In All Patients With Vitiligo, What is the Efficacy of Applying Tacrolimus or Pimecrolimus vs. Placebo or an Active Treatment in Terms of Condition Progression, Area Reduction and Quality of Life Score?
The calcineurin inhibitors have found use in a variety of inflammatory skin diseases and have been tried in vitiligo.
Four papers met the criteria for inclusion as used for topical corticosteroids. Studies on children will be considered separately from those on adults.
Coskun and colleagues, in a left-vs.-right comparison over an 8-week period in 10 adults, compared topical pimecrolimus with topical clobetasol. They found topical pimecrolimus resulted in 50-100% repigmentation in eight of 10 patients, most noticeable for lesions on the trunk or extremities, compared with an equivalent degree of repigmentation in seven of 10 patients treated with clobetasol. No skin atrophy was noted but burning was a side-effect with pimecrolimus. The number of subjects in this study is small, making a reliable conclusion difficult.
In an open proof-of-concept study of 26 children aged over 6years and adults with generalized symmetrical forms of vitiligo, treated for head and neck lesions with topical 1% pimecrolimus twice daily, total repigmentation of a target lesion was found in 50% of patients after 6months of therapy.
Twenty children treated over 8weeks with either topical clobetasol or tacrolimus were shown to have repigmentation that amounted to 41% with clobetasol and 49% with tacrolimus. Lesions on the face and thorax responded better than those on the abdomen or legs: lesions on hands did not respond. Skin atrophy was noted in five of the 20 treated with the steroid, while two of 20 who received tacrolimus noted burning.
Comparisons have been made of topical tacrolimus alone with tacrolimus and Excimer UV radiation. In one study of 14 patients aged over 12years, 23 vitiligo lesions received a combination of tacrolimus ointment twice daily and Excimer UV twice weekly for 12weeks and were compared with 20 lesions that received Excimer UV alone for 12weeks. For the combination of topical tacrolimus and Excimer UV, 16 of 23 had 75% or more repigmentation compared with four of 20 lesions treated using the Excimer alone (P<0·001). In UV-exposed areas, i.e. face, neck, trunk or limbs, 75% or more repigmentation was seen in 10 of 13 using the combination treatment compared with none of 13 lesions that received the Excimer alone (P<0·001). Side-effects included stinging in the tacrolimus group, moderate erythema at least once in all patients, and bullous lesions in four of 43 lesions. Another study that included only 20 lesions in eight adults, comparing Excimer plus topical tacrolimus vs. Excimer plus placebo, found repigmentation to be more in the tacrolimus/Excimer group.
Further studies on the efficacy of topical calcineurin inhibitors are required. The long-term side-effects of the calcineurin inhibitor drugs are unknown and this should be borne in mind if prolonged treatment (e.g. longer than 12 months) is proposed.
Evidence to Recommendations
In adults with generalized symmetrical types of vitiligo, in a small study, topical pimecrolimus for 8weeks induced 50-100% repigmentation (a similar degree to that seen with topical clobetasol) for lesions on the trunk or extremities. Stinging was a side-effect. In children with generalized symmetrical vitiligo, topical tacrolimus used over an 8-week period induced nearly 50% repigmentation of vitiligo lesions (a similar degree to that seen with topical clobetasol) for lesions on the face or thorax but not the hands. Stinging was a side-effect. The combination of topical tacrolimus with Excimer UV radiation appeared to enhance the degree of repigmentation over that for Excimer alone, for UV-sensitive sites but not for areas over bony prominences.
In adults with symmetrical types of vitiligo, topical pimecrolimus should be considered as an alternative to the use of a topical steroid, based on evidence from one study. The side-effect profile of topical pimecrolimus is better than that of a highly potent topical steroid.
Grade of recommendation C Level of evidence 2+
In children with vitiligo, topical pimecrolimus or tacrolimus should be considered as alternatives to the use of a highly potent topical steroid in view of their better short-term safety profile.
Grade of recommendation B Level of evidence 1+
Further research is needed to clarify the roles of tacrolimus and pimecrolimus in adults and children with vitiligo. A head-to-head study of tacrolimus vs. pimecrolimus is suggested.
The British Journal of Dermatology. 2008;159(5):1051-1076. © 2008 Blackwell Publishing
Cite this: Guideline for the Diagnosis and Management of Vitiligo - Medscape - Nov 01, 2008.