Treatment for Vitiligo

Treatment for Vitiligo

What Are Our Options Really?

Dr Melvin Ee

Vitiligo is a common acquired disorder characterised by patches of depigmentation. The frequency varies from 0.5% to 2% in various global populations. About 20-30% of patients report vitiligo in first- or second-degree relatives. Genetic data support a non-Mendelian, multi-factorial, polygenic inheritance. Vitiligo does not discriminate. It affects all races, skin types, and ethnicities. Given the stark contrast between depigmented and normal skin, the disease is most disfiguring in darker racial ethnic groups. It affects both males and females almost equally, with an average age of onset at 20 years. It may appear anytime though hardly seen in infancy or old age. Nearly all cases of vitiligo are acquired relatively early in life. Vitiligo is no doubt one of the most psychologically devastating diseases in dermatology.

Pathogenesis

Genetics may play an important role. About 6-38% of cases have a positive family history, possibly controlled by recessive genes at three to four autosomal loci. A positive association has been found between vitiligo and HLA-DR4, and recently HLA-DQA1 and DQB1 were reported as the susceptible alleles in Hans Chinese.

The precise cause of loss of epidermal melanocytes in vitiligo is unknown. Many hypotheses have been proposed. These mechanisms may occur independently or in combination.

Autoimmune Mechanism

Autoimmunity remains the most popular hypothesis. Autoimmune diseases, in particular Hashimoto’s thyroiditis, are increased in patients with vitiligo. In addition, a plethora of humoural and cell-mediated immune aberrations have been characterised. Autoantibodies targeting melanocyte surface antigens and cytoplasmic antigens are numerous. This hypothesis also accounts for persons with vitiligo associated with other autoimmune diseases, including pernicious anaemia, Addison’s disease, myasthenia gravis and diabetes mellitus.

Autocytotoxic Mechanism

This is a defective free-radical defence, with melanocytes’ death as a result of increased sensitivity to oxidative stress.

Neural Mechanism

Neurochemical released at peripheral nerve endings resulting in melanocytotoxicity mechanism has been proposed. This hypothesis supports the distribution in segmental vitiligo.

Melanocytorrhagy of Gauthier

Gauthier et al recently proposed a new theory of melanocytorrhagy based on the in vivo observation of melanocyte detachment from the basal cell layer, followed by trans-epidermal migration and death of melanocytes.

Pathology

There is marked absence of melanocytes and melanin in the epidermis. Histochemical studies show a lack of dopa-positive melanocytes in the basal layer of the epidermis [Figures 1a and 1b].

Figure 1a. Melanocytes in normal epidermis Figure 1b. Marked absence of melanocytes and melanin in the epidermis

Clinical Features

Vitiligo is usually gradually progressive, sometimes extending centrifugally quickly over weeks to months before taking a senescence for many months to years. It is characterised by hypomelanosis of the diseased area. The margins are usually sharp but may be ill defined in early stages [Figure 2]. Trichrome vitiligo has been described where there are white, intermediate and normal hues from the centre to the periphery of the lesion. Its size can be variable measuring from millimetres to centimetres in size.

The hypomelanotic macules are usually noted on the sun-exposed areas of the skin, on the perioral, periorbital, dorsum of nose, feet or dorsum of the hands. Many of the most common sites of occurrence are areas subjected to repeated trauma, including the following: elbow, extensor forearm, ventral wrists, dorsum hands and the phalanges. Involvement of the mucous membranes often occurs around body orifices such as the lips, genitals, gingiva, areolas, and nipples. Leukotrichia (white hair) may occur in vitiliginous patches. Vitiligo may also develop over an area of injury such as a cut or burn.

Associated cutaneous features include leukotrichia, halo naevi, koebnerisation and melanoma. Associated autoimmune diseases include thyroid disease (7.5%), diabetes mellitus, pernicious anaemia (0.8%) and Addison’s disease (1.3%). The most consistent association is with thyroid disease.

Differential Diagnoses

The diagnosis is usually straightforward and is further suggested by the distribution, onset and hyperpigmented border contrasting drastically with the non-pigmented skin.

Differential diagnoses include hypopigmented conditions:

• Genetic – naevus depigmentosus, naevus anaemicus, hypomelanosis of Ito

• Inflammatory – lichen sclerosus, scleroderma, tinea versicolour, leprosy (tuberculoid and indeterminate types), pityriasis alba, post-inflammatory hypopigmentation, tuberous sclerosis, mycosis fungoides, idiopathic guttate hypomelanosis

Depigmented disorders such as post-inflammatory depigmentation, chemical leukoderma, piebaldism, and leucoderma of melanoma should also be considered. For childhood-onset vitiligo, consider naevus depigmentosus, ash-leaf macules and naevus anaemicus.

Figure 2. Vitiligo of the chest

Investigation

Routine screening for autoimmune disease is not indicated unless supported by clinical suspicions. If any doubt persists of the diagnosis antinuclear antibody, full blood count and thyroid function test may be performed. Although the diagnosis of vitiligo generally is made on the basis of clinical findings, biopsy is occasionally helpful for differentiating vitiligo from other hypopigmentary disorders.

Treatment

Several forms of treatment are available, but the response to treatment varies with each person and site affected.

General Measures

Areas affected by vitiligo are very prone to sunburn as they lack protective pigments. Photoprotection with sunblock is important to protect the vitiliginous skin. Care must be taken to avoid trauma, especially in the extensor areas, to minimise the risk of koebnerisation. Camouflage cosmetics and skin dyes, such as Vitadye®, can be prescribed to mask the lesions, especially if they are extensive and causing psychological distress. Vitadye® (dihydroxyacetone) is applied for three hours daily until the optimal colour is achieved. Cover-up cosmetics can also be recommended for patients; camouflage is particularly useful for white patches on the face and back of the hands.

Topicals

• Corticosteroid Creams

Corticosteroid creams are effective in many patients, but regular monitoring by a doctor is necessary to prevent side effects. These creams are most useful for localised vitiligo of recent onset. Potent topical corticosteroids (eg, mometasone cream) carry a modest success rate of approximately 50% plus of cases achieving greater than 75% repigmentation. Response is expected within three months. When some repigmentation has begun, topical steroids can be continued under close supervision for side effects, such as cutaneous atrophy and telangiectasia.

• Topical tacrolimus or pimecrolimus

These are creams known as topical immunomodulators. They work by modulating the immune attack against melanocytes on the skin and by stimulating the function of melanocytes. They may be combined with other treatment modalities. In a randomised double-blind trial, its effectiveness was comparable to that of 0.05% clobetasol propionate cream.

• Topical calcipotriol monotherapy

This may play a role in stimulating melanogenesis as well as modifying defective epidermal calcium homeostasis in patients with vitiligo. In an open study, Ameen et al treated 22 patients with twice-daily topical calcipotriol. After six months, 23% showed >90% improvement, 32% had 50-90% improvement, 23% had 30-50% improvement, while the remaining 23% had <30% or no improvement. Those who responded poorly had a long history of vitiligo, extensive lesions or involvement of non-hair bearing areas of the body.

• Ultra violet light treatments

Narrow-band ultraviolet B (NBUVB) is now the treatment of choice for patients with moderate to severe vitiligo. Several studies have documented its efficacy and safety in children and adults. The major advantages of NBUVB include ease of treatment, lack of need for post-treatment ocular protection, and lack of systemic side effects. Unlike psoralen plus ultraviolet A (PUVA), phototoxic reactions are minimal, and there is no increase in skin cancers in vitiligo patients treated with narrowband. In a recent meta-analysis, NBUVB therapy has a higher success rate (63%) of achieving >75% repigmentation than broad-band UVB (57%) or oral PUVA (51%) therapies.

• NBUVB

With NBUVB there is no need to take oral tablets before treatment. Treatment is given two or three times a week, and treatment time is no longer than 10 minutes. To achieve almost complete repigmentation, 100-200 treatments may be required [Figures 3a and 3b]. Pregnant and breastfeeding women and children can be treated with this technique.

Figure 3a. Before NBUVB Figure 3b. After multiple sessions of NBUVB

• Psoralen photochemotherapy, or PUVA

PUVA is a combination treatment involving the use of a drug called psoralen and then exposing the skin to ultraviolet A. Psoralen makes the skin temporarily sensitive to UVA which forms part of the natural sunlight. Psoralen can either be applied to the skin as a solution (topical PUVA) or ingested orally (oral PUVA) with subsequent exposure to UVA. It is contraindicated in pregnant and breastfeeding women, children, and those with photosensitivity disorders. Close medical supervision is necessary. Use of PUVA may result in sunburn and blister, while nausea and vomiting is associated with the ingested psoralen.

• Excimer laser

Unlike NBUVB and PUVA, the 308nm excimer can selectively treat single vitiliginous patches, sparing non-affected areas. Rapid therapeutic responses have been reported, which may facilitate lowering cumulative UV dosing. Lesions are treated twice weekly. More than 50% of patients tested showed 75% or more pigmentation of their lesions after 30 treatments or less, with the face demonstrating the best response. A treatment period of more than 12 weeks is necessary to obtain a satisfactory clinical repigmentation.

Others

• Systemic corticosteroids

Oral corticosteroids have been used to manage extensive and rapidly spreading vitiligo. Oral corticosteroids can be given daily at a low dose. With daily prednisolone, 70% of patients showed some repigmentation after four months of treatment, while arrest of progression was 87%. Treatment of systemic steroids may produce unacceptable side effects and must be closely monitored by specialist.

• Surgical options

Surgical transplants are meant for patients with stable vitiligo that fail to respond to topical or phototherapies. Stable vitiligo refers to patients having no new lesions or progression of lesions over 12 to 24 months. These options work best for patient with segmental or focal vitiligo. The surgical techniques include tissue and cellular grafting. Types of autologous grafts include suction epidermal grafts, mini-grafts, split skin thickness grafts, cultured epidermal/melanocyte suspensions. Similar to all surgical procedures, suitability must be assessed. Surgical grafting is used in combination with NBUVB therapies.

• Depigmentation

This is only considered for patients with extensive vitiligo and who have failed all other forms of treatment. A 20% monobenzylether of hydroquinone is applied daily or twice daily over 9-12 months, until the skin is bleached evenly. The result is irreversible and the decision should be reached only after careful discussion and consideration.

Dr Melvin Ee is consultant dermatologist at Specialist Skin Clinic, Orchard Building. He subspecialises in aesthetic dermatology, skin cancers, Mohs micrographic surgery and laser surgery in addition to general dermatology. Dr Ee was formerly the Chief of the Skin Cancer Clinic and Mohs micrographic surgical service at the National Skin Centre, where he pioneered and established the Mohs micrographic surgical technique in Singapore.

 

 

 

 

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