Initially, a minimally sedating second- or third-generation antihistamine, such as loratadine,39 fexofenadine hydrochloride,40 and cetirizine hydrochloride,41-44 should be given at a once-daily oral dosing. When one antihistamine is not helpful, it is usually worth trying a different one, and some physicians combine 2 or more antihistamines at the same time.3 It is common practice to exceed the licensed dose in severely affected patients.31 High doses of antihistamines have effects beyond the blockade of histamine receptors, and actions that are not due to antagonism of H1 receptors may account for the efficacy of older antihistamines.45 As a general rule, antihistamines are safe and have few substantial adverse effects; drug interactions are rare. If possible, it is best to avoid all antihistamines in pregnancy, though none have been proven teratogenic. If one is used, the consensus is that chlorpheniramine maleate is among the safest.46
Addition of a sedating first-generation antihistamine such as hydroxyzine at night can be helpful, especially if nocturnal pruritus prevents sleep. The use of a sedating antihistamine as monotherapy is less desirable because of impairment of cognitive function, including driving performance and concentration. The addition of a H2 antagonist to conventional H1 antihistamines may be helpful in some patients.3,47 Doxepin hydrochloride at low doses (10–50 mg) is used for its potent H1 and H2 receptor antagonist properties. Doxepin hydrochloride is highly sedative and especially suitable for patients with associated depression.48
Oral corticosteroids given in short reducing courses may be needed for severe exacerbations not responding to full-dose antihistamines. Relatively high doses of up to 40 to 60 mg of prednisone may be needed for disease control. Alternate-day ste-roids may be used for patients with severe disease.6 Long-term administration should be avoided.1
Many patients feel reassured by carrying an epinephrine pen for self-administration if they are prone to severe attacks. Leukotriene antagonists (zafirlukast and montelukast sodium) have been shown to be superior to placebo in the treatment of patients with chronic urticaria.49,50 Nifedipine has a small effect in chronic urticaria and often is used for patients with concomitant hypertension. Thyroxine recently was reported to suppress CIU symptoms associated with antithyroid autoantibodies in some patients.51
Given the role of the immune system in a subset of patients, immunosuppressive therapy is considered for patients with a severe disabling course. Cyclosporine at 2.5 to 5 mg/kg per day is of proven value in autoantibody-positive chronic urticaria52 but also is effective in most cases of severe autoantibody-negative disease.15 Tacrolimus also has shown promise in a recent trial.53 Other options include plasmapheresis54 and intravenous immunoglobulin.55,56 Optimal treatment protocols have yet to be confirmed. Treatments for CIU with only limited or anecdotal supportive evidence include sulfasalazine, methotrexate, rofecoxib, colchicine, dapsone, and cyclophosphamide.3
Future treatment may involve development of selective immunotherapy targeting the IgE receptor or vaccinations to down-regulate and induce tolerance to the IgE receptor. Other potential strategies include blocking formation of C5a and use of therapeutic antibodies such as anti-IgE, anti–tumor necrosis factor α, and anti–interleukin 5.2
Conclusion
There is no single way to manage urticaria and angioedema. Most patients are treated successfully with antihistamines. However, patients with severe antihistamine-resistant urticaria may be very disabled by their disease, and the treatment can pose a major challenge to the physician.