Management of patients with vitiligo

Hairs on vitiliginous skin initially remain pigmented, but after a prolonged time, leucotrichia (whiteness of the hair) or poliosis may occur.

The disease was recognised in ancient times, but was not differentiated from leprosy. Hippocrates included lichen, leprosy and vitiligo under the same category. In the Koran, Arabic names used to describe vitiligo were translated as leprosy in many languages.^1-3

This association with leprosy is an important reason for the social stigma attached to vitiligo. Men and women with white patches of skin were not respected in society and were disqualified from marriage. If the white spots occurred after marriage, they provided acceptable grounds for divorce.^1,2

Vitiligo has a major impact on patients' quality of life and may negatively affect sexual relationships.^4-6 Patients experience a number of psychological problems, such as shame, depression and anxiety, which lead to low self-esteem and social isolation.⁷

They also experience discrimination and believe they do not receive adequate support from doctors, friends or family.^6,8 In a survey of Vitiligo Society UK members, more than half (56.6%) of the respondents indicated that vitiligo moderately or severely affected their quality of life.⁹ Disappointingly, most obtained information about their disease from non-medical sources: 431 (83%) from Vitiligo Society UK and 129 (25%) from the internet, compared with 61 (12.5%) from dermatologists.⁹

Mood disturbances are common, particularly in teenagers. Childhood vitiligo can be associated with significant psychological trauma and those with the condition often avoid or restrict their sporting activities.⁵

Classification of vitiligo

Vitiligo can be classified into NSV and SV.¹⁰ 'Vitiligo' can be used as an umbrella term for all non-segmental forms. Clinical subtypes of NSV include generalised, acrofacial, mucosal and universal vitiligo.¹⁰

Mixed vitiligo is characterised by the presence of both non-segmental and segmental vitiliginous macules in the same patient and is classified as a subgroup of vitiligo.^11,12

NSV is characterised by symmetrical, bilateral patches and is the most common form of this disease. It may initially have an acrofacial distribution, but can progress to the generalised or universal form.

SV usually has a unilateral distribution that may totally or partially match a dermatome. It usually has an early age of onset and rapid stabilisation, and is classified as unisegmental, bisegmental or plurisegmental. In SV, the most commonly involved areas are the face (51.1%), anterior trunk (21.5%) and extremities (10.8%).^1,13

Focal lesions (small, isolated, depigmented lesions) that have not evolved into NSV or SV after one or two years are termed 'unclassifiable' vitiligo. Rare variants, such as follicular vitiligo and vitiligo minor, have also been reported.^10,14

Epidemiology of vitiligo

Most papers refer to an estimated 0.5-1% worldwide prevalence for vitiligo, although rates as high as 8.8% have been reported in India.¹⁵ This may be due to the inclusion of cases with chemically induced depigmentation.¹⁶

A study conducted in the French West Indies concluded that the prevalence of vitiligo in black people is comparable to, or slightly lower than, the currently accepted data in white people.¹⁷

The largest epidemiological study was performed on the island of Bornholm in Denmark in 1977, where vitiligo affected 0.38% of the population.¹⁸ Overall, the highest incidence rates have been recorded in India, followed by Mexico and Japan.

The disparity between prevalence data and incidence figures may be due to higher reporting of vitiligo, where attached social and cultural stigma may force patients to seek early consultation and/or the lesions are more prominent because of the darker skin colour of the population.¹⁶

Vitiligo develops at all ages and affects both sexes equally. It usually occurs in young people between the age of 10 and 30 years.^16,18-20 However, the epidemiological study in Denmark found that almost 50% of those who developed vitiligo did so after the age of 40 years.¹⁸ It is estimated that almost half of patients present before the age of 20 years, and nearly 70-80% before the age of 30 years.¹⁶

Childhood onset vitiligo is common and affects 32% of patients, with most (89%) having a disease onset after the age of four years.²¹ NSV can occur at any age, whereas SV tends to occur in young patients.²¹ SV accounts for 5-16% of overall cases of vitiligo.¹³

A review of prevalence studies showed that the prevalence of vitiligo increases with age and ranges from 0.06% to 2.28% in the general population and from 0% to 2.16% in children.²²

Aetiology and pathogenesis

The aetiology of vitiligo is poorly understood. It is not clear whether the melanocytes in vitiligo lesions have disappeared or are simply not functioning, and why this is happening. Several theories have been developed to explain the pathogenesis of this disease. Immunological and genetic theories seem to provide the most robust evidence to date.^23-27

The autoimmune aetiology of vitiligo has been considered, based on reports of its frequent association with other autoimmune disorders, such as thyroiditis. Studies have shown that the frequency of vitiligo and other autoimmune diseases is higher in relatives of patients with vitiligo, supporting a genetic component to the disease.

An epidemiological survey of 374 white patients with generalised vitiligo (most with sporadic occurrence) and their families, in the UK and the US, showed that 19.4% of patients aged at least 20 years with vitiligo reported a clinical history of autoimmune thyroid disease, compared with 2.39% of the overall white population of the same age.^1,28

Recent genome-wide association analyses have identified several susceptibility loci for vitiligo, including the gene encoding tyrosinase (TYR).^29,30 Tyrosinase is a major autoantigen in vitiligo.³¹ One study found a susceptibility variant for NSV in the TYR gene in white European people, rarely found in patients with melanoma, suggesting a genetic dysregulation of immunosurveillance against the melanocytic system.³⁰ In the same study, nearly all of the susceptibility genes that were identified encode components of the immune system and support the hypothesis of a deregulated immune response in vitiligo.³⁰

In addition, antibodies to melanocytes have been detected in patients with vitiligo.³² The presence of these melanocyte antibodies has been linked to disease activity.³³ However, it is unclear whether these antibodies play an initiating role in the development of vitiligo, or are a secondary result of it.³⁴

Several other theories have been suggested, such as the oxidative stress theory, the Koebner phenomenon, the cytokines theory and the neuronal theory.¹

Management of vitiligo

During the initial consultation, it is important to assess the extent of the vitiligo, using Wood's lamp examination where necessary. Detailed personal and family history, skin phototype, previous treatments and their effectiveness, disease duration, extent and activity are important in assisting the choice of management option. The Vitiligo European Task Force has developed a useful assessment form, which summarises all of the above, including clinical examination findings.¹¹

Vitiligo lesions have been described at sites of repeated trauma, such as repeated friction or pressure, and scars, burns, wounds and other types of abrasions. Consequently, it has been hypothesised that many NSV lesions could be related to repeated friction occurring during washing, dressing, personal care, sports and other activities, known as the Koebner phenomenon.^35-39 Special recommendations can be made to prevent triggering factors during daily activities.^39,40

Cosmetic camouflage is an important part of the global management of vitiligo, considering the negative impact of the disease on the patient's body image and self-confidence.

Various products, such as self-tanners, cover creams, dyes and semi-permanent and permanent tattoos, are available. The latter should be used with caution, owing to the unpredictable course of the disease and the Koebner phenomenon.⁴¹

The patient's psychological profile and way of coping with vitiligo should be carefully examined. A vitiligo-specific quality of life instrument (VitiQoL) may be used to evaluate the disease's impact on the patient's daily life.⁴² All patients should be offered psychological support and counselling, if possible.⁴³

Associated autoimmune diseases

Many autoimmune diseases have been associated with vitiligo, including thyroiditis, type 1 diabetes, pernicious anaemia, Addison's disease, systemic lupus erythematosus, psoriasis and rheumatoid arthritis.^28,44 In one study, a history of autoimmune thyroid disease was found in 34% of patients with vitiligo, suggesting that checking thyroid function or presence of autoantibodies to thyroid antigens may be helpful in the management of vitiligo in patients with suggestive symptoms or a personal/family history.^45,46

Treatment guidelines

Treatment results vary between individuals and are often unsatisfactory. In general, the best results are reported on the face, while acral lesions usually respond poorly.⁴⁷ Treatment appears to be more efficient in recently developed lesions than in older ones, which argues for early intervention.^48-50

The British Association of Dermatologists clinical guidelines for the diagnosis and management of vitiligo recommend the use of narrow-band UVB, tacrolimus and topical steroids.⁴⁶ These guidelines were based on evidence from a 2006 Cochrane systematic review and expert consensus, taking into account patient choice and clinical expertise.⁴⁶

An updated Cochrane systematic review in 2010 concluded that no firm clinical recommendations can be made for the treatment of vitiligo, mainly because of heterogeneity in the design of trials and small numbers of included patients.⁴⁷

A new guideline on vitiligo was developed by the European Dermatology Forum in 2013, which brought several changes to the proposed management of the condition.⁴¹ This guideline aims to bring clarity to the treatment options available for various types of vitiligo and provides expert advice based on the best available evidence and specialist consensus.⁴¹

Skin grafting is one therapeutic option in patients with vitiligo (Photograph: Science Photo Library)

First-line treatments

Topical therapies, such as topical corticosteroids and topical calcineurin inhibitors, are recommended as first-line treatment for vitiliginous lesions.⁴¹ Potent topical corticosteroid preparations are recommended, such as 0.1% betamethasone valerate and 0.05% clobetasol propionate. These should preferably be applied once daily in a discontinuous scheme, for example, 15 days per month for six months, to avoid side-effects such as skin atrophy, telangiectasia, hypertrichosis, acneiform eruptions and striae. Topical calcineurin inhibitors, such as pimecrolimus or tacrolimus, are recommended as an alternative to topical steroids, mainly for the face and neck. Twice-daily applications are recommended, initially for six months.⁴¹

Second-line treatments

Treatment with narrow-band UVB or psoralen and UVA light therapy (PUVA) can be effective.^41,46 Narrow-band UVB phototherapy (311nm) has been found to be at least equally effective as PUVA, with fewer side-effects due to psoralens.⁵¹

Targeted phototherapies (laser and non-laser) can be used for localised vitiligo, in particular for lesions of recent onset and childhood vitiligo; for example, excimer lamp or lasers (peak at 308nm). There is no consensus as to the optimum treatment duration of phototherapy.

Phototherapy is usually discontinued if no repigmentation occurs within three months. However, in some cases, it starts to occur later than this. In addition, potent topical steroids applied once a day (three weeks out of four) can be used for the three first months of phototherapy in difficult vitiliginous areas.⁴¹

Oral minipulse of moderate doses of betamethasone/dexamethasone (2.5mg per day) for three to six months can be considered in fast-spreading vitiligo to stop progression.^41,52

Third-line treatments

Surgical treatments are an option in patients with SV and those with stable NSV (no new lesions or progression of old lesions for at least one year) in the absence of the Koebner phenomenon. Only a small number of patients with vitiligo are suitable.

Different techniques include tissue grafts (split-thickness grafts, full-thickness punch grafts and suction blister grafts) and cellular grafts (cultured melanocytes and non-cultured epidermal cellular grafts).⁴¹

The tissue grafting methods seem to have comparable success rates. Although the percentage of repigmentation using cellular grafting has been found to be slightly inferior to tissue grafts, larger areas can be treated with cellular grafts.^41,53,54 Adverse events seem to be less frequently associated with cellular grafts, but are often reported in tissue grafting.^41,55

Fourth-line treatments

Depigmenting treatments should only be considered in extensive (>50%), refractory and disfiguring vitiligo.⁴¹ Various skin-bleaching methods are available, such as monobenzone ethyl ester or 4-methoxyphenol, laser therapy (for example, Q-switched alexandrite 755nm or Q-switched ruby 694nm) and cryotherapy.^41,56,57

Conclusion

Vitiligo is a multifactorial disease. Treatment of the condition can be unsatisfactory, although recent guidelines propose more robust treatment options, including a combination of topical agents with phototherapy.

Alongside medical and surgical treatments, it is important to consider cosmetic camouflage and psychological support for patients with vitiligo.

• Dr Viktoria Eleftheriadou is a postdoctoral clinician scientist with an interest in vitiligo at the Centre of Evidence-Based Dermatology, University of Nottingham

Click here to take a test on this article and claim a certificate on MIMS Learning

Competing interests: None declared

Further resources

• Chandler D, Bewley A. Managing the psychosocial impact of vitiligo. MIMS Dermatology 2012; 8(3): 29-32
• British Association of Dermatologists www.bad.org.uk/
• Vitiligo Society UK www.vitiligosociety.org.uk/

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