Topical tacrolimus therapy for vitiligo

Therapeutic responses and skin messenger RNA expression of proinflammatory cytokines

Grimes, Pearl E. MD
Morris, Robert MD
Avaniss-Aghajani, Erik PhD
Soriano, Teresa MD
Meraz, Maria BS
Metzger, Allan MD

^aVitiligo and Pigmentation Institute of Southern California, David Geffen School of Medicine, University of California, Los Angeles, California
^bDivision of Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California
^cDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California

Reprint requests: Pearl E. Grimes, MD, 321 N Larchmont Blvd, Suite 609, Los Angeles, CA 90004. E-mail: [email protected].

This study was funded by a research grant from Fujisawa Healthcare.

Conflicts of interest: None identified.

The data were presented as a poster exhibit and oral presentation for the Society of Investigative Dermatology, Los Angeles, California, May 18, 2002.

Accepted for publication December 6, 2003

Journal of the American Academy of Dermatology 51(1):p 52-61, July 2004.

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.