J Gastroenterol 2008; 43:741750 DOI 10.

1007/s00535-008-2230-5

Review Eosinophilic gastroenteritis: a review

HWA EUN OH1,2 and RUNJAN CHETTY1
1

Department of Pathology, University Health Network/Toronto Medical Laboratories, University of Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada 2 Department of Pathology, Myongji Hospital, Kwandong University, College of Medicine, Goyang, Korea

Eosinophilic gastroenteritis is a clinicopathological disease affecting both children and adults that is characterized by patchy or diffuse eosinophilic inltration of the gastrointestinal tract with variable resultant clinical gastrointestinal manifestations. The eosinophil, eotaxin, and Th-2 cytokines are important in pathogenesis of this disease entity. It may be confused with parasitic and bacterial infections (including Helicobacter pylori), inammatory bowel disease, hypereosinophilic syndrome, myeloproliferative disorders, periarteritis, allergic vasculitis, scleroderma, drug injury, and drug hypersensivity. Obtaining the correct diagnosis is important, and a pathologist usually makes this distinction. Effective treatments include systemic/topical corticosteroids, specic food elimination or an elemental diet, certain drugs, and even surgery. A variety of new therapeutic approaches are now under trial. Key words: eosinophilic gastroenteritis, esophagitis, eosinophilia, gastrointestinal tract

Introduction Eosinophilic gastroenteritis (EG) is an uncommon disease characterized by eosinophilic inltration of the gastrointestinal tract, resulting in a variety of gastrointestinal symptoms. EG belongs to a group of primary eosinophilic gastrointestinal disorders (EGIDs) that are dened as disorders which selectively affect the gastrointestinal tract with eosinophil-rich inammation in the absence of known causes for eosinophilia (e.g., drug reactions, parasitic infections, malignancy). These disorders include eosinophilic esophagitis (EE), eosino-

philic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis and are being diagnosed with increasing frequency.1 EG was originally described in 1937 by Kaijser.2 In 1961, Ureles et al. classied it into three groups: polyenteric, monoenteric, and regional.3 Klein et al. classied this disorder into three major pathological types: predominant mucosal layer type, predominant muscle layer type, and predominant subserosal layer type.4 In 1984, Oyaizu et al. presented evidence for the hypothetical IgE-induced, mast cellmediated mechanism of eosinophilic chemotaxis in patients with EG.5 In 1990, Talley et al. categorized 40 patients with EG according to the classication established by Klein et al.6 They suggested the following diagnostic criteria: (1) the presence of gastrointestinal symptoms, (2) biopsies showing eosinophilic inltration of one or more areas of the gastrointestinal tract from esophagus to colon, or characteristic radiologic ndings with peripheral eosinophilia, and (3) no evidence of parasitic or extraintestinal disease.6 Recently, a number of basic studies have identied potential roles for eosinophils as important participants in the inammatory cascade within the gastrointestinal microenvironment. This review focuses on the molecular pathogenesis, clinical features, and treatment of this disease, and, nally, considers EE separately, as this appears to be a newly described entity surrounded by some controversy.

Pathogenesis The eosinophil Eosinophils are multifunctional leukocytes implicated in the pathogenesis of numerous inammatory processes, including parasitic helminth infections and allergic diseases,79 and were rst described by Paul Ehrlich in 1879.10

Received: November 9, 2007 / Accepted: May 28, 2008 Reprint requests to: R. Chetty

742

H.E. Oh and R. Chetty: Review of eosinophilic gastroenteritis

Eosinophils are derived from bone marrow pluripotential stem cells, which rst differentiate into a hybrid precursor with shared properties of basophils and eosinophils and then into a separate eosinophil lineage.11 Eosinophil lineage specicity is dictated by the interplay of at least three classes of transcription factors, including GATA-1 (a zinc nger family member), PU.1 (an ETS family member), and C/EBP members (CCAAT/enhancer-binding protein family).1214 Of these transcription factors, GATA-1 is the most important for eosinophil lineage specicity, as revealed by the loss of the eosinophil lineage in mice harboring a targeted deletion of the high-afnity GATA-binding site in the GATA-1 promoter15 and by eosinophil differentiation experiments in vitro.16 The proliferation and maturation of eosinophil are controlled by three cytokines, interleukin (IL)-3, IL-5, and granulocytemacrophage colony-stimulating factor (GM-CSF).1720 Of these three cytokines, IL-5 is the most specic to the eosinophil lineage and is responsible for selective differentiation of eosinophils.21 IL-5 also stimulates the release of eosinophils from the bone marrow into the peripheral circulation.22 Mice lacking IL-5 develop a signicant reduction in mucosal eosinophilia23,24 whereas mice overexpressing IL-5 show markedly increased peripheral eosinophilia.2528 Eosinophils tether, roll, and diapedese as they leave the vascular space and enter the mucosa. Depending on the target organ, eosinophils cross the endothelium into tissues by a regulated process involving the coordinated interaction between networks involving the chemokine eotaxin-1, eosinophil adhesion molecules (4C1, 4C7, 4LC2), and adhesion receptors on the endothelium (MAdCAM-1, VCAM-1, and ICAM-1).29 Under homeostatic conditions, eosinophils trafc into the thymus, mammary gland, uterus, and most prominently into the gastrointestinal tract.3032 The trafcking of eosinophils into inammatory sites involves a number of cytokines (in particular, Th-2 and endothelial cell products IL-4, IL-5, and IL-13),3335 adhesion molecules,29 chemokines (e.g., RANTES and the eotaxins),36 and other recently identied molecules (e.g., acidic mammalian chitinase).37 Tissue eosinophils likely can survive for at least 2 weeks based on in vitro observations.33 Of the cytokines implicated in modulating leukocyte recruitment, only IL-5 and the eotaxins selectively regulate eosinophil trafcking.38 IL-5 regulates growth, differentiation, activation, and survival of eosinophils and provides an essential signal for the expansion and mobilization of eosinophils from the bone marrow into the lung following allergen exposure.39 Recent studies have showed an important role for the eotaxin subfamily of chemokines in eosinophil recruitment to the lung.36 Other studies suggest that eotaxin-1 has a key role in the

modulation of eosinophil accumulation in the gastrointestinal tract and that its effect is primarily tissue specic.40 For example, eotaxin-1-decient mice have a defect in eosinophil trafcking to the gastrointestinal tract and are protected from experimental oral antigeninduced gastrointestinal pathology.41 These studies have identied the eotaxins as critical tissue recruitment factors. Eotaxin was initially discovered using a biological assay in guinea pigs designed to identify the molecules responsible for allergen-induced eosinophil accumulation in the lungs.38,42,43 Eotaxin is produced by a number of different cells including resident cells (epithelium, broblasts) and recruited cells (macrophages, eosinophils).44,45 The eotaxin chemokines cooperate with IL-5 in the induction of tissue eosinophilia. Furthermore, when given exogenously, eotaxins cooperate with IL-5 to induce substantial production of IL-13 in the lung.36 The nding that IL-4 and IL-13 are potent inducers of the eotaxin chemokines by a STAT6-dependent pathway provides an integrated mechanism to explain the eosinophilia associated with Th-2 responses.36 Recent evidence that IL-13 delivery into the lung induces eosinophilic esophagitis further implicates Th-2 cells and cytokines in the immunopathogenesis of eosinophilic esophagitis.46 Eosinophils are bilobed granulocytes with eosinophilic staining secondary granules. The secondary granules contain four primary cationic proteins, designated eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN).47 All four proteins are cytotoxic molecules; in addition, ECP and EDN are ribonucleases.48 Eosinophils respond to diverse stimuli, including nonspecic tissue injury, infections, allografts, allergens, and tumors. In addition to releasing their preformed cationic proteins, eosinophils can also release a variety of cytokines [IL-1, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-16, IL-18, GM-CSF, transforming growth factor (TGF)-alpha/beta, tumor necrosis factor (TNF)], chemokines [eotaxin, regulation upon activation normal T-cell expressed and secreted (RANTES), MIP-1], lipid mediators (leukotrienes, platelet-activating factor), and neuromediators (substance P, vasoactive intestinal polypeptide) (Fig. 1).38,49 The gastrointestinal tract is the main nonhematopoietic organ where eosinophils reside in the healthy state. Eosinophils are normally present in the lamina propria, but the number of eosinophils regarded as pathological for various sites along the gastrointestinal tract is debated; the highest concentrations are found in the cecum and appendix. Within the gastrointestinal tract, the esophageal epithelium is unique in being devoid of eosinophils under noninammatory conditions.50

H.E. Oh and R. Chetty: Review of eosinophilic gastroenteritis

743

Clinical features EG is a heterogeneous disorder affecting both children and adults and characterized by the presence of an intense eosinophilic inltrate seen histopathologically in one or multiple segments from the esophagus to the rectum.51,56 The majority of the cases of EG are reported in whites, with some cases occurring in Asians. A slight male preponderance has been reported. The majority of patients clinically present in the third to fth decades, but the disease can affect any age group.2,46 In published reports, the most frequently affected organs were the small intestine and stomach.6,57 The involvement of different layers of the intestinal wall usually gives rise to different clinical manifestations. The mucosal form, which is the most common EG subtype, presents with vomiting, abdominal pain (that can even mimic acute appendicitis), diarrhea, fecal blood loss, anemia, and weight loss secondary to malabsorption or proteinlosing enteropathy.51,58 The muscularis form is characterized by inltration of eosinophils predominantly in the muscularis layer, leading to thickening of the bowel wall, which might result in gastrointestinal obstructive symptoms mimicking pyloric stenosis or other causes of gastric outlet obstruction.59,60 The subserosal form occurs in a minority of patients with EG, and it is characterized by exudative ascites with higher peripheral eosinophil counts compared with the other forms.6,59 EG can also present as obstructive jaundice and with symptomatology mimicking acute surgical conditions such as appendicitis, small bowel obstruction, and pancreatic cancer.6165 Extraintestinal manifestations such as eosinophilic cystitis, eosinophilic splenitis, and hepatic dysfunction have also been described.6668

Fig. 1. The eosinophil and its multifunctional effects in eosinophilic gastroenteritis Eosinophils respond to diverse stimuli and can also release a variety of cytotoxic granules, cytokines, chemokines, lipid mediators, and neuromediators. Eosinophils directly communicate with T cells and mast cells in a bidirectional manner. Eosinophilic secretions mediate tissue damage. IL, interleukin; GM-CSF, granulocyte-macrophage colony-stimulating factor; APC, antigen-presenting cell; TH2 and B, lymphocytes; PC, plasma cell; Ig, immunoglobulin; MC, mast cell; E, eosinophil

The allergic mechanism Many patients with EG have history of seasonal allergies, food sensitivities, eczema, asthma, atopy, and elevated serum IgE levels. These ndings suggest that the hypersensitivity response plays a major role in pathogenesis.51,52 A majority of patients have positive skin test responses to a variety of food antigens but do not have typical anaphylactic reactions, which is consistent with a delayed type of food hypersensitivity syndrome. Indeed, experimental induction of delayed EG (involving the esophagus, stomach, and intestine) in mice is accomplished by means of oral allergen administration (in the form of enteric-coated allergen beads) to sensitized mice.53 Notably, the mice had eosinophilassociated gastrointestinal dysfunction, including gastromegaly, delayed food transit, and weight loss, all strongly dependent on the chemokine eotaxin-1.41 In clinical studies, increased secretion of IL-4 and IL-5 by peripheral blood T cells has been reported in patients with EG.54 Furthermore, T cells derived from the lamina propria of the duodenum of patients with EG preferentially secrete Th-2 cytokines (especially IL-13) when stimulated with milk proteins.55

Diagnosis No standards for the diagnosis of EG exist, but a high index of clinical suspicion is important.51 Denitive diagnosis requires the presence of increased eosinophils in biopsy specimens from the gastrointestinal tract wall. However, the clinical history, laboratory ndings, radiological ndings, and endoscopy are needed to make a rm diagnosis. Many patients with EG have a history of seasonal allergies, food sensitivities, eczema, asthma, and atopy.51,52 Talley et al. reported a history of allergy in 20 of 40 patients with EG.6

Laboratory ndings EGIDs typically occur independent of peripheral blood eosinophilia more than 50% of the time.1 It may or may not be accompanied by higher counts of eosinophils in

744

H.E. Oh and R. Chetty: Review of eosinophilic gastroenteritis

the peripheral blood.69 In one study, peripheral eosinophilia was absent in 9 of 40 patients.6 In another study, 11 of 15 patients had hypoalbuminemia (serum albumin <3.5 g/dl).59 Parasitic infection or other extraintestinal diseases associated with eosinophilia should be evaluated. Allergy evaluation includes total IgE; the use of commonly available tests include skin prick tests (SPT) and radioallergosorbent tests (RAST) detecting IgE antibody specic to inhaled and ingested allergens.70 Indeed, increased total IgE and food-specic IgE levels have been detected in the majority of patients.1 SPT are sensitive, so negative SPT are very useful in conrming the absence of IgE-mediated reactions, if good-quality food extracts are used. In those older than 1 year of age, SPT are associated with a high negative predictive value and positive predictive value of 50% or lower.1 The most common foods reported to be positive by SPT include common food allergenspeanuts, eggs, soy, cow milk, and wheatin addition to beans, rye, and beef.71 Radiology Radiographically, EG does not have a pathognomonic appearance, and changes are variable and nonspecic. In one study, a string sign was demonstrated in gastric outlet obstruction as a result of antral EG.72 Eosinophilic inltration of the small bowel manifests as thickening of the circular folds and wall.73 An abdominal ultrasound is useful in detecting ascites. Computerized tomography may show nodular, irregular folds and thickening of the stomach and small intestine in EG. Deep inltration may result in rigid bowel loops, simulating lymphoma.74 White blood cell count and Tc-99 m scintigraphy may be used to determine the extent of inammation in EG but will probably not help in differentiating from other causes of intestinal inammation.75 Endoscopy The endoscopic appearance in eosinophilic gastroenteritis is nonspecic, including erythematous, friable, nodular, and occasional ulcerative changes.76 In one study, 10 of 15 patients had only nonspecic gastritis or colitis, while 2 of 15 patients had shallow gastric or duodenal ulcers.59 Pathology The diagnosis of EG is conrmed by biopsies that reveal eosinophils exceeding 20 per high-power eld on

microscopic examination.6,77,78 Eosinophilic inltrates are usually patchy in distribution and may be present in otherwise normal, noninamed bowel wall. Therefore, multiple biopsies may be required to avoid missing the diagnosis.78

Differential diagnosis EGIDs are classied into primary and secondary subtypes. The primary subtype includes the atopic, non-atopic, and familial variants, and the secondary subtype is divided into two groups, one composed of systemic eosinophilic disorders and the other of noneosinophilic disorders (Table 1).1 The secondary subtype of EG includes parasitic and bacterial infections (including Helicobacter pylori), inammatory bowel disease (IBD), hypereosinophilic syndrome (HES), myeloproliferative disorders, periarteritis, allergic vasculitis, scleroderma, drug injury, and drug hypersensitivity.79 Therefore, these diseases can be excluded with careful examination. Tissue eosinophilia from intestinal parasites is associated with hookworms (Ancylostoma caninum), pinworms (Enterobius vermicularis), Eustoma rotundatum, Giardia lamblia, Anisakis, Trichinella spiralis, Ascaris, Trichuris, and Schistosoma.8088 Eosinophilic ascites has occurred with Toxocara canis and Strongyloides stercoralis.89,90 Fasciola hepatica can cause eosinophilia, right upper quadrant pain, fever, and hepatomegaly.91 A stool examination or endoscopy in the stomach for the larvae of Anisakis is needed. On multiple biopsies of stomach, careful histological examination is also needed for Helicobacter pylori.
Table 1. Classication of eosinophilic gastroenteritis Primary (mucosal, muscular, and serosal forms) Atopic Non-atopic Familial Secondary Eosinophilic disorders Hyper eosinophilic syndrome Non-eosinophilic disorders Iatrogenic Infection Inammatory bowel disease Celiac disease Connective tissue disease (scleroderma) Vasculitis (ChurgStrauss syndrome) Autoimmune disorders Transplantation stimulation Tissue injury Infection Allergens Allografts Tumors

H.E. Oh and R. Chetty: Review of eosinophilic gastroenteritis

745

IBD might be associated with peripheral and intestinal eosinophilia, but this can usually be excluded by biopsy because this disease typically lacks orid eosinophilia and usually shows other histological ndings.92 HES is an idiopathic condition associated with gastroenteritis and is dened as marked peripheral eosinophilia exceeding 1500 cells/l that persists for at least 6 months; there is organ dysfunction.93 Target-organ damage mediated by eosinophils is highly variable among patients, with involvement of skin, heart, lungs, and central and peripheral nervous systems in more than 50% of cases.94 In the ChurgStrauss syndrome and polyarteritis nodosa, vasculitis is characterized by an eosinophilic inltrate involving the small vessels in the intestinal tract and extraintestinal organs such as kidney, lung, nervous system, and skin.95,96 Patients with scleroderma, dermatomyositis, or polymyositis may have episodic peripheral eosinophilia, and a bandlike inltrate of eosinophils and mast cells may occur between the small intestinal crypts and the muscularis mucosae.97,98 A drug allergy may result in gastrointestinal eosinophilia. For example, an association between gold salts and the onset of EG has been reported.99 Other medications implicated in inducing EG include azathioprine,100 gembrozil,101 carbamazepine,102 and clofazimine.103 Treatment There has been no consensus regarding optimal treatment of patients affected by EG. Thus, the factors deserving consideration when deciding on the best treatment for an individual patient include the patients age and the severity of the clinical manifestations. One study suggested this therapeutic strategy.104 First, they recommended specic allergy avoidance (airborne and dietary). If this failed to improve EGID pathology, then they recommended glucocorticoid therapy, rst starting with topical delivery and then considering systemic delivery. They also advocated elemental diet trials aimed at avoiding all protein antigen exposure.104 Diet Eliminating the dietary intake of the foods implicated by skin prick testing (or RASTs) has variable effects, but complete resolution is generally achieved with amino acid-based elemental diets.105 In one institution, an appropriate therapeutic approach includes a trial of food elimination if sensitization is found on the basis of food skin testing, RAST, or both. If no sensitization is found or if specic food avoidance is not feasible, elemental formulas are instituted.1 One study showed an 11-year-old girl known to have multiple food allergies since the age of 3 years, with an

unusual presentation of allergic EG with widespread gastric and proximal small intestinal mucosal disease consisting of diffuse ulcerations and pseudopolyps, despite minimal clinical symptoms. Her endoscopic and histological abnormalities improved dramatically following 9 weeks of dietary therapy with an amino acid-based formula.106 Steroids Systemic or topical steroids are the main therapy in cases in which diet restriction is not feasible or has failed to improve the disease.1 Many studies have demonstrated an important role for corticosteroids with good symptomatic responses.1,6,59,71,77,107 The benecial effects of steroids in eosinophilic disorders are mediated by inhibition of eosinophil growth factors, IL-3, IL-5, and GM-CSF. Steroids provide prompt and effective relief of symptoms within a few days to weeks, but long-term response and histological correlation have not been studied in a prospective manner in EG.70 Risk factors associated with long-term use of systemic corticosteroids include growth abnormalities, bone abnormalities, mood disturbances, and adrenal axis suppression.71 There are several forms of topical glucocorticoids designed to deliver drugs to specic segments of the gastrointestinal tract (e.g., budesonide tablets designed to deliver the drug to the ileum and proximal colon).1 Budesonide is a corticosteroid that acts locally, with an efcacy similar to that of prednisone. Its main advantage is a high rst-step metabolism; this carries a lower risk for adrenal suppression.107 Most patients receive prednisolone in doses from 20 to 40 mg/day for 68 weeks with various schemes of dose tapering. Other drugs Other drugs, such as sodium chromoglycate and ketotifen (antihistamine and mast cell-stabilizing agents), suplatast tosilate (antiallergic drug that suppresses cytokines production), and montelukast (leukotriene receptor antagonist), were found to be effective in the management as well as steroid-sparing agents in some case reports but not in others.108113 Sodium chromoglycate resulted in a positive response in a case of serosal EG at a dose of 200 mg four times a day.108 Ketotifen, administered in doses of 24 mg/day for 14 months, has been effective in improving symptoms and peripheral and intestinal eosinophilia in patients with EG.114 Montelukast selectively and competitively antagonizes the leukotriene receptor Cys-LT1 expressed on bronchial smooth muscle cells and eosinophils, thereby blocking the actions of LTD4, a potent and specic eosinophil chemoattractant. It has the potential for being a relatively safe and effective steroid-sparing therapy for EG.111 Some reports indicate that montelukast use for

746

H.E. Oh and R. Chetty: Review of eosinophilic gastroenteritis

several months in a dose range of 1040 mg orally per day induced an improvement in peripheral eosinophilia and symptoms.58 Preliminary studies drew attention to the potential utility of anti-IL-5, antieotaxin-1, and antiCCR3 antagonists.36 There was an uncontrolled study using a humanized monoclonal antibody against IL-5 in four patients with HES.115 The therapeutic effects of several anti-eosinophil agents including eosinophil selective adhesion molecules, a monoclonal eotaxin antibody (CAT-213), and agents to enhance eosinophil apoptosis are under investigation.116 Surgery Surgical treatment is required for patients with intestinal perforation and/or obstruction.6,59,64 One study showed a case of EG that underwent emergency laparotomy for acute intestinal obstruction of the ileum.64 Eosinophilic esophagitis EE has come into prominence as a result of patients who were thought to have gastroesophageal reux disease (GERD) but did not respond to high-dose proton pump inhibitors or indeed surgical management for GERD.71 Since the initial description of EE in 1978 by Landres et al., much of the medical literature has focused on pediatric cases of EE.117 In addition to its rarity, the entity has been described under several names: idiopathic eosinophilic esophagitis, primary eosinophilic esophagitis, allergic eosinophilic esophagitis, and atopic esophagitis.71,118 Over the ensuing years, several case reports and/or small series have appeared in the literature, and within the last 2 years, several critical reviews on EE have appeared.119122 This work has culminated in a consensus document published in 2007.71 Epidemiology In the past 10 years, the diagnosis of EE has been made with increasing frequency.118,123,124 Two recent surveys in the United States have revealed prevalence gures of 4.3 cases per 100 000 in children and 2.5 cases per 100 000 in adults.125,126 Whether this does in fact reect a true increase in incidence is a moot point. As Chang and Anderson have noted, this is most likely the result of an increase in awareness of the condition by both gastroenterologists and pathologists.118 Denition The clinical denition of EE is difcult because the symptoms are somewhat nonspecic and overlap with the commonly encountered GERD.71 At the end of the day, the diagnosis of EE is a clinicopathological: one

suggested by the biopsy and also the patient not responding to reux therapy. Clinical and laboratory features The patients present with the following symptoms: heartburn, chest pain, dysphagia, odynophagia, and food impaction. The majority of children have a history of atopy: asthma, allergic rhinitis, eczema, and atopic dermatitis, and they usually present with feeding problems, vomiting, and abdominal pain.71,127 Dysphagia and food impaction were encountered in older children.71 Adults usually present with dysphagia.128 Recently, a genetic/familial predisposition has also been postulated.129 Overall, 71%78% of pediatric patients and 60%69% of adult patients with eosinophilic esophagitis (EE) had elevated total IgE levels.71 One adult study demonstrated that peripheral IgE levels remained elevated for years in EE patients not undergoing pharmacological intervention.130 Endoscopic features A wide range of features are encountered at endoscopy: longitudinal furrowing and shearing, friability, edema, white specks and exudates, Schatzki rings (multiple rings), felinization, strictures, and a crepe paper mucosa.71,122 In a proportion of symptomatic patients, esophageal endoscopy may be normal.122 Histopathology When reporting an esophageal biopsy that contains eosinophils, the pathologist should be mindful of the differential diagnosis: GERD, EE, EG, Crohns disease, connective tissue disorders, hypereosinophilic syndrome, infections (Candida, herpes), and hypersensitivity to drugs.71 If a dense inltrate of eosinophils is seen, equal to 1520 eosinophils or more per high-power eld, then the diagnosis of EE can be suggested with clinicopathological correlation needed to clinch the diagnosis. Additional histological features that may be of some use include clustering of 4 or more eosinophils to form an eosinophil microabscess, predominance of eosinophils toward the luminal aspect of the mucosa, basal hyperplasia, and brosis of the lamina propria/subepithelial tissue.71,122 Lymphocytes (CD3/CD8+ve)131, neutrophils, and mast cells may accompany the eosinophils. Other diagnostic modalities and treatment regimes are as for GE. Conclusion EG is a rare disease with various gastrointestinal symptoms characterized by an eosinophilic inltration. The

H.E. Oh and R. Chetty: Review of eosinophilic gastroenteritis

747
18. Rothenberg ME, Pomerantz JL, Owen WF, Avraham S, Soberman RJ, Austen KF, et al. Characterization of a human eosinophil proteoglycan, and augmentation of its biosynthesis and size by interleukin 3, interleukin 5, and granulocyte/macrophage colony stimulating factor. J Biol Chem 1988;263:139018. 19. Lopez AF, Sanderson CJ, Gamble JR, Campbell HD, Young IG, Vadas MA. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med 1988;167: 21924. 20. Takatsu K, Takaki S, Hitoshi Y. Interleukin-5 and its receptor system: implications in the immune system and inammation. Adv Immunol 1994;57:14590. 21. Sanderson CJ. Interleukin-5, eosinophils, and disease. Blood 1992;79:31019. 22. Collins PD, Marleau S, Grifths-Johnson DA, Jose PJ, Williams TJ. Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 1995;182:116974. 23. Foster P, Hogan S, Ramsay A, Matthaei K, Young I. Interleukin-5 deciency abolishes eosinophilia, airway hyperreactivity and lung damage in a mouse asthma model. J Exp Med 1996; 183:195201. 24. Kopf M, Brombacher F, Hodgkin PD, Ramsay AJ, Milbourne EA, Dai WJ, et al. IL-5-decient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity 1996;4: 1524. 25. Dent LA, Strath M, Mellor AL, Sanderson CJ. Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med 1990;172: 142531. 26. Tominaga A, Takaki S, Koyama N, Katoh S, Matsumoto R, Migita M, et al. Transgenic mice expressing a B cell growth and differentiation factor (interleukin 5) develop eosinophilia and autoantibody production. J Exp Med 1991;173:42937. 27. Lee JJ, McGarry MP, Farmer SC, Denzler KL, Larson KA, Carrigan PE, et al. Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J Exp Med 1997;185:214356. 28. Mishra A, Hogan SP, Brandt EB, Wagner N, Crossman MW, Foster PS, et al. Enterocyte expression of the eotaxin and interleukin-5 transgenes induces compartmentalized dysregulation of eosinophil trafcking. J Biol Chem 2002;277:440612. 29. Bochner BS, Schleimer RP. The role of adhesion molecules in human eosinophil and basophil recruitment. J Allergy Clin Immunol 1994;94:42738. 30. Gouon-Evans V, Rothenberg ME, Pollard JW. Postnatal mammary gland development requires macrophages and eosinophils. Development (Camb) 2000;127:226982. 31. Rothenberg ME, Mishra A, Brandt EB, Hogan SP. Gastrointestinal eosinophils in health and disease. Adv Immunol 2001; 78:291328. 32. Mishra A, Hogan SP, Lee JJ, Foster PS, Rothenberg ME. Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin Invest 1999;103:171927. 33. Rothenberg ME, Owen WF Jr, Silberstein DS, Soberman RJ, Austen KF, Stevens RL. Eosinophils co-cultured with endothelial cells have increased survival and functional properties. Science 1987;237:6457. 34. Sher A, Coffman RL, Hieny S, Cheever AW. Ablation of eosinophil and IgE responses with anti-IL-5 or anti-IL-4 antibodies fails to affect immunity against Schistosoma mansoni in the mouse. J Immunol 1990;145:39116. 35. Horie S, Okubo Y, Hossain M, Sato E, Nomura H, Koyama S, et al. Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis. Intern Med 1997; 36:17985. 36. Zimmermann N, Hershey GK, Foster PS, Rothenberg ME. Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol 2003;111:22742.

disease is often a chronic, waxing and waning disorder. The eosinophil, eotaxin, and Th-2 cytokines are important in pathogenesis. Because the clinical presentation is nonspecic, the most reliable diagnostic nding is evidence of eosinophilic inltration on the biopsied tissue. To date, restricted diets, steroids, some drugs, and surgery are the treatments of this disease. A variety of new therapeutic approaches are now underway. It is hoped that the therapy and follow-up procedures will advance in the future.

References
1. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol 2004;113:1128. 2. Kaijser R. Allergic disease of the gut from the point of view of the surgeon. Arch Klin Chir 1937;188:3664. 3. Ureles AL, Alschibaja T, Lodico L, Stabins SJ. Idiopathic eosinophilic inltration of the gastrointestinal tract, diffuse and circumscribed. A proposed classication and review of the literature, with two additional cases. Am J Med 1961;30:898 909. 4. Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH. Eosinophilic gastroenteritis. Medicine (Baltim) 1970;40:299319. 5. Oyaizu N, Uemura Y, Izumi H, Morii S, Nishi M, Hioki K. Eosinophilic gastroenteritis, immunohistochemical evidence for IgE mast cell mediated allergy. Acta Pathol Jpn 1985;35: 75966. 6. Talley NJ, Shorter RG, Phillips SF, Zinsmeister AR. Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer and subserosal tissues. Gut 1990;31:548. 7. Gleich GJ, Loegering DA. Immunobiology of eosinophils. Annu Rev Immunol 1984;2:42959. 8. Weller PF. Eosinophils: structure and functions. Curr Opin Immunol 1994;6:8590. 9. Rothenberg ME. Eosinophilia. N Engl J Med 1998;338:1592 600. 10. Jay V. Paul Ehrlich. Arch Pathol Lab Med 2001;125:72425. 11. Boyce JA, Friend D, Matsumoto R, Austen KF, Owen WF. Differentiation in vitro of hybrid eosinophil/basophil granulocytes: autocrine function of an eosinophil developmental intermediate. J Exp Med 1995;182:4957. 12. McNagny K, Graf T. Making eosinophils through subtle shifts in transcription factor expression. J Exp Med 2002;195: F437. 13. Nerlov C, Graf T. PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev 1998;12: 240312. 14. Nerlov C, McNagny KM, Doderlein G, Kowenz-Leutz E, Graf T. Distinct C/EBP functions are required for eosinophil lineage commitment and maturation. Genes Dev 1998;12:241323. 15. Yu C, Cantor AB, Yang H, Browne C, Wells RA, Fujiwara Y, et al. Targeted deletion of a high-afnity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med 2002;195:138795. 16. Hirasawa R, Shimizu R, Takahashi S, Osawa M, Takayanagi S, Kato Y, et al. Essential and instructive roles of GATA factors in eosinophil development. J Exp Med 2002;195:137986. 17. Lopez AF, Begley CG, Williamson DJ, Warren DJ, Vadas MA, Sanderson CJ. Murine eosinophil differentiation factor. An eosinophil-specic colony-stimulating factor with activity for human cells. J Exp Med 1986;163:108599.

748
37. Zhu Z, Zheng T, Homer RJ, Kim YK, Chen NY, Cohn L, et al. Acidic mammalian chitinase in asthmatic Th2 inammation and IL-13 pathway activation. Science 2004;304:167882. 38. Rankin SM, Conroy DM, Williams TJ. Eotaxin and eosinophil recruitment: implications for human disease. Mol Med Today 2000;6:207. 39. Collins PD, Marleau S, Grifths-Johnson DA, Jose PJ, Williams TJ. Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 1995;182:116974. 40. Matthews AN, Friend DS, Zimmermann N, Sara MN, Luster AD, Pearlman E, et al. Eotaxin is required for the baseline level of tissue eosinophils. Proc Natl Acad Sci U S A 1998;95: 62738. 41. Hogan SP, Mishra A, Brandt EB, Royalty MP, Pope SM, Zimmermann N, et al. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inammation. Nat Immunol 2001;2:35360. 42. Jose PJ, Grifths-Johnson DA, Collins PD, Walsh DT, Moqbel R, Totty NF, et al. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inammation. J Exp Med 1994;179:8817. 43. Rothenberg ME, Luster AD, Lilly CM, Drazen JM, Leder P. Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung. J Exp Med 1995;181:12116. 44. Garcia-Zepeda EA, Combadiere C, Rothenberg ME, Sara MN, Lavigne F, Hamid Q, et al. Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inammation that signals through the CC chemokine receptors (CCR)-2 and -3. J Immunol 1996;157:561326. 45. Rothenberg ME. Eotaxin. An essential mediator of eosinophil trafcking into mucosal tissues. Am J Respir Cell Mol Biol 1999;21:2915. 46. Mishra A, Rothenberg ME. Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology 2003;125:141927. 47. Gleich GJ, Adolphson CR. The eosinophilic leukocyte: structure and function. Adv Immunol 1986;39:177253. 48. Slifman NR, Loegering DA, McKean DJ, Gleich GJ. Ribonuclease activity associated with human eosinophil-derived neurotoxin and eosinophil cationic protein. J Immunol 1986;137: 29137. 49. Hogan SP, Rothenberg ME, Forbes E Smart VE, Matthaei KI, Foster PS. Chemokines in eosinophil-associated gastrointestinal disorders. Curr Allergy Asthma Rep 2004;4:7482. 50. Straumann A, Simon HU. The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract. Allergy 2004;59:1525. 51. Kelly KJ. Eosinophilic gastroenteritis. J Pediatr Gastroenterol Nutr 2000;30:S2835. 52. Von Wattenwyl F, Zimmermann A, Netzer P. Synchronous rst manifestation of an idiopathic gastroenteritis and bronchial asthma. Eur J Gastroenterol Hepatol 2001;13:7215. 53. Hogan SP, Mishra A, Brandt EB, Foster PS, Rothenberg ME. A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy. Proc Natl Acad Sci USA 2000;97:66816. 54. Jaffe JS, James SP, Mullins GE, Braun-Elwert L, Lubensky I, Metcalfe DD. Evidence for an abnormal prole of interleukin-4 (IL-4), IL-5, and gamma-interferon (gamma-IFN) in peripheral blood T cells from patients with allergic eosinophilic gastroenteritis. J Clin Immunol 1994;14:299309. 55. Beyer K, Castro R, Birnbaum A, Benkov K, Pittman N, Sampson HA. Human milk-specic mucosal lymphocytes of the gastrointestinal tract display a TH2 cytokine prole. J Allergy Clin Immunol 2002;109:70713. 56. Khan S, Orenstein SR. Eosinophilic gastroenteritis: epidemiology, diagnosis and management. Paediatr Drugs 2002;4:56370.

H.E. Oh and R. Chetty: Review of eosinophilic gastroenteritis

57. Kim NI, Jo YJ, Song MH, Kim SH, Kim TH, Park, YS, et al. Clinical features of eosinophilic gastroenteritis (in Korean with English abstract). Korean J Gastroenterol 2004;44:21723. 58. Friesen CA, Kearns GL, Andre L, Neustrom M, Roberts CC, Abdel-Rahman SM. Clinical efcacy and pharmacokinetics of montelukast in dyspeptic children with duodenal eosinophilia. J Pediatr Gastroenterol Nutr 2004;38:34351. 59. Chen MJ, Chu CH, Lin SC, Shih SC, Wang TE. Eosinophilic gastroenteritis: clinical experience with 15 patients. World J Gastroenterol 2003;9:28136. 60. Tursi A, Rella G, Inchingolo CD, Maiorano M. Gastric outlet obstruction due to gastroduodenal eosinophilic gastroenteritis. Endoscopy 2007;39(suppl 1):E184. 61. Whitaker IS, Gulati A, McDaid JO, Bugajska-Carr U, Arends MJ. Eosinophilic gastroenteritis presenting as obstructive jaundice. Eur J Gastroenterol Hepatol 2004;16:4079. 62. Polyak S, Smith TA, Mertz H. Eosinophilic gastroenteritis causing pancreatitis and pancreaticobiliary ductal dilation. Dig Dis Sci 2002;47:10915. 63. Tran D, Salloum L, Tshibaka C, Moser R. Eosinophilic gastroenteritis mimicking acute appendicitis. Am Surg 2000;66: 9902. 64. Yun MY, Cho YU, Park IS, Choi SK, Kim SJ, Shin SH, et al. Eosinophilic gastroenteritis presenting as small bowel obstruction: a case report and review of the literature. World J Gastroenterol 2007;13:175860. 65. Christopher V, Thompson MH, Hughes S. Eosinophilic gastroenteritis mimicking pancreatic cancer. Postgrad Med J 2000; 78:4989. 66. Gregg JA, Utz DC. Eosinophilic cystitis associated with eosinophilic gastroenteritis. Mayo Clin Proc 1974;491857. 67. Zhou HB, Chen JM, Du Q. Eosinophilic gastroenteritis with ascites and hepatic dysfunction. World J Gastroenterol 2007; 13:13035. 68. Robert F, Omura E, Durant JR. Mucosal eosinophilic gastroenteritis with systemic involvement. Am J Med 1977;62:13943. 69. Mndez-Snchez N, Chvez-Tapia NC, Vazquez-Elizondo G, Uribe M. Eosinophilic gastroenteritis: a review. Dig Dis Sci 2007;52:290411. 70. Khan S. Eosinophilic gastroenteritis. Best Pract Res Clin Gastroenterol 2005;19:17798. 71. Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007;133:134263. 72. Khan S, Orenstein SR. Eosinophilic gastroenteritis masquerading as pyloric stenosis. Clin Pediatr (Phila) 2000;39:557. 73. Teele RL, Katz AJ, Goldman H, Kettell RM. Radiographic features of eosinophilic gastroenteritis (allergic gastroenteropathy) of childhood. Am J Roentgenol 1979;132:57580. 74. Horton KM, Corl FM, Fishman EK. CT of nonneoplastic diseases of the small bowel: spectrum of disease. J Comput Assist Tomogr 1999;23:41728. 75. Imai E, Kaminaga T, Kawasugi K, Yokokawa T, Furui S. The usefulness of 99 mTc-hexamethylpropyleneamineoxime white blood cell scintigraphy in a patient with eosinophilic gastroenteritis. Ann Nucl Med 2003;17:6013. 76. Katsumi N, Yamaguchi Y, Yamato T, Morozumi K, Abe T, Ishida H, et al. Multiple ulcerative lesions of the stomach: a rare case of eosinophilic gastroenteritis. Gastrointest Endosc 2002; 56:7624. 77. Lee CM, Changchien CS, Chen PC, Lin DY, Sheen IS, Wang CS, et al. Eosinophilic gastroenteritis: 10 years experience. Am J Gastroenterol 1993;88:704. 78. Lee M, Hodges WG, Huggins TL, Lee EL. Eosinophilic gastroenteritis. South Med J 1996;89:18994. 79. Ahmad M, Soetikno RM, Ahmed A. The differential diagnosis of eosinophilic esophagitis. J Clin Gastroenterol 2000;30: 2424.

H.E. Oh and R. Chetty: Review of eosinophilic gastroenteritis

80. Alamo Martinez JM, Ibanez Delgado F, Galindo Galindo A, Bernnal Bellido C, Duren Ferreras I, Suarez Artacho G, et al. Intestinal obstruction by eosinophilic jejunitis. Rev Esp Enferm Dig 2004;96:141927. 81. Walker NI, Croese J, Clouston AD, Parry M, Loukas A, Prociv C. Eosinophilic enteritis in northeastern Australia. Pathology, association with Ancylostoma caninum, and implications. Am J Surg Pathol 1995;19:32837. 82. Macedo T, MacCarty RL. Eosinophilic ileocolitis secondary to Enterobius vermicularis: case report. Abdom Imaging 2000; 25:5302. 83. Ashby BS, Appleton PJ, Dawson I. Eosinophilic granuloma of gastrointestinal tract caused by herring parasite Eustoma rotundatum. Br Med J 1964;5391:11415. 84. Esteve C, Resano A, Diaz-Tejeiro P, Fernandez-Benitez M. Eosinophilic gastritis due to Anisakis: a case report. Allergol Immunopathol (Madr) 2000;28:213. 85. Repiso Ortega A, Alcantara Torres M, Gonzalez de Frutos C, de Artaza Varasa T, Rodriguez Merlo R, Valle Munoz J, et al. Gastrointestinal anisakiasis. Study of a series of 25 patients (in Spanish with English abstract). Gastroenterol Hepatol 2003;26: 3416. 86. Takeyama Y, Kamimura S, Suzumiya J, Oh K, Okumura M, Akahane H, et al. Case report: eosinophilic colitis with high antibody titre against Ascaris suum. J Gastroenterol Hepatol 1997;12:2046. 87. Hong ST, Lim HS, Kim DH, Kim SJ. A case of gastroenteritis associated with gastric trichuriasis. J Korean Med Sci 2003; 18:42932. 88. Bogers J, Moreels T, De Man J, Vrolix G, Jacobs W, Pelckmans P, et al. Schistosoma mansoni infection causing diffuse enteric inammation and damage of the enteric nervous system in the mouse small intestine. Neurogastroenterol Motil 2000;12: 43140. 89. Van Laethem JL, Jacobs F, Braude P, Van Gossum A, Deviere J. Toxocara canis infection presenting as eosinophilic ascites and gastroenteritis. Dig Dis Sci 1994;39:13702. 90. Corsetti M, Basilisco G, Pometta R, Allocca M, Conte D. Mistaken diagnosis of eosinophilic colitis. Ital J Gastroenterol Hepatol 1999;31:6079. 91. Saba R, Korkmaz M, Inan D, Mamikoglu L, Turhan O, Gunseren F, et al. Human fascioliasis. Clin Microbiol Infect 2004;10:3857. 92. Levy AM, Gleich GJ, Sandborn WJ, Tremaine WJ, Steiner BL, Phillips SF. Increased eosinophil granule proteins in gut lavage uid from patients with inammatory bowel disease. Mayo Clin Proc 1997;72:11723. 93. Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltim) 1975;54:127. 94. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood 1994,83:275979. 95. Solans R, Bosch JA, Perez-Bocanegra C, Selva A, Huguet P, Alijotas J, et al. ChurgStrauss syndrome: outcome and longterm follow-up of 32 patients. Rheumatology (Oxf) 2001;40: 76371. 96. Blackshaw AJ, Levison DA. Eosinophilic inltrates of the gastrointestinal tract. J Clin Pathol 1986;39:17. 97. DeSchryver-Kecskemeti K, Clouse RE. A previously unrecognized subgroup of eosinophilic gastroenteritis. Association with connective tissue diseases. Am J Surg Pathol 1984;8:17180. 98. Clouse RE, Alpers DH, Hockenbery DM, DeSchryverKecskemeti K. Pericrypt eosinophilic enterocolitis and chronic diarrhea. Gastroenterology 1992;103:16876. 99. Michet CJ Jr, Rakela J, Luthra HS. Auranon-associated colitis and eosinophilia. Mayo Clin Proc 1987;62:1424. 100. Riedel RR, Schmitt A, de Jonge JP, Hartmann A. Gastrointestinal type 1 hypersensitivity to azathioprine. Klin Wochenschr 1990;68:502.

749
101. Lee JY, Medellin MV, Tumpkin C. Allergic reaction to gembrozil manifesting as eosinophilic gastroenteritis. South Med J 2000;93:8078. 102. Shakeer VK, Devi SR, Chettupuzha AP, Mustafa CP, Sandesh K, Kumar SK, et al. Carbamazepine-induced eosinophilic enteritis. Indian J Gastroenterol 2002;21:1145. 103. Ravi S, Holubka J, Veneri R, Youn K, Khatib R. Clofazimineinduced eosinophilic gastroenteritis in AIDS. Am J Gastroenterol 1993;88:6123. 104. Hogan SP, Rothenberg ME. Review article: The eosinophil as a therapeutic target in gastrointestinal disease. Aliment Pharmacol Ther 2004;20:123140. 105. Justinich C, Katz A, Gurbindo C, Lepage G, Chad Z, Bouthillier L, et al. Elemental diet improves steroid-dependent eosinophilic gastroenteritis and reverses growth failure. J Pediatr Gastroenterol Nutr 1996;23:815. 106. Chehade M, Sicherer SH, Magid MS, Rosenberg HK, Morotti RA. Multiple exudative ulcers and pseudopolyps in allergic eosinophilic gastroenteritis that responded to dietary therapy. J Pediatr Gastroenterol Nutr 2007;45:3547. 107. Tan AC, Kruimel JW, Naber TH. Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. Eur J Gastroenterol Hepatol 2001;13:4257. 108. Perez-Millan A, Martin-Lorente JL, Lopez-Morante A, Yuguero L, Saez-Royuela F. Subserosal eosinophilic gastroenteritis treated efcaciously with sodium cromoglycate. Dig Dis Sci 1997;42:3424. 109. Katsinelos P, Pilpilidis I, Xiarchos P, Christodoulou K, Papagiannis A, Tsolkas P, et al. Oral administration of ketotifen in a patient with eosinophilic colitis and severe osteoporosis. Am J Gastroenterol 2002;97:10724. 110. Bolukbas FF, Bolukbas C, Uzunkoy A, Baba F, Horoz M, Ozturk E. A dramatic response to ketotifen in a case of eosinophilic gastroenteritis mimicking abdominal emergency. Dig Dis Sci 2004;49:17825. 111. Schwartz DA, Pardi DS, Murray JA. Use of montelukast as steroid-sparing agent for recurrent eosinophilic gastroenteritis. Dig Dis Sci 2001;46:178790. 112. Quack I, Sellin L, Buchner NJ, Theegarten D, Rump LC, Henning BF. Eosinophilic gastroenteritis in a young girl: longterm remission under Montelukast. BMC Gastroenterol 2005;5: 248. 113. Daikh BE, Ryan CK, Schwartz RH. Montelukast reduces peripheral blood eosinophilia but not tissue eosinophilia or symptoms in a patient with eosinophilic gastroenteritis and esophageal stricture. Ann Allergy Asthma Immunol 2003;90: 237. 114. Suzuki J, Kawasaki Y, Nozawa R, Isome M, Suzuki S, Takahashi A, et al. Oral disodium cromoglycate and ketotifen for a patient with eosinophilic gastroenteritis, food allergy and protein-losing enteropathy. Asian Pac J Allergy Immunol 2003;21:1937. 115. Garrett JK, Jameson SC, Thomson B, Collins MH, Wagoner LE, Freese DK, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol 2004; 113:1159. 116. Bochner BS. Verdict in the case of therapies versus eosinophils: the jury is still out. J Allergy Clin Immunol 2004;113:39. 117. Landres RT, Kuster GG, Strum WB. Eosinophilic esophagitis in a patient with vigorous achalasia. Gastroenterology 1987;74: 1298301. 118. Chang F, Anderson S. Clinical and pathological features of eosinophilic oesophagitis: a review. Pathology 2008;40:38. 119. Furuta GT, Straumann A. Review article: the pathogenesis and management of eosinophilic oesophagitis. Aliment Pharmacol Ther 2006;24:17382 120. Katzka DA. Eosinophilic esophagitis. Curr Opin Gastroenterol 2006;22:42932. 121. Brown-Whitehorn T, Liacouras CA. Eosinophilic esophagitis. Curr Opin Pediatr 2007;19:57580.

750
122. Pasha SF, DiBaise JK, Kim HJ, De Petris G, Crowell MD, Fleischer DE, et al. Patient characteristics, clinical, endoscopic, and histologic ndings in adult eosinophilic esophagitis: a case series and systematic review of the medical literature. Dis Esophagus 2007;20:3119. 123. Straumann A, Simon HU. Eosinophilic esophagitis: escalating epidemiology? J Allergy Clin Immunol 2005;115:4189. 124. Cherian S, Smith NM, Forbes DA. Rapidly increasing prevalence of eosinophilic oesophagitis in Western Australia. Arch Dis Childhood 2006;91:10004. 125. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med 2004;351:9401. 126. Guajardo J, Plotnick L, Fende J, Collins MH, Putnam PE, Rothenberg ME. Eosinophil-associated gastrointestinal disorders: a world-wide-web based registry. J Pediatr 2002;141: 57681. 127. Liacouras CA, Spergel JM, Ruchelli E, Verma R, Mascarenhas M, Semeao E, et al. Eosinophilic esophagitis: a 10-year experi-

H.E. Oh and R. Chetty: Review of eosinophilic gastroenteritis

ence in 381 children. Clin Gastroenterol Hepatol 2005;3:1198 206. Kerlin P, Jones D, Remedios M, Campbell C. Prevalence of eosinophilic esophagitis in adults with food bolus obstruction of the esophagus. J Clin Gastroenterol 2007;41:35661. Zink DA, Amin M, Gebara S, Desai TK. Familial dysphagia and eosinophilia. Gastrointest Endosc 2007;65:3304. Straumann A, Spichtin HP, Grize L, Bucher KA, Beglinger C, Simon HU. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology 2003;125:16609. Lucendo AJ, Navarro M, Comas C, Pascual JM, Burgos E, Santamara L, et al. Immunophenotypic characterization and quantication of the epithelial inammatory inltrate in eosinophilic esophagitis through stereology: an analysis of the cellular mechanisms of the disease and the immunologic capacity of the esophagus. Am J Surg Pathol 2007;31:598 606.

128.

129. 130.

131.