What medications can cause eosinophilic gastrointestinal disease (EGID)?

Drugs Causing Eosinophilic Gastrointestinal Disease

Medications are a recognized cause of eosinophilic gastrointestinal disease (EGID), though specific drug culprits are rarely identified in clinical practice, and drug-induced EGID remains primarily a diagnosis of exclusion after ruling out more common causes like food allergens and parasitic infections. 1, 2

Primary Non-Infectious Causes of Eosinophilia

In populations with low endemic helminth infections, the most common causes of eosinophilia are:

• Allergy and atopy (asthma, eczema, hay fever) represent the leading cause, accounting for approximately 80% of cases in non-exposed populations 1, 3
• Drug reactions are the second most common non-infectious cause after allergic conditions 1
• Rarer but serious causes include systemic vasculitis and malignancies (lymphomas, myeloid neoplasms) 1

Drug-Induced Eosinophilic Colitis

Eosinophilic colitis (EC) in older children and adults can manifest as a drug allergy reaction or autoimmune disease manifestation, distinguishing it from the benign delayed food allergy form seen in infants 2. This represents a difficult-to-treat severe inflammatory condition requiring drug discontinuation and often corticosteroid therapy 2.

Diagnostic Approach to Drug-Induced EGID

Before attributing EGID to medications, you must systematically exclude:

• Helminthic infections - the most important cause in travelers/migrants (19-80% of cases), requiring detailed geographic exposure history including freshwater swimming, barefoot walking, and dietary exposures 3
• Food allergen-driven inflammation - particularly for eosinophilic esophagitis and gastritis, which are often triggered by food antigens causing Th2-mediated inflammation 2, 4
• Hypereosinophilic syndrome - persistent eosinophilia ≥1.5 × 10⁹/L for >3 months with potential end-organ damage affecting heart, lungs, and central nervous system 1, 3

Critical Clinical Pitfall

Do not assume drug causation without temporal correlation: Document the timing of medication initiation relative to symptom onset and eosinophilia development. Drug-induced EGID should improve with medication discontinuation, though this may take weeks 2, 5.

When Drug-Induced EGID is Suspected

If you suspect a medication is causing EGID:

• Discontinue the suspected drug and monitor for resolution of eosinophilia and symptoms over 4-8 weeks 2
• Obtain endoscopy with biopsy to document baseline eosinophil counts (≥15 eos/hpf for esophageal involvement) before and after drug withdrawal 4, 5
• Consider empirical corticosteroid therapy if symptoms are severe, as systemic corticosteroids remain the most effective treatment for eosinophilic enteritis and other EGIDs 6

Medications That Do NOT Cause EGID But Are Ineffective Treatments

These drugs are commonly confused as potential causes but are actually ineffective therapies:

• Sodium cromoglycate - no clinical efficacy despite laboratory immunological effects 1, 6
• Montelukast - no benefit in controlled trials (OR 0.48, p=0.33) 1, 3
• Antihistamines - no demonstrated efficacy for EGID management 1, 6

Referral Threshold

Patients with EGID refractory to drug discontinuation and/or with significant concomitant atopic disease require joint management by a gastroenterologist and specialist allergist to optimize treatment and identify alternative causes 1.