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 begins 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 greater 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 3 times more common in haematology patients that have had allogeneic bone marrow and stem-cell transplants, than in the normal population.
What causes vitiligo?
Vitiligo is due to 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.
The exact cause of vitiligo is unknown. It is thought to be a systemic autoimmune disorder, associated with deregulated innate immune response, although this has been disputed for segmental vitiligo. There is a genetic susceptibility and vitiligo is a component of some rare syndromes. The gene encoding the melanocyte enzyme tyrosinase, TYR, is likely involved.
There are three theories on the cause of vitiligo:
- The pigment cells are injured by abnormally functioning nerve cells.
- There may be an autoimmune reaction against the pigment cells.
- Autotoxic theory – the pigment cells self-destruct.
Current investigations are evaluating the pattern of cytokines (messenger proteins), 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, finger tips and toes), body folds (armpits, groin), nipples, navel, lips and genitalia.
- Vitiligo also favours sites of injury (cuts, scrapes, 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 3 shades of skin colour. Very rarely, there are 4 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 individual. There is no way to predict how much pigment an individual will lose or how fast it will be lost.
- Vitiligo appears more obvious 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 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.
- Pigment has occasionally been reported to be lost from the entire skin surface.
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 classification of vitiligo in 2007. They decided on 4 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 2 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 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 is based on SCORAD scoring system for atopic dermatitis. The VETF assesses 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, 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 normally a clinical diagnosis, and no tests are necessary to make the diagnosis. The white patches may be seen more easily under Wood lamp examination (black light).
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.
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 sun"
- Micropigmentation or tattooing for stable vitiligo
- 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 obvious
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 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 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)
Phototherapy probably works in vitiligo by 2 mechanisms.
- Immune suppression—preventing 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 important to avoid burning (red, blistered, peeling, itchy or painful skin), as this could cause the vitiligo to get worse.
A meta-analysis included 35 unique studies reporting outcome after phototherapy for generalised vitiligo. 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 trunk, which responded better than extremities. It was not very effective on hands and feet.
Systemic treatments for vitiligo include:
- Oral minocycline, a tetracycline antibiotic with anti-inflammatory properties
- Mini-pulses of oral steroids for 3 to 6 months, eg dexamethasone 2.5 mg, 2 days per week
- Subcutaneous afamelanotide
It is anticipated that monoclonal antibody biologic agents will be developed to treat vitiligo.
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.
- 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, using monobenzyl ether of hydroquinone, may be considered in severely affected, dark skinned individuals.
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 effects 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.