Vitiligo is an acquired idiopathic, dermatological disorder characterized by well-circumscribed milky white macules devoid of identifiable melanocytes. These asymptomatic white macules can be psychologically extremely damaging, even leading to attempted suicide in some cases. It affects approximately 1% of the world’s population and approximately 3-4% of the Indian population. The most common sites of involvement are the face (24.5%), neck (18.8%), and scalp (11.2%).
The exact etiology of vitiligo is unknown. It is believed that vitiligo is a polygenic trait and that a convergence theory combining elements of different etiological theories across a spectrum of expression is the most accurate etiology.
In general, topical monotherapy is indicated for mild-to-moderate vitiligo. Current treatment options for vitiligo include medical, surgical and adjunctive treatments.
Medical treatment targets the immune system and helps to arrest the spread of depigmentation. In cases of stable vitiligo, repigmentation can be achieved by dermatosurgical techniques and adjunctives includes use of cosmetics. Both surgical and medical treatment have their own limitations. Adjunctive can only cover the patch and be used along with surgical or medical treatments.
The best studied and most commonly used medical treatment options are corticosteroids, psoralens and depigmenting agents.
Corticosteroids: Topical steroids are often first-line therapy, especially in children or for localized disease. Moderately potent to potent topical corticosteroids are used. However, vitiligo requires prolonged use of these agents, often much longer than the usual “safe” recommended periods of use for inflammatory dermatoses. This results in significant, therapy-limiting side-effects like atrophy, hypertrichosis, peri-lesional hypopigmention etc. It is obvious that currently available dosage formulations do not provide site-specific drug delivery.
Phototherapy: Phototherapy is one of the oldest forms of treatment of vitiligo and remains the bedrock of vitiligo therapy even today. Out of three [5-MOP (bergapten), 4, 5, 8-trimethylpsoralen (TMP) and 8-MOP (methoxsalen)] different types of psoralens, 8-MOP is the most commonly used. Topical psoralen photochemotherapy (PUVA) is often used for people with limited disease (affecting less than 20% of the body). It is also used for children 12 years and older, who have localized patches for vitiligo. Severe sunburn, blistering and abnormally dark repigmentation are major potential side-effects of topical PUVA therapy. This is due to the uncontrolled photo- reaction of psoralen with ultra-violet A irradiation in the epidermis because drug is freely available from currently available dosage formulations, for reaction on surface after topical application. In recent years, narrow-band UVB (NB-UVB, 311 nm) has become the preferred phototherapy for vitiligo.
Calcium modulators: Recently, calcium modulators, the vitamin D3 analogues (calcipotriol and tacalcitol), have also been tried in the treatment of vitiligo. Defective calcium transport has been shown in melanocytes and keratinocytes harvested from patients with vitiligo Further, vitamin D3 has been shown to activate melanin synthesis. There are contradictory reports of their efficacy in vitiligo, both as monotherapy and in combination with both PUVA and NB-UVB phototherapy. The most common adverse effect of calcipotriol is lesional irritation and potential hypercalcemia if applied in quantity > 100mg in a week. So, controlled delivery can potentially deliver better results by modifying currently available dosage formulations, minimizing both systemic absorption and local irritation.
Calcineurin inhibitors: Calcineurin inhibitors (tacrolimus, pimecrolimus) are some of the newest topical drugs in dermatology . However, tacrolimus and pimercrolimus are effective only in vitiligo lesions on the head and neck region. The main difficulty with topical calcineurin inhibitors, and one that is probably responsible for lack of efficacy in non-facial vitiligo, is their high molecular weight. This precludes efficient delivery of the drug at the level of the basal cells, since the stratum corneum allows very poor absorption of any molecules over “500Da” in weight. This has recently been proved by an elegant study where greatly enhanced repigmentation with pimecrolimus was achieved by using it after performing microdermabrasion on the lesional skin. Hence, carrier mediated drug delivery can substantially increase their effectiveness bypassing the stratum corneum barrier and delivering these drugs in adequate concentration to the melanocytes and keratinocytes.