Topical Tacrolimus Found to Reduce Vitiligo Size
By: DAMIAN MCNAMARA
TORONTO — Topical tacrolimus significantly decreased the size of vitiligo lesions and spurred repigmentation, compared with pretreatment and unaffected skin, the results of a small study found.
“The most encouraging result was the concentration of [interleukin]-10,” Dr. Zaki Taher said.
There was a statistically significant increase in interleukin-10 (IL-10) expression in vitiligo lesions treated twice daily with the agent compared with untreated lesions and normal skin. This finding supports an autoimmune mechanism for vitiligo and encourages more cytokine-directed therapies in the future, Dr. Taher said at the annual conference of the Canadian Dermatology Association.
Topical tacrolimus caused a statistically significant mean decrease of 41% in the size of vitiligo lesions among the 17 patients who completed the 3-month study.
The research was supported by Astellas Pharma Inc., maker of topical tacrolimus (Protopic). Dr. Taher has no affiliation with Astellas, but disclosed that some of his coworkers received honoraria or served as advisory board members.
Of the three proposed mechanisms for vitiligo, including autocytoxicity and neurohormonal factors, “the autoimmune theory is getting more and more attention,” said Dr. Taher, a first year resident in the division of dermatology and cutaneous sciences at the University of Alberta, Edmonton.
Encouraged by an initial report of moderate to excellent repigmentation in five of six vitiligo patients treated with tacrolimus ointment by Dr. Pearl E. Grimes and her associates (J. Am. Acad. Dermatol. 2002;47:789–91), Dr. Taher and his associates enrolled 20 consecutive adults with vitiligo. They used a Wood’s lamp to measure baseline size and pigmentation of the most active lesion. They also took punch biopsies from lesions and nonvitiliginous skin before and after treatment.
The theory behind twice-daily treatment with this topical calcineurin inhibitor is that it increases IL-10 expression in active lesions. The immunosuppressive action would then downregulate the T1 response and T-lymphocyte activity, thereby reducing melanocyte destruction and permitting repigmentation of the skin.
“Participants had ‘fairly impressive’ repigmentation,” Dr. Taher said, suggesting survival of melanocytes within the vitiligo lesions.
There was no significant difference in IL-10 levels between normal skin and vitiligo lesions at baseline. However, there was a significant increase in IL-10 for lesions compared with both pretreatment levels and unaffected skin, Dr. Taher said. “Our results demonstrate that topical tacrolimus upregulates immunosuppressive IL-10.”
The researchers identified 10 lesions above the umbilicus and 10 that were below, Dr. Taher said. “Of those above, four were head and neck, and they had a better response.”
They measured lesions, took photos, and asked participants about adverse events at 2 weeks and at 1, 2, and 3 months. A total of 17 subjects returned for the 3-month follow-up. No adverse events were reported in the study, Dr. Taher said. Most study participants were happy with the treatment and were compliant with the twice-daily regimen.
A meeting attendee asked how the investigators distinguished between improvement from IL-10 and spontaneous improvement over time. “We looked at why Dr. Grimes’ study worked the first time. In cultured keratocytokines, an in vitro increased expression of IL-10 was seen,” Dr. Taher responded.
Another attendee asked about pretreatment with narrow-band UVB. “I think three or four had previous treatment, but we had a 4-month washout period,” Dr. Taher replied.
He concluded that the recent findings “will affect clinical practice in terms of research leading to future cytokine-directed therapies.”