Vitiligo

Read about Clinuvel's program for nonsegmental vitiligo here.

Snapshot

Other common terms: Leucoderma, white spot disease

ICD-10 classification: L80

Prevalence: Affects 0.5-2% of the population

Causes: Unknown. Generally believed to be an autoimmune disease.

Symptoms: Pigment loss in the skin. Severity differs between patients.

Treatments/cures: No universally effective cure. Treatment efficacy varies greatly.

Differential diagnosis: Albinism

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Vitiligo is a common pigmentary disorder in which the pigment producing cells of the skin (melanocytes) are absent or non-functional. As a result, lighter patches of skin appear on various parts of the body due to the lack of melanin (pigment). Lesions on the face and the back of the hands are common and prominent; sites of injury or scarring are also commonly affected. Mucous membranes, such as the tissue inside the mouth, nose and the retina of the eye may be affected and the hair growing on depigmented skin can also turn white (poliosis).

Incidence

Depigmented skin caused by vitiligo
Figure 1. Depigmented skin characteristic of vitiligo

The incidence of vitiligo in the population is thought to range from 0.5% - 2%, affecting as many as 65 million people. It has been found to affect both genders and all races equally, however it is more noticeable in individuals with a darker complexion due to the greater contrast between natural skin colour and depigmented areas. A slight female predominance of vitiligo has been reported but remains statistically insignificant; these discrepancies may be attributed to female patients having a higher reporting rate due to cosmetic concerns. Disease onset can occur at any age but is more common in youth, with over half of cases commencing before 20 years of age.

Causes

The specific cause of vitiligo is unknown but it is generally accepted to be an autoimmune disease where the individual’s own immune system destroys the melanocytes. The variety of clinical and experimental features along with different family histories suggests that vitiligo might be the end product of several pathological pathways. In all likelihood, vitiligo is a multifactorial disease with a combination of interrelating factors resulting in different degrees and rates of progression. It is thought that genetic factors, accumulation of toxic compounds, altered cellular environment, autoimmunity and impaired melanocyte function could all contribute to vitiligo.

Autoimmune disease

There is much evidence to suggest that abnormalities in the immune system lead to the destruction of melanocytes in vitiligo patients. Antibodies are proteins, present in the blood, which the body produces in response to foreign objects, such as viruses and bacteria.  The antibodies are like tags, which signal to other cells in the immune system to destroy the target. Patients with vitiligo usually have auto antibodies which complement their own melanocytes, a strong indicator that the immune system is attacking its own body cells.

Lymphocytes are the white blood cells which detect and destroy the targeted pathogens, often by releasing cytotoxic (cell-killing) chemicals or by engulfing them. Patients with active vitiligo have been discovered as having an increased number of these cells circulating in their blood. Furthermore, these lymphocytes in vitiligo patients are reactive to the antigens (molecule on the surface of a cell) on melanocytes. Studies have also shown an abundance of T-cells (a type of lymphocyte) in the areas affected by inflammatory vitiligo, some suggest that these specific T cells may mediate the destruction of melanocytes.

Vitiligo has been linked to a number of other autoimmune diseases, with vitiligo patients at greater risk of developing thyroid disease, diabetes mellitus, Addison’s disease, pernicious anemia, rheumatoid arthritis, psoriasis and Grave’s disease, among others.

Genetic factors

There appears to be a genetic component to vitiligo, as 10% of patients have a family history of the condition and blood relatives have an increased risk of developing it. Multiple genes are likely to be involved, with different combinations inherited by different people. This is perhaps partially responsible for the extreme variability seen in vitiligo sufferers. Genes which could potentially be involved in the development of vitiligo include those responsible for autoimmunity regulation or melanin synthesis and degradation. The human leukocyte antigen (HLA) gene encodes many elements essential to immune system function in humans; this site is frequently associated with vitiligo.

Environmental triggers

Certain environmental conditions may interplay with the hereditary component of the disease, creating additional risk factors. Environmental triggers are not well-understood, though illness, emotional stress, severe sunburn and pregnancy have all been implicated as possible aggravating factors.

Neural association

The pattern of lesions in one type of vitiligo, called ‘segmental vitiligo’, tend to correspond to underlying nerves. In such cases, it has been suggested that certain chemical mediators released from nerve endings may be toxic to melanocytes. Some vitiligo patients have been shown to have mild degenerative or regenerative changes in nerve cells beneath the depigmented areas.

Self destruction

Melanocytes possess a protective mechanism to eliminate toxic melanin precursors (e.g. dopa, dopachrome) and free radicals. Experts suggest that vitiligo may incorporate a disturbance of this mechanism, leading to an accumulation of toxic intermediates and free radicals which can damage melanocytes.

It has also been found that the red blood cells (erythrocytes) of vitiligo patients have lower levels of the antioxidant glutathione. Antioxidants mop up excess reactive oxygen species which can damage skin cells. It is thought that in the absence of sufficient glutathione, the reactive oxygen species produced by the body can damage or completely destroy the melanocytes.

Symptoms

Vitiligo commonly affects sun-exposed areas, or areas of injury on the body, including the face, lips, hands, arms and feet. Vitiligo often starts as a small area of white skin, the pigment loss can then spread and become larger over time. Other common areas for patches to appear are the groin, armpits, torso, wrists, elbows, knees, nostrils and genitals. The severity of vitiligo varies with the individual and there is no way to predict how much pigment a person will lose or the rate at which it will spread. Other less common symptoms of vitiligo include: premature graying of the hair, eyelashes, eyebrows or other facial hair; loss of colour in the retina (inner layer of the eye) and loss of colour in the mucous membranes (i.e. the skin that lines the inside of the mouth). While vitiligo does not cause physical impairment, many patients suffer psychological impacts; such as low self-esteem, emotional distress and depression; which can significantly affect their quality of life.

Types of vitiligo

Vitiligo is classified into three main types, based on the distribution of the lesions. These categories are further subdivided depending on specific features of the disease.

Localised: Presents in distinct sections.

  • Focal - lesions are limited to one or two areas; commonly in a pattern parallel to the trigeminal nerve, which lies beneath the face.
  • Segmental - lesions develop in patches on one side of the body only. Occurs most frequently in children.
  • Mucosal - affects mucous membranes only (i.e. inside the mouth and eyes).

Generalised/Nonsegmental (NSV): Widespread across the body; the most common form of vitiligo.

  • Acrofacial - affects the face and other extremities.
  • Vulgaris - Lesions are scattered all over the body with a symmetrical distribution.
  • Mixed - some combination of acrofacial, vulgaris and segmental vitiligo.

Universal: Near complete loss of pigment (over 80% of the body); this type of vitiligo is rare.

In addition to the different classes of vitiligo there are a number of clinical variants based on the appearance of the lesion.

  • Trichrome Vitiligo - between the unaffected skin and the unpigmented area appears an intermediate zone of moderate pigmentation. This results in 3 shades of color; brown, tan, and white; in the same patient.
  • Quadrachrome Vitiligo - this reflects the presence of a fourth band around the lesion. It is usually a hyperpigmented band which develops during spontaneous repigmentation.
  • Inflammatory Vitiligo - the depigmented lesion is surrounded by a raised, inflamed border. It can be present from the onset or develop over time
  • Blue Vitiligo - this occurs when the patches develop a blue colouration. It has been observed in patients who have developed vitiligo on areas of skin where there was previously post-inflammatory hyperpigmentation (dark spots which occur following inflammation or injury).

    Treatments

    The main goal of treating vitiligo is to improve the appearance of the skin. However, to date, no universally effective and safe therapy exists. Many treatment options have been developed but challenges persist, as not all patients respond to available therapies and relapse is common. Their effect varies greatly and complete repigmentation is rarely accomplished. Factors such as the extent, distribution and rate of progression of the depigmentation dictate the choice of treatment. Self care, phototherapy, surgery and topical treatments may be used alone or in combination.

    Self care

    There are effective ways for patients to protect their skin and improve the appearance of vitiligo without medical intervention:

    • Solar protection - minimising sun exposure and ensuring that protective clothing and sunscreen are worn whilst in the sun to protect against UV radiation.
    • Camouflage - the use of cosmetics, such as make-up and tanning lotions, to cover up the patches of depigmented skin.

    Topical treatments

    Many of the medical therapies available are applied topically and can reduce the appearance of vitiligo:

    • Corticosteroids - topical steroid creams, such as Mometasone furoate, may aid in the repigmentation of patches of depigmented skin in vitiligo patients. They act by suppressing the immune system to prevent the destruction of melanocytes, slowing the progression of vitiligo and allowing for repigmentation. Corticosteroids are most effective on small areas of the face and repigmentation by this method is more successful in dark-skinned individuals. The steroids may take several months to take effect, this can exceed the safe period for exposure to these medications. Therefore, side-effects can arise, including; atrophy of the skin, telangiectasias (dilated blood vessels) and hypertrichosis (abnormal hair growth).
    • Depigmentation therapy - in cases where vitiligo is extensive (greater than 80%), some opt to undergo depigmentation to lighten the remaining pigmented areas of skin to match their depigmented skin. This treatment is quite extreme and involves the use of topical monobenzyl ether of hydroquinone (Benoquin). The entire process usually takes somewhere between 6 months and two years to complete. Patients can suffer irritant dermatitis from the Benoquin and must also practice strict photoprotection afterwards. A more recently developed method involves the use of lasers and topical 4-methoxyphenol (4-MP) to remove pigment.
    • Immunomodulators - creams containing agents such as tacrolimus and pimecrolimus can be used to reduce the immune response against melanocytes. These drugs down regulate the expression of certain genes involved in inflammation and immune response (interleukins and TNF-α), allowing for repigmentation to occur.
    • Calcium modulators - research shows that calcium transport in the melanocytes of vitiligo patients is often defective. Since vitamin D3 aids in calcium transport, it's analogues (calcipotriol and tacalcitol) have been trialed as a vitiligo treatment with varying success. Vitamin D3 has also been shown to activate melanin synthesis.

    Surgical intervention

    Surgical therapies are only recommended for patients with stable vitiligo. That is, patients whose patches have not grown or spread for at least 6 months. Surgery is usually very costly and can leave scarring, hence, it is only considered after other therapies have proven ineffective.

    • Skin grafts - surgeons remove healthy skin from the patients’ own body, or from a donor, and transplant it to the affected area.
    • Tattooing (micropigmentation) - manual tattooing of depigmented areas is a cheaper alternative, however is it difficult to find an exact match for skin colour. In addition, the tattooed skin may not remain the same colour as the surrounding skin as it will not naturally change tone in response to environmental influences.
    • Melanocyte transplantation - a promising treatment still in experimental trials, melanocyte transplantation involves culturing normal melanocytes from a skin sample and transferring the new cells into the depigmented patches.

    Phototherapy

    Ultraviolet (UV) radiation can be used as a therapy to restore pigment to the skin. Multiple sessions over several months may be required before the patient sees results. The extent of the response to phototherapy is highly variable and it is possible for relapse to occur. In the case of successful treatment, vitiligo patches may stabalise or further extend in the future.

    • Psolaren plus ultraviolet A radiation (PUVA) - Oral and topical medications called psolarens (photosensitisers) are combined with UVA radiation to repigment areas of skin. PUVA is a moderately effective treatment with a high relapse rate and potential side effects, including: nausea, sunburn, blistering, scaling, abnormally dark repigmentation and rarely, skin malignancies.
    • Narrowband ultraviolet B (NB-UVB) radiation - Light therapy using a narrow range of UVB radiation (wavelength of 311 nm), has been shown to be an effective treatment of vitiligo and produces minimal adverse effects. The repigmentation achieved by NB-UVB is generally very acceptable cosmetically, matching well with the surrounding skin. Children and individuals with a darker complexion tend to see better results from this type of phototherapy. Targeted phototherapy using an excimer laser is another source of NB-UVB. Useful for specifically targeting depigmented areas, this form of treatment can be expensive. Excimer laser treatment shows best results on the face, with the hands and feet being less responsive.

    Prognosis

    Vitiligo is highly unpredictable, it may be confined or it may spread to other areas of the body. The rate of depigmentation may be slow or rapid. Periods of pigment loss may be followed by periods of stability in which the skin does not change; such cycles can persist for a lifetime. Occasionally, depigmented areas of skin can spontaneously repigment without known cause. The prognosis of vitiligo is poor as patient responses to therapy are immensely variable. Patients generally need emotional support and are advised to seek dermatological assessment.

    Vitiligo and skin cancer

    In the absence of functional melanocytes and protective melanin pigment, one might expect to see an increased risk of skin cancer in vitiligo patients. To date, there is not conclusive evidence of this and the results of studies in this area are conflicting.  One 2002 study, involving a large number of subjects, showed no evidence for significantly increased levels of sun damage or skin cancer for vitiligo patients. The researchers suggest that this may be due to increased expression of a tumour suppressor gene in these patients which reduces the incidence UV radiation-induced damage and non-melanoma skin cancers. Further research may be required in order to clarify the association between vitiligo and skin cancer. Nonetheless, it is recommended that vitiligo patients maintain adequate sun protection in order to minimise any potential risk of skin cancer.

    Related posts on the Clinuvel Blog

    References

      • American Academy of Dermatology, 2009, Vitiligo, accessed 2nd August 2010, <http://www.aad.org/public/publications/pamphlets/common_vitilgo.html>.
      • Australasian College of Dermatologists, 2006, A-Z of Skin: Vitiligo, accessed 2nd August 2010, <http://www.dermcoll.asn.au/public/a-z_of_skin-understanding_vitiligo.asp>.
      • Garg, B.J et al., 2010, ‘Topical treatment in vitiligo and the potential uses of new drug delivery systems’, Indian Journal of Dermatology, Venereology and Leprology, 76(3):231-238.
      • Groysman, V, 2008, ‘Vitiligo’, eMedicine, retrieved 2nd August 2010, <http://emedicine.medscape.com/article/1068962-overview>.
      • Halder, R.M, 2006, Dermatology and Dermatological Therapy of Pigmented Skins, Taylor & Francis Group, pp.93-99.
      • Hann, S & Nordlund, J.J, 2000, Vitiligo: A Monograph on the Basic and Clinical Science, Blackwell Publishing, ch.16.
      • Huggins, R.H, Schwarts, R.A & Janniger, C.K, 2005, ‘Vitiligo’, Acta Dermatovenerologica Alpina, Panonica, et Adriatica 14(4):137-42, 144-5.
      • Kishan, K.Y.H et al., 2009, 'Evaluation of narrow-band UVB phototherapy in 150 patients with vitiligo.', Indian Journal of Dermatology, Venereology and Leprology, 75(2):162-6.
      • Mahmoud, B.H, 2008, ‘An Update on New and Emerging Options for the Treatment of Vitiligo’, Skin Therapy Letter, 13(2):1-10.
      • Njoo, M.D & Westerhoff, W, 2001, ‘Vitiligo. Pathogenesis and treatment’, American Journal of Clinical Dermatology, 2:167-181.
      • Schallreuter, K.U, Tobin, D.J & Panske, A, 2002, ‘Decreased photodamage and low incidence of non-melanoma skin cancer in 136 sun-exposed caucasian patients with vitiligo.’, Dermatology, 204(3):194-201.
      • Sehgal, V.N & Srivastava, G, 2007, ‘Vitiligo: Compendium of clinico-epidemiological features’, Indian Journal of Dermatology, Venereology and Leprology, 73:149-156.
      • Therapeutic Guidelines: Dermatology, Version 2, 2004, Therapeutic Guidelines Limited, North Melbourne.
      • Wolff, K et al., 2003, Fitzpatrick's Dermatology in General Medicine, 7th edn, The McGraw Hill Companies, ch. 72.

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