Penetration Pushes Pigmentation in Vitiligo: Calcineurin Inhibitors Under Occlusion
Therapeutic options in vitiligo include photochemotherapy, ultraviolet B (UVB)-therapy, systemic steroids, or, as more recent studies have proposed, vitamin D3-analoga, excimer laser or topical calcineurin inhibitors (1). Meta-analysis of controlled studies has revealed that there is no one therapeutic option that could be considered the gold standard in vitiligo. Therapeutic efficacy depends rather on the type of vitiligo, areas of involvement, and duration of disease (1).
In this issue Hartmann et al. publish their study investigating 30 patients with vitiligo (pp. ?–?). The authors report that treatment of vitiligo with the topical calcineurin inhibitor tacrolimus 0.1% is also effective in longstanding vitiligo. Moreover, not only does tacrolimus 0.1% effectively treat vitiligo of the face and neck, as published previously (81% response), but therapeutic efficacy of tacrolimus 0.1% in vitiligo was also achieved in other skin areas, such as the arms, by using overnight occlusion therapy (80% response) (1). However, and confirming previous studies, acral skin also remained unresponsive to this type of treatment.
Calcineurin inhibitors are believed mainly to inhibit T cell function by specifically blocking calcineurin. Activated calcineurin normally allows nuclear factor of activated T cells-mediated gene transcription to induce the expression of T cell cytokines and many other T-cell-activation-induced proteins. Therefore, suppression of auto-aggressive T cells is considered the main mode of action of calcineurin inhibitors in vitiligo. However, recent work has emphasized that tacrolimus may directly enhance the proliferation of both melanocytes and melanoblasts, and the present study also states that patients with darker skin responded better (2). As occlusive application is thought to regulate penetration of an active compound into the skin, the present study indicates that penetration pushes pigmentation in vitiligo when treated with calcineurin inhibitors. This effect may be mediated both by blocking T cell activation and by direct promotion of pigmentation, which should start at the site of the hair follicles. Thus, skin penetration of calcineurin inhibitors determines therapeutic efficacy in vitiligo.
Treatment of atopic dermatitis with topical application of calcineurin inhibitors has been studied in depth, and is now a well-accepted therapeutic option. Other indications are being investigated, and among them there is good evidence that calcineurin inhibitors are also effective in diseases such as flexural psoriasis, seborrhoeic and contact dermatitis, lichen sclerosus, lichen planus, erosive oral lichen planus, and, last but not least, vitiligo of the face and neck (3–5). One major concern when applying topical calcineurin inhibitors, especially under occlusive treatment, is elevation of blood levels with systemic immune suppression. Importantly, in the present study with limited parts of the body being treated, there was no significant elevation in tacrolimus blood levels. Thus, in conclusion, only occlusive application of tacrolimus may allow effective treatment of vitiligo in some areas that are otherwise unresponsive to this treatment option. Further studies are needed to assess the blood levels of tacrolimus and its long-term effects when larger areas are treated under occlusion.
1. Forschner T, Buchholtz S, Stockfleth E. Current state of vitiligo therapy – evidence-based analysis of the literature. J Dtsch Dermatol Ges 2007; 5: 467–476.
2. Lan CC, Chen GS, Chiou MH, Wu CS, Chang CH, Yu HS. FK506 promotes melanocyte and melanoblast growth and creates a favourable milieu for cell migration via keratinocytes: possible mechanisms of how tacrolimus ointment induces repigmentation in patients with vitiligo. Br J Dermatol 2005; 153: 498–505.
3. Luger T, Paul C. Potential new indications of topical calcineurin inhibitors. Dermatology 2007; 1: 45–54.
4. Day I, Lin AN. Use of pimecrolimus cream in disorders other than atopic dermatitis. J Cutan Med Surg 2008; 12: 17–26.
5. Volz T, Caroli U, Lüdtke H, Bräutigam M, Kohler-Späth H, Röcken M, Biedermann T. Pimecrolimus cream 1% in erosive oral lichen planus – a prospective randomized double-blind vehicle-controlled study. Br J Dermatol 2008 (in press).