What is the likely cause of eosinophilic gastritis in a patient with schizophrenia taking clozapine (clozapine)?

Clozapine-Induced Eosinophilia

In a patient with schizophrenia taking clozapine, eosinophilic gastritis is most likely caused by clozapine itself, as clozapine-induced eosinophilia occurs in approximately 1% of patients and can be associated with organ-specific inflammation including colitis, hepatitis, pancreatitis, and nephritis. 1

Mechanism and Incidence

• Clozapine causes eosinophilia (defined as blood eosinophil count >700/µL) in approximately 1% of patients in clinical trials, though some studies report incidence as high as 2.2% 1, 2
• Women have a significantly higher risk of developing clozapine-induced eosinophilia (23%) compared to men (7%), with p<0.01 3
• The eosinophilia typically occurs during the first month of treatment, most commonly between weeks 3-5 1, 3

Organ Involvement Pattern

• Clozapine-related eosinophilia can be associated with organ-specific disease including myocarditis, pancreatitis, hepatitis, colitis, and nephritis 1
• This pattern is consistent with drug reaction with eosinophilia and systemic symptoms syndrome (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS) 1
• Eosinophilic gastritis in this context represents gastrointestinal organ involvement from the systemic eosinophilic reaction to clozapine 1

Critical Management Decision Points

If eosinophilia develops with organ involvement (such as gastritis):

• Evaluate promptly for signs and symptoms of systemic reactions including rash, allergic symptoms, myocarditis, or other organ-specific disease 1
• If clozapine-related systemic disease is suspected, discontinue clozapine immediately 1

If eosinophilia develops without organ involvement:

• Continue clozapine under careful monitoring, as eosinophilia can resolve spontaneously without intervention in many cases 1, 2
• Monitor complete blood count with differential closely to track eosinophil count 2
• The eosinophilia typically resolves within 3 weeks despite ongoing clozapine treatment, suggesting an acute allergic reaction mechanism 2

Important Caveats

• Rule out alternative causes of eosinophilia before attributing it to clozapine, including asthma, allergies, collagen vascular disease, parasitic infections, and specific neoplasms 1
• If an unrelated cause is identified, treat the underlying condition and continue clozapine 1
• Successful rechallenge after discontinuation has been reported in cases where clozapine was stopped due to eosinophilia without organ inflammation 4
• The pathophysiology remains unknown, but spontaneous resolution despite continued treatment suggests a transient hypersensitivity mechanism 2

Monitoring Protocol

• Obtain baseline complete blood count before initiating clozapine 1
• If eosinophilia develops with gastritis or other organ involvement, immediate discontinuation is mandatory 1
• If eosinophilia continues to increase over several weeks without systemic disease, the decision to interrupt therapy should be made in consultation with an internist or hematologist 1