Depigmentation Therapies in Vitiligo

*Sanjeev Mulekar, Madhulika Mhatre and Swapnil Mulekar*

### **Abstract**

Vitiligo is a chronic condition characterized by white patches on normalappearing skin. It runs an unpredictable course. Main reason of stress in vitiligo patients is the presence of two colors on the skin surface. The aim of the treatment is to achieve normal skin color. Depigmentation is considered when repigmentation is not possible or the patient is willing to accept that repigmentation is not possible and opt for irreversible depigmentation. The only agent approved for depigmentation is monobenzyl ether of hydroquinone or monobenzone for patients with more than 50% of body surface area affected with vitiligo. The scope of this chapter is to describe modality of depigmentation and its risks and benefits.

**Keywords:** extensive vitiligo, vitiligo, depigmentation, MBEH

#### **1. Introduction**

Vitiligo is a skin condition characterized by loss of pigments on normal skin with a worldwide prevalence of 0.1–2%. Due to its cosmetic impact, vitiligo can impact the quality of life in children and adults. There are multiple therapies used for repigmentation beginning from topical corticosteroids, calcineurin inhibitors, and narrowband ultraviolet B (NB-UVB) to oral systemic medications and surgery. Even though a good number of patients may achieve successful repigmentation, there may be a few in whom the progression of vitiligo may affect extensive body surface areas making repigmentation an uphill task. The aim in such patients with extensive vitiligo (more than 50% body surface area) would be to achieve a uniform skin tone by depigmenting the remaining pigmented sites [1].

Depigmentation therapy is an accomplishable alternative therapy in patients who are extensively affected by vitiligo. It can be used in all skin types. Most readily used and available depigmenting agents are monobenzyl ether of hydroquinone (MBEH), 4-methoxyphenol, and phenol. Other therapies such as lasers and cryotherapy have also been used. The depigmentation process is a gradual one and can take anywhere between 1 and 3 years. In the author's experience, those who have undergone depigmentation are satisfied and happy with the therapeutic outcome if one achieves uniform color.

#### **1.1 What the research says**

The depigmentation approach is quite recent and is derived from the observations of unwanted depigmenting action of the phenol derivatives [2]. However, there are very few published studies on it. The aim of the researchers was to explain the possible mechanism of action for this class of compounds. Tyrosinase was the first suggested target. Also the potential of different phenol derivatives to act as an alternative substrate of the enzyme or as a competitive inhibitor was evaluated. Thus, it was hypothesized that this class of substances, or some of them, may be used for the treatment of skin disorders caused due to hyperpigmentation or melanocyte hyperproliferation. Further structural studies have indicated that the role of the position and type of substitutes in the phenolic ring allow the compound to be hydroxylated or oxidated by tyrosinase [3]. Considering phenol derivatives have a role in this process, hydroquinone was evaluated. Hydroquinone (HQ ) belongs to the phenol/catechol class of chemical agents. Tyrosinase gets inhibited by HQ when interaction occurs with copper at the active site. This further decreases the amount of intracellular glutathione and induces the production of oxygen-reactive species. Thus, HQ acts as an alternative substrate, according to most part of phenol/catechol compounds, because it is similar to tyrosine. The enzyme can thus oxidize HQ without generating the pigment. The quinones produced are able to react with the sulfhydryl residues of the proteins, generating oxidative damage and affecting the cell growth. The depigmenting action is the result of the oxidative damage, involving both lipids and proteins of the cellular membranes. Functional studies have demonstrated that HQ and other phenolic compounds, such as tert-butylphenol, may even act through different mechanisms, including the oxidation of TRP1, and by interfering with RNA and DNA synthesis. HQ has been identified as the main depigmenting agent, whereas among the various phenolic derivatives, the monobenzyl ether of hydroquinone (MBEH) appeared as the more handful one. In this chapter, we will review and compare various established and potential depigmentation agents as well as emerging therapies that can be used in extensive and universal vitiligo.
