Vitiligo medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Alonso Alvarado, M.D. [2]

## Overview

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Potent topical corticosteroids (mometasone) and topical calcineurin inhibitors are first-line therapy to achieve repigmentation of vitiligo lesions. Phototherapy has been proven effective for the treatment of generalized vitiligo. Combined treatment with both topical calcineurin inhibitors plus phototherapy have proven more effective in achieving repigmentation in a shorter period of time than single treatments.

## Medical Therapy

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### Topical corticosteroids Adapted from the 2012 Guidelines for the management of vitiligo: the European Dermatology Forum consensus[1]

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* Topical corticosteroids along, with topical calcineurin inhibitors (such as tacrolimus and pimecrolimus), are considered the first line treatment for limited lesions.
* Topical corticosteroids have shown repigmentation rates of up to 75%.
* Best results have been observed in areas exposed to sunlight (neck and face), dark skin and new lesions.
* Since no difference has been observed between the efficacy of potent (mometasone) versus the even more potent topical corticosteroid (clobetasol), then potent corticosteroids should be first line therapy.
* Two schemes are recommended by the European Dermatology Forum consensus for the treatment of facial and extrafacial lesions:

* Discontinuous scheme (preferred scheme): Daily application of a potent topical corticosteroid during 15 days a month for a total of 6 months.
* Continuous scheme: Daily application of a potent topical corticosteroid during 3 months.
* Photographs should be taken to evaluate the response to the treatment.

* Both schemes are recommended for children and adults.
* If large areas are affected and risk of systemic absorption is a concern (specially in children), then mometasone furoate or methylprednisolone aceponate are the preferred options as this drugs present less systemic side effects.

### Topical calcineurin inhibitors Adapted from the 2012 Guidelines for the management of vitiligo: the European Dermatology Forum consensus[1]

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* Topical calcineurin inhibitors (TCI) are recommended for patients in which prolonged use of topical corticosteroids is contraindicated.
* TCI inhibit the destruction of melanocytes by the immune system and enhance melanocyte migration and differentiation in the lesion site.
* TCIs have demonstrated efficacy in the treatment of vitiligo lesions involving the face and neck.
* Data from randomized clinical trials (RCT) shows similar efficacy between tacrolimus, pimecrolimus and topical corticosteroids (clobetasol).
* One open label RCT demonstrated that tacrolimus could be effective for the treatment of segmental vitiligo.
* No available data about the most effective administration scheme is available. It has been proven that twice-daily applications are more effective than daily applications.
* Data regarding the optimal treatment period or regarding the effectiveness of intermittent long-term treatment is not available.
* TCIs are associated with fewer side-effects than potent topical corticosteroids.
* Recommendations of the European Dermatology Forum consensus for the treatment of vitiligo are the following:

* TCI treatment is recommended for adults and children with lesions involving the face and neck and other selected areas.
* Twice daily applications are administered over a period of 6 months along with moderate daily sunlight exposure.
* Treatment should be prolonged up to a period of 1 year if proven efficacious during the first 6 months.

### Phototherapy

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#### Photochemotherapy Adapted from the 2012 Guidelines for the management of vitiligo: the European Dermatology Forum consensus[1]

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* PUVA: Use of long-wave UVA radiation in combination with psoralens (administered orally or topically).

* Partial repigmentation can be achieved in 70% to 80%, but complete repigmentation is only achieved in 20% of the patients.
* The rate of relapse is as high as 75% over a 1 to 2 year period.
* Recommended psoralen oral dosages: 8-methoxypsoralen 0.6-0.8 mg/kg, 5-methoxypsoralen 1.2-1.8 mg/kg or trimethylpsoralen 0.6 mg/kg. Psoralen should be administered 3 hours previous to exposure. Treatment should be administered for a period of 6 months, if the response is positive the treatment should be prolonged to 1 to 2 years to achieve maximum repigmentation.
* Recommended regimen for topical PUVA: 8-methoxypsoralen 0.001% 30 minutes before exposure. Fewer applications and therefore fewer UVA cumulative concentrations needed are the main advantage of this regimen.

* KUVA: Use of long-wave UVA radiation in combination with khellin.

* KUVA has less phototoxicity than UVA and produces less darkening to the skin. Khellin has less mutagenic potential than psoralens.
* Topical recommended regimen: Use a concentration of 3% to 5% 2 hours before exposure.
* Data comparing the efficacy of KUVA versus PUVA is not available yet.
* The dosage of oral KUVA is 100 mg 2 hours before exposure, but this form of administration has been abandoned because of the high rate of liver toxicity (30%).

#### Narrowband UVB Adapted from the 2012 Guidelines for the management of vitiligo: the European Dermatology Forum consensus[1]

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* RCT have demonstrated the efficacy of Narrowband UVB therapy, however more studies are needed to assess it's efficacy versus PUVA.
* The recommended dosage for Narrowband UVB therapy is 150 to 250 mJ/m2 administered two or three times per week.
* Treatment should be administered until the repigmentation ceases.
* Mild erythema after the administration of Narrowband UVB radiation is considered a good sign. Erythema usually appears within the first the first 12 to 24 hours after the administration of the therapy and usually disappears 24 hours after 24 hours.

#### European Dermatology Forum consensus recommendations for the use of phototherapy Adapted from the 2012 Guidelines for the management of vitiligo: the European Dermatology Forum consensus[1]

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* PUVA admminitered orally is the second-line treatment for adults with genelalized disease.
* To achieve total repigmentation, 1 to 2 year of continuous PUVA may be necessary to achieve total repigmentation.
* There are not enough evidence to support the use of topical KUVA as RCT haven't been performed.
* Narrowband UVB] treatment is recommended for patients with nonsegmental generalized vitiligo.
* No consensus have been made about the treatment time. Usually the treatment is discontinued if no repigmentation is achieved within the first 3 months or if less than 25% repigmentation is achieved before the first 6 months. If repigmentation is observed, the treatment is generally continued until cessation of repigmentation is observed or to a maximum period of 12 to 24 months.

#### Consequences of phototherapy

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* The risk of skin cancer is increased in patients who receive PUVA.

### Combination therapies Adapted from the 2012 Guidelines for the management of vitiligo: the European Dermatology Forum consensus[1]

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* The use of topical calcineurin inhibitors associated with phototherapy has shown better results than the use of each treatment alone. The long-term consequences of this combination with regard to possible carcinogenicity has not been studied.

## References

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1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Taieb A, Alomar A, Böhm M, Dell'anna ML, De Pase A, Eleftheriadou V; et al. (2013). "Guidelines for the management of vitiligo: the European Dermatology Forum consensus". Br J Dermatol. 168 (1): 5–19. doi:10.1111/j.1365-2133.2012.11197.x. PMID 22860621.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

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