Sulfasalazine, dapsone: Good alternative options for treatment of chronic urticaria

Philadelphia - In patients with chronic urticaria who do not respond to standard antihistamine treatment, the older drugs sulfasalazine and dapsone represent promising new treatment alternatives, Lisa A. Beck, M.D. said here at the 2006 meeting of the American College of Allergy, Asthma & Immunology (ACAAI).

Dr. Beck, an associate professor at the University of Rochester Medical Center, reported her positive experience with alternative agents in the treatment of patients with antihistamine-resistant or antihistamine-intolerant chronic urticaria.

In particular, Dr. Beck and colleagues have had great success treating resistant patients with sulfasalazine, a Food and Drug Administration-approved treatment for rheumatoid arthritis and inflammatory bowel disease.

Frustrating experience

Treating patients with chronic urticaria can be a frustrating experience for both patient and physician.

While the majority of patients respond to treatment with antihistamines - often not at standard doses but double, triple or even quadruple the regular doses - some will remain symptomatic. As second-line therapy, some clinicians rely on leukotriene antagonists, H2 antagonists, which have varying success rates. Some clinicians will try immunosuppressive agents such as cyclosporine or systemic glucocorticoids, which are well known for their side effects.

In contrast, the anti-inflammatory medication sulfasalazine has a favorable safety profile and has been used clinically for many years, according to Dr. Beck.

Doses usually range from 1 gram to 4 grams per day (given in two doses). Side effects such as GI discomfort can be kept to a minimum if a cumulative daily dose of 2 grams (to which the majority of patients will respond) is not exceeded. There is, however, a small risk of agranulocytosis, hepatitis and nephritis, and thus, occasional monitoring of blood count differential, liver function tests and urinalysis are required.

In Dr. Beck's experience with antihistamine-refractory chronic urticaria referred to her tertiary care center at Johns Hopkins Medical Institution, the majority of her 19 patients (14 patients, or 74 percent) had significant improvement of their symptoms. All patients who previously required systemic corticosteroids for urticaria control (n = 13) were able to stop or reduce steroid doses during treatment with sulfasalazine.

Adverse effects such as nausea and headache were reported in 7 patients (37 percent), but all remained on therapy. A report on this case series was recently published in the Archives of Dermatology.

Neutrophil-rich skin biopsy

While sulfasalazine shows promise as a "third line" of treatment, the actual approach to a particular patient might best be guided by evaluation of skin biopsy samples, according to Dr. Beck.

While a biopsy may not provide any specific clues to the etiology of the urticaria, the histological findings may still aid in the selection of the treatment drug.

"I want to know what the major leukocyte is in their biopsy - neutrophil-rich or lymphocyte-rich," Dr. Beck says, adding that, in her experience, the majority of infiltrates are mainly lymphocytic, and only 10 percent are mainly neutrophilic.

Published reports suggest that for the neutrophil-predominant type, the antibiotic agent dapsone has been used very successfully. Dapsone has been FDA-approved for treatment of leprosy and dermatitis herpetiformis, in addition to prophylaxis against Pneumocystis jiroveci (Pneumocystis carinii).

"I am thrilled when (patients) are neutrophil-predominant, because they respond beautifully and very quickly to dapsone," Dr. Beck says. The usual target dose of dapsone is 50 mg once or twice per day; however, it needs to be titrated upward slowly with blood count and liver function monitoring due to a risk of dose-related hemolysis and hepatitis. In the appropriate patient a G6PD level should be checked before initiation of therapy.

In patients with lymphocyte-rich infiltrate who are not responding to antihistamines, sulfasalazine (500 mg QD – 2 g BID), olsalazine (125 mg QD up to 500 mg BID) or hydroxychloroquine (200 mg BID) can be tried, though hydroxychloroquine may take longer to have an effect, according to Dr. Beck.