A 32 yo woman has a history of diffuse urticaria from ibuprofen. She had been taking ibuprofen for 3 days and awoke with hives. There was no angioedema, anaphylaxis, or other symptoms. She also avoids aspirin (never taken it because her sister and mother have had anaphylaxis to it). On exam she has dermatographism. She wants to be able to take an anti-inflammatory when needed. Is it safe to challenge her in the office? I would consider using aspirin for the challenge. Would a regimen of 3mg, 30mg, 40 mg, 81 mg, 162 mg, each dose 30 minutes apart(total 316 mg) be sufficient?


Thank you for your inquiry.

Before proceeding with a direct answer, I would like to call your attention to two recent very helpful articles which discuss the issues highlighted by your patient (1, 2). The article by Marek Kowalski and colleagues (2) is a very comprehensive review of reactions to nonsteroidal antiinflammatory drugs (NSAIDs), and discusses the classification of reactions to these drugs in detail. It also has excellent treatment algorithms. The article by Yilmaz, et al. (1), has detailed protocols for challenge to various nonsteroidal antiinflammatory drugs.

Urticaria due to a nonsteroidal antiinflammatory drug can be due to two mechanisms. In one instance, the patient will react to other nonsteroidals, and in the other, they will not. That is, they can be both drug and class specific. In our experience, the vast majority are drug specific, and therefore challenges are safe and very helpful to the patient because they allow the patient to use a nonsteroidal. Thus, I would proceed in your case with a challenge, and we have personally done all challenges (when urticaria was the manifestation) in-office. This contrasts to the Yilmaz article where challenges were done in-hospital, but the Yilmaz article was done in children and we have found in adults these challenges have been safe in-office. The question then becomes the choice of the challenge drug and the protocol to be used.

As noted, the Yilmaz article presents protocols to a number of different NSAIDs including ibuprofen, naproxen, tolmetin, ketoprofen, nimesulide, and meloxicam. You can of course use these as prototypes to design a challenge protocol for any NSAID. As far as the choice is concerned, you might consider, in place of aspirin, another NSAID that could be used for chronic arthritis symptoms as well as fever and pain.

Of course, naproxen sodium would be an excellent choice because it is available over-the-counter and in a syrup form. However, the downside of using naproxen is that it is a member of the same class (arylpropionic acid derivatives) as ibuprofen and therefore, theoretically more likely to be cross-reactive. Other NSAIDs from different classes (meloxicam, for example) are also available in liquid form and could be selected instead of aspirin.

In addition, if she did not react to aspirin, you could do a separate challenge to allow her to have an alternative NSAID more commonly used for arthritis symptoms as well.

In summary, in our experience, it has been safe to do challenges to NSAIDs in-office. Your protocol for aspirin is reasonable, but you could also consider using a nonsteroidal antiinflammatory drug from a different class or challenge to aspirin, and if negative, do a second challenge to an alternative NSAID later.

Finally, the two references that we cited above should be very helpful to you.

Thank you again for your inquiry and we hope this response is helpful to you.

1. Challenge-proven nonsteroidal anti-inflammatory drug hypersensitivity in children O. Yilmaz et al. Allergy, Volume 68, Issue 12, pages 1555–1561, December 2013.

2. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. M.L.Kowalski, et al. Allergy, Volume 68, Issue 10, pages 1219–1232, October 2013.

Phil Lieberman, M.D.

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