Vitiligo

What is vitiligo?

Vitiligo is an acquired depigmenting disorder of the skin, in which pigment cells (melanocytes) are lost. It presents with well-defined milky-white patches of skin (leukoderma). Vitiligo can be cosmetically very disabling, particularly in people with dark skin.

Who gets vitiligo?

Vitiligo affects 0.5–1% of the population, and occurs in all races. It may be more common in India than elsewhere, with reports of up to 8.8% of the population affected. In 50% of sufferers, pigment loss begins before the age of 20, and in about 80% it starts before the age of 30 years. In 20%, other family members also have vitiligo. Males and females are equally affected.

Even though most people with vitiligo are in good general health, they face a higher risk of having autoimmune diseases such as diabetes, thyroid disease (in 20% of patients over 20 years with vitiligo), pernicious anaemia (B12 deficiency), Addison disease (adrenal gland disease), systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and alopecia areata (round patches of hair loss).

A vitiligo-like leukoderma may occur in patients with metastatic melanoma. It can also be induced by certain drugs, such as immune checkpoint inhibitors (pembrolizumab, nivolumab) and BRAF inhibitors (vemurafenib, dabrafenib) used to treat metastatic melanoma. Vitiligo is also three times more common in haematology patients that have had allogeneic bone marrow and stem-cell transplants, than in the healthy population.

What causes vitiligo?

Vitiligo is due to the loss or destruction of melanocytes, which are the cells that produce melanin. Melanin determines the colour of skin, hair, and eyes. If melanocytes cannot form melanin or if their number decreases, skin colour becomes progressively lighter.

Vitiligo is thought to be a systemic autoimmune disorder, associated with deregulated innate immune response, although this has been disputed for segmental vitiligo. There is genetic susceptibility. Vitiligo is a component of some rare syndromes, such as the Vogt-Koyanagi-Harada syndrome. The gene encoding the melanocyte enzyme tyrosinase, TYR, is likely involved. It has been reported to be drug induced in association with the methylphenidate transdermal system.

Current investigations are evaluating the pattern of cytokines, particularly Interferon (IFN)-γ,  and the role of the hair follicle in repigmentation.

What are the clinical features of vitiligo?

Vitiligo can affect any part of the body. Complete loss of pigment can affect a single patch of skin, or it may affect multiple patches. Small patches or macules are sometimes described as confetti-like.

• Common sites are exposed areas (face, neck, eyelids, nostrils, fingertips and toes), body folds (armpits, groin), nipples, navel, lips and genitalia.
• Vitiligo also favours sites of injury (cuts, scrapes, acne, thermal burns and sunburn). This is called the Koebner phenomenon.
• New-onset vitiligo also sometimes follows emotional stress.
• Vitiligo may occasionally start as multiple halo naevi.
• Loss of colour may also affect the hair on the scalp, eyebrows, eyelashes and body. White hair is called ‘leukotrichia’ or ‘poliosis’.
• The retina at the back of the eye may also be affected. However, the colour of the iris does not change.

The colour of the edge of the white patch can vary.

• It is usually the colour of unaffected skin, but sometimes it is hyperpigmented or hypopigmented.
• The term trichrome vitiligo is used to describe three shades of skin colour. Very rarely, there are four shades of pigment (white, pale brown, dark brown and normal skin).
• Occasionally, each patch of vitiligo has an inflamed, red border.

The severity of vitiligo differs with each person. There is no way to predict how much pigment an individual will lose or how fast it will be lost.

• Vitiligo appears more evident in patients with naturally dark skin.
• Extension of vitiligo can occur over a few months, then it stabilises.
• Some spontaneous repigmentation may occur. Brown spots arise from the hair follicles, and the overall size of the white patch may reduce.
• At some time in the future, the vitiligo begins to extend again.
• Cycles of pigment loss followed by periods of stability may continue indefinitely.
• Light skinned people usually notice the pigment loss during the summer as the contrast between the affected skin and suntanned skin becomes more distinct.
• The pigment has occasionally been reported to be lost from the entire skin surface.

Koebnerised vitiligo

Mucosal vitiligo

Acral vitiligo

Segmental vitiligo

Trichrome vitiligo

Poliosis

Red border

Follicular repigmentation

See more images of vitiligo.

Vitiligo may be associated with a reduced risk of malignancy

It has been observed that patients that develop a form of vitiligo during treatment with an immune checkpoint inhibitor (such as nivolumab or pembrolizumab prescribed for metastatic melanoma) have enhanced survival rates compared to those who do not develop this complication of the treatment. A nationwide population cohort study published in 2019 reported that patients in Korea with a diagnosis of vitiligo had a reduced incidence of internal malignancies such as cancer of the colon, rectum, ovary and lung. The risk of melanoma and keratinocyte cancer also appears to be less in vitiligo patients than in similar patients without vitiligo. However, it should be noted that the risk of thyroid cancer is higher in patients with vitiligo compared to patients without vitiligo.

How is vitiligo classified?

Classifications have identified clinical, genetic, pathobiological, epidemiological, and molecular characteristics of vitiligo.

The Vitiligo European Taskforce came to a consensus about the classification of vitiligo in 2007. They decided on four main categories with subtypes.

How is the severity of vitiligo assessed?

In most cases, the severity of vitiligo is not formally assessed. However, clinical photographs may be taken to monitor the condition.

At least two scoring systems have been devised for vitiligo and are used in clinical trials.

• Vitiligo Area Scoring Index (VASI)
• Vitiligo European Task Force (VETF) system

VASI

VASI is based on the PASI scoring system for psoriasis. It measures the extent and degree of depigmentation in 6 sites: hands, upper extremities, trunk, lower extremities and feet, head/neck.

VETF

VETF is based on SCORAD scoring system for atopic dermatitis. The VETF assesses the extent, staging and spreading/progression in 5 sites: head/neck, trunk, arms, legs and hands/feet. It grades from 0 (normal pigmentation) to 4 (complete hair whitening). Spreading is assessed using the following scores: 0 (stable disease), -1 (regressive disease) and +1 (progressive disease).

VETF includes a clinical assessment form to record the sex, age, duration of disease, age of onset, episodes of repigmentation, the impact of vitiligo on quality of life, family history, additional medical conditions and the Fitzpatrick skin type of the patients.

How is vitiligo diagnosed?

Vitiligo is usually a clinical diagnosis, and no tests are necessary to make the diagnosis. The white patches may be seen more easily under Wood lamp examination (blacklight). Dermoscopy characteristically shows a white glow.

Occasionally skin biopsy may be recommended, particularly in early or inflammatory vitiligo, when a lymphocytic infiltration may be observed. Melanocytes and epidermal pigment are absent in established vitiligo patches.

Blood tests to assess other potential autoimmune diseases or polyglandular syndromes may be arranged, such as thyroid function, B12 levels and autoantibody screen.

Clinical photographs are useful to document the extent of vitiligo for monitoring. Serial digital images may be arranged on follow-up. The extent of vitiligo may be scored according to the body surface area affected by depigmentation.

How is vitiligo treated?

Treatment of vitiligo is currently unsatisfactory. Repigmentation treatment is most successful on face and trunk; hands, feet and areas with white hair respond poorly. Compared to longstanding patches, new ones are more likely to respond to medical therapy.

When successful repigmentation occurs, melanocyte stem cells in the bulb at the base of the hair follicle are activated and migrate to the skin surface. They appear as perifollicular brown macules.

General measures

Minimise skin injury: wear protective clothing.

• A cut, a graze, a scratch may lead to a new patch of vitiligo.

Cosmetic camouflage can disguise vitiligo. Options include:

• Make-up, dyes and stains
• Waterproof products
• Dihydroxyacetone-containing products "tan without the sun."
• Micropigmentation or tattooing for stable vitiligo.

Sun protection: stay indoors when sunlight is at its peak, cover up with sun protective clothing and apply SPF 50+ sunscreen to exposed skin.

• White skin can only burn on exposure to ultraviolet radiation (UVR); it cannot tan.
• Sunburn may cause vitiligo to spread.
• Tanning of normal skin makes vitiligo patches appear more visible.

Sunburn in vitiligo

Sunburn in vitiligo

Topical treatments

Topical treatments for vitiligo include:

• Corticosteroid creams. These can be used for vitiligo on trunk and limbs for up to 3 months. Potent steroids should be avoided on thin-skinned areas of the face (especially eyelids), neck, armpits and groin.
• Calcineurin inhibitors (pimecrolimus cream and tacrolimus ointment. These can be used for vitiligo affecting eyelids, face, neck, armpits and groin.
• Experimental treatment with topical ruxolitinib, a Janus kinase inhibitor,  shows great promise for facial vitiligo.

Phototherapy

Phototherapy refers to treatment with ultraviolet (UV) radiation. Options include:

• Whole-body or localised broadband or narrowband (311 nm) UVB
• Excimer laser UVB (308 nm) or targeted UVB for small areas of vitiligo
• Oral, topical, or bathwater photochemotherapy (PUVA)
• In-office or home phototherapy.

Phototherapy probably works in vitiligo by two mechanisms.

• Immune suppression—preventing the destruction of the melanocytes
• Stimulation of cytokines (growth factors)

Treatment is usually given twice weekly for a trial period of 3–4 months. If repigmentation is observed, treatment is continued until repigmentation is complete or for a maximum of 1–2 years.

• Phototherapy is unsuitable for very fair-skinned people.
• The treatment intensity aims for the vitiligo skin to be a light "carnation" pink.
• If repigmentation is observed, treatment is continued until repigmentation is complete or for a maximum of 1–2 years.
• Treatment times are generally brief. The aim is to cause the treated skin to appear very slightly pink the following day.
• It is essential to avoid burning (red, blistered, peeling, itchy or painful skin), as this could cause the vitiligo to get worse.

A meta-analysis included 35 different studies reporting outcome after phototherapy for generalised vitiligo. A marked or clinically useful response was achieved in 36% after 12 months of NBUVB and in 62% after 12 months of PUVA. Face and neck responded better than the trunk, which responded better than extremities. It was not very effective on hands and feet. 

Systemic therapy

Systemic treatments for vitiligo may include:

• Mini-pulses of oral steroids for 3 to 6 months, such as dexamethasone 2.5–4 mg, two consecutive days per week for 3–6 months
• Methotrexate
• Ciclosporin
• Mycophenolate mofetil
• Oral minocycline 100 mg/day, a tetracycline antibiotic with anti-inflammatory properties
• Subcutaneous afamelanotide.

None of these treatments is based on randomised controlled trial data in treating vitiligo. The aim is to stop the progression of the disease (stabilisation) and so immune-modulating treatments should be considered at an early stage, particularly for vitiligo affecting the face.

It is anticipated that monoclonal antibody biologic agents will be developed to treat vitiligo. To date, the results of JAK inhibitor trials in vitiligo have been encouraging, but there are high rates of relapse.

Surgical treatment of stable vitiligo

Surgical treatment for stable and segmental vitiligo requires removal of the top layer of vitiligo skin (by shaving, dermabrasion, sandpapering or laser) and replacement with pigmented skin removed from another site.

Techniques include:

• Non-cultured melanocyte-keratinocyte cell suspension transplantation.
• Punch grafting
• Blister grafts, formed by suction or cryotherapy
• Split skin grafting
• Cultured autografts of melanocytes grown in tissue culture.

Depigmentation therapy

Depigmentation therapy, using monobenzyl ether of hydroquinone, may be considered in severely affected, dark-skinned individuals.

Cryotherapy and laser treatment (eg, 755-nm Q-switched alexandrite or 694 nm Q-switched ruby) have also been used successfully to depigment small areas of vitiligo.

Psychosocial effects of vitiligo

Vitiligo results in reduced quality of life and psychological difficulties in many patients, especially in adolescents and in females. The psychosocial impacts of vitiligo tend to be more severe in some countries, cultures and religions than in others. Family support, counselling and cognitive behavioural treatment can be of benefit.