Eosinophilic gastroenteritis

Eosinophilic gastroenteritis
H&E Stain: Dense Eosinophilic infiltration of gastro-duodenal wall
ICD-10	K52.8
ICD-9	558.3
DiseasesDB	32555
eMedicine	med/688

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Fatimo Biobaku M.B.B.S [2]

Synonyms and keywords: Eosinophilic esophagitis; eosinophilic gastritis; Eosinophilic enteritis; Eosinophilic colitis; Eosinophilic proctocolitis, Eosinophilic gastrointestinal disorders

Overview

Eosinophilic gastroenteritis is a rare, heterogenous disorder characterized by localized patchy or diffuse eosinophilic infiltration of the gastrointestinal tract. Most of the data available in the literature are based on few documented case reports/case series. The presentation of eosinophilic gastroenteritis may vary depending on the location, depth and extent of bowel wall involvement. The cause of eosinophilic gastroenteritis is idiopathic although there is a significant association with allergy. Non-specific gastrointestinal symptoms such as episodic abdominal pain, vomiting and diarrhea are common. Eosinophilic gastroenteritis is a diagnosis of exclusion and other causes of GIT symptoms with gastrointestinal tissue eosinophilia must be ruled out. Biopsy of the GIT is the primary diagnostic modality. The mainstay of treatment is corticosteroid therapy. Majority of patients respond well to treatment but the disease may run a chronic relapsing course.

Historical Perspective

The first description of eosinophilic gastroenteritis was by Kaijser et al. in 1937, and it was described as an allergic disease of the gut. Klein et al. subsequently classified it into three types (predominant mucosal, muscular, and subserosal layer disease) based on the depth of eosinophilic infiltration.

Classification

Eosinophilic gastroenteritis can be subdivided into three groups according to the Klein classification:

• Mucosal eosinophilic gastroenteritis

1. Most common subtype of eosinophilic gastroenteritis.
2. Mucosal infiltration by eosinophils, and/or presence of mucosal edema on barium studies.
3. Absent histological evidence of muscle infiltration.
4. No evidence of gastrointestinal obstruction or eosinophilic ascites.

• Muscular eosinophilic gastroenteritis

1. Documentation of complete/incomplete bowel obstruction, and/or infiltration of the tunica muscularis by eosinophils.
2. No evidence of eosinophilic ascites.

• Subserosal eosinophilic gastroenteritis

1. Eosinophilic infiltration of the gut
2. Presence of eosinophilic ascites (may occasionally progress to an eosinophilic pleural effusion)

Causes

The cause of eosinophilic gastroenteritis is unknown.

Risk Factors

• Allergy: A study conducted in 40 patients with eosinophilic gastroenteritis demonstrated a history of allergy in half of the patients. Food intolerance or allergy is more commonly seen in mucosal eosinophilic gastroenteritis, affecting over 50% of patients with mucosal disease according to a study.

Pathophysiology

Pathogenesis

• Eosinophilic gastroenteritis is a rare disease with poorly understood pathophysiology.
• Eosinophils are normally seen in the entire GIT (except in the esophagus) of healthy individuals.
• In patients with eosinophilic gastroenteritis, there is varying degrees of increased eosinophilic infiltration of the GIT (in the absence of other known causes of tissue eosinophilia).
• Any part of the GIT from the esophagus to the colon can be affected. Occasionally, eosinophilic gastroenteritis affects the entire gastrointestinal tract. The stomach and proximal small intestine are most commonly affected, while the colon is usually the least affected part of the GIT.
• The etiology of the excessive eosinophilic infiltration of the GIT is not clear. Destruction of the GIT epithelium caused by the release of eosinophilic basic protein and activated degranulating eosinophils has been proposed.
• Inflammatory mediators such as Th-2 cytokines (IL-3, IL-5, GM-CSF and IL-13), monocyte generating chemokines such as IL-8, monocyte chemotactic proteins, mast cells, granulocytes, eosinophils, and eosinophilic mediators such as eotaxin have been strongly implicated.
• The inflammatory mediators associated with the pathogenesis of eosinophilic gastroenteritis have well established roles in the pathogenesis of allergy and asthma. A significant number of patients with eosinophilic gastroenteritis have also been documented to have allergies/allergy-related disorders, suggesting a hypersensitivity reaction is involved in the pathogenesis of eosinophilic gastroenteritis.

Differentiating Eosinophilic gastroenteritis from Other Diseases

Diseases with peripheral eosinophilia and gastrointestinal symptoms should be differentiated from eosinophilic gastroenteritis. It is also important to consider eosinophilic gastroenteritis in the differential diagnosis of unexplained gastrointestinal symptoms (even when peripheral eosinophilia is not present). Most diseases that can manifest with gastrointestinal symptoms and peripheral eosinophilia are easily differentiated from eosinophilic gastroenteritis via detailed history taking, laboratory investigations, and histologic examination of endoscopic biopsies. Some of these diseases include:

• Intestinal parasitic infections: Stool examination for ova and parasites can be utilized for diagnosis.
• Inflammatory bowel disease (IBD): Biopsy can easily distinguish IBD from eosinophilic gastroenteritis.
• Hypereosinophilic syndrome: It usually presents with markedly elevated peripheral eosinophilia (>1500 cells/μL) for more than six consecutive months. Eosinophilic gastroenteritis is observed in association with eosinophilic infiltration of other organ systems. The organs that are commonly affected in hypereosinophilic syndrome are the lungs, skin, GIT, kidneys, heart and brain.
• Helicobacter pylori infecton: This is not a common cause of tissue eosinophilia. Histology of gastric biopsies using silver staining can rule out Helicobacter pylori infection.
• Vasculitic disorders such as churg-strauss syndrome and polyarteritis nodosa: Eosinophilic infiltration of small blood vessels in the GIT is seen. Autoantibodies are usually present and markers of inflammation are elevated.
• Connective tissue disorders such as scleroderma, polymyositis, dermatomyositis, systemic lupus erythematosus.
• Celiac disease: Serology and biopsy can differentiate it from eosinophilic gastroenteritis.
• Drugs: Some medications have been documented to cause eosinophilic infiltration of the GIT. Examples of such medications include gold compounds, rifampicin, clofazimine, gemfibrozil, azathioprine, enalapril, naproxen and other NSAIDS, interferon, tacrolimus, etc.

Epidemiology and Demographics

Incidence

The estimated incidence of eosinophilic gastroenteritis is approximately 1-20 per 100,000 patients. It is a rare disease with approximately 300 reported cases in published literature.

Age

Eosinophilic gastroenteritis can present at any age. However, a higher incidence has been observed in the third to fifth decade of life. In pediatric patients with eosinophilic gastroenteritis, the esophagus is usually the involved organ (eosinophilic esophagitis). The youngest documented pediatric case of eosinophilic gastroenteritis occurred in a full-term 10month old infant.

Sex

There is a slightly higher incidence in adult males.

Race

Eosinophilic gastroenteritis has been documented in all races. However, most of the cases reported occurred in Caucasians.

Screening

There is no screening guideline for eosinophilic gastroenteritis.

Natural History, Complications, and Prognosis

Natural History

Eosinophilic gastroenteritis is an idiopathic disease. A history of allergy/allergy-related disorders have been documented in a significant number of patients with the disease.

Complications

Complications of eosinophilic gastroenteritis can include the following:

• Gastric outlet obstruction: Pyloric outlet obstruction has been documented in patients with muscular eosinophilic gastroenteritis, and surgical intervention is often required in severe cases.
• Esophageal narrowing/strictures: Seen when there is esophageal involvement.
• Biliary tract disease such as biliary tract fibrosis and obstruction.
• Intestinal perforation
• Intussusception
• Acute pancreatitis

Prognosis

The prognosis is good with treatment but relapses are common, which may necessitate chronic low dose steroid therapy for maintenance of remission. If eosinophilic gastroenteritis is left untreated, patients may develop severe malabsorption and malnutrition. Spontaneous remission can also occur.

Diagnosis

History and Symptoms

History

It is important to obtain the following history from the patient:

• Presenting symptoms
• Duration of symptoms
• History of allergy: A history of food allergy/intolerance, drug allergy, allergy-related conditions such as seasonal allergies, atopy, asthma, and nasal polyps should be obtained.

Symptoms

Eosinophilic gastroenteritis can present with several nonspecific gastrointestinal symptoms. The manifestations often depend on the site affected in the GIT, and the involved layer of the gastrointestinal wall. The following are the gastrointestinal symptoms seen in eosinophilic gastroenteritis:

Common symptoms

• Episodic abdominal pain
• Nausea
• Vomiting
• Diarrhea
• Poor appetite
• Weight loss
• Steatorrhea
• Hematochezia
• Abdominal bloating and ascites: Seen more often in patients with subserosal disease.

Uncommon symptoms

• Dysphagia: This has been documented in patients with esophageal involvement.
• Hematemesis
• Jaundice

Physical Examination

The physical examination findings in eosinophilic gastroenteritis are non-specific, and are mostly dependent on the site and depth of bowel involvement. The following findings may be present:

HEENT

• Anemia

Gastrointestinal system

• Abdominal tenderness
• Ascites
• Hematochezia on rectal exam

Skin

Eczema may be seen in patients with atopy.

Laboratory Findings

The following laboratory findings can be seen:

• CBC: Peripheral blood eosinophilia is often seen, but it may be absent in >20% of affected patients. Patients with subserosal disease often have a higher eosinophil count. Anemia can also be present (iron deficiency anemia is a frequent finding).
• Elevated serum IgE is a common finding.
• Elevated ESR: This can be moderately elevated in 25% of patients with eosinophilic gastroenteritis.
• Hypoalbuminemia: This can occur as a result of severe malabsorption and protein losing enteropathy.
• Fecal fat test: Mild-moderate steatorrhea is sometimes seen.
• Stool α-1 antitrypsin clearance: For assessment of fecal protein loss.
• Allergy testing: Tests such as skin-prick and RAST testing may be done when specific food and environmental allergies are strongly suspected as triggers for the disease.

Microscopic Findings

Eosinophilic gastroenteritis is a diagnosis of exclusion. There are no well standardized pathologic criteria for making a diagnosis of eosinophilic gastroenteritis. There are three widely utilized diagnostic criteria:

1. Presence of gastrointestinal symptoms
2. Biopsy demonstrating eosinophilic infiltration of one or more areas of the GIT (from the esophagus to colon)
3. Exclusion of other causes of tissue eosinophilia.

Biopsy

• Biopsy is widely used for making a diagnosis. In the absence of other causes of tissue eosinophilia, eosinophilic infiltration of the GIT on biopsy and/or the presence of eosinophilic ascitic fluid in a patient with gastrointestinal symptoms is diagnostic for eosinophilic gastroenteritis.

• Eosinophilic infiltration of the gastrointestinal tract is seen on histology following endoscopic/surgical biopsies. Abnormal eosinophilic infiltration of the GIT can be defined as the presence of diffuse or multifocal eosinophils ≥20 per high power field.

• The diagnosis can occasionally be missed, especially in patients with the localized patchy infiltration. Multiple biopsy samples throughout the GIT (including visually normal areas) should be taken.

Endoscopic biopsy of ileum showing distinct eosinophilic infiltration

Paracentesis

• In cases of suspected eosinophilic ascites, it is important to perform a diagnostic paracentesis.

Imaging Findings

Radiological studies are of limited diagnostic value in patients with eosinophilic gastroenteritis. The findings on imaging are often variable and non-specific. Imaging studies may reveal the following:

Ultrasonography

• Presence of bowel thickening/folds, ascites and peritoneal nodules.
• Response to therapy

CT scan

• Prominent nodular, irregular folds/thickening of the stomach and intestines (similar findings can be seen in other diseases such as Crohn’s disease and lymphoma).
• Ascites

Barium studies

• Antral stenosis and mucosal irregularity of the stomach. A string sign appearance can be seen on barium studies when complications such as gastric outlet obstruction occur.
• Thickened mucosal folds of the small intestine due to edema.

Endoscopy

• Normal appearance of the GIT.
• Gross findings such as gastric pseudopolyps.
• Other non-specific findings such as mucosal erythema, friability, and fine granularity in the stomach may be seen. Mucosal ulcerations/erosions, thickening of gastric mucosal folds and mucosal nodules or whitish specks are sometimes seen.

Tc-99m hexamethylpropyleneamine oxime(HMPAO) scintigraphy scanning

• Radionuclide scan using Tc-99m HMPAO-labeled leukocyte SPECT may be useful for assessing the extent of disease and the response to treatment
• It cannot differentiate eosinophilic gastroenteritis from other causes of GIT inflammation, hence, it is not a diagnostic test.

Treatment

There is no guidelines/definitive consensus for the management of eosinophilic gastroenteritis, and the treatment is usually based on the severity of the disease. Steroids are widely recognized as the mainstay of treatment for eosinophilic gastroenteritis. Chronic relapses frequently occur and continued maintenance on low dose steroid therapy may be necessary.

Medical Therapy

The medical management of eosinophilic gastroenteritis entails the following:

Preferred therapy

• Corticosteroids: This is the mainstay of therapy for eosinophilic gastroenteritis. A dramatic response to corticosteroid therapy is commonly seen in patients with subserosal disease. A 90% response rate to corticosteroid therapy has been documented in some studies.
• Dietary modification

1. Elimination of identified food allergies from the diet.
2. Introduction of elemental diets.

Alternate therapy

These medications can be used alone or in combination with steroids for treatment and/or maintenance therapy.

• Ketotifen
• Cromolyn sodium
• Montelukast: Either used alone or in combination with steroids as a steroid-sparing agent. Some patients treated with montelukast alone did not have a relapse.
• Suplatast tosilate
• Biologic medications such as omalizumab, reslizumab, and mepolizumab.

Surgical Therapy

There are no indications for surgery in the primary management of eosinophilic gastroenteritis. However, surgical management may be required when complications such as intestinal perforation or severe gastric outlet obstruction occur.

Prevention

There are no guidelines for the prevention of eosinophilic gastroenteritis. Elimination of identified triggers such as food allergies may be beneficial.