New urticaria guidelines update antihistamine recommendations
Acta Eruditorum
Dr. Schwarzenberger is the former physician editor of DermWorld. She interviews the author of a recent study each month.
By Kathryn Schwarzenberger, MD, June 1, 2018
In this month's Acta Eruditorum column, Physician Editor Kathryn Schwarzenberger, MD, talks with Diane Baker, MD, about a recent Allergy article, "The EAACI/GA²LEN/EDF/WAO Guideline for the Definition, Classification, Diagnosis and Management of Urticaria. The 2017 Revision and Update."
Dr. Schwarzenberger: You recently represented the AAD in an international collaboration on the diagnosis and management of urticaria. The 2017 update has recently been published in the journal Allergy. Can you briefly tell us about the workgroup and how you became involved?
Dr. Baker: In 2016 the American Academy of Dermatology was contacted by the Global Allergy and Asthma European Network, the organization responsible for overseeing and organizing the guideline update process; the AAD was asked if we wanted to send a delegate to participate in the update process. Dr. Abel Torres, then-President of the AAD, appointed me to take part in the process and attend the consensus conference on behalf of the AAD.
Dr. Schwarzenberger: These guidelines are an update of a previous version. What, if anything, changed between versions?
Dr. Baker: This is the fifth update of these urticaria guidelines, originally written as a report of the first consensus conference of European allergologists in 2000. The most recent update prior to the 2017 one was published in 2013. The most substantial change from the 2013 revision concerns the recommendation for treatment of chronic spontaneous urticaria in the patient who fails to respond to updosing of second-generation H1 antihistamines. The 2013 guidelines suggest a trial of the leukotriene inhibitor montelukast as add-on therapy to updosed amounts of antihistamines. That recommendation was, however, a weak recommendation based on a low level of evidence. The experts at the 2017 consensus conference decided the evidence was so weak that they could not make a recommendation with respect to montelukast as add-on treatment to H1 antihistamines in patients with chronic urticaria unresponsive to H1 antihistamines. Likewise the evidence for the usefulness of the addition of an H2 antihistamine to H1 antihistamines to treat chronic urticaria is so weak that no recommendation for their use can be made. This differs from the recommendations in the 2014 Practice Parameters on Urticaria and Angioedema published by the AAAAI, the ACAAI, and the Joint Council on Allergy, Asthma and Immunology, which do recommend a trial of leukotriene receptor antagonists and H2 antihistamines as add-on therapy in patients unresponsive to updosed amounts of H1 antihistamines.
Dr. Schwarzenberger: Antihistamines have long been a treatment mainstay in the management of urticaria. Do the guidelines give us any guidance regarding their best use?
Dr. Baker: Non-sedating, also referred to as second-generation H1, antihistamines are indeed the first-line treatment for all cases of urticaria and all guidelines agree that if FDA approved or licensed doses of non-sedating H1 antihistamines do not control a patient’s hives then evidence supports the updosing of non-sedating antihistamines to four times the licensed dose. It is also strongly recommended that in the treatment of chronic urticaria second-generation H1 antihistamines be taken regularly, that is daily, in the dose needed to control hives rather than taking them on demand. At our clinic we still see patients with hives referred to us whose disease has not been controlled only because they haven’t been taking their antihistamines on a daily basis.
Dr. Schwarzenberger: What about omalizumab? Should dermatologists be comfortable using this and, if so, when?
Dr. Baker: The approval of omalizumab by the FDA for the treatment of antihistamine-resistant cases of chronic urticaria has been a significant addition to our armamentarium. The 2017 update recommends going directly to a trial of omalizumab as add-on therapy to second-generation H1 antihistamines as third-line treatment in cases of severe antihistamine-resistant urticaria. This is because of evidence for its effectiveness as shown in several double-blind placebo-controlled clinical trials. Cyclosporine is the only other drug that has substantial evidence for its effectiveness in chronic urticaria and the side effects of cyclosporine treatment are well known. The problem with omalizumab is its high cost and the necessity for prior authorization. The other thing that makes some dermatologists insecure about omalizumab prescribing is the warning on its label about anaphylaxis. In truth there is very low risk of anaphylaxis and there were no cases of anaphylaxis in the clinical trials for urticaria. The cases of anaphylaxis reported were all in asthma patients; omalizumab was approved for the treatment of allergic asthma several years before it was approved for the treatment of chronic urticaria, and most of those cases were in patients who had prior episodes of anaphylaxis.
Dr. Schwarzenberger: Did working on the guidelines change anything about the way you manage urticaria?
Dr. Baker: One thing that I learned that is not in the guidelines was that some patients are late responders to omalizumab. We have gotten so used to seeing a rapid response that I was tending to assume patients were nonresponders if there was no improvement in their urticaria after three doses. Recent publications support the idea that it may take 3 – 6 months before some cases of urticaria respond to omalizumab.
Dr. Schwarzenberger: Your workgroup included members from many different countries. Did you observe any differences in how American dermatologists and physicians from other countries think about urticaria?
Dr. Baker: One difference is that European allergy and dermatology specialists tend to believe that food additives play a role in some cases of chronic spontaneous urticaria and they are therefore more likely to try food-additive-free diets to treat chronic urticaria patients. There was also considerable difference in the availability of some treatment choices in some countries, often based on cost, making it more likely that H2 antihistamines or leukotriene inhibitors would be tried for treatment of antihistamine-resistant cases of chronic urticaria in those countries. It would also be more likely that oral corticosteroids, while not recommended for long-term use, would be the only other choice to treat severe cases of chronic urticaria in those countries.
Dr. Schwarzenberger: Can you share any other pearls for managing chronic urticaria?
Dr. Baker: Two important pearls are:
A. Convince your patients with chronic urticaria that they must take their antihistamines on a daily basis. It helps if you explain the mechanism of action of antihistamines which is that of an inverse agonist, that is H1 antihistamines keep the H1 receptor in the “off” position, so it makes sense that it’s important to take them on a daily basis
B. Don’t be afraid to up your chronic urticaria patients’ non-sedating H1 antihistamine up to 4 times the FDA-approved dose.
Dr. Baker practices at Baker Allergy, Asthma, and Dermatology in Portland, Oregon and served as AAD President in 2007. The guideline she helped create appeared in Allergy. doi:10.1111/all.13397.
