Guidelines for the Management of Vitiligo

The European Dermatology Forum Consensus

A. Taieb; A. Alomar; M. Böhm; M.L. Dell'Anna; A. De Pase; V. Eleftheriadou; K. Ezzedine; Y. Gauthier; D.J. Gawkrodger; T. Jouary; G. Leone; S. Moretti; L. Nieuweboer-Krobotova; M.J. Olsson; D. Parsad; T. Passeron; A. Tanew; W. van der Veen; N. van Geel; M. Whitton; A. Wolkerstorfer; M. Picardo


The British Journal of Dermatology. 2013;168(1):5-19. 

In This Article



Photochemotherapy with psoralen plus UVA radiation (PUVA) combines the use of psoralens with long-wave (320–340 nm) UVA radiation. Photochemotherapy with khellin plus UVA radiation (KUVA) combines the use of khellin with long-wave (320–340 nm) UVA radiation. Psoralens can be given orally or topically (solutions, creams or bath) followed by exposure to UVA. PUVA-induced stimulation of melanogenesis involves the photoconjugation of psoralens to DNA leading to proliferation of melanocytes, increased synthesis of tyrosinase, formation and melanization of melanosomes, and increased transfer of melanosomes to keratinocytes.[31–33]

Narrowband Ultraviolet B and Targeted Phototherapies

Narrowband UVB radiation (NB-UVB, 311 nm) currently represents the phototherapy of choice for active and/or widespread vitiligo. Side-effects are less frequent than in PUVA therapy and efficacy is at least equivalent.[34,35] Targeted phototherapy devices (excimer laser or lamp) deliver light in the UVB range (peak at 308 nm) and are particularly suitable for treating localized disease.[36]


Photochemotherapies. Repigmentation is noted in 70–80% of patients with PUVA, but complete repigmentation is obtained in only 20% of patients. Relapse can occur in 75% of patients after 1 or 2 years. It is not recommended in children aged under 10–12 years because of the risk of retinal toxicity. For oral PUVA, 8-methoxypsoralen (8-MOP; 0·6–0·8 mg kg−1), 5-methoxypsoralen (5-MOP; 1·2–1·8 mg kg−1) or trimethylpsoralen (0·6 mg kg−1) is given orally 1–3 h before exposure to UVA. Patients should be motivated to continue PUVA therapy for at least 6 months before being considered nonresponsive, and 12–24 months of continuous therapy may be necessary to acquire maximal repigmentation. Darker skin types show maximal responses to PUVA and maximal repigmentation occurs in patients achieving erythema grade 2.[34,37,38]

For topical PUVA, a thin coat of 8-MOP cream or ointment at very low concentration (0·001%) should be applied 30 min before UVA exposure, with possible further concentration increments. The advantage of topical therapy is the need for fewer treatments and considerably smaller cumulative UVA doses, as well as lower plasma levels and consequently less systemic and ocular phototoxicity.[39] The main disadvantages are severe blistering reactions, perilesional hyperpigmentation and lack of effectiveness in limiting the progression of actively spreading vitiligo.

Another photochemotherapy regimen, KUVA, consists of khellin as the photosensitizer, a furanochrome extracted of the plant Amni visnaga (5,8-dimethoxy-2 methyl-4,5-furo-6,7 chromone) and UVA.[40,41] KUVA's lack of phototoxicity makes it safe for use as a home treatment or treatment with natural sunlight, even in a daily regimen. It is also less mutagenic than psoralens and it promotes less darkening of normal skin. Khellin is given orally at 100 mg 2 h before treatment. The efficacy rate of this treatment can be compared with PUVA, but is limited because approximately 30% of patients present liver toxicity (cytolysis). Khellin can also be topically applied in a moisturizing cream or carbopol gel at a concentration of 3–5%. Systemic KUVA has nowadays been largely abandoned. Topical 'KUVA–sun' is still sometimes used in sunny countries; however, its efficacy in comparison with oral PUVA or other therapeutic modalities has not been established.

Narrowband Ultraviolet B Total Body and Targeted Therapies. Narrowband UVB is easy to perform but a proper dosimetry is mandatory to achieve optimal treatment results. Patients with vitiligo have traditionally been regarded as skin type I and consequently were treated with very low initial NB-UVB doses (150–250 mJ cm−2). However, minimal erythemal dose (MED) values in vitiligo skin are on average only 35% (95% confidence interval 31–39%) lower than in normal skin of the same individual, suggesting photoadaptation.[42–46] Treatment is usually given twice or three times weekly and is continued as long as there is ongoing repigmentation. The extent and the disease activity at onset of treatment do not seem to affect the likelihood of repigmentation.

Narrowband UVB appears to be more effective than other phototherapies. A randomized, double-blind trial confirmed the higher efficacy of NB-UVB vs. oral PUVA (8-MOP or 5-MOP) in 50 patients with NSV. At the end of the study, the PUVA group had received a mean number of 47 treatments as opposed to 97 treatments in the NB-UVB-group. Sixty-four per cent of patients in the NB-UVB group had 50% or more improvement compared with 36% of patients in the PUVA group. Moreover, among the patients with more than 48 sessions of treatments, the reduction of depigmented surface area was significantly greater for NB-UVB than for PUVA. The colour match of repigmented skin was excellent in all patients treated with NB-UVB but in only 44% of those treated with PUVA. Accordingly, NB-UVB was superior to oral PUVA, and most treatment centres currently consider NB-UVB as the first-line treatment for NSV.[38] Moreover, 5-MOP is currently unavailable, further limiting the use of PUVA therapy. Only a few long-term follow-up studies have investigated the persistence of repigmentation after discontinuation of NB-UVB, showing relapse rates of 21% and 44% within 1 year, and 55% within 2 years.

New therapeutic devices deliver high fluency light, laser or incoherent, selectively to the lesions.[47–51] High energy monochromatic light sources provide rapid induction of repigmentation, and fewer treatments are required to achieve repigmentation compared with conventional NB-UVB. A recent study demonstrated the greater efficacy of the 308-nm excimer laser treatment over NB-UVB in producing a more rapid and intense repigmentation.[51]

Tolerance of Phototherapies

The long-term risk of skin cancer is well established for PUVA. NB-UVB, as well as targeted UVB phototherapies, are well tolerated. The most common acute adverse reaction is skin type- and dose-dependent erythema, usually occurring 12–24 h after irradiation, continuing within another 24 h and disappearing before the next treatment session. Thus, it is essential to ask the patients whether, and to what extent they have developed erythema in response to the previous irradiation. A slight erythema reaction in lesional skin is generally considered a good guideline for adequate dosimetry. Higher doses are commonly applied with targeted phototherapies. Therefore, erythematous reactions may occur more often and with greater intensity than with NB-UVB. However, these reactions are confined to small areas of the treated skin and do not impair the general well-being of the patient.

Data supporting the safety of phototherapies in childhood are limited, and caution is recommended.