Allergic reaction to diphenhydramine

The first reported case of diphenhydramine anaphylaxis was reported by Barranco et al in 1998. Prick skin test to diphenhydramine was negative but the intradermal (using 1mg/ml diphenhydramine) was positive with appropriate controls. They performed a simple blind controlled oral challenge, which I suspect was a single-blind challenge, and within 20 minutes the patient reacted with the same symptoms she had during her previous reactions. They also performed blinded oral challenges to second generation antihistamines, which were negative, in order to determine if these could be safely administered should they be needed in the future.

In 2013, Shakouri and Bahna published a review of hypersensitivity to antihistamines which included a section on diagnostic testing. They noted that the diagnostic reliability of skin testing was not high; skin prick tests were frequently negative and intradermal tests were positive just over half the time, though the total number of cases was low. They went on to discuss that oral challenge testing using a blinded approach is the most conclusive method to establish the diagnosis. A placebo dose may be performed at the start. Then, an initial dose of 10% or less of the therapeutic antihistamine dose may be administered followed by 50-100% increments at 20-to-30-minute intervals. After the full dose has been administered, an observation period of at least 1 hour was recommended.

So, oral challenge to confirm diphenhydramine as the trigger and also challenge to establish which alternative antihistamine(s) may be used in the future would be appropriate next steps to take.

References:
Barranco P, Lopez-Serrano MC, Moreno-Ancillo A. Anaphylactic reaction due to diphenhydramine. Allergy 1998;53:814.

Shakouri AA and Bahna SL. Hypersensitivity to antihistamines. Allergy Asthma Proc. 2013;34:488-496.

Jacqueline A. Pongracic, MD, FAAAAI