What is the best course of treatment for a patient with schizophrenia taking clozapine (clozapine) who develops eosinophilic gastritis, a condition that can progress to eosinophilic gastroenteritis?

Management of Clozapine-Induced Eosinophilic Gastritis/Gastroenteritis

Discontinue clozapine immediately when eosinophilic gastritis or gastroenteritis is diagnosed, as this is a recognized adverse drug reaction that resolves with medication cessation. 1

Immediate Action Required

Stop clozapine as soon as eosinophilic colitis/gastroenteritis is confirmed. The evidence is clear that clozapine can cause eosinophilic colitis, and symptoms completely resolve after discontinuation 1. While this case report specifically describes colitis, the same principle applies to eosinophilic gastritis given the shared pathophysiology of drug-induced eosinophilic gastrointestinal disorders 2.

Diagnostic Confirmation

Before attributing the condition solely to clozapine, ensure proper diagnosis:

• Obtain endoscopy with at least 6 biopsies from different anatomical sites to confirm eosinophilic infiltration (≥15 eosinophils per 0.3 mm² or high-power field) 3, 4
• Rule out secondary causes including food allergies, parasitic infections, and other inflammatory disorders before finalizing the diagnosis 5, 6
• Check peripheral blood for eosinophilia, which commonly accompanies tissue eosinophilia in drug-induced cases 1

Treatment Strategy After Clozapine Discontinuation

Initial Management (First 8-12 Weeks)

Start systemic corticosteroids for moderate to severe symptoms:

• Prednisone 1-2 mg/kg/day (maximum 60 mg) for severe cases 4
• Clinical symptoms typically improve within 7 days, with histological improvement within 4 weeks 4
• Continue treatment for at least 8-12 weeks before evaluating histological response 5, 4

Consider proton pump inhibitors as complementary therapy:

• Omeprazole 20 mg twice daily for 8-12 weeks 5, 6
• PPIs may provide additional benefit even though this is not PPI-responsive eosinophilic esophagitis 3

Dietary Considerations

Involve a registered dietitian if food allergies are suspected as contributing factors:

• Begin with two-food elimination diet (milk +/- wheat or egg) for 8-12 weeks 5
• Dietary elimination should only be conducted under dietitian supervision 5, 4
• Perform endoscopic and histological assessment 8-12 weeks after each dietary change 5

Monitoring Response

Repeat endoscopy with biopsy at 8-12 weeks while on treatment:

• Symptoms do not always correlate with histological activity 5, 4
• If symptoms recur during treatment, repeat endoscopy immediately 3, 5
• Regular clinic visits to assess symptoms, compliance, and adverse effects are essential 3, 6

Managing the Schizophrenia After Clozapine Discontinuation

This presents a critical clinical dilemma since clozapine is the only medication licensed for refractory schizophrenia 7. However, continuing clozapine with active eosinophilic gastroenteritis risks progression to more severe complications including perforation, stricture formation, and protein-losing enteropathy 8, 9.

Switch to alternative antipsychotic strategies:

• Consider clozapine alternatives including high-dose monotherapy with other second-generation antipsychotics 3
• Antipsychotic polypharmacy may be appropriate, particularly combining partial D2 agonists with other agents 3
• Long-acting injectable antipsychotics may improve adherence during this transition 3
• Ensure adequate dosing and confirmed adherence before concluding treatment failure 3

Refractory Cases

If eosinophilic gastroenteritis persists despite clozapine discontinuation and corticosteroids:

• Joint management by gastroenterologist and allergist specialist is recommended 5, 6
• Novel biologics (dupilumab, benralizumab, mepolizumab) have shown promise in eosinophilic disorders 3, 5, 6
• Anti-TNF and anti-integrin therapies are NOT recommended 3, 5

Critical Pitfalls to Avoid

Do not continue clozapine while treating the eosinophilic gastroenteritis. The pathophysiology is drug-induced hypersensitivity, and continued exposure will perpetuate the condition 1. Unlike other clozapine adverse effects that can be managed while continuing the medication, eosinophilic colitis requires discontinuation 1.

Do not rely on symptom resolution alone. Histological disease may persist despite clinical improvement, requiring endoscopic confirmation of remission 5, 4.

Monitor for Candida esophagitis if using topical or systemic corticosteroids, which should be treated with topical antifungals while continuing steroids 3, 4.

Address the psychological impact of both the gastrointestinal condition and the schizophrenia management changes, as anxiety and depression commonly accompany these conditions 3, 6.