What is depigmentation?

Depigmentation therapy is used to improve the appearance of someone who has widespread but incomplete vitiligo on the face and/or other areas.

Monobenzyl ether of hydroquinone is the most often used depigmenting agent (MBEH). Combination therapy or other treatments may be considered if the patient cannot tolerate MBEH or if treatment fails.

Who is suitable for depigmentation therapy?

Treatment-resistant vitiligo that affects more than 50% of the body surface area or affects cosmetically sensitive, exposed body areas may benefit from depigmentation therapy.

Informed consent for treatment with depigmentation agents

Before beginning depigmentation therapy, the patient should be aware of the following:

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

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

Monobenzyl ether of hydroquinone

Monobenzone, often known as MBEH, is the most commonly used depigmenting agent in vitiligo. The FDA has approved it as the only depigmentation therapy for severe vitiligo (Food and Drug Agency, United States of America).

MBEH is a hydroquinone derivative. It usually produces irreversible depigmentation, unlike hydroquinone, since it induces melanocyte death (the cells that make skin pigment or melanin).

MBEH is available in a 20 percent cream, but it can be made up to 40% for tough areas like the elbows and knees. Benoquin® 20 percent cream is the brand name in the United States. MBEH is not licensed for use in New Zealand by Medsafe, however it can be obtained from the manufacturer under Section 29 by medical practitioners. The patient is responsible for the entire expense of treatment.

Adverse reactions from monobenzyl ether of hydroquinone

Most reactions to MBEH are mild

• Transient irritation: stop treatment if burning sensation is severe.
• Contact irritant dermatitis (blistering, scaling, dry skin, swelling of treated sites): stop treatment and apply topical corticosteroids to affected areas. When the dermatitis subsides, consider using a weaker strength of MBEH.
• Less often, sensitisation or allergy to MBEH causes contact allergic dermatitis: stop treatment permanently and apply topical corticosteroids to affected areas.
• Loss of colour (leukoderma) at sites away from the area of application of the cream.
• Exogenous ochronosis (ashy brown pigmentation) after prolonged use of MBEH may include pigment deposition in the conjunctiva and cornea of the eyes.
• There is no safety data available for use of MBEH in women who may be pregnant or breastfeeding.
• Safety of MBEH in children below 12 years of age has not been established.

How do I use monobenzyl ether of hydroquinone?

• Tolerance to MBEH should be tested prior to commencing treatment on facial skin. Apply MBEH cream once daily for two weeks to a small area, such as the inner upper arm, then increase to twice daily.
• If tolerated, a thin layer of MBEH cream should be rubbed in twice daily to the pigmented areas to be lightened.
• Do not apply the cream to the eyelids or mucosal surfaces.
• Avoid sun exposure at all times to prevent the color returning in patches.

Depigmentation normally takes 1–4 months, although it might take up to 12 months for a specific spot to be completely depigmented.

If the expected results are not attained after four months, the treatment should be stopped. Once the desired level of depigmentation has been attained, the cream can be used on a weekly basis to preserve it.

After treatment, the white skin will remain sun sensitive for the rest of one’s life. Apply broad-spectrum SPF50+ sunscreen to all white skin at least once a day.

Monomethyl ether of hydroquinone

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

• MMEH exhibits melanocytotoxic characteristics similar to MBEH.
• MMEH is most commonly formulated as a 20% cream.
• MMEH is used in the same way that MBEH is.
• MMEH takes longer to depigment than MBEH, taking between 4 and 12 months on average.
• MMEH causes less skin irritation and is less severe than MBEH.

Phenol solution

Phenol is a comparatively low-cost substance. It’s been used for deep chemical peels for a long time. Melanocytes are poisoned by phenol, which inhibits them from producing melanin. Because high-dose phenol (e.g., 88 percent) is systemically hazardous, it should not be used in wide areas. It must be handled with extreme caution because it can result in serious chemical burns, cardiac arrhythmias, and other complications.

Phenol is used to cure tiny areas of vitiligo that have persistent pigment, such as 20% of the face or neck. Use only 0.5-1 ml per session for safety, and the application time should not exceed 60 minutes. Phenol should only be used by a qualified physician.

• Cleanse the skin with alcohol
• Apply a cotton swab moistened with phenol to treat small areas until frosting is achieved.
• Maximum permissible amount per session is 1 ml.
• A burning sensation lasts about a minute, and gradually decreases in intensity over minutes to hours.
• Two treatments given 6 weeks apart are usually sufficient.
• Post-procedure care includes normal saline soaks and mild-moderate topical corticosteroids.

Risks and side effects of phenol include:

• Scarring
• Dyschromia (irregular pigmentation/depigmentation)
• Localised or disseminated herpes simplex virus infection. Anti–viral prophylaxis with aciclovir should be considered.
• Corrosion of any tissue it comes in contact with, by inhalation, ingestion, or direct skin contact.
• The 88% concentration rapidly coagulates the epidermis and thereby prevents it own percutaneous penetration, as compared to the traditional 40-50% phenol peels.
• Systemic toxicity results in cardiovascular shock, cardiac arrhythmias, bradycardia, and metabolic acidosis. These have been reported within 6 hours of peeling procedures with phenol.

Lasers

Ruby (694 nm), alexandrite (755 nm), and Nd:YAG (532 nm and 1064 nm) Q-switched lasers can be used alone or in combination with topical depigmenting chemicals like MBEH or MMEH. By selectively eliminating melanin and melanin-bearing cells, these lasers act as depigmenting agents.

The following are the primary drawbacks of lasers in depigmentation therapy:

• High cost
• Potential need for local anaesthetics due to pain
• Possible treatment failure
• Recurrence of pigmentation.

Combination therapies

According to some reports, combining MBEH or MMEH with a topical retinoid like tretinoin can help overcome treatment resistance and improve treatment efficacy. Retinoids aid by blocking the glutathione S-transferase enzyme in melanocytes.

MBEH or MMEH can be used in conjunction with cryotherapy or laser therapy.

Other potential treatments

Imatinib

Depigmentation of the skin has been described as a side effect of imatinib, a medicine used to treat chronic myeloid leukemia, within 4-12 weeks of treatment. Imatinib mesylate, a tyrosine kinase inhibitor, is thought to work by interfering with the generation of melanin.

Imiquimod

Imiquimod is an immunomodulator that is extensively used to treat superficial skin malignancies and genital warts. Permanent hypopigmentation, which might occur after 3 months of treatment, is one of the negative effects of treatment. The proposed mechanism of action is that imiquimod causes melanocyte apoptosis.

Diphencyprone

Diphencyprone, also known as diphenylcyclopropenone, is a dermatological treatment for alopecia areata and other disorders characterized by altered immune processes. Due to its immunomodulatory actions, diphencyprone solution has been known to cause hypopigmentation or full depigmentation on treated areas. Depigmentation is said to start after 10 months, and it can happen even at concentrations as low as 0.0001 percent.

Experimental agents

A number of phenolic chemicals are being studied in animals for their depigmenting effects, including hydroquinone at concentrations greater than 4%, 4-ethoxyphenol, and 4-methylcatechol. IFN-, busulfan, and certain melanoma vaccinations (immunotherapy) are thought to have depigmenting properties.

Herbal products and depigmentation

Traditional healers in Africa commonly employ the following herbs for voluntary depigmentation:

• Brillantaisia cicatricosa Lindau (Acanthaceae)
• Chenopodium ugandae (Aellen) Aellen (Chenopodiaceae)
• Dolichopentas longiflora Oliv. (Rubiaceae)
• Protea madiensis Oliv. (Proteaceae)
• Sesamum angolense Welw. (Pedaliaceae).
• Ethanolic extracts of the leaves of Myrica rubra.

These herbs may have an effect on the generation of melanin by melanocytes, according to in vitro studies. This is an area that could be investigated further in the future.