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Antihistamine Touted
Ebastine offers advantages in treatment of AA
Aug 1, 2003
By: Barbara J. Rutledge, Ph.D.
Special Report
Male patient, age 54, with 50-74 percent loss of scalp hair before ebastine treatment (top) and 90-percent hair regrowth after five months of treatment. (Photographs courtesy of Yusuke Yoshizawa, M.D.)
Barcelona - Ebastine, a second-generation antihistamine currently marketed in Europe and Japan, offers many advantages as a treatment for mild to moderate alopecia areata, according to Yusuke Yoshizawa, M.D., assistant professor of dermatology, Nippon Medical School, Tokyo.
Alopecia areata is a T-cell mediated autoimmune disorder targeting the hair follicles. "The pathogenesis of alopecia areata is still unclear," Dr. Yoshizawa said, "but expression of certain cell surface molecules on the hair follicle cells and the presence of peribulbar lymphocytic infiltrates are consistent and reproducible immunological abnormalities seen in alopecia areata."
Key players responsible for hair loss in alopecia areata appear to be interferon-gamma, IL-1, and substance P, among others.
T cells produce interferon-gamma, which induces expression of a variety of cell surface molecules such as MHC receptors, HLA-DR, and ICAM-1 on hair follicular keratinocytes and dermal papilla cells.
"IL-1 is thought to be the crucial inducer of hair loss in alopecia areata," Dr. Yoshizawa said at the 10th European Hair Research Society meeting. "IL-1b mRNA can be detected in skin lesions of alopecia areata. IL-1b has been shown to inhibit hair growth in vitro and stimulate ICAM-1 expression in endothelial cells."
Substance P may be responsible for stimulating expression of the IL-1 family in keratinocytes. The anti-inflammatory effects of second-generation antihistamines such as ebastine include inhibition ofcell activation, inhibition of expression of various cell surface molecules stimulated by interferon-gamma, and inhibition of histamine-induced expression of substance P.
Immunosuppressive and immunomodulatory agents have traditionally been used for treatment of alopecia areata, although often with limited success. Corticosteroid therapy is associated with potentially serious side effects and is no longer widely used. Diphenylcyclopropenone (DCPC) and squaric acid dibutylester (SADBE) solutions are used in Europe and Canada. However, local immunotherapy is more complicated for an inexperienced dermatologist to administer, and application of DCPC or SADBE solution to alopecia lesions causes contact dermatitis, resulting in itching and discomfort for the patient. By contrast, ebastine is an oral medication, and is generally well tolerated, with slight sedation as the most common side effect.
Dr. Yoshizawa described two clinical trials evaluating ebastine for treatment of alopecia areata. The first study looked at ebastine as a second-line treatment for patients who had failed diazepam. Nine patients with alopecia areata were initially treated with diazepam, and one patient responded favorably. The remaining eight patients were treated with ebastine for several months. After four to eight months, six patients showed improvement, with three patients considered cured.
Dr. Yoshizawa
In a second study, 29 patients with alopecia areata were treated initially with ebastine. Patients with mild or moderate alopecia areata had a response rate of 75 percent or 46 percent, respectively. Only one of two patients with severe alopecia areata and only one of six patients with alopecia totalis or alopecia universalis responded to ebastine treatment.
In total, 37 patients were treated with ebastine, and the efficacy of treatment based on both hair re-growth and cosmetic acceptance were evaluated. Thirty-seven patients with alopecia areata were treated with ebastine. Patients were classified into four groups based on the extent of the loss of scalp hair: mild, 25 to 49 percent loss, 13 patients; moderate, 50 to 74 percent loss, 15 patients; severe, 75 to 99 percent loss, 3 patients; and alopecia totalis or alopecia universalis, six patients. Percentages of patients in each group with at least 50 percent hair re-growth after 12 months were 69, 57, 67, and 14 percent, respectively. Patients with atopic dermatitis were significantly less likely to respond to treatment. Of 20 patients with at least 50 percent hair regrowth, only one had atopic dermatitis, compared to six of 17 patients with less than 50 percent hair re-growth (p<0.01).
Cosmetic acceptance was determined by the patient, and generally was regarded as a maximum of two or three small patchy lesions. Compared to hair re-growth, cosmetic acceptance was reported in slightly smaller percentages of patients in the study groups, occurring in 61, 43, 33, and 0 percent of patients in each of the four groups, respectively. "These rates of cosmetic acceptance were almost half the rates that have been reported following DPCP therapy," said Dr. Yoshizawa.
Overall, ebastine therapy was not as efficacious as DPCP therapy. "However, ebastine therapy was well tolerated, and the procedure was very simple, even for dermatologists not familiar with taking care of patients with alopecia areata," said Dr. Yoshizawa. "We recommend second-generation antihistamine therapy for alopecia areata in patients with mild to moderate alopecia without concomitant atopic dermatitis, who are more than 30 years old at the onset of the first episode and who have less than one year history of alopecia."
Ebastine is marketed by Almirall Prodesfarma (Barcelona). Dr. Yoshizawa reported no conflicts of interest.
