampullary adenoma. J Clin Gastroenterol 34:240–242 56. Lucendo Villarin AJ, Carrion Alonso G, Navarro Sanchez M, Martin Chavarri S, Gomez Senent S, Castillo Grau P, Pascual Springer

Dig Dis Sci (2007) 52:2904–2911

57.

58.

59.

60.

61.

62.

63. 64.

65.

66.

67.

68.

69.

70.

71.

72.

73.

74.

75.

Turrion JM, Gonzalez Sanz-Agero P (2005) Eosinophilic esophagitis in adults, an emerging cause of dysphagia. Description of 9 cases. Rev Esp Enferm Dig 97:229–239 Patel SM, Falchuk KR (2005) Three brothers with dysphagia caused by eosinophilic esophagitis. Gastrointest Endosc 61:165– 167 Dahms BB (2004) Reflux esophagitis:sequelae and differential diagnosis in infants and children including eosinophilic esophagitis. Pediatr Dev Pathol 7:5–16 Potter JW, Saeian K, Staff D, Massey BT, Komorowski RA, Shaker R, Hogan WJ (2004) Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features. Gastrointest Endosc 59:355–361 Cury EK, Schraibman V, Faintuch S (2004) Eosinophilic infiltration of the esophagus: gastroesophageal reflux versus eosinophilic esophagitis in children—-discussion on daily practice. J Pediatr Surg 39:e4–e7 Alexakis N, Campbell F, Eardley N, Smart HL, Garvey C, Neoptolemos JP (2005) T cell lymphoplasmacellular and eosinophilic infiltration of the pancreas with involvement of the gallbladder and duodenum in non-alcoholic duct-destructive chronic pancreatitis. Langenbecks Arch Surg 390:32–38 Euscher E, Vaswani K, Frankel W (2000) Eosinophilic pancreatitis: a rare entity that can mimic a pancreatic neoplasm. Ann Diagn Pathol 4:379–385 Tefferi A (2005) Blood eosinophilia: a new paradigm in disease classification, diagnosis, and treatment. Mayo Clin Proc 80:75–83 Tella R, Gaig P, Lombardero M, Garcia-Ortega P, Bartra J, Papo M, Batlle X (2004) Allergic eosinophilic gastroenteritis in a child with Crohn’s disease. J Invest Allergol Clin Immunol 14:159–161 Buljevac M, Urek MC, Stoos-Veic T (2005) Sonography in diagnosis and follow–up of serosal eosinophilic gastroenteritis treated with corticosteroid. J Clin Ultrasound 33:43–46 Lantto E, Jarvi K, Krekela I, Lantto T, Taavitsainen M, Vedenkangas H, Vorne M (1992) Technetium-99m hexamethyl propylene amine oxine leucocytes in the assessment of disease activity in inflammatory bowel disease. Eur J Nucl Med 19:14–18 Lee K, Hahm K, Kim Y, Kim J, Cho S, Jie H, Park C, Yim H (1997) The usefulness of Tc-99m HMPAO labeled WBC SPECT in eosinophilic gastroenteritis. Clin Nucl Med 22:536–541 Straumann A, Spichtin HP, Bucher KA, Heer P, Simon HU (2004) Eosinophilic esophagitis: red on microscopy, white on endoscopy. Digestion 70:109–116 Kim N, Kim JW, Hwang JH, Lee DH, Lee HS, Lee KH, Kim SW (2005) Visualization of jejunal bleeding by capsule endoscopy in a case of eosinophilic enteritis. Korean J Intern Med 20:63–67 Guilhon de Araujo Sant’Anna AM, Dubois J, Miron MC, Seidman EG (2005) Wireless capsule endoscopy for obscure small-bowel disorders: final results of the first pediatric controlled trial. Clin Gastroenterol Hepatol 3:264–270 Carpenter H, Talley NJ (2000) The importance of clinicopathological correlation in the diagnosis of inflammatory conditions of the colon: histological patterns with clinical implications. Am J Gastroenterol 95:878–896 Tan AC, Kruimel JW, Naber TH (2001) Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. Eur J Gastroenterol Hepatol 13:425–427 Melamed I, Feanny SJ, Sherman PM, Roifman CM (1991) Benefit of ketotifen in patients with eosinophilic gastroenteritis. Am J Med 90:310–314 Bolukbas FF, Bolukbas C, Uzunkoy A, Baba F, Horoz M, Ozturk E (2004) A dramatic response to ketotifen in a case of eosinophilic gastroenteritis mimicking abdominal emergency. Dig Dis Sci 49:1782–1785 Neustrom MR, Friesen C (1999) Treatment of eosinophilic gastroenteritis with montelukast. J Allergy Clin Immunol 104:506

Dig Dis Sci (2007) 52:2904–2911 76. Daikh BE, Ryan CK, Schwartz RH (2003) Montelukast reduces peripheral blood eosinophilia but not tissue eosinophilia or symptoms in a patient with eosinophilic gastroenteritis and esophageal stricture. Ann Allergy Asthma Immunol 90:23–27 77. Quack I, Sellin L, Buchner NJ, Theegarten D, Rump LC, Henning BF (2005) Eosinophilic gastroenteritis in a young girl—long term remission under Montelukast. BMC Gastroenterol 5:24 78. Di Gioacchino M, Pizzicannella G, Fini N, Falasca F, Antinucci R, Masci S, Mezzetti A, Marzio L, Cuccurullo F (1990) Sodium cromoglycate in the treatment of eosinophilic gastroenteritis. Allergy 45:161–166

2911 79. Shirai T, Hashimoto D, Suzuki K, Osawa S, Aonahata M, Chida K, Nakamura H (2001) Successful treatment of eosinophilic gastroenteritis with suplatast tosilate. J Allergy Clin Immunol 107:924–925 80. Al-Herz W, Mehta D, McGeady S (2001) Eosinophilic gastroenteritis in children and adolescents. J Allergy Clin Immunol 107:S193 81. Straumann A, Spichtin HP, Grize L, Bucher KA, Beglinger C, Simon HU (2003) Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology 125:1660–1669

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