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Print version ISSN 0365-0596
On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.86 no.1 Rio de Janeiro Jan./Feb. 2011
Tacrolimus 0,1% ointment in the treatment of vitiligo: a series of cases*
Carla TamlerI; Bruna Duque-EstradaI; Patrícia Azevedo OliveiraII; João Carlos R. AvelleiraIII
IDermatologist member of the Brazilian Society of Dermatology - Preceptress at the Professor Rubem David Azulay Dermatology Institute from the Santa Casa de Misericórdia Hospital of Rio de Janeiro (SCMRJ) - Rio de Janeiro (RJ), Brazil
IIDermatologist member of the Brazilian Society of Dermatology - Post graduate course from the Professor Rubem David Azulay Dermatology Institute from the Santa Casa de Misericórdia Hospital of Rio de Janeiro (SCMRJ) - Rio de Janeiro (RJ), Brazil
IIIPhD from the Federal University of Rio de Janeiro (UFRJ) - Associate Professor from the post graduation course at the Professor Rubem David Azulay Dermatology Institute from the Santa Casa de Misericórdia Hospital of Rio de Janeiro (SCMRJ) and from the post graduation Medical School from the Catholic University of Rio de Janeiro (PUC-RJ) - Rio de Janeiro (RJ), Brazil
Vitiligo is a dermatosis of difficult treatment and significant psychosocial impact. The objective of this study was to evaluate the response to tacrolimus 0,1% ointment for vitiligo treatment. Ten patients took part in the present study: six patients with lesions on the cephalic and cervical regions had more than 75% of repigmentation. As for extremities and trunk results varied from good to excellent in 27% of the cases. The association with other therapeutic options could possibly increase the efficacy of the treatment.
Keywords: Tacrolimus; Treatment outcome; Vitiligo
Vitiligo is characterized by achromatic spots related to the loss of melanocytes in the epidermis and the hair follicle. It happens at any age, affects both sexes and in some regions, affects up to 2% of the population. It influences considerably the quality of life of the patients. None of the therapeutic alternatives is fully satisfactory either because its improvement is unpredictable and the treatment is long or because of the side effects and operational difficulty of appplication of the medication. For these reasons we carried out an open study, not controlled, assessing the response to tacrolimus 0,1%, 2 b.i.d., in lesions on the face, neck and limbs. Twelve patients, phototypes III-VI and with lesions simultaneously on the head and extremities were treated for 120 days, with clinical evaluation every 15 days. For the trunk and limbs it was used, as ipsilateral control, the lesions on the right side which did not have the ointement applied on them (Picture 1A). Exclusion criteria were: report of spontaneous repigmentation or treatment in the last 6 months. Therapeutic response was observed according to the evaluation of both doctor and patient. The medical evaluation was based on standardized digital photos and it was considered a score of 0% of repigmentation at the beginning of the treatment and classified, at the end of the study, according to the levels of repigmentation as follows: none (0%), regular repigmentation (1-25%), moderate (26-50%), good (51-75%) and excellent (>75%). All patients signed a consent form and the study was approved by the CEP (Ethic Commission of Research) of SCMRJ. Ten patients took part in the study (4 women and 6 men) and two were excluded for noncompliance. In the final evaluation (16th week), the best answer were observed in patients with phototypes varying from IV to VI. Six patients with lesions on the cephalic region showed excellent response / more than 75% of repigmentation (Picture 1B and 1C). As for extremities and chest, results varied from good to excellent in 27% of the cases (Table 1). According to patients evaluation the level of repigmentation of 50 % was considered cosmetically satisfactory. The only adverse effect observed in 2 patients was mild burning that regressed spontaneously. Among the established therapies phototherapy (UVB-NB) and photochemotherapy (PUVA) have limited use for reasons such as adverse reactions1, difficult access to the sources of light and time spent during treatment. Recent study evaluated the effectiveness and tolerability of UVB-NB, pimecrolimus and topical tracolimus and the improvement was better using pimecrolimus and tracolimus for facial lesions and UVB-NB for the cervical2 area. Regarding topical corticosteroids a double-blind randomized study compared tacrolimus 0,1% to ointment of clobetasol 0,05%, with repigmentation of 49,3% related to clobetasol and of 41,3% related to tacrolimus. Despite the best answer, the side effects associated with corticosteroids, mainly in the acrofacial lesions, are relevant3. Analogues of Vitamin D3 presented better results when combined with phototherapy.4,5 Surgical techniques and excimer laser are limited by variables such as activity/extension of the disease, Köebner phenomenon and high cost.6 Grimes et al. Shwed showed the role of tracolimus in the repigmentation of lesions2 in 2002. Tracolimus is an immunosuppressant macrolide derived from the fungus Streptomyces tsukubaesnis that acts through the inhibition of phosphorylation depending of calcineurin, which leads to the inhibition of the production of various inflammatory cytokines derived from T lymphocytes. The hypothesis of increased carcinogenesis associated with the combination of tacrolimus and phototherapy so far has not been proven in humans or animals.4-6 Furthermore, the occurence of skin cancer in patients with vitiligo is unsual suggesting an innate resistance to the development of cutaneous malignancy on the skin affected by the dermatosis. 7 Grimes et al. show the increased expression of cytokines such as interferon γ (IFN-γ), tumor necrosis factor· (TNF-α) and interleukin 10 (IL-10) in viltiligo lesions and adjacencies. The decreased expression of TNF-α in the same areas after the treatment with tacrolimus (FK506), suggests that the suppression of these molecules would be involved in the repigmentation process.8 It is probable that the inhibitors of calcineurin beyond blocking the production of inflammatory cytokines by T lymphocyte, interfere in melanogenesis. In 2005, Lan et al. observed the growth and migration of melanocytes and melanoblasts in vitro under the action of tacrolimus. 9 Kang et al confirmed, in culture of melanocytes, increase of biosynthesis of melanin due to a greater activity of tyrosinase apart from the migration of melanocytes. 10 In the present study, it was observed the effectiveness of topical tracolimus in the repigmentation of lesions in the cephalic and cervical regions. The possibility of synergy with other therapies will probably increase the effectiveness of the treatments available for vitiligo.
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7. Schallreuter KU, Tobin DJ, Panske A. Decreased photodamage and low incidence of non-melanoma skin cancer in 136 sun-exposed caucasian patients with vitiligo. Dermatology. 2002;204:194-201. [ Links ]
8. Grimes PE, Morris R, Avaniss-Aghajani E, Soriano T, Meraz M, Metzger A. Topical tacrolimus therapy for vitiligo: Therapeutic responses and skin Messenger RNA expression of proinflmmatory citokines. J Am Acad Dermatol. 2004;51:52-61. [ Links ]
9. 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. [ Links ]
10. Kang HY, Choi YM. FK506 increases pigmentation and migration of human melanocytes. Br J Dermatol. 2006;155:1037-40. [ Links ]
Received on 27.10.2009. * Work carried out at the Vitiligo Phototherapy ambulatory from the Professor Rubem David Azulay Dermatology Institute from the Santa Casa de Misericórdia Hospital of Rio de Janeiro - (SCMRJ) - Rio de Janeiro (RJ), Brazil.
Approved by the Advisory Board and accepted for publication on 18.04.2010.
Conflict of interest: None
Financial funding: None
Received on 27.10.2009.
* Work carried out at the Vitiligo Phototherapy ambulatory from the Professor Rubem David Azulay Dermatology Institute from the Santa Casa de Misericórdia Hospital of Rio de Janeiro - (SCMRJ) - Rio de Janeiro (RJ), Brazil.