AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Eosinophilic gastroenteritis (EGE) is an uncommon gastrointestinal disease affecting both children and adults. EGE is characterized by the following:

• The presence of abnormal GI symptoms, most often abdominal pain
• Eosinophilic infiltration in one or more areas of the GI tract, defined as 20 or more eosinophils per high-power field
• The absence of an identified cause of eosinophilia
• The exclusion of eosinophilic involvement in organs other than the GI tract

A history of atopy or food allergies is often present.

Clinical symptoms are determined by the anatomical locations of eosinophilic infiltrates and the depth of GI involvement. Kaijser was probably the first to report a patient with EGE in 1937; since then, the number of case reports has increased. Treatments are often unsatisfactory, and long-term outcomes are uncertain.

Pathophysiology

The underlying molecular mechanism predisposing to the clinical manifestation of EGE is unknown. Eosinophilic gastritis, enteritis, and gastroenteritis are diseases characterized by the selective infiltration of eosinophils in the stomach, small intestine, or both. The disorders are classified into primary and secondary subtypes. The primary subtypes, which have also been called idiopathic or allergic GE, include the atopic, nonatopic, and familial subtypes.

In patients, manifestations of their diseases are based on histologic involvement: mucosal, muscularis, or serosal forms. Any layer of the GI tract can be involved. The secondary subtypes may be divided into 2 groups: systemic eosinophilic disorders (ie, hypereosinophilic disorders) and noneosinophilic disorders (eg, celiac disease, inflammatory bowel disease, vasculitis).

Although these diseases are idiopathic, recent investigations support the role of eosinophils, T helper 2 (Th2) cytokines (interleukin [IL]-3, IL-4, IL-5, and IL-13), and eotaxin as the critical factors in the pathogenesis of EGE. Eosinophils function as antigen presenting cells as they express major histocompatibility complex (MHC) class II molecules. In addition, eosinophils can mediate proinflammatory effects, including the up-regulation of adhesion systems, modulation of cell trafficking, and cellular activation states by releasing cytokines (IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-16, IL-18, and transforming growth factor [TGF]-alpha/beta), chemokines (RANTES and eotaxin), and lipid mediators (platelet activating factor [PAF] and leukotriene C4).

Finally, eosinophils can serve as major effector cells, inducing tissue damage and dysfunction by releasing toxic granule proteins (major basic protein [MBP], eosinophilic cationic protein [ECP], eosinophil peroxidase [EPO], and eosinophil-derived neurotoxin [EDN]) and lipid mediators, which are cytotoxic.

Atopy is present in a subset of patients, as these patients demonstrate increased total immunoglobulin E (IgE) on food-specific IgE radioallergosorbent assay test (RAST) or skin tests. Furthermore, lamina propria T cells from the duodenum of these patients proliferated in response to milk proteins and secreted Th2 cytokines (IL-13). However, other studies suggest a non–IgE-mediated mechanism.

Frequency

United States

The disease is rare, and the incidence is difficult to estimate. However, since the description of EGE by Kaijser in 1937, more than 280 cases have been reported in the medical literature.

International

Although cases have been reported worldwide, the exact incidence of EGE is unclear. A confounding factor is lack of diagnostic precision.

Kim et al reported 31 new cases of EGE in Seoul, Korea, between January 1970 and July 2003.

Chen et al reported on 15 patients, including 2 children, with EGE who were evaluated over an 18-year period at a hospital in China in 2003.

Venkataraman et al reported 7 new diagnoses of EGE over a 10-year period in India.

Mortality/Morbidity

• Death from EGE has been reported only rarely.
• Morbidity includes malnutrition and intestinal obstruction and perforation.

Race

Cases of EGE are reported mostly in whites, with some cases occurring in Asians.

Sex

A slight male preponderance has been reported.

Age

Patients present clinically in the third to fifth decades of life, but the disease can affect any age group, from infancy through the seventh decade.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Patients may have various clinical presentations depending on the region of the GI tract involved and the depth of the bowel wall involvement. The disease most often involves the stomach and the small bowel. A history of atopy and allergies is present in many of the cases.

• The mucosal form of EGE is characterized by vomiting, dyspepsia, abdominal pain, diarrhea, blood loss in the stools, iron deficiency anemia, malabsorption, protein-losing enteropathy, and failure to thrive.
• The muscularis form, characterized by infiltration of eosinophils predominantly in the muscularis layer, may present with gastrointestinal obstructive symptoms mimicking pyloric stenosis or gastric outlet syndrome.
• The serosal form, which is less common, presents with significant bloating, exudative ascites, and higher peripheral eosinophil counts.

Physical

The heterogeneity in the clinical presentation of EGE is determined by the site and depth of eosinophilic intestinal infiltration.

• Approximately 50% of patients have a history of atopy (hay fever, asthma, food allergy). In children, a history of allergy is even more common.
• Children and adolescents can present with growth retardation, failure to thrive, delayed puberty, or amenorrhea. Adults have abdominal pain, diarrhea, or dysphagia.
• Patients with muscle layer involvement typically present with pyloric or intestinal obstruction.
• • The eosinophilic involvement often is localized to the stomach but can involve small bowel.
  • Cramping and abdominal pain associated with nausea and vomiting occur frequently.
  • Food allergy and past history of allergy are less common in these patients than in patients with mucosal layer disease.
• Involvement of the serosal layer is the least common form of the disease.
• • The entire GI wall usually is involved.
  • These patients typically present with eosinophilic ascites.
  • Serosal and visceral peritoneal inflammation leads to leakage of fluids.

Causes

The cause or mechanism of eosinophilic infiltration is not known.

• Patients with EGE have elevated IgE and eosinophilia of tissue and blood. An imbalance in the T-cell paradigm causing an increase in the production of IL-13, IL-4, and IL-5 and cytokines has been postulated as the cause of IgE synthesis and eosinophilia.
• In one study, immunohistochemistry detected IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5 in the granule matrix of eosinophils, the release of which is thought to be involved in the perpetuation of intestinal eosinophil infiltration and inflammation.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Drugs (acetylsalicylic acid [ASA], sulfonamides, penicillin, cephalosporin, carbamazepine, azathioprine, L-tryptophan, gold salts)
Parasites (Ancylostoma caninum, giardiasis, strongyloidosis, other zoonoses)
Connective-tissue disease (scleroderma, dermatomyositis, polymyositis)
Lymphoma
Cow milk enteropathy and related entities
Granulomatous gastritis
Hypereosinophilic syndrome
Gluten-sensitive enteropathy
Vasculitis (Churg-Strauss syndrome, polyarteritis nodosa)
Celiac disease

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• The evaluation of EGE starts with a comprehensive history and physical examination.
• • General workup includes a CBC and differential. Peripheral blood eosinophilia is found in 20-80% of cases.
  • Average count is 2000 eosinophils (eos)/µL in patients with mucosal layer involvement, 1000 eos/µL in patients with muscular layer involvement, and 8000 eos/µL in patients with serosal involvement.
• Mean corpuscular volume
• • Iron-deficiency anemia may be evident.
  • Serum albumin may be low, especially in patients with mucosal layer involvement.
• Although usually unnecessary, fecal protein loss can be measured by measuring alpha1-antitrypsin in a 24-h feces collection.
• • This test is used to identify the inability to digest and absorb proteins in the GI tract.
  • The normal value is 0-54 mg/dL. Patients with EGE have elevated alpha1-antitrypsin in their feces.
  • Obtain a stool sample (minimum 2-g portion). Keep it refrigerated.
• Protein loss also can result in a low level of quantitative immunoglobulins.
• The erythrocyte sedimentation rate (ESR) and serum IgE level can be elevated.
• Obtain 3 separate stool specimens to rule out parasitic infection. Perform a wet mount or stain smear.
• Mild-to-moderate steatorrhea is present in approximately 30% of patients. This can be measured by qualitative and quantitative stool tests.
• Skin prick tests to inhalant allergens and food help identify sensitization to specific allergens.
• The diagnosis of EGE depends on microscopic evaluations of endoscopic biopsy specimens. Examine specimens from each intestinal segment with particular attention to the following: (1) eosinophil quantification; (2) the location of eosinophils especially if present in the intraepithelial, superficial mucosal, and intestinal crypts; (3) the presence of extracellular eosinophilic granules; (4) associated pathologic abnormalities; and (5) the absence of other primary disorders (ie, vasculitis).

Imaging Studies

• Radiographically, EGE does not have a pathognomic appearance. Radiographic changes are variable, nonspecific, and/or absent in at least 40% of patients.
• • Gastric folds can be enlarged, with or without nodular filling defects.
  • Valvular conniventes may be thickened and flattened. Strictures, ulceration, or polypoid lesions may occur.
  • In EGE involving the muscle layer, localized involvement of the antrum and pylorus may occur, causing narrowing of the distal antrum and gastric retention. The small intestine also may be dilated, with an increase in the thickness of the folds. Prominent mucosal folds also may be observed in the colon.
  • Rarely, diffuse esophageal narrowing or achalasialike motor abnormalities may occur.
• Further studies include ultrasound and CT scans.
• • Ultrasound and CT scans may show thickened intestinal walls and, sometimes, localized lymphadenopathy.
  • Ascitic fluid usually is detected in patients with serosal layer involvement.

Other Tests

• Exploratory laparotomy may be indicated, especially in patients with serosal EGE.

Procedures

• Endoscopy and biopsy
• • Due to possible sampling error, when performing endoscopy, obtain at least 6 biopsy specimens from normal and abnormal areas of the bowel.
  • Grossly prominent mucosal folds, hyperemia, ulceration, or nodularity may be apparent.
  • In patients with esophageal or colonic symptoms, obtain additional biopsy specimens from the relevant sites to aid in diagnosis. Gastroesophageal reflux can cause tissue eosinophilia in the distal esophagus.
• Patients with serosal disease present with ascites. Abdominal paracentesis demonstrates a sterile fluid with a high eosinophil count. Pleural effusion also may be present. Laparoscopy may show hyperemia and/or nodularity of the GI wall.

Histologic Findings

Histopathology usually demonstrates increased numbers of eosinophils (often >50 eos per high-power field) in the lamina propria. Large numbers of eosinophils often are present in the muscularis and serosal layers. The localized eosinophilic infiltrates may cause crypt hyperplasia, epithelial cell necrosis, and villous atrophy. The gross appearance of EGE upon endoscopy shows erythematous, friable, nodular, and, often, ulcerated mucosa. Diffuse enteritis with complete loss of villi, submucosal edema, infiltration of the GI wall, and fibrosis may be apparent. Mast cell infiltrates and hyperplastic mesenteric lymph nodes infiltrated with eosinophils may be present. Due to errors in sampling or to mucosal sparing, 10% of mucosal biopsies are not helpful for diagnosis.

Histologic analysis of the small intestine reveals increased deposition of extracellular major basic proteins (MBPs) and eosinophilic cationic proteins (ECPs).

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Elimination of foods implicated by skin testing has variable effects, but resolution of symptoms can sometimes be achieved with amino acid–based elemental diets.

• Supportive treatment with pharmacotherapy, mainly oral glucocorticosteroids, is indicated for those with obstructive symptoms.
• Patients with mucosal layer involvement may benefit from anti-inflammatory medications (eg, oral glucocorticoids, oral cromolyn) and/or diet elimination therapy, particularly if they report a history of food intolerance or allergy.
• Drugs such as montelukast, ketotifen, suplatast tosilate, mycophenolate mofetil (inosine monophosphate dehydrogenase inhibitor), and alternative Chinese medicines have been advocated but are generally not successful.

Surgical Care

• Avoid surgery if at all possible, unless it is necessary to relieve persistent pyloric or small bowel obstruction.
• Most patients respond to conservative measures and oral glucocorticosteroids.
• Reoccurrence is possible, even after surgical excision.

Consultations

• Refer patients with persistent abdominal symptoms and peripheral eosinophilia to a GI specialist for workup, endoscopy, and biopsies.
• Refer patients to an allergy/immunology specialist for food skin testing and evaluation of eosinophilia and high IgE levels.

Diet

• The strong association of EGE with food allergies has prompted the use of restrictive or elemental diets.
• Initially, a trial elimination diet that excludes milk, eggs, wheat and/or gluten, soy, and beef may be helpful. RAST or skin testing can identify food hypersensitivity. If a prohibitive number of food reactions are found, an amino–acid-based diet or elemental diet may be considered.

Activity

• Encourage normal activities.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Oral glucocorticosteroids with anti-inflammatory properties are the primary therapy, especially for patients with obstructive symptoms and eosinophilic ascites. Most patients with EGE respond dramatically to oral glucocorticosteroids within 2 months. Successful treatment with other anti-inflammatory medications, such as leukotriene modifiers (eg, montelukast) and mast cell stabilizers (eg, cromolyn) has been reported.

Drug Category: Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Category: Mast cell stabilizers

Inhibit degranulation of sensitized mast cells following exposure to allergens.

Drug Category: Leukotriene receptor antagonists

Prevent or reverse some of the pathologic features associated with the inflammatory process mediated by leukotrienes C₄, D₄, and E₄. Successful treatment of EGE has been reported.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

• Patients can be monitored with visits to the clinic every 6 months.

Complications

• GI obstruction is the most common complication.

Prognosis

• The natural history of EGE has not been well documented. EGE is a chronic, waxing and waning condition. Mild and sporadic symptoms can be managed with reassurance and observation, whereas disabling GI symptom flare-ups can often be controlled with oral corticosteroids. When the disease manifests in infancy and specific food sensitization can be identified, the likelihood of disease remission by late childhood is high.
• Fatal outcomes are rare.
• GI obstruction is the most common complication.
• Risk of cancer is not increased.

Patient Education

• Educate patients to avoid foods they cannot tolerate and to seek medical care when needed.
• For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education article, Gastroenteritis.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• EGE is a rare disease that can be misdiagnosed in clinical practice. A high degree of suspicion is required, and upper endoscopy biopsies are necessary for diagnosis. In general, patients often have symptoms for an extended period of time (mean of 4 y) before a diagnosis of EGE is made.

Special Concerns

• Offer patients who have traveled or lived in areas that put them at high risk for parasitic infections an empirical trial of antiparasite therapy, ie, mebendazole at 10 mg twice a day for 3 days.
• Monitor medications closely in pregnant and elderly patients.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Biopsy specimen: Eosinophilic gastroenteritis.
	View Full Size Image
Media type:  Image

Media file 2:  Biopsy specimen: Eosinophilic gastroenteritis.
	View Full Size Image
Media type:  Image

Media file 3:  Biopsy specimen: Eosinophilic gastroenteritis.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Buchman AL, Wolf D, Gramlich T. Eosinophilic gastrojejunitis associated with connective tissue disease. South Med J. Mar 1996;89(3):327-30. [Medline].
• Chehade M, Magid MS, Mofidi S, et al. Allergic Eosinophilic Gastroenteritis With Protein-losing Enteropathy: Intestinal Pathology, Clinical Course, and Long-term Follow-up. J Pediatr Gastroenterol Nutr. May 2006;42(5):516-521.
• Chen MJ, Chu CH, Lin SC, et al. Eosinophilic gastroenteritis: clinical experience with 15 patients. World J Gastroenterol. Dec 2003;9(12):2813-6.
• Desreumaux P, Bloget F, Seguy D, et al. Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis. Gastroenterology. Mar 1996;110(3):768-74. [Medline].
• Gay SP, Shaffer HA, Futterer SF, et al. Gastrointestinal case of the day. Eosinophilic gastroenteritis. AJR Am J Roentgenol. Jul 1996;167(1):241, 244. [Medline].
• Jaffe JS, James SP, Mullins GE, et al. 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. J Clin Immunol. Sep 1994;14(5):299-309. [Medline].
• Kelly KJ. Eosinophilic gastroenteritis. J Pediatr Gastroenterol Nutr. 2000;30 Suppl:S28-35. [Medline].
• Khan S. Eosinophilic gastroenteritis. Best Pract Res Clin Gastroenterol. Apr 2005;19(2):177-98. [Medline].
• Kim NI, Jo YJ, Song MH, et al. Clinical features of eosinophilic gastroenteritis [in Korean]. Korean J Gastroenterol. Oct 2004;44(4):217-23. [Medline].
• Lee M, Hodges WG, Huggins TL, Lee EL. Eosinophilic gastroenteritis. South Med J. Feb 1996;89(2):189-94. [Medline].
• Matsushita M, Hajiro K, Morita Y, et al. Eosinophilic gastroenteritis involving the entire digestive tract. Am J Gastroenterol. Oct 1995;90(10):1868-70. [Medline].
• Moots RJ, Prouse P, Gumpel JM. Near fatal eosinophilic gastroenteritis responding to oral sodium chromoglycate. Gut. Sep 1988;29(9):1282-5. [Medline].
• Neustrom MR, Friesen C. Treatment of eosinophilic gastroenteritis with montelukast. J Allergy Clin Immunol. Aug 1999;104(2 Pt 1):506. [Medline].
• Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol. Jan 2004;113(1):11-28; quiz 29. [Medline].
• Talley N. Eosinophilic Gastroenteritis. In: Feldman M, Scharschmidt BF, Sleisenger M, Zorab R, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/ Management. 6th ed. Philadelphia, Pa: WB Saunders; 1998:. 1679-86.
• Urek MC, Kujundzic M, Banic M, et al. Leukotriene receptor antagonists as potential steroid sparing agents in a patient with serosal eosinophilic gastroenteritis. Gut. Sep 2006;55(9):1363-4.
• Van Dellen RG, Lewis JC. Oral administration of cromolyn in a patient with protein-losing enteropathy, food allergy, and eosinophilic gastroenteritis. Mayo Clin Proc. May 1994;69(5):441-4. [Medline].
• Venkataraman S, Ramakrishna BS, Mathan M, et al. Eosinophilic gastroenteritis--an Indian experience. Indian J Gastroenterol. Oct-Dec 1998;17(4):148-9.

Article Last Updated: Nov 6, 2006