Eosinophilic Gastritis

Comprehensive Clinical Guide: Eosinophilic Gastritis (EG)

1. Introduction and Clinical Overview

Eosinophilic Gastritis (EG) is a rare, chronic, inflammatory disorder characterized by the infiltration of eosinophils into the mucosal, muscular, or serosal layers of the stomach wall. It is a subset of Eosinophilic Gastrointestinal Disorders (EGIDs), which represent a spectrum of conditions where eosinophilic inflammation occurs in the absence of secondary causes such as parasitic infection, malignancy, or vasculitis.

While the stomach is less frequently involved than the esophagus (as seen in Eosinophilic Esophagitis), EG presents a complex clinical picture that often mimics other gastric pathologies, leading to diagnostic delays. The disorder can manifest as localized gastric inflammation or as part of a more diffuse eosinophilic gastroenteritis.

2. Etiology and Pathophysiology

The precise etiology of Eosinophilic Gastritis remains multifactorial, involving a complex interplay between genetic predisposition, immune dysregulation, and environmental triggers.

The Mechanisms of Inflammation

• Th2-Mediated Immune Response: Current evidence suggests that EG is driven by a T-helper type 2 (Th2) immune response. This involves the upregulation of cytokines such as Interleukin-5 (IL-5), IL-4, and IL-13.
• Eosinophil Recruitment: IL-5 is the primary driver of eosinophil maturation, activation, and survival. Eotaxins (chemokines) facilitate the migration of these cells from the peripheral blood into the gastric lamina propria.
• Degranulation: Once in the gastric tissue, eosinophils release cytotoxic granules, including Major Basic Protein (MBP), Eosinophil Peroxidase (EPO), and Eosinophil-Derived Neurotoxin (EDN). These proteins cause significant tissue damage, leading to mucosal erosion, edema, and fibrosis.

Classification by Anatomical Depth (Klein’s Classification)

The clinical presentation is largely dictated by the depth of eosinophilic infiltration:

3. Clinical Presentation and Diagnostic Criteria

Standard Presentation

Patients typically present with non-specific upper gastrointestinal symptoms. Because these symptoms mirror common conditions like GERD or peptic ulcer disease, clinical suspicion is often low.
* Common Symptoms: Epigastric pain, nausea, postprandial vomiting, early satiety, and bloating.
* Systemic Signs: Approximately 50% of patients have a history of atopy (asthma, eczema, or allergic rhinitis).

Diagnostic Requirements

A definitive diagnosis requires the integration of clinical, endoscopic, and histological findings:
1. Presence of Symptoms: Consistent with gastrointestinal inflammation.
2. Histopathological Evidence: Biopsy demonstrating dense eosinophilic infiltration (typically defined as >30 eosinophils per high-power field (HPF) in at least 5 HPFs).
3. Exclusion of Secondary Causes: The "Rule-Out" phase is critical.

4. Differential Diagnosis: The "Rule-Out" Checklist

Before confirming a diagnosis of primary EG, the clinician must exclude secondary causes of gastric eosinophilia:

• Parasitic Infections: Helicobacter pylori (rarely causes high eosinophilia but must be excluded), Anisakis, and Strongyloides.
• Malignancy: Gastric adenocarcinoma, lymphoma, or mastocytosis.
• Autoimmune/Connective Tissue: Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis), systemic sclerosis, or vasculitis.
• Drug-Induced: Reactions to medications (e.g., NSAIDs, gold salts).
• Inflammatory Bowel Disease: Crohn’s disease involving the stomach.

5. Diagnostic Testing Protocols

Endoscopy

Esophagogastroduodenoscopy (EGD) is the gold standard. Visual findings may include:
* Erythema (redness)
* Edema (swelling)
* Friability (bleeding on contact)
* Ulcerations or polypoid lesions

Crucial Note: The gastric mucosa may appear entirely normal in some cases. Therefore, "blind" biopsies are mandatory even if the stomach appears macroscopically normal.

Laboratory Investigations

• Complete Blood Count (CBC): Peripheral eosinophilia is present in only 50-75% of cases; its absence does not rule out EG.
• Serum Albumin: Assessment for protein-losing enteropathy.
• IgE Levels: Often elevated, indicating an allergic diathesis.
• Stool Studies: To rule out parasitic infection.

6. Management and Therapeutic Strategies

Management is centered on suppressing the inflammatory response and identifying dietary triggers.

Pharmacotherapy

1. Corticosteroids: The first-line therapy. Systemic prednisone (0.5–1 mg/kg/day) is highly effective for inducing remission. Tapering must be slow to prevent rebound inflammation.
2. Mast Cell Stabilizers: Cromolyn sodium may be utilized for its ability to inhibit mast cell degranulation, which often precedes eosinophil activation.
3. Biologics: Emerging research into anti-IL-5 monoclonal antibodies (e.g., Mepolizumab, Benralizumab) shows promise for refractory cases.
4. Proton Pump Inhibitors (PPIs): While not curative, they are often used to manage symptoms of acid reflux and to rule out PPI-responsive eosinophilic disorders.

Dietary Interventions

• Elemental Diet: A strictly amino-acid-based formula. Highly effective but difficult to maintain.
• Elimination Diet: Removal of common allergens (dairy, soy, wheat, eggs, nuts, seafood) based on allergy testing or empiric elimination.

7. Risks, Side Effects, and Contraindications

• Steroid Toxicity: Prolonged use of systemic corticosteroids carries significant risks, including osteoporosis, hyperglycemia, adrenal suppression, and weight gain.
• Nutritional Deficiencies: Patients with mucosal EG are at high risk for iron-deficiency anemia and hypoproteinemia due to malabsorption.
• Surgical Risks: Surgery should be avoided unless there is evidence of mechanical obstruction or perforation, as the friable, inflamed tissue heals poorly in patients with active EG.

8. Long-Term Prognosis

EG is a chronic, relapsing-remitting condition. There is currently no "cure." Long-term management focuses on:
* Maintaining clinical and histological remission.
* Monitoring for complications (gastric outlet obstruction, fibrosis).
* Transitioning from systemic steroids to steroid-sparing agents or dietary modifications.
* Quality of life preservation.

9. Frequently Asked Questions (FAQ)

1. Is Eosinophilic Gastritis a form of cancer?
No. EG is an inflammatory condition. However, because it causes chronic inflammation, patients should be monitored to ensure the diagnosis is not masking an underlying malignancy like lymphoma.

2. Can food allergies cause Eosinophilic Gastritis?
Yes. Many cases of EG are driven by food hypersensitivity. Eliminating trigger foods can often lead to significant symptomatic improvement.

3. Does peripheral eosinophilia always indicate EG?
No. Peripheral eosinophilia is a non-specific finding that can be caused by allergies, parasites, or hematologic disorders. A biopsy is required for a definitive diagnosis.

4. How is the diagnosis confirmed?
Diagnosis is confirmed through an EGD with multiple biopsies showing >30 eosinophils/HPF and the exclusion of other diseases that cause eosinophilic infiltration.

5. What is the role of PPIs in treating EG?
PPIs are used primarily to rule out PPI-responsive esophageal/gastric eosinophilia and to manage acid-related symptoms, though they do not address the underlying eosinophilic pathology.

6. Is surgery ever required?
Surgery is generally reserved for complications such as severe gastric outlet obstruction that does not respond to medical therapy or in cases of perforation.

7. Can children get Eosinophilic Gastritis?
Yes, it can occur in both children and adults, though the clinical presentation in children is often more varied and may include failure to thrive.

8. What is the difference between EG and Eosinophilic Esophagitis (EoE)?
EoE is limited to the esophagus. EG involves the stomach. They share similar inflammatory mechanisms and are often managed by similar dietary and pharmacological approaches.

9. Will I need to be on medication forever?
Many patients require long-term maintenance, often using diet or safer, non-steroid medications to keep the disease in remission.

10. What are the most common triggers?
Common food triggers include cow’s milk, soy, wheat, eggs, peanuts, and seafood. However, environmental factors and medications can also play a role.

10. Clinical Summary Table

Disclaimer: This guide is intended for educational purposes for healthcare professionals and clinical students. It does not replace professional medical judgment. Always consult current clinical guidelines (such as those from the AGA or ACG) for the management of specific patients.