Depigmentation therapy for vitiligo

Author: Lizbeth Intong, MD, FACD and Monisha Gupta, MD, FACD, Dermatologists, Sydney, Australia. Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, April 2014.

What is vitiligo?

Vitiligo is a common autoimmune skin disorder that results in partial loss of skin pigmentation, ie white patches of skin. More information ...

What is depigmentation therapy?

Depigmentation therapy refers to medical treatments that remove skin pigmentation causing contact leukoderma. Depigmentation therapy is used in someone that has widespread, but incomplete, vitiligo on the face and/or other sites, in an attempt to improve their appearance.

The most commonly used depigmenting agent is monobenzyl ether of hydroquinone (MBEH). If the patient cannot tolerate MBEH, or if treatment fails, combination therapies or other treatments may be considered.

Who is suitable for depigmentation therapy?

Depigmentation therapy may be considered in the management of treatment-resistant vitiligo affecting more than 50% of the body surface area or affecting cosmetically sensitive, exposed body sites.

Informed consent for treatment with depigmentation agents

Prior to starting depigmentation therapy, the patient should understand:

  1. The permanent nature of the treatment
  2. The need for lifelong, strict sun protection to maintain benefits and reduce the risk of sun damage including skin cancer.
  3. The slow response to treatment and need for ‘touch–up’ sessions
  4. The potentially high cost of treatment
  5. Common and uncommon side effects and safety issues
  6. Risk that repigmentation will be patchy and incomplete
  7. Psychosocial and cultural issues that may arise from change in skin colour.

Patients should be given the opportunity to discuss treatment options with their family and friends.

Monobenzyl ether of hydroquinone

MBEH or monobenzone is the most commonly used depigmenting agent used in vitiligo. It is the only depigmentation treatment for extensive vitiligo that has been approved by the FDA (Food and Drug Agency, United States of America).

MBEH is a derivative of hydroquinone. Unlike hydroquinone, it almost always causes irreversible depigmentation, as it results in death of melanocytes (the cells that make skin pigment or melanin).

MBEH is available as a 20% cream, although it may be formulated up to 40% for difficult areas such as the elbows and knees. In the US, it is available as Benoquin® 20% cream. MBEH is not approved by Medsafe for use in New Zealand but may be obtained by medical practitioners from the manufacturer under Section 29. The full cost of the treatment must be paid by the patient.

Adverse reactions from monobenzyl ether of hydroquinone

Adverse reactions from MBEH are mostly mild.

How do I use monobenzyl ether of hydroquinone?

Depigmentation is usually achieved after 1–4 months, however it may take up to 12 months for complete depigmentation of a particular site.

Treatment should be discontinued if the desired results are not achieved after 4 months of use. Once the desired degree of depigmentation is achieved, the cream may be applied intermittently to maintain this, usually twice a week.

Following treatment, the white skin will be sun sensitive lifelong. Apply SPF50+ broad-spectrum sunscreen to all white skin at least daily.

Monomethyl ether of hydroquinone

Monomethyl ether of hydroquinone (MMEH) is also known as 4-methoxyphenol, mequinol, or p-hydroxyanisole.

  1. MMEH has similar melanocytotoxic properties to MBEH.
  2. MMEH is usually compounded as a 20% cream.
  3. MMEH is applied in a similar manner to MBEH.
  4. Compared to MBEH, MMEH takes longer to achieve depigmentation, usually between 4 and 12 months.
  5. Skin irritation from MMEH is less common and less severe than with MBEH.

Phenol solution

Phenol is relatively inexpensive. It has been traditionally used for deep chemical peels. Phenol is toxic to melanocytes, and prevents them from synthesising melanin. High-dose phenol (eg 88%) is also systemically toxic and must not be applied to large areas. It must be used very cautiously because it can cause severe chemical burns, heart arrhythmias and other dangers.

Phenol is used to treat small areas of persisting pigment in vitiligo, i.e. <20% of the face or neck area. For safety, use only 0.5-1 ml per session and the application duration should be no longer than 60 minutes. Phenol must be applied by an experienced physician.

Side effects and risks of phenol include:


Q-switched lasers, such as the ruby (694 nm), alexandrite (755 nm) and Nd:YAG (532 nm and 1064 nm) may be used alone or in combination with topical depigmenting agents such as MBEH or MMEH. These lasers work as depigmenting agents by selectively destroying melanin and melanin-bearing cells.

The main disadvantages of lasers in depigmentation therapy are:


Cryotherapy with liquid nitrogen is a cost-effective permanent depigmenting treatment when rapid depigmentation of a small area is desired. It is simple, easy for an experienced physician to perform, and only requires a short preparation time. Melanocytes are exquisitely sensitive to cryodamage compared to keratinocytes and cryotherapy can result in permanent loss of colour (depigmentation) after treatment.

The disadvantages of cryotherapy include:

Combination therapies

There are some reports that MBEH or MMEH combined with a topical retinoid such as tretinoin may overcome treatment resistance and enhance treatment efficacy. Retinoids help by inhibiting the melanocyte enzyme glutathione S-transferase.

MBEH or MMEH may also be used in combination with cryotherapy, or laser treatment.

Other potential depigmentation treatments


Imatinib is a medication used for chronic myeloid leukaemia, where depigmentation of the skin has been reported as a side effect within 4-12 weeks of receiving this medication. The suggested mechanism of action is that imatinib mesylate, a tyrosine kinase inhibitor, interferes in the production of melanin.


Imiquimod is an immune response modifier, used most commonly in the treatment of superficial skin cancers and genital warts. One of the side effects of treatment is sometimes permanent hypopigmentation, which may occur after 3 months of treatment. The postulated mechanism of action is that imiquimod can induce apoptosis of melanocytes.


Diphencyprone, also called diphenylcyclopropenone, is used in dermatology to treat conditions with altered immunological states, such as alopecia areata. Diphencyprone solution has been noted to sometimes result in hypopigmentation or complete depigmentation on treated areas, possibly due to its immunomodulatory effects. The onset of depigmentation is reported to occur after 10 months, and can occur even with concentrations as low as 0.0001%.

Experimental agents

A number of phenolic compounds, including hydroquinone in concentrations higher than 4%, 4-ethoxyphenol, and 4-methylcatechol, are being tested for their depigmenting effects in animals, and appear promising. There is some suggestion that IFN-γ, busulfan and some melanoma vaccines (immunotherapy) have depigmenting activity.

Herbal products and depigmentation

The most common herbs used by traditional healers for voluntary depigmentation in Africa are:

In vitro studies have indicated that these herbs may have effects on the production of melanin by melanocytes. This represents a potential area for future studies.

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