Background

Eosinophilic gastroenteritis can affect any level of the gastrointestinal tract. This article deals with the primary idiopathic form but secondary causes of this condition, such as secondary to medications and parasitic infecitons, must be excluded.

Outline

Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms
Internet Links

DISEASE ASSOCIATIONS	CHARACTERIZATION
Eosinophilic gastroenteritis presenting with colitis and cholangitis. Schoonbroodt D, Horsmans Y, Laka A, Geubel AP, Hoang P. Department of Gastroenterology, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium.	Dig Dis Sci 1995 Feb;40(2):308-14 Abstract quote Eosinophilic gastroenteritis (EG) is a rare condition that most commonly affects the stomach and intestine. Large bowel involvement has also been described. We report a case of EG presenting with colitis and cholangitis. This is the first case of associated cholangitis demonstrated radiologically and histologically. Simultaneous biliary and gastrointestinal tract involvement suggest a common link between EG and hypereosinophilic syndrome (HES). However, HES requires high peripheral hypereosinophilia and several organs including gastrointestinal tract, lung, heart, infiltrated with eosinophils. The patient's condition improved with corticosteroids.
Eosinophilic hepatic necrosis in hypereosinophilic syndrome. Ung KA, Remotti H, Olsson R. Department of Medicine, Sahlgrenska University Hospital, Goteborg, Sweden.	J Clin Gastroenterol 2000 Dec;31(4):323-7 Abstract quote Hypereosinophilic syndrome has been reported to be associated with liver disease, predominantly in men, in the form of acute and chronic active hepatitis with an inflammatory infiltrate that is mainly composed of eosinophils. We describe a female patient with peripheral blood and bone marrow eosinophilia, in whom liver biopsy displayed areas of necrosis with eosinophilic inflammation, with other regions showing features of chronic hepatitis. The patient also had antimitochondrial antibodies in serum. She responded favorably to immunosuppressive therapy.
Synchronous first manifestation of an idiopathic eosinophilic gastroenteritis and bronchial asthma. von Wattenwyl F, Zimmermann A, Netzer P. Gastrointestinal Unit, Inselspital, University Hospital of Berne, Switzerland.	Eur J Gastroenterol Hepatol 2001 Jun;13(6):721-5 Abstract quote Eosinophilic gastroenteritis is a rare disease of the gastrointestinal tract in which the eosinophils seem to play an important role in the inflammation of the gut wall. We report on a case with a synchronous first manifestation of eosinophilic gastroenteritis and bronchial asthma, which also occurred synchronously in all further episodes. The diagnosis was first made at the end of the second episode during which the patient lost more than 13 kg in weight. Under steroid therapy, symptoms of both diseases disappeared quickly in the third episode. We assume that participation of the gastrointestinal tract in patients with bronchial asthma occurs more frequently than expected. In asthma patients with abdominal symptomatology, eosinophilic gastroenteritis should also be considered.
Enalapril-induced eosinophilic gastroenteritis. Barak N, Hart J, Sitrin MD. University of Chicago, Chicago, Illinois, USA.	J Clin Gastroenterol 2001 Aug;33(2):157-8 Abstract quote Eosinophilic gastroenteritis is a rare disorder of unknown etiology. We describe a case of a 63-year-old woman with chronic diarrhea and eosinophilia. Small bowel biopsy revealed eosinophils in large clusters in the lamina propria with focal infiltration of the epithelium. The patient's diarrhea and eosinophilia started shortly after enalapril was prescribed. When the patient was instructed to stop taking that drug, her diarrhea promptly ceased, and the blood eosinophil level returned to normal. This is the first reported case of eosinophilic gastroenteritis associated with an angiotensin-converting enzyme inhibitor. Eosinophilic gastroenteritis should be entertained in the differential diagnosis of patients taking angiotensin-converting enzyme inhibitors who develop diarrhea or other gastrointestinal symptoms.

 

PATHOGENESIS	CHARACTERIZATION
Deposition of eosinophil granule major basic protein in eosinophilic gastroenteritis and celiac disease. Talley NJ, Kephart GM, McGovern TW, Carpenter HA, Gleich GJ. Division of Gastroenterology and Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota.	Gastroenterology 1992 Jul;103(1):137-45 Abstract quote Degrees of eosinophil infiltration and eosinophil degranulation, as evidenced by localization of the eosinophil granule major basic protein (MBP), were compared in patients with eosinophilic gastroenteritis, patients with celiac disease, and healthy controls using a specific indirect immunofluorescence technique for the localization of MBP. Formalin-fixed, paraffin-embedded biopsy specimens from the mucosa of the stomach and small intestine of 11 patients with eosinophilic gastroenteritis, from the small intestine of 4 patients with celiac disease, and from the stomach and/or upper small intestine of 18 healthy asymptomatic volunteers were tested. Degrees of eosinophil infiltration and extracellular deposition of MBP were graded by two blinded observers; each section was given a score from 0 (nil) to 4 (marked). In the small bowel biopsy specimens, both eosinophil infiltration and extracellular MBP deposition scores were significantly greater in patients with eosinophilic gastroenteritis and in patients with celiac disease than in controls. In the gastric biopsy specimens, extracellular MBP deposition scores were significantly increased in patients with eosinophilic gastroenteritis compared with controls even though eosinophil infiltration scores did not differ significantly at this site. The results support the hypothesis that the eosinophil, through toxic cationic proteins such as MBP, plays a role in the pathogenesis of these diseases.
Evidence for an abnormal profile of interleukin-4 (IL-4), IL-5, and gamma-interferon (gamma-IFN) in peripheral blood T cells from patients with allergic eosinophilic gastroenteritis. Jaffe JS, James SP, Mullins GE, Braun-Elwert L, Lubensky I, Metcalfe DD. Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.	J Clin Immunol 1994 Sep;14(5):299-309 Abstract quote Allergic eosinophilic gastroenteritis is characterized by elevated total IgE, specific IgE to food antigens, and eosinophilia of tissue and blood. Because the lymphokines IL-4, IL-5, and gamma-interferon, regulate IgE synthesis, and eosinophilopoiesis in vitro, we examined whether there is an imbalance in their production in allergic eosinophilic gastroenteritis. To explore this hypothesis, three adult patients with allergic eosinophilic gastroenteritis were studied. Flow cytometric studies of peripheral blood mononuclear cells from these patients did not reveal evidence of T cell activation or disturbance of T cell numbers or subsets. T cells were capable of normal mitogenic activation in vitro. IL-4 and IL-5 production were markedly elevated with mitogenic stimulation. Most IL-4 and IL-5 production was by CD4+ T cells. Synthesis of IL-5 by CD4+ T lymphocytes in three patients and CD8+ T lymphocytes in two patients occurred in the absence of mitogen. Mitogen-stimulated GM-CSF and gamma-interferon synthesis by CD4+ T cells was normal. Lymphokine mRNA in total cellular RNA derived from endoscopic biopsies was examined by reverse transcription/polymerase chain reaction. Mucosal biopsies from control subjects and most biopsies from allergic eosinophilic gastroenteritis patients contained less than 10(-8) micrograms IL-5 mRNA/1 microgram total cellular mRNA. gamma-Interferon mRNA was not detected by reverse transcription/polymerase chain reaction in biopsies from patients with allergic eosinophilic gastroenteritis but was present in controls. These lymphokine abnormalities are consistent with the elevated IgE and eosinophilia seen in allergic eosinophilic gastroenteritis and suggest that strategies targeting T lymphocytes may be efficacious in treatment of this disease.
Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis. Desreumaux P, Bloget F, Seguy D, Capron M, Cortot A, Colombel JF, Janin A. Clinique des Maladies de l'Appareil Digestif, Hopital Claude Huriez, Centre Hospitalier et Universitaire Lille, France.	Gastroenterology 1996 Mar;110(3):768-74 Abstract quote BACKGROUND & AIMS: Eosinophilic gastroenteritis (EG) is characterized by an eosinophilic infiltration of the gastrointestinal tract. The mechanism for the intestinal recruitment of eosinophils in EG remains unknown. Eosinophil recruitment and activation is induced by three main cytokines: interleukin (IL) 3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5. The aim of this study was to examine the immunoreactivity for IL-3, GM-CSF, and IL-5 within the duodenal and colonic mucosa of 10 patients with EG. METHODS: Endoscopic biopsy specimens were obtained from 10 patients with EG and 10 controls. IL-3, GM-CSF, and IL-5 was evaluated by immunohistochemistry. Electron microscopy combined with immunogold staining was used to identify the labeled cells and to localize these growth factors ultrastructurally. RESULTS: A significant increase in the number of eosinophils was found in both duodenal and colonic mucosa from all 10 patients with EG compared with controls. In the same tissue, immunohistochemistry detected IL-3, GM-CSF, and IL-5 in 9 of 10 patients with EG. The one exception had received treatment with steroids. These cytokines were not detected in the control group. Ultrastructurally, IL-3, GM-CSF, and IL-5 were localized in the granule matrix of eosinophils. CONCLUSIONS: The release of these cytokines with autocrine and/or paracrine activities by eosinophils may be involved in the persistence of intestinal eosinophil infiltration.
Immunnohistological assessment of intestinal eosinophil activation in patients with eosinophilic gastroenteritis and inflammatory bowel disease. Bischoff SC, Mayer J, Nguyen QT, Stolte M, Manns MP. Department of Gastroenterology and Hepatology, Medical School of Hannover, Germany.	Am J Gastroenterol 1999 Dec;94(12):3521-9 Abstract quote OBJECTIVE: To assess the activation grade of intestinal eosinophils in patients with eosinophilic gastroenteritis (EOG), ulcerative colitis (UC), Crohn's disease (CD), and controls by immunohistochemistry. METHODS: Cecal biopsies were collected from healthy controls and from patients with EOG, CD, UC, and other noninflammatory GI diseases. Immunohistochemistry was performed in sequential sections stained with monoclonal antibodies directed against eosinophil cationic protein (ECP) or eosinophil protein X (EPX) stored in eosinophil granules (EG1) and that secreted by activated eosinophils (EG2). The ratio of EG1 to EG2-positive eosinophils expressed as percentage of lamina propria cells was calculated. ECP and EPX were measured in serum and feces. RESULTS: The percentage of EG1 and EG2-positive lamina propria cells was elevated in EOG and slightly, but not significantly, in UC. The ratio of EG1 to EG2-positive cells was decreased in CD, UC, and other patients as compared to healthy controls. Particularly low EG1 to EG2 ratios were found in EOG. Correspondingly, fecal and serum levels of ECP and EPX, respectively, were highest in patients with EOG. The EG1 to EG2 ratio was negatively correlated with fecal ECP and EPX levels. At sites of actively inflamed mucosa, the EG1 to EG2 ratio was lower than in noninflamed tissue. CONCLUSIONS: Our data strongly suggest that the EG1 to EG2 ratio may be a marker of tissue eosinophil activation. Low ratios (<1) indicate eosinophil activation, whereas ratios > or =1 are found in healthy controls. Furthermore, we show that EOG is characterized by a pronounced intestinal eosinophil accumulation and activation, whereas in CD and UC, eosinophils seem to be activated but their number is not or only slightly elevated compared to controls.

 

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
Nonmucosal eosinophilic gastroenteritis: sonographic appearance at presentation and during follow-up of response to prednisone therapy. Maroy B. Maison Medicale de Lunesse, France.	J Clin Ultrasound 1998 Nov-Dec;26(9):483-6 Abstract quote This case describes the sonographic appearance of eosinophilic gastroenteritis before and during prednisone treatment. The dramatic clinical and sonographic response to prednisone therapy confirmed the diagnosis. Sonography is a quick, low-cost, and noninvasive means of diagnosing eosinophilic gastroenteritis and together with other clinical, laboratory, and endoscopic data may prevent unnecessary and potentially dangerous abdominal surgery.
LABORATORY MARKERS
IgE antibodies against bovine serum albumin in a case of eosinophilic gastroenteritis. Verdaguer J, Corominas M, Bas J, Valls A, Mestre M, Romeu A, Gonzalez L, Massip E, Buendia E. Immunology Service, Hospital Duran i Reynals, Barcelona, Spain.	Allergy 1993 Oct;48(7):542-6 Abstract quote Eosinophilic gastroenteritis is a disease characterized histologically by an eosinophilic infiltration of the gut. The cause of this disease remains unclear, although both food allergy and food intolerance have been implicated in its pathogenesis. We report the case of a 22-year-old man in whom gastrointestinal symptoms first appeared in childhood, with involvement of mucosa and muscularis layers of stomach and bowel. He presented high IgE blood levels, and his prick test was positive to bovine, pig, and lamb sera. Immunoblots from calf, pig, and lamb sera, incubated with the patient's serum and revealed by autoradiography, demonstrated the presence of a 65-kDa protein band that was recognized by IgE antibodies but not by IgG. This band corresponded to bovine serum albumin, while IgE did not show reactivity with human albumin. These data suggest a possible role for IgE-mediated hypersensitivity mechanisms in the pathogenesis of eosinophilic gastroenteritis.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
The spectrum of eosinophilic gastroenteritis. Report of six pediatric cases and review of the literature. Steffen RM, Wyllie R, Petras RE, Caulfield ME, Michener WM, Firor HV, Norris DG. Department of Pediatrics, Cleveland Clinic Foundation, Ohio 44195.	Clin Pediatr (Phila) 1991 Jul;30(7):404-11 Abstract quote Eosinophilic gastroenteritis is an inflammatory disease of unknown etiology characterized by infiltration of the gastrointestinal tract with eosinophilic leukocytes, accompanied by varying abdominal symptoms and usually by peripheral blood eosinophilia. We report our experience with six pediatric cases presenting to the Cleveland Clinic Foundation over the past eight years. Unusual findings in our patients included ascitic fluid without eosinophilia and eosinophilic pericarditis (one patient), and eosinophilic cholecystitis (one patient). Endoscopic examination and biopsy helped to establish the diagnosis in all patients. Bone marrow aspiration supported the diagnosis by demonstrating eosinophilia and identifying reactivation of the disease, even in cases without peripheral eosinophilia. All six patients responded promptly to prednisone. Diagnosis is challenging and eosinophilic gastroenteritis may be more common than is recognized. This series of cases significantly expands the spectrum of the disease in children, and documents the usefulness of diagnostic endoscopy in this condition.
Massive eosinophilic ascites: differential diagnosis between idiopathic hypereosinophilic syndrome and eosinophilic gastroenteritis. Vandewiele IA, Maeyaert BM, Van Cutsem EJ, Geboes KR, Knockaert DC. Department of Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium.	Acta Clin Belg 1991;46(1):37-41 Abstract quote This paper describes a patient with massive eosinophilic ascites as presenting manifestation probably due to idiopathic hypereosinophilic syndrome. Eosinophilic ascites and stomach wall involvement were the first detected abnormalities. The subsequent course was characterised by interstitial pulmonary disease and pleural and pericardial effusion. Grand mal epilepsy and numbness of the left arm indicated central nervous system involvement. Treatment with corticosteroids resulted in complete remission. The differential diagnosis of eosinophilic gastroenteritis and idiopathic hypereosinophilic syndrome is discussed.
Eosinophilic gastroenteritis mimicking acute appendicitis. Tran D, Salloum L, Tshibaka C, Moser R. Department of Surgery, St. Francis Medical Center, Trenton, New Jersey, USA.	Am Surg 2000 Oct;66(10):990-2 Abstract quote Eosinophilic gastroenteritis is a rare entity that can be treated successfully with glucocorticoid therapy if the appropriate diagnosis is made. However, it may present with symptomatology mimicking acute surgical conditions. We present the case of a 26-year-old man who presented with diffuse epigastric pain, nausea, vomiting, and diarrhea. Extensive workup including upper endoscopy and imaging study revealed gastritis with ulcer and ascites. The patient developed right lower quadrant pain with localized peritonitis and leukocytosis. He underwent appendectomy and small bowel biopsy. Pathology revealed eosinophilic cellular infiltrate of both the appendiceal and small intestinal wall. The unique features of this condition are reviewed and surgical approaches are discussed.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL	Increased eosinophils within the lamina propria
VARIANTS

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Parastic infection	Strongyloidosis Anisakis

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
Eosinophilic gastroenteritis: 10 years experience. Lee CM, Changchien CS, Chen PC, Lin DY, Sheen IS, Wang CS, Tai DI, Sheen-Chen SM, Chen WJ, Wu CS. Department of Medicine, Chang Gung Memorial Hospital and Medical College, Taiwan, R.O.C.	Am J Gastroenterol 1993 Jan;88(1):70-4 Abstract quote Eight patients (five men, three women), mean age 36.9 +/- 13.5 (17-60) yr, were diagnosed to have eosinophilic gastroenteritis. The condition was proved in five patients by biopsies through endoscope, and in three, by operation. All had hypereosinophilia (absolute eosinophil count of 1,337-21,787/cm3). According to Klein classification, two had mucosal disease, three had muscle layer disease, and three, subserosal disease. The most common symptoms were abdominal pain (100%), diarrhea (62.5%), vomiting (62.5%), and nausea (50%). Four patients (50%) had symptoms for more than 1 yr before diagnosis. Barium studies revealed mucosal edema and/or thickening of the small intestinal wall in three cases (including one case with ulceration), partial gastric outlet obstruction in one case, and narrowing of lumen of the terminal ileum in one case. Hypotonic duodenogram revealed double contour in one case. Ultrasound examination revealed thickening of the intestinal wall in two cases; computer tomography revealed thickening of the intestinal wall in one case. All patients were treated with steroid (40 mg/day for initial dose and relapse; 5-10 mg/day for maintenance). The symptoms subsided and the eosinophil counts returned to normal within 2 wk in seven patients and 1 month in one. Of six patients being followed up for 2-10 yr, one had remission, four needed small maintenance dose of steroid, and one suffered from relapse with intestinal perforation.
Long-term outcome of idiopathic hypereosinophilic syndrome--transition to eosinophilic gastroenteritis and clonal expansion of T-cells. Bauer S, Schaub N, Dommann-Scherrer CC, Zimmermann DR, Simon HU, Wegmann W. Department of Internal Medicine, Gastroenterology, Kantonsspital Bruderholz, Switzerland.	Eur J Gastroenterol Hepatol 1996 Feb;8(2):181-5 Abstract quote We describe a patient with idiopathic hypereosinophilic syndrome, without initial gastrointestinal symptoms, and their transition to eosinophilic gastroenteritis. This patient, a 65-year-old man, presented with fever, constitutional symptoms, peripheral and bone marrow eosinophilia 20 years ago. During the course of the disease, diarrhoea and malabsorption became prominent, whereas bone marrow eosinophilia regressed completely and blood eosinophilia regressed partially. Biopsies showed a severe eosinophilic gastroenteritis of the mucosal type involving the stomach, small bowel and colon. During the final years of the patient's disease, mucosal eosinophilia became less intense and a mucosal infiltration with T-cells dominated. At autopsy, immunopathological studies of small intestines and colon specimens showed a clonal expansion of morphologically normal T-cells in the intestinal mucosa, which expressed the abnormal phenotype CD2+CD3+CD4-CD5-CD8-. Flow cytometry examination of peripheral blood revealed a corresponding abnormal population of CD3+CD4-CD8- T-cells, indicating a systemic spread of the process. The patient eventually died of non-obstructive small bowel infarction with peritonitis 20 years after the onset of the first symptoms. We postulate that the destructive eosinophilic/lymphocytic inflammation is caused by a clonal proliferation of T-lymphocytes with probable secretion of Type 2 T(helper) cell cytokines and consecutive stimulation of eosinophils.
TREATMENT
Hypoallergenicity and efficacy of an amino acid-based formula in children with cow's milk and multiple food hypersensitivities. Sicherer SH, Noone SA, Koerner CB, Christie L, Burks AW, Sampson HA. Division of Pediatric Allergy and Immunology, Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.	J Pediatr 2001 May;138(5):688-93 Abstract quote OBJECTIVE: To determine the hypoallergenicity and efficacy of a pediatric amino acid-based formula (AAF), EleCare, for children with cow's milk allergy (CMA) and multiple food allergies (MFA). STUDY DESIGN: Hypoallergenicity was determined by performing blinded oral food challenges in 31 consecutive children with documented CMA. Growth, tolerance, and biochemical response were evaluated during a nonrandomized feeding study with each child serving as his or her own control. RESULTS: Thirty-one children (median age, 23.3 months; range, 6 months to 17.5 years) were recruited; 29 had MFA, 17 had acute reactions and cow's milk-specific IgE antibody, and 14 had allergic eosinophilic gastroenteritis. At study entry, 23 were receiving another AAF; 13 had not tolerated extensively hydrolyzed formula. Eighteen subjects with allergic eosinophilic gastroenteritis and/or MFA were followed up while receiving AAF for a median of 21 months (range, 7 to 40 months), with biochemical analysis performed at 4 months. No statistically significant differences were observed in the change in weight or height National Center for Health Statistics z scores from entry; the percent of expected growth exceeded 90%. There was a small decline in percent eosinophils and increase in hemoglobin, hematocrit, and serum ferritin level (P < .05). Except for small increases in plasma leucine and valine levels (P < or = .006), the remaining biochemical markers were unchanged. CONCLUSIONS: The AAF was hypoallergenic and effective in maintaining normal growth for children with CMA and MFA.
Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. Tan AC, Kruimel JW, Naber TH. Department of Gastroenterology and Hepatology, University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.	Eur J Gastroenterol Hepatol 2001 Apr;13(4):425-7 Abstract quote A patient who presented with upper abdominal pain, nausea and ascites together with peripheral eosinophilia is described. Based on a surgical full-thickness biopsy of the antrum, the diagnosis of eosinophilic gastroenteritis was made. Treatment with prednisone resulted in a clinical response, but the prednisone dose could not be lowered below 5 mg. We preferred to treat the patient with corticosteroids with minimal systemic side effects. As there was gastric involvement, we could not give enteric-coated budesonide capsules. Therefore, we treated the patient with budesonide tablets, which were designed originally for use as a clysma but now are given orally. With this treatment regimen, the patient has been in remission for more than 2 years.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.

Gastrointestinal Tract

Last Updated 11/30/2001

Send mail to psdermpath@earthlink.net with questions or comments about this web site.
Copyright © 2002 The Doctor's Doctor