Topical tacrolimus therapy for vitiligo: therapeutic responses and skin messenger RNA expression of proinflammatory cytokines

Abstract

Background Previous studies have documented humoral and cell-mediated immunologic defects in patients with vitiligo. Objective This 24-week study assessed the efficacy and safety of tacrolimus 0.1% ointment in patients with generalized vitiligo as well as the pretreatment and post-treatment expression of cytokines in the depigmented and normal skin of patients compared with controls. Methods Twenty-three patients were enrolled in this investigation, and 19 patients completed the study; 8 were male and 11 were female. Fifteen age-, race-, and sex-matched control subjects were also included. Patients were treated with tacrolimus 0.1% ointment applied twice daily. Repeat evaluations were performed at 4, 8, 12, 16, 20, and 24 weeks. Three-millimeter punch biopsy specimens were taken from the depigmented, non-sun-exposed skin and adjacent normal skin of patients at baseline and 24 weeks, and from normal, non-sun-exposed skin of controls. Cellular messenger RNA expression for interleukin 2 (IL-2), IL-4, IL-10, tumor necrosis factor alfa (TFN-α), and interferon gamma (IFN-γ) were determined by real-time quantitative polymerase chain reaction. Results At 24 weeks, 17 of 19 patients (89%) achieved varying levels of repigmentation. There was a statistically significant decrease in overall disease severity scores at 24 weeks. Thirteen patients (68%) had greater than 75% repigmentation of face and/or neck lesions. Signs and symptoms of irritation were minimal. At baseline, compared with healthy controls, vitiligo patients demonstrated a statistically significant increase in the expression of IFN-γ in involved and adjacent uninvolved skin ( P = .05 and P = .02, respectively); significantly increased TNF-α expression in involved and uninvolved skin ( P = .01 and P = 0.02, respectively); and significantly increased IL-10 expression in involved and uninvolved skin ( P = .01 and P = .04, respectively). Posttreatment, TNF-α expression decreased in the depigmented and adjacent uninvolved skin ( P < .001). There was no statistically significant change in IL-10 or IFN-γ posttreatment. These data suggest that tacrolimus 0.1% ointment is a safe and effective therapy for patients with vitiligo. It further suggests that an imbalance in local cytokine expression may play a role in the pathogenesis of vitiligo. Suppression of TNF-α after topical tacrolimus application may be associated with repigmentation of vitiligo.