Can I undergo allergy testing while taking Benadryl (diphenhydramine)?

Allergy Testing and Diphenhydramine: Incompatible Timing

Diphenhydramine (Benadryl) must be discontinued a few days before allergy skin testing as it will interfere with test results and potentially lead to false negatives. 1

Why Diphenhydramine Interferes with Allergy Testing

Allergy skin testing is a bioassay that works by introducing specific allergens into the skin to observe the body's reaction. The mechanism relies on:

• The interaction between allergens and IgE antibodies on mast cells 1
• Release of histamine from mast cells that creates a wheal and flare reaction 1
• Diphenhydramine directly blocks this histamine response, which is essential for accurate test interpretation 1, 2

Required Medication Discontinuation Timeline

For accurate allergy skin testing results, the following medication discontinuation periods are necessary:

• First-generation antihistamines (including diphenhydramine): Must be discontinued at least 3 days before testing 2
• Second-generation antihistamines: Must be discontinued at least 3 days before testing 2
• Tricyclic antidepressants: Should be discontinued if possible (56.5% positive histamine control rate even when discontinued) 2
• Benzodiazepines: Should be discontinued if possible (85.7% positive histamine control rate) 2

Clinical Implications and Recommendations

When planning allergy testing:

• Schedule the test at least 3-7 days after stopping diphenhydramine 1
• Inform the allergist about all medications you are taking 1
• Do not take diphenhydramine on the day of testing or for several days before 1
• Note that oral and inhaled corticosteroids do not need to be discontinued before testing 1

Alternative Options

If you need allergy testing but have recently taken diphenhydramine:

• Reschedule the skin test for at least 3-7 days after stopping diphenhydramine 1, 2
• Consider blood testing (specific IgE) as an alternative that is not affected by antihistamine use 1
• Blood testing advantages include no risk of anaphylaxis and not being affected by medications 1

Important Considerations

• Skin testing is generally considered more sensitive than blood testing for detecting allergies 1
• False negative results are likely if testing is performed while taking antihistamines 1
• For accurate diagnosis, the histamine control must produce a positive reaction, which diphenhydramine prevents 2
• Some patients may require diphenhydramine for symptom management, but must understand the need to temporarily discontinue it before testing 3

Pitfalls to Avoid

• Never undergo skin testing while taking diphenhydramine as results will be unreliable 1, 2
• Don't assume that all antihistamines have the same washout period before testing 2
• Be aware that some medications with antihistamine properties (like certain antidepressants) can also interfere with testing 2
• Remember that blood testing is a viable alternative if you cannot stop taking diphenhydramine 1