Chronic urticaria

Internal Medicine News, Jan 1, 2005 by Elizabeth Mechcatie

Antihistamines are the mainstay of treatment for chronic idiopathic urticaria. Determining which to use depends on symptom severity, cost, tolerability, and other factors. Most allergists initiate treatment with a nonsedating antihistamine or one that might be slightly sedating. These drugs are usually well tolerated and have not been associated with the cardiac toxicity observed with the first-generation nonsedating antihistamines that are no longer available.

Antihistamines are often used in combination. For example, the slightly sedating antihistamine cetirizine (Zyrtec) can be given at night, with a nonsedating agent such as fexofenadine (Allegra) in the morning. Patients whose itching at night interferes with sleep may be better off taking one of the older sedating antihistamines such as hydroxyzine (Atarax) or diphenhydramine (Benadryl) in the evening. The most severe patients, however, may require dosages of these agents at 25-50 mg q.i.d. In addition, these older sedating antihistamines are still used for some patients who do not respond to nonsedating antihistamines and for patients who cannot afford the more expensive nonsedating formulations.

With the exception of elderly patients, most patients with urticaria require higher dosages than are used for allergic rhinitis: A patient with hives may need to take a drug twice daily that is given only once daily for hay fever. For older patients who are more susceptible to somnolent effects, a standard dosage of a nonsedating agent given at night only is preferred. But here, too, the dosage and class of antihistamine used depend on severity. A rare consideration in older patients is the possibility that urticaria is a symptom of malignancy, such as leukemia or lymphoma. Younger patients do not generally need an extensive work-up before starting antihistamine therapy, unless the history or physical suggests a possible systemic disease or infection.

When initiating therapy, some allergists recommend a short course of prednisone to help break the cycle of itching. Even if hives clear promptly with this treatment, it's advisable to have the patient continue the antihistamine for 1 or 2 months beyond this because recurrence is common.

Several other options--namely, a leukotriene antagonist, an [H.sub.2]-blocker, or an [H.sub.1]/[H.sub.2]-blocker--are considered for patients whose symptoms cannot be controlled with high doses of antihistamines. Although most histamine receptors in the skin are the [H.sub.1] subtype, about 15% are the [H.sub.2] subtype, so one of the [H.sub.2]-blockers or doxepin (Sinequan), an antidepressant that is an [H.sub.1]/[H.sub.2]-blocker, is sometimes tried empirically. Since doxepin is potentially sedating, it is usually taken at night. The [H.sub.2]-blockers used are cimetidine (Tagamet), ranitidine (Zantac), or famotidine (Pepcid). Doxepin at a dosage of 10-50 mg q.i.d. can cause significant adverse effects, such as profound sedation and urinary retention, and is used only for patients refractory to the more benign leukotriene antagonists and [H.sub.2]-blockers.

Only when all these agents have been tried at maximal dosages are corticosteroids used on a low-dose or alternate-day basis. The initial dosage of prednisone is typically 15-25 mg every other day with a 2.5- to 5-mg decrease every 2-3 weeks and a goal of 10 mg or less every other day (administered as a single morning dose to minimize the potential for adverse effects). Immunosuppressive therapy with low-dose cyclosporine is an alternative to corticosteroids for severely afflicted patients who cannot take prednisone, but this approach requires monitoring of blood pressure and kidney function and is handled by specialists.

Chlorpheniramine (Chlor-Trimeton) or diphenhydramine (Benadryl) are the antihistamines most commonly used in pregnancy. If sedation becomes problematic, loratadine (Claritin) and cetirizine are low-risk agents in pregnancy and may be considered, particularly after the first trimester. Montelukast (Singulair) is also a low-risk drug in pregnancy but should be used only for difficult cases that do not respond to antihistamines.

If antihistamines are needed during breast-feeding, one of the older first-generation drugs such as diphenhydramine is preferable because these drugs are short acting, and dosing can be adjusted to minimize fetal exposure. [H.sub.2]-blockers also are acceptable for use during pregnancy and nursing. Systemic corticosteroids should be avoided during the first trimester but may be used during the second and third trimesters if absolutely necessary. They also can be used at most dosages during breast-feeding. There have been reports of adverse effects in newborns, birth defects, and toxicity in nursing infants with oral doxepin, so it should not be used in pregnancy or during breast-feeding.