Use of Tacrolimus Ointment in Vitiligo Alone or in Combination Therapy

S. Berti, MD; G. Buggiani, MD; T. Lotti, MD

Disclosures

Skin Therapy Letter. 2009;19(4) 

In This Article

Abstract and Introduction

Abstract

Current treatments for vitiligo are largely unsatisfactory. Topical corticosteroids and phototherapy (narrow-band UVB and psoralen+UVA) are the most prescribed, however, these therapies are often not effective and have important side-effect, especially when used for a long time. Many studies have reported the efficacy and safety of tacrolimus ointment in adults and children with vitiligo, particularly when located on the head and neck. Successful treatment is possible when it is combined with other therapies, such as narrow-band UVB, microphototherapy, helium-neon laser, or narrow-band excimer laser.

Introduction

Vitiligo, an acquired pigmentary skin disorder affecting 1% of the world’s population, is characterized by depigmented macules that correspond histologically with reduced or absent cutaneous melanocytes.[1] Although the mechanism of melanocyte dysfunction and disappearance is still unclear, there are 2 major theories regarding its pathogenesis: the autoimmune theory and the autotoxicity theory.[2] Current treatments, e.g., topical corticosteroids, narrow-band UVB (NBUVB), and psoralen+UVA (PUVA), are the most prescribed,[3] but are not often effective, and corticosteroids aplied to the face may lead to cutaneous atrophy, telangiectasia, and ocular complications. NBUVB treatment requires expensive equipment and trained personnel, and PUVA has been associated with a risk of carcinogenesis.[3] Phototherapy and corticosteroids have limited effectiveness, particularly on the acral regions.[4]

Immunomodulators, such as tacrolimus ointment 0.1% and 0.03% (Protopic®, Astellas), and pimecrolimus cream 1% (Elidel®, Novartis) are approved for treating atopic dermatitis in adult patients and pediatric patients over 2 years of age.[2] Tacrolimus can be used as an alternative to topical steroids in many other forms of dermatitis, such as vitiligo. This ointment does not cause the atrophy, telangiectasia, or adverse ocular effects of topical corticosteroids, which has limited application to the face and intertriginous areas.[1]

Tacrolimus acts on T cells and mast cells, inhibiting T cell activation and the production of proinflammatory cytokines, such as Tumor Necrosis Factor (TNF), whose levels are higher in vitiligo lesional skin.[5] Moreover, it prevents the release of proinflammatory mediators in mast cells by degranulation.[1] Recently, the successful treatment of vitiligo with tacrolimus has been reported (See Table 1 ).

Xu et al.[1] studied 30 vitiligo patients who were treated with tacrolimus ointment for 4 months or more. Of these, 83.3% patients showed some repigmentation at the end of 4 months. In particular, 1 patient achieved excellent (100%) repigmentation at the end of 14 weeks, and another 2 patients exhibited 100% repigmentation at the end of 16 weeks. Of these 25 patients, repigmentation was graded as complete in 20%, moderate in 20%, mild in 23.3%, and minimal in 20%. Of the patients with segmental vitiligo of the head and neck, 80% showed the some response, but there was no statistical significance between segmental and vulgaris vitiligo. Patients who had vitiligo for more than 5 years also responded well. Repigmentation is notoriously difficult to achieve. The mean percentage of repigmentation on the head and neck was greater than that seen on the trunk and extremities. The only reported side-effect was initial burning on application in 4 patients. The study found that tacrolimus was a safe and effective therapy for vitiligo, especially when it involved the head and neck.

In 2008, Choi et al.[2] studied 79 patients; 52 were treated with tacrolimus and 27 with topical corticosteroids. Topical immunomodulators were found to be as effective as topical steroids and patient response was faster than that once obtained by topical steroids. The patients studied were then divided in 3 groups according to the location of vitiligo lesions: 59 had lesions on the face, 53 on the hands, and 23 on the feet. After treatment, 38 showed repigmentation on the face, 31 on the hands, and 9 on the feet. The investigators could not find any statistically significant differences in the ratio of lesions, which showed response among these 3 groups. They further divided their study into 2 groups: long-duration (>12 months) and short-duration (<12 months). The short-duration group showed a higher rate of response that was statistically significant. There was no statistical difference between the group of younger (i.e., <18 years of age) and older (i.e., >18 years of age) patients. The faster response of topical immunomodulators may be related to their effects on melanocytes, i.e., the proliferation of melanocytes is enhanced by a tacrolimustreated keratinocyte supernatant, which is rich with stem cell factor and matrix metallopeptidase-9.2 These results coincide with those of Lepe et al.[7] who, in a study of 20 patients, documented that clobetasol and tacrolimus showed more than 75% repigmentation in 5 patients. There were no statistically significant differences between these 2 treatments (p>0.05).

In a placebo-controlled 12-month prospective study of 31 vitiligo patients, Hartmann et al.[4] documented the safety and efficacy of tacrolimus, even in those with disease of long-standing duration and in those who received long-term treatment. Tacrolimus may significantly improve the quality of life of affected patients. In the region beyond the face and neck, additional occlusion with polyurethane foil or hydrocolloid dressing may significantly enhance the therapeutic results and may shorten the time until the start of repigmentation. When tacrolimus was applied occlusively, repigmentation was documented in 81% of patients with facial lesions, and in 80% of patients with lesions on the extremities.

Many studies suggest the associated use of tacrolimus with other therapeutic options to improve the rate of repigmentation.[8,9,10] Lotti et al.[8] studied 458 patients with vitiligo that affected less than 10% of their skin surface. A 311nm narrow-band microphototherapy (Bio Skin®, Cropper Medical) was given alone or in combination with topical treatment, (i.e., tacrolimus, pimecrolimus, betamethasone dipropionate 0.05%, calcipotriol, or phenylalanine cream). The investigators reported that targeted combination therapies in vitiligo were remarkably more effective than a single treatment. Fai et al.[9] studied 110 patients with chronic and refractory vitiligo in a period of 30 months, and suggested that the combination of topical tacrolimus with NBUVB phototherapy as an alternative approach that could be highly effective for the treatment of refractory vitiligo located on the face, trunk, and limbs. However, longterm data and randomized controlled trials on a large number of patients are required.

The association of tacrolimus with NBUVB excimer laser has been reported to improve the repigmentation rate, but it is associated with the possibility of unexpected burns.[10] Recently, an association between helium-neon laser and topical tacrolimus has been proposed to be effective without infringing on the issue of additional photocarcinogenic risk. Since the underlying repigmentation mechanisms of these 2 modalities are different, it is reasonable to propose that combining them may produce better clinical results.[11] It is important to remember that NBUVB, microphototherapy, UVB narrow-band excimer laser, and helium-neon laser still have the potential to produce skin cancer. In fact they are effective for treating vitiligo, especially when combined with tacrolimus ointment. Based on the evidence, these treatment options appear to be safe and well tolerated, even though they may have carcinogenic potential, which is extremely important for children affected by vitiligo.

Silverberg et al.[12] reported that the use of tacrolimus ointment is an effective alternative treatment for vitiligo in children, particularly involving head and neck areas. Kanwar et al. studied 25 Asian children with vitiligo (i.e., 54.5% had vitiligo vulgaris, 40.9% had focal vitiligo, and 4.5% had segmental vitiligo). In this study, application with topical 0.03% tacrolimus applied twice daily for 12 weeks was shown to be an effective and well-tolerated treatment. Response was graded as complete (i.e., >75% repigmentation) in 57.9% of the patients, moderate (i.e., 50%-75% repigmentation) in 26.3%, mild (i.e., <50% repigmentation) in 15.7%, and 3 patients had no response. Side-effects, such as pruritus and burn, which was noted in only 3 patients, were minimal.[13]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....