Tacrolimus Helpful for Vitiligo Treatment CME

News Author: Laurie Barclay, MD
CME Author: Bernard M. Sklar, MD, MS
Authors and Disclosures

To earn CME credit, read the news brief, the paragraphs that follow, and answer the questions below.
Release Date: May 28, 2003; Valid for credit through May 28, 2004

This activity has expired.

CME in this activity indicates that it was developed according to ACCME guidelines and was certified for credit by an accredited CME provider. Medscape cannot attest to the timeliness of expired CME activities.

May 28, 2003 — Tacrolimus was about as effective in the treatment of vitiligo as clobetasol and may be the preferred first-line treatment for sensitive skin areas, according to the results of a randomized, double-blind trial published in the May issue of the Archives of Dermatology.

"We hypothesized that given its immunomodulatory properties and safer profile than corticosteroids, tacrolimus ointment might carry an improved benefit-toxic effect ratio and provide a new therapeutic alternative to topical corticosteroids in children with vitiligo," write Veronica Lepe, MD, and colleagues from the Universidad Autónoma de San Luis Potosi in Mexico. "We know from experience that clobetasol is the most effective topical corticoid therapy for vitiligo because it very often produces pigmentation where other topical steroids have failed. For that reason we selected clobetasol propionate rather than other midpotency steroids for this trial."

The 20 children enrolled in this study had vitiligo untreated with any topical or systemic therapy for two months before study entry. In each child, two symmetrical lesions of about the same size and evolution time were selected; one was treated with topical 0.1% tacrolimus and the other with 0.05% clobetasol propionate for two months.

Of the 20 patients, 18 (90%) experienced some repigmentation seen on digital morphometry, 49.3% repigmentation for clobetasol and 41.3% for tacrolimus. Adverse events were atrophy in three lesions and telangiectasias in two lesions treated with clobetasol, and a burning sensation in two lesions treated with tacrolimus.

"Tacrolimus proved almost as effective as clobetasol propionate to restore skin color in lesions of vitiligo in children," the authors write. "Because it does not produce atrophy or other adverse effects, tacrolimus may be very useful for younger patients and for sensitive areas of the skin such as eyelids, and it should be considered in other skin disorders currently treated with topical steroids for prolonged periods.... It would be interesting to see whether longer periods of therapy, combinations of tacrolimus with other topical agents, or increased concentrations of tacrolimus could produce better results than those obtained in this series and whether the negative results obtained in acral areas could be overturned with any of these approaches."

In an accompanying editorial, Heidi Plettenberg, MD, Till Assmann, MD, and Thomas Ruzicka, MD, from Heinrich-Heine University in Düsseldorf, Germany, review phototherapy and other recent treatment options for vitiligo. They point out that tacrolimus is usually most effective in head and neck lesions, and they suggest that the low response rate in this study may have been caused by the limited duration of therapy.

"In conclusion, the data...indicate that topical tacrolimus may represent a new effective treatment option of childhood vitiligo, with convenient use and limited adverse effects," they write. "The effectiveness of this immunomodulating drug provides new evidence for the autoimmune hypothesis of melanocyte destruction in vitiligo."

Dr Ruzicka has served as a paid consultant to Fujisawa Healthcare Inc. in Deerfield, Illinois, a manufacturer of tacrolimus.

Arch Dermatol. 2003;139:581-585, 651-654

Learning Objectives

Upon completion of this activity, participants will be able to:

· Discuss the prevalence, possible etiology, and treatment of vitiligo in children.

· Describe the results of a study comparing the effect of tacrolimus and clobetasol on vitiligo lesions in children.

Clinical Context

According to the editorial accompanying this paper, vitiligo is an acquired pigment disorder, clinically characterized by the development of white macules caused by damage to melanocytes in the affected skin. The prevalence of the disease in the U.S. and Europe has been estimated at around 1%. Half of all patients develop the disease in childhood and adolescence before age 20 years.

Generalized vitiligo is the most common clinical presentation and typically involves extensor surfaces of joints and bony prominences, periorificial areas of the face, neck, and anogenital region, and acral areas of the extremities. Although the disease is asymptomatic and does not adversely affect mortality and physical morbidity, depigmentation in visible areas leads to severe cosmetic disfigurement and may be a source of considerable psychological distress, particularly in persons with a dark complexion.

Most patients develop the disease during puberty, when cosmetic problems cause severe psychological and social conflicts, but even when the disease begins in early childhood, it can be associated with significant psychological trauma that may have lasting effects on the person's self-esteem. Therefore, there is a strong need for therapeutic repigmentation strategies not only for the treatment of adults but also of children.

According to the authors of the current study, "abnormal humoral and cell-mediated immune mechanisms are probably the most commonly involved aspect of pathogenesis in vitiligo." The relative success of clinical use of topical corticosteroids supports this theory.

Tacrolimus is an immunosuppressor macrolide lactone capable of inhibiting the activation and maturation of T cells. Systemic tacrolimus has been used in a number of applications, particularly to avoid graft rejection. Topical tacrolimus is a safe and effective treatment for inflammatory skin diseases, particularly atopic dermatitis, psoriasis, pyoderma gangrenosum, alopecia areata, and other illnesses with immunologic disarrangement. Pruritus, burning sensation, and erythema are the adverse reactions observed from topically applied tacrolimus.

The authors hypothesized that, given its immunomodulatory properties and safer profile than corticosteroids, tacrolimus ointment might carry an improved benefit-toxic effect ratio and provide a new therapeutic alternative to topical corticosteroids in children with vitiligo. Clobetasol was chosen to compare with tacrolimus because clobetasol is the most effective topical corticosteroid therapy for vitiligo.

Study Highlights

· The objective of the study was to assess the safety and efficacy of topical 0.1% tacrolimus vs. 0.05% clobetasol propionate in the treatment of vitiligo in children.

· In a randomized, double-blind trial, two symmetrical lesions of about the same size and evolution time were selected from 20 children with vitiligo. The lesions had not received any topical or systemic therapy for 2 months prior to inclusion.

· One of the lesions on each child was treated with topical tacrolimus for 2 months while the other lesion on the same child was treated with clobetasol for 2 months.

· The grade of repigmentation was evaluated by color slides at baseline and again at every 2-week visit. The slides were analyzed by 2 clinicians unrelated to the study and by a morphometric digitalized computer program. Characteristics of pigment, time of response, symptoms, telangiectasias, and atrophy were evaluated every 2 weeks.

· 18 (90%) of the 20 patients experienced some repigmentation. The mean percentage of repigmentation was 49.3% for clobetasol and 41.3% for tacrolimus. Lesions in 3 patients using clobetasol showed atrophy, and 2 lesions developed telangiectasias; tacrolimus caused a burning sensation in 2 lesions.

Pearls for Practice

· Tacrolimus proved almost as effective as clobetasol propionate in restoring skin color in lesions of vitiligo in children.

· Because tacrolimus does not produce atrophy or other adverse effects, it may be useful for younger patients and for sensitive areas of the skin such as eyelids; it should be considered in other skin disorders currently treated with topical steroids for prolonged periods.