Vitiligo: An Update on Pathophysiology and Treatment Options

Reinhart Speeckaert; Nanja van Geel


Am J Clin Dermatol. 2017;18(6):733-744. 

In This Article

Therapeutic Options in Vitiligo

Because of its complex pathogenesis, the management of vitiligo remains challenging. The conclusions of the most recent updated Cochrane systematic review were hampered by the heterogeneity of the performed clinical trials.[56]

Because of the wide range of interventions, limited number of participants, and different study designs, firm management recommendations could not be proposed. Therefore, the management of vitiligo is currently based on the most recent consensus guidelines.[57,58] The management of vitiligo involves a personalized approach and several factors influence the therapeutic choice (disease duration, impact, skin type, extent, sex, age, involved areas, social life, and cultural influences). Dermatologists should be aware of the patients' expectations and explain thoroughly the expected results (Table 1).

General Measures

Avoiding Koebnerizing factors (friction, trauma) can help to limit the triggering factors that develop new depigmentations. A good sun protection with sunscreens or clothing prevents sunburn on depigmented areas. Moreover, sun protection can help to diminish the bothersome enhanced contrast between depigmented and tanned pigmented skin, which occurs during summer. However, both spontaneous and treatment-induced repigmentation are mostly observed during summer periods on ultraviolet (UV)-exposed areas. This indicates that a moderate UV exposure could be a useful strategy to induce repigmentation in vitiligo.[59]

Topical Treatment

Topical Corticosteroids. Topical corticosteroids are still the first-line option for the treatment of vitiligo. The anti-inflammatory effects might decrease disease progression, although the cessation of spread has been rarely used as an outcome measure.[60] Most repigmentation can be observed in the face and neck while the trunk, extremities, and especially the hands display usually only limited repigmentation.[61] Recent lesions have a higher tendency for repigmentation. The efficacy between potent and ultra-potent corticosteroids seems to be similar. Side effects include skin atrophy, telangiectasia, and striae, which are rare if a discontinuous treatment scheme is used (e.g., 15 days of application per month). In the case of the occurrence of acneiform eruptions (especially in the face), a switch to topical immunomodulators may be advisable. Treatment with potent topical corticosteroids is often continued for at least 6 months to monitor its efficacy.[58] In our experience, this treatment is sufficient for the majority of patients with vitiligo. However, it should be clearly explained to the patient that the primary aim of topical treatment is to achieve disease stability. Repigmentation can be observed especially in the summer period on the face, while in other areas, the absence of progression should be considered as a successful treatment result.

Topical Immunomodulators. Topical tacrolimus and pimecrolimus are calcineurin inhibitors attenuating T-cell activity and decreasing the production of proinflammatory cytokines. In-vitro experiments document that they enhance melanocyte migration and pigmentation.[62,63] Similar to corticosteroids, topical immunomodulators show the most repigmentation in the face, while the results are moderate at other sites of the body. Overall, the results of topical immunomodulators are comparable to corticosteroids.[64] Twice-daily application of tacrolimus has been shown to be more effective compared with once-daily application.[65] The responses of tacrolimus seem slightly higher compared with pimecrolimus.[66] The higher potency of tacrolimus compared with pimecrolimus has also been demonstrated in an invivo Koebner induction model.[67] The most frequent side effect of topical immunomodulators is a burning sensation during the first 10–14 days of application, which is usually transient. Flushing after alcohol intake is also often observed and can be bothersome for some patients. Topical immunomodulators can be used in the case of side effects owing to topical corticosteroids (e.g., acneiform eruptions) or to attempt repigmentation in the face when treatment with topical corticosteroidids shows no signs of recovery.

Topical Antioxidants. Although still relatively frequently prescribed, the efficacy of topical antioxidants has only been observed in a limited number of trials.[68,69] Currently, consensus guidelines do not recommend the use of topical antioxidants.


Phototherapy has long been recognized as an efficient treatment to induce repigmentation. Nonetheless, the patient should be informed about the expected results, side effects, and the expected duration of the treatment. Narrow-band UVB is the phototherapy of choice and is usually carried out two to three times weekly. Signs of repigmentation are observed in the majority of patients. Nonetheless, complete repigmentation is only found in a small minority of patients.[70] Njoo et al. found only 6% complete repigmentation after 12 months of NB-UVB monotherapy in children.[71] Complete clearance was slightly higher (16.5%) in another study including patients with vitiligo of all ages.[70] Additionally, the patient should be informed about the risk of relapse after discontinuation of the therapy. Approximately half of patients will develop vitiligo lesions in repigmented skin within the first year if untreated.[72,73] According to Caron-Schreinemachers et al., the minimal erythemal dose of vitiligo is 35% lower compared with normal skin, which requires an adaptation of the UVB dose.[74] This treatment is continued provided the repigmentation continues for a maximum of 1–2 years. An evaluation of the evolution based on follow-up photographs can be recommended every 3 months. After stopping phototherapy, continuation of a topical treatment may be advisable to prevent recurrence. Twice-daily application of tacrolimus has been shown to decrease the rate of recurrent lesions.[75]

Photochemotherapy shows less repigmentation compared with NB-UVB and is associated with increased side effects.[76] The 308-nm excimer laser may show faster repigmentation compared with NB-UVB, although no studies found significant differences for ≥50% repigmentation between an excimer laser or NB-UVB.[77]

Side effects include a dose-dependent burning of the skin and hyperpigmentation of the skin. Targeted phototherapy devices have been developed, which can be useful especially on visible areas such as the face and the hands. The risk of skin cancer development is correlated with an increased number of phototherapy sessions.[78] While this association is clear for photochemotherapy, the carcinogenic risk of NB-UVB treatment is less evident. No consensus exists on the maximum number of NB-UVB treatments considered to be safe in vitiligo. Despite being one of the most effective treatments to induce repigmentation, the limitations of phototherapy should be clearly explained to the patient. Complete repigmentation is rarely observed and recurrences after phototherapy are frequent, especially without a (topical) maintenance treatment.[75] Ultraviolet-induced tanning results in an increased contrast between pigmented and depigmented areas, which can be bothersome and a reason to stop phototherapy.

Systemic Agents

Oral Corticosteroids. Oral corticosteroid mini-pulse therapy involves the use of moderate doses of corticosteroids (e.g., 2.5–10 mg dexamethasone 2 consecutive days in a week) to arrest disease progression. Oral corticosteroid mini-pulse (10 mg dexamethasone two times/weekly) therapy has been shown to stop disease progression in 88% of patients after 18.2 weeks of treatment.[79] However, repigmentation is only rarely observed. Side effects include weight gain, acne, sleep disturbances, agitation, hypertrichosis, and menstrual abnormalities, which limits long-term use.[79] Combination with NB-UVB is effective to stop progression and induce rapid repigmentation, although caution is warranted for long-term side effects when combining UVB with systemic immunosuppressants.[80]

Antioxidants. A very heterogeneous collection of clinical trials has been published on the use of oral antioxidants. Most studies are hampered by a limited patient size and confirmatory results are mostly lacking. As some studies document that the combination of oral antioxidants (e.g., polypodium leucotomos, vitamin E, vitamin C) and NBUVB leads to increased repigmentation rates, oral antioxidants can be considered in patients undergoing phototherapy.[81,82]


Pigment cell transplantation may offer a valuable alternative in a selected group of patients with vitiligo. Different pigment cell transplantation techniques have been developed including cellular graft transplantation and tissue grafting (e.g., punch grafting, split-thickness grafting, epidermal blister grafting). Regardless of the used technique, the stability of the lesions is a major criterion linked to the outcome of the procedure. Pigment cell transplantation is most effective in patients with stable segmental vitiligo.[83] In patients with non-segmental vitiligo, pigment cell transplantation has a higher chance of an acceptable repigmentation if the disease is stable for at least 1–2 years and no Koebner phenomenon is present.[58,83]

Combination Treatments

It should be noted that most treatments have an anti-inflammatory/immunosuppressive capacity that halts the immune attack in vitiligo but has no direct effect on melanocyte differentiation, migration, and proliferation. Most patients with vitiligo seem to retain melanocyte stem cells in the hair follicle bulge, which needs to be activated to induce repigmentation.[84] Because of its complex pathogenesis, it makes sense to combine different treatments for vitiligo.[85] Currently, NB-UVB is only rarely been used as monotherapy. The combination of NB-UVB with topical corticosteroids and topical immunomodulators has been shown to increase repigmentation rates.[86] Some concerns have been raised about the combined use of two immunosuppressants on the risk of skin cancer. In particular, the combination of NB-UVB and topical immunomdulators has been a topic of debate.[87] No clear safety risks have currently been demonstrated, although long-term follow-up data are not yet available.


In patients with very extensive vitiligo (body surface area >50 to 60%) or disfiguring refractory vitiligo on the face or the hands, depigmentation of the remaining pigmented areas can be considered. Different methods of depigmentation exist such as bleaching creams (e.g., monobenzone ethyl ester), laser treatment, or cryotherapy. Monobenzone ethyl ester requires a relatively long duration of treatment and a 5- to 12-month period can be necessary to achieve satisfactory depigmentation. For laser and cryotherapy, multiple sessions are required. Repigmentation of previously depigmented areas can occur regardless of the used method. Therefore, strict sun protection during and after depigmentation procedures is advised to limit the chance of repigmentation.[88]

Cosmetic: Camouflage

Camouflage may be a valuable option.[89] A wide range of cosmetic products (including cover creams, self-tanners) is available. Owing to individual differences in skin type, affected body locations, and personal preferences, patients often need to be referred for specialized advice for camouflaging their vitiligo, which could reduce the daily impact of the disease and social stress related to vitiligo. Caution is advised for permanent camouflage and tattoos as vitiligo can progress over time. This could lead to unsatisfying results.