KAUAI, HAWAII – Don’t waste your time on “yet another antihistamine” when first- and second-line therapies fail for refractory urticaria.

That’s what Dr. Joseph Eastern advised physicians at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

“There is just not enough evidence to support using antihistamines and playing roulette with your patient’s health,” Dr. Eastern said, noting that the degree of disability, both socially and occupationally, that accompanies chronic urticaria is on par with that of a patient awaiting triple coronary bypass.

Also not on Dr. Eastern’s list of go-to treatments for the condition are thyroxine replacement, special diets, or anti-Helicobacter pylori treatment, despite some in the field who believe there is an overlap in the pathogenesis of urticaria and this gastrointestinal infection. “None of these are supported by credible evidence,” Dr. Eastern, a dermatologist in private practice in Belleville, N.J., said in an interview.

Once second-line therapies such as doxepin, leukotriene antagonists, corticosteroids, dapsone, sulfasalzine, and even narrow-band UVB are exhausted, Dr. Eastern suggested using off-label immunosuppressants for chronic urticaria as third-line treatment. He discussed three in particular:

• Cyclosporine. At least three randomized controlled trials support the safety and efficacy of cyclosporine in chronic urticaria. Dr. Eastern noted that, in a 2011 study, the drug was particularly effective in chronic urticaria that had shorter duration of disease and a CU (chronic urticaria) index of 10 or less (Ann. Allergy Asthma Immunol. 2011;107:523-8).

The most effective dosing seems to be between 3 mg/kg per day and 6 mg/kg per day, given over the course of 2-3 months (Br. J. Dermatol. 2000;143:365-72). Approximately 80% of patients responded well to treatment (J. Dermatol. 2008;35:276-82). Of those, one-third experienced complete remission of symptoms, another third experienced mild relapse, and one-third relapsed more severely. Dr. Eastern noted that long-term use of cyclosporine is associated with risks of hypertension and renal impairment.

• Methotrexate. Although there are no randomized controlled studies to support the use of methotrexate for chronic urticaria, there have been reported anecdotal successes, Dr. Eastern said. The benefits seem to be in the drug’s anti-inflammatory and immunosuppressive effects (Br. J. Dermatol. 2010;162:191-4).

“Methotrexate may be of benefit independently of the pathogenic mechanism of urticaria and is a viable option in situations where the cost of therapy is a significant concern,” he said in the interview.

• Omalizumab. This recombinant humanized monoclonal antibody, which selectively binds to, and lowers, serum IgE, is “the new kid on the block,” Dr. Eastern said. “The results are impressive, particularly in patients with demonstrable autoantibodies to IgE, but insurance approval is often difficult to obtain, due to the drug’s expense.”

Two other treatments clinicians could consider are high-dose intravenous immunoglobulin (0.4 g/kg for 5 days) and plasmapheresis, according to Dr. Eastern. The former’s mechanism of action is unclear at this point, but in patients with severe, unremitting chronic urticaria, plasmapheresis was shown to eliminate the functional autoantibodies, favoring a pathogenic role.

When all else fails, Dr. Eastern urged physicians to reconsider the diagnosis.

“The presence of systemic symptoms could mean the urticarial rash is not ordinary urticaria,” he said, suggesting that vasculitis, Schitzler’s syndrome, adult-onset Still’s disease, an autoinflammatory syndrome, or urticarial dermatitis could be at play.

Dr. Eastern disclosed that he serves as a consultant to Genentech, which markets omalizumab as Xolair.

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