What to Do With Refractory Urticaria Patients

Abstract

A urticaria patient said to be refractory to treatment ordinarily implies inadequate responsiveness to antihistamines. Thus, it is necessary to define at what point antihistamine therapy has failed. Although virtually any first-generation or second-generation antihistamine has efficacy for treatment of urticaria, few studies have compared one agent to the others, and dose-escalation studies are much in need. For the past 40 years, when firstgeneration antihistamines were all we had, I advocated use of hydroxyzine (Atarax; Pfizer, New York, NY) or diphenhydramine (Benadryl; McNeil-PPC, Fort Washington, PA) at doses up to 50 mg four times daily before assuming a patient to be refractory [1]. These agents ware relatively short-acting and were meant to be used in divided doses four times daily when necessary. For patients with physically induced hives such as cold urticaria or cholinergic urticaria, one could readily titrate the antihistamine dose and determine that 3 or 4 doses/d are frequently required where 1 or 2 doses do not provide adequate symptom control. Once the relatively nonsedating, second-generation, long-acting drugs were available, they were commended once daily for urticaria, as was recommended for allergic rhinitis. This turned out to be effective only in the mildest of cases of urticaria. Recently, when loratadine was tested for efficacy in the treatment of cold urticaria, it was clear that 4>3>2>1 tablets/d (ie, more is better, and side effects are minimal). In spite of the evidence of sedation with first-generation antihistamines [2–5], when they are used in high doses, sedation rapidly wears off, and they can still be recommended in countries in which second-generation agents are not available [6, 7]. There are, in fact, very few studies of sedation with use of such agents for more than a week in patients with chronic urticaria rather than in healthy volunteers. Nevertheless, for most purposes, this becomes a moot point, particularly when cost ceases to be an issue. Thus, over-the-counter generic cetirizine can be obtained inexpensively, and 6 tablets/d is roughly equivalent to hydroxyzine, 200 mg/d.