Chronic Urticaria: Following Practice Guidelines

Erin P. Westby, MD; Charles Lynde, MD, FRCPC; Gordon Sussman, MD, FRCPC, FACP, FAAAI


Skin Therapy Letter. 2018;23(3):1-4. 

In This Article


Prevention of mast-cell degranulation through blockade of histamine on H1-receptors remains the mainstay of treatment for chronic urticaria. Modern second-generation non-impairing, non-sedating H1-antihistamines have been widely adopted as first-line treatment of chronic urticaria and have essentially replaced older first-generation antihistamines (Figure 1). They are effective and safe and do not possess the significant anticholinergic and sedating side effects that plague the first-generation antihistamines. Furthermore, current guidelines recommend against the use of first-generation H1-antihistamines in the treatment of chronic urticaria, especially in the pediatric and geriatric populations, given their side effect profile.[6,7]

Figure 1.

Step-wise approach to the management of chronic urticaria according to the updated and revised 2016 guidelines by a joint initiative of the EAACI Dermatology Section, GA2LEN, EDF, WAO, and CSACI.

If adequate control is not attained after 2–4 weeks or earlier if symptoms are intolerable, a trial of up to a fourfold increase in the standard therapeutic dose of modern second generation H1– antihistamine is suggested. This has been proven to be safe and effective and is preferred over alternative treatments as second-line treatment based on recommendations by the updated and revised international guidelines.[5,6,13–15] First generation H1-antihistamines are not recommended, but can still be used as adjunct therapy. H2-antihistamines are not recommended as first-, second- or third-line therapy.[6,8,15–17] Similarly, antidepressants with potent H1– and H2-antagonism, such as hydroxyzine or doxepin, are not recommended given their sedating and anticholinergic nature, as well as the multiple drug-drug interactions.[18,19]

The third-line treatment for resistant chronic urticaria, i.e., inadequate control after 2–4 weeks or earlier if symptoms are intolerable, includes the addition of omalizumab, an anti-IgE humanized monoclonal antibody (Figure 1).[1,5,6] In large, randomized, double-blind, placebo-controlled trials, omalizumab has been demonstrated to be efficacious, safe, and well-tolerated.[20–24] Omalizumab has been shown to have few side effects and requires minimal ongoing monitoring. Omalizumab should be trialed for 6 months, unless symptoms are intolerable, before moving on to fourth-line therapy, cyclosporin A. Although trials using cyclosporin A have shown promising results when treating refractory chronic urticaria, continuous monitoring of blood pressure, renal function, serum drug levels, and other metabolic factors is important, in order to avert possible toxicity.[25,26] It is important to note that leukotriene receptor antagonists are no longer in the treatment algorithm for chronic spontaneous urticaria.[5]

At any stage of the disease, a short course of an oral corticosteroid could be added for treating acute exacerbations. Long-term treatment with corticosteroids should be avoided (Figure 1).[7,13,27]

Use of other pharmacologic agents, such as sulfasalazine, hydroxychloroquine, colchicine, tacrolimus, mycophenolate mofetil, intravenous immunoglobulin, and dapsone have been used in the treatment for chronic urticaria with inconsistent results. These agents have limited utility because of their side effect profile, modest benefit seen in clinical trials, or lack of available data.[6,27,28]