Does histamine (histamine) or antihistamine use affect Immunoglobulin E (IgE) testing results?

Effect of Antihistamines on IgE Testing

Antihistamines can significantly suppress IgE testing results and should be discontinued prior to testing to ensure accurate results. The American Academy of Allergy, Asthma, and Immunology recommends discontinuing antihistamines like Benadryl at least 3-7 days before serum allergen-specific IgE testing 1.

Impact of Antihistamines on Different Testing Methods

Skin Testing

Antihistamines have a pronounced effect on skin testing results:

• Skin prick/intradermal tests: These are particularly affected by antihistamines, as they rely on histamine-mediated wheal and flare reactions
• Timing of discontinuation:
  • Chlorpheniramine or terfenadine: 24 hours before testing 2
  • Diphenhydramine or hydroxyzine: 4 days before testing 2
  • Astemizole: 3 weeks before testing 2

Histamine controls are specifically used during skin testing to ensure that results are not falsely negative due to antihistamine effects 2. When the histamine control fails to produce a reaction, it indicates that antihistamine medications may be suppressing the test results.

Serum IgE Testing

• Less affected by antihistamines than skin testing
• Can be used when patients cannot discontinue antihistamine medications 1
• Provides an alternative when skin conditions (dermatographism, extensive dermatitis) make skin testing unreliable 1

Mechanism of Interference

Antihistamines block the histamine receptors that mediate the allergic response measured in skin testing. Research shows that:

• Different antihistamines vary in their suppressive effect on skin test reactivity 3
• Hydroxyzine produces the most significant skin test suppression 3
• Chronic use of antihistamines can lead to partial tolerance to their suppressive effects 3

Clinical Implications

1. Test selection considerations:

   • For patients who cannot discontinue antihistamines, serum-specific IgE testing is preferred over skin testing 1
   • Skin testing is generally more sensitive but requires antihistamine discontinuation 1

2. Medication management before testing:

   • Create a clear discontinuation schedule based on the specific antihistamine
   • Longer washout periods for longer-acting antihistamines

3. Test interpretation:

   • False negatives may occur if antihistamines are not properly discontinued
   • Histamine controls should always be used with skin testing to validate results 2

Common Pitfalls to Avoid

• Inadequate washout period: Different antihistamines require different discontinuation periods
• Overlooking hidden antihistamines: Some OTC medications and supplements contain antihistamines
• Misinterpreting negative results: When histamine controls are negative, test results are unreliable
• Assuming serum IgE tests are unaffected: While less impacted than skin tests, very high doses of antihistamines might still influence results

Conclusion

When planning IgE testing, antihistamine use must be carefully managed to ensure accurate results. Serum-specific IgE testing provides a valuable alternative when antihistamines cannot be discontinued, though skin testing remains the more sensitive option when properly performed without interfering medications.