Vitiligo is a common skin disorder affecting approximately 0.5% ‐ 1% of the population worldwide, irrespective of race or ethnic origin (Perrot 1973, Srivastava 1994). It is mainly present in the skin where the loss of functioning melanocytes results in white patches. The hair and rarely, the eyes may also lose colour. It is sometimes referred to as a form of leucoderma. Anyone of any age can develop vitiligo but it is rarely reported to be present at birth when it could be misdiagnosed as piebaldism (a genetic defect in pigment production). In a Dutch study 50% of participants reported that the disease became apparent before the age of 20 (Westerhof 1996).
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Vitiligo patches can appear anywhere on the skin but common sites are usually around the orifices, the genitals, or any sun exposed areas such as the face and hands. Attempts have been made to classify vitiligo either by distribution of the patches, age of onset or degree of loss of colour. The most common form of vitiligo, general vitiligo or vitiligo vulgaris, is symmetrical. Koga and Tango named it class A vitiligo (Koga 1977) and from their observations concluded that it had a different pathogenesis to the rare Class B or segmental type where only one area of the body is affected (Koga 1988). This may have implications for the treatment of the disease.

Though neither lethal nor symptomatic, (except that depigmented patches burn easily when exposed to the sun) its effects can be cosmetically and psychologically devastating (Lerner 1978) resulting in a lower self‐esteem (Papadopoulos 1999), poor body image (Porter 1979) and difficulties in sexual relationships (Porter 1990). Many people with vitiligo are frightened because they do not know what is causing it and because of the unpredictability of the course of the disease which can spread to cover the entire body surface.

There is a stigma attached to vitiligo among certain ethnic groups due to its confusion with leprosy, which can also cause loss of pigment. Some sufferers experience discrimination in employment, particularly in jobs where they have to deal with the public (Porter 1987). Anecdotal evidence suggests that vitiligo patients also feel isolated and when exposed areas such as the face are affected it can lead to avoidance of some social situations, difficulty in forming relationships, total withdrawal and sometimes acute depression. In Asian communities young people with vitiligo themselves or with affected family members often find it difficult to find a marriage partner. The effect of vitiligo on the quality of life of those who suffer from it is often overlooked (Kent 1996). There are reports of children being cruelly teased and bullied at school. This may have serious psycho‐social implications which should not be underestimated (Njoo 2000a).

Sufferers have experienced disinterest from their doctors (Agarwal 1998) who may consider vitiligo to be no more than a cosmetic problem. In the UK there is no licensed treatment for the condition apart from cosmetic camouflage creams. However, over the years physicians from many countries have used a range of treatments in an attempt to halt the spread of the disease or to repigment the patches, with varying degrees of success. Incomplete response to treatment is common so patient well being is not necessarily improved. In many cases new areas of depigmentation occur and pigment loss recurs in areas which have regained colour with the treatment. On the one hand doctors may experience frustration as the treatment they can offer is generally unsatisfactory. On the other hand patients do not feel they receive support and understanding from their doctor. As a result many doctors do not prescribe anything and patients are discouraged from seeking treatment (Porter 1978).

The cause of vitiligo is uncertain but seems to be dependent on the interaction of genetic, immunological and neurogenic factors (Perrot 1973). Although there are few epidemiological studies, it is believed that about a third of patients report close family members affected by vitiligo (Bhatia 1992). Studies are now underway to find the genes responsible. Some studies have shown that stress may be implicated in the onset and exacerbation of skin disease in some individuals (Al'Abadie 1994). In a study of vitiligo patients, participants displayed a significantly higher number of stressful life events than controls, suggesting that stress is an important factor in the disease (Papadopoulos 1998).

Vitiligo has sometimes been associated with autoimmune diseases such as pernicious anaemia, thyroid disorders, diabetes mellitus and Addison's disease. Vitiligo patients have been found to have antibodies directed against melanocytes and some develop antibodies to other tissues and either suffer from the above‐mentioned autoimmune diseases themselves or have close relatives that do (Bystryn 1988; Klaus 1984; Cui 1995). These observations have been used to support the popular hypothesis that vitiligo is an autoimmune disease.

Current Treatments
The following list of treatments is not exhaustive but illustrates the unsatisfactory nature of treatments available to patients. It is also important to note that up until the time of writing this review there are no licensed treatments for vitiligo. Vitiligo skin which lacks melanin tends to burn when exposed to sunlight. Although this is not always the case covering up or a high factor sunblock is usually recommended for exposed, affected areas.

Psoralen and ultraviolet A light (PUVA)
PUVA (psoralen and ultraviolet A light ) was developed from a traditional Egyptian treatment using the giant hogweed, a photosensitising plant, and sunlight. Modern psoralens developed in the laboratory can be taken orally, added to bath water or applied to the skin which is then exposed to ultra violet A light or sunlight. It is claimed to be effective, particularly on darker skinned individuals. However, elements of the treatment such as reported side effects, the length of time needed for repigmentation to take place, the fact that the repigmentation is not necessarily permanent, make some dermatologists reluctant to prescribe it.

Topical corticosteroids
The theory that vitiligo is an autoimmune disease led to the use of corticosteroids in its treatment.
Topical corticosteroids have been shown in some studies to halt the spread of vitiligo and by arresting the attack on pigment cells by the immune system they can also encourage some repigmentation, particularly in dark skinned patients (Kumari 1984). Intralesional corticosteroids (Goldstein 1992) , orally administered corticosteroids (Kim 1999), and recently, intravenous pulsed steroids (Seiter 2000), have also been tried, all of which can have serious side effects. A novel treatment combining corticosteroid creams with UVA light is reported to be more effective than topical steroids alone (Westerhof 1999). Side effects of topical treatment include atrophy (thinning of the skin), telangiectasia (thread veins) and striae (stretch marks).

Ultraviolet B Light

Both broad band and narrow band (310‐315 nm) ultraviolet B (UVB) monotherapy have been used for vitiligo with some reported success. Narrow band UVB may be more effective than topical PUVA with sunlight and does not have the concomitant side effects (Westerhof 1997). Narrow band UVB monotherapy may be safe and effective for children (Njoo 2000b).

Grafting
Various types of grafting, using the patient's own normal skin have been tried. This form of treatment appears to work best on stable vitiligo and on segmental forms so careful selection of suitable patients is important for this technique (Boersma 1995).

Melanocyte transplantation
Melanocyte transplantation can also be used where cells are cultured from the patient's unaffected skin and injected into blisters on the depigmented areas or directly into dermabraded skin (Olsson 1995). This technique is expensive and there is a concern about the effect of the culture medium, TPA, which is a potent tumour promoter, on the transplanted cells. It is also possible to transplant melanocyte and keratinocyte grown in the same culture medium with reported good effect.

Depigmentation
Depigmentation of the remaining normal skin with monobenzyl ether of hydroquinone is sometimes recommended when a large proportion of the total body area is affected. It is also possible to use the Q‐switched ruby laser with topical 4‐methoxylphenol to destroy remaining melanocytes (Njoo 2000c). This has the advantage of fewer side effects. However, depigmentation therapy requires careful counselling of the patient as it leaves the skin without protection from sunlight and depigmentation is not considered reversible. Patients from dark skinned races may be traumatised by their complete loss of colour which may be perceived as a loss of identity.

Cosmetic Camouflage
Cosmetic camouflage creams can be prescribed especially when the face, neck and hands are affected. The creams, properly applied, can give a convincing result and normally remain waterproof for up to 8 hours. However, it may be difficult to find a suitable colour match and the creams tend to rub off on areas where there is friction such as the cuffs and neckline. Most men are reluctant to apply them, they are not suitable for very young children and they have to be applied daily.

Fake Tanning
Fake tanning preparations are suitable for some paler skin types and can provide a cosmetically acceptable colour for 3‐4 days after which time the top layer of skin is normally shed. They do not rub off or wash off though they fade gradually with time. They are helpful for large exposed areas such as the arms and legs but can sometimes produce an orange tinge and are more useful in the summer when normal skin tans. They are not effective on dark brown or black skins. Another drawback is that they do not offer sun protection so patients need to be advised to use high factor sunscreens on affected, exposed areas.

Micropigmentation
Micropigmentation, a form of tattooing, has been used on recalcitrant areas such as the lips and the tips of the fingers. This technique is best suited to stable vitiligo because of the risk of starting another patch of vitiligo at sites of damage (Koebner phenomenon) (Halder 1989).

Pseudocatalase
The discovery that vitiligo patients have high levels of hydrogen peroxide in both affected and unaffected skin, and low levels of the enzyme catalase, which inactivates hydrogen peroxide, has led to a new experimental treatment. This replacement therapy uses an analogue of normal human catalase containing calcium and manganese (pseudocatalase) in a moisturising cream base in conjunction with narrow band UVB to stimulate melanocyte activity (Schallreuter 2000). Clinical trials are planned for this treatment (Schallreuter 1995).

Complementary Therapies
When there is no improvement with conventional therapies many sufferers turn in desperation to complementary treatments (Orecchia 2000). These include a human placental extract (melagenina) used topically, vitamin supplements including B12, vitamin C and folic acid (Montes 1999), and Chinese and Indian herbal medications. These herbal remedies have not been subjected to toxicological tests and often the constituents of the medication are unknown. Reliable evidence of the efficacy and safety of these treatments needs to be established. However, a common herb, black pepper, shows evidence of a proliferative effect on mouse melanocytes in culture (Lin 1999).

Psychological Therapy
Although vitiligo does not affect general health, the psycho‐social effects can be devastating. Recent work has suggested that patients can benefit from cognitive behavioural therapy to help cope with the disease from day to day (Papadopoulos 1999). This form of therapy could enhance the well‐being of the patient and may also improve the disease.

We found the reviews of the literature and the meta analysis of non‐surgical therapies in vitiligo by Dr Njoo of great value in preparing this review (Njoo 2000a). However, they are limited in scope, dealing only with certain types of therapies and have not been prepared according to the strict Cochrane criteria in respect of methodology or updating requirements.

We have undertaken this review not only to assess the relative effectiveness of various treatments but also to highlight the gaps in research. The review will include experimental, complementary and psychological interventions. It may be clinically useful to general practitioners and dermatologists in treating their patients and it could form the basis for treatment guidelines for vitiligo. It will also contribute towards setting future research priorities. We hope that as a result vitiligo patients will be more likely to be offered appropriate and effective interventions.