Identifying pathogenic mechanisms will help treat chronic urticaria

According to Allen Kaplan, M.D., chronic urticaria is defined as spontaneously occurring hives that are not caused by IgE-mediated hypersensitivity or any other exogenous stimulus. Individual lesions lasting four to 36 hours are present on most days for a period longer than six weeks.

Dr. Kaplan, who is head of the Urticaria Program at The National Allergy, Asthma and Urticarial Center, Charleston, S.C., discussed the difficulties in diagnosing and treating these conditions at the American College of Allergy, Asthma and Immunology meeting here.

Beyond distinctions related to lesion duration and identifiable cause, Dr. Kaplan notes that 40 percent of patients with either chronic autoimmune or chronic idiopathic urticaria have associated angioedema.

Possible causes

Dr. Kaplan maintains that many causation theories discussed in the literature remain unproven, including that hives occur as a consequence of infection with Helicobacter pylori. He also says theories about psychophysiologic reactions, food allergies, adverse reactions to food additives and cutaneous fungal infections (id reactions) have been dispelled as myths or erroneous associations and do not have a cause-and-effect relationship.

"My own view is that none of these are common as a cause of chronic hives or swelling," Dr. Kaplan tells Dermatology Times. "However, as long as a large idiopathic group exists, ideas may come and go until clinical or basic studies that are reproducible lead to a consensus regarding cause, as has emerged for the 'autoimmune' subgroup. Recently 'pseudo-allergy' to foods is being touted as a precipitant of urticaria and requires confirmation by carefully controlled studies."

Treatment considerations

Dr. Kaplan says the mainstay of initial treatment is the use of antihistaminic agents active at the H1 receptor. Medications that he considers to be useful adjunctive agents include H2 receptor antagonists and leukotriene antagonists. For patients with severe disease, he may use alternate-day steroids and immunosuppressive agents, such as cyclosporine.

Use of antihistamines can be tricky in patients already receiving them regularly, and their use in chronic urticaria is quite different from their use in allergic rhinitis. Dr. Kaplan uses the example of dermatographism to demonstrate some of the issues, while admitting that chronic urticaria is more complicated.

"Although one would think that any of the nonsedating histamines would suffice, it is a common experience that patients presenting with severe symptoms might already be taking one of them regularly. Increasing the dose (eg, fexofenadine 180 in the morning plus citirazine, 10 mg twice daily) might provide further relief, but some patients remain significantly symptomatic with a clear dermatographic response still present. Next, one may employ either hydroxyzine or diphenhydramine at 25 to 50 mg four times daily. The typical result is relief of symptoms within 72 hours, and scratching the skin yields no wheal, although a prominent flare always persists."

Sedation a concern

One concern regarding the use of antihistaminic agents in this dose range, he says, is sedation.

"It has been reported that impairment of performance, when tested acutely with diphenhydramine, can be as impairing as alcohol. Nonetheless, the perception of sedation wears off in one week and the use of doses as described above for chronic urticaria, which has a more complex pathogenesis than dermatographism, is warranted if there is relief of pruritis and lessening of the hives, swelling and disability, and this is certainly true if they are steroid-sparing. The degree of performance impairment of patients with urticaria on round-the-clock treatment for more than a week (if any) has never been studied."

Dr. Kaplan emphasizes the differences between these conditions.