Depigmentation Therapy for Vitiligo
Wednesday, January 18, 2012
Most patients with vitiligo desire repigmentation of the
affected areas. Several treatments are available, including topical
corticosteroids and phototherapy; however, these are mostly helpful
for patients with small lesions of short duration. Patients with
more extensive, long-standing lesions may have too much involvement
for these treatments to be practical. As the outlook for
significant repigmentation is poor in these individuals,
depigmentation therapy may be chosen to remove the remaining
pigment, eliminate the spottiness of the skin, and present an even
appearance. In general, more than 50% depigmentation must be
present on a body area in order for depigmentation therapy to be
feasible. In this article, we discuss the use, mechanisms of action
and side effects of several depigmentation therapies in patients
Monobenzylether of Hydroquinone
Monobenzylether of hydroquinone (MBEH) has been the most
commonly used depigmentation therapy in vitiligo treatment for over
half a century. It is currently the only drug approved by the Food
and Drug Administration (FDA) for depigmentation in the
US.1 Its depigmentation properties were discovered
incidentally when tannery workers reported the appearance of white
patches on their arms and forearms. Patch testing revealed the
causative agent to be Agerite Alba, an impure form of MBEH found in
rubber gloves.2 Following this discovery, MBEH was found
to improve many conditions of hyperpigmentation, such as melasma,
post-inflammatory hyperpigmentation, nevi, and ephelides, and was
even thought to be a "miracle cure" for these
disorders.3,4 However, side effects such as irritation,
depigmentation at distant sites, and dyschromia soon
emerged.5 Hydroquinone - a molecule similar to MBEH -
was introduced into the clinical setting after the side effects of
MBEH surfaced. It was shown to be an effective treatment for
hyperpigmentation without the risk of permanent
depigmentation.6 Subsequently, the use of MBEH has been
limited to only those who desire permanent
The depigmentation success rate of MBEH is over 60%.5
Therapy involves twice daily application of MBEH cream and results
in a progressive lightening of the skin (Figures 1 and 2). Full
depigmentation may require 4-12 months of therapy and generally
takes longer in those with darker skin.1,5
Figure 1. Left cheek of a patient with
extensive vitiligo who desired depigmentation therapy.
Figure 2. Left cheek of the same patient
seen in Figure 1 after 3 months of twice-daily topical
monobenzylether of hydroquinone; the patient also used sunscreens
and practiced sun avoidance.
Mechanism of Action
The mechanism of action of MBEH is not fully understood, but
initial studies theorized that MBEH is converted to hydroquinone in
the skin, thereby preventing melanin formation.7
Recently, it has been shown that MBEH induces necrosis of
non-follicular human melanocytes, which probably accounts for the
ability of MBEH to produce permanent depigmentation.8 So
far, no studies have compared the degree of depigmentation seen
with MBEH on different skin types, but melanin and tyrosinase have
been identified as key factors affecting depigmentation.
Correlative studies between melanin concentration and melanocyte
viability after exposure to MBEH show that, as the concentration of
melanin increases, less melanocyte death occurs.8 If
melanin is protective against MBEH-induced cell death, this could
explain the reduced MBEH-induced depigmentation response in
patients with darker skin.
Conversely, other studies propose that tyrosinase is the enzyme
responsible for MBEH-induced depigmentation by causing covalent
interactions that consequently inactivate the melanin-producing
enzyme.9 This would suggest a greater response in darker
skin; however, it has been shown that there is little variation in
the amount of tyrosinase protein among different skin types. The
melanin content varies owing to the higher activity of tyrosinase
in darker complexions, a result of tyrosinase-related
The most frequent side effect of MBEH in the treatment of
vitiligo is irritant contact dermatitis in pigmented areas of
skin.11 13% of patients using MBEH experience contact
dermatitis, with reactions ranging from mild erythema to painful
vesicular eruptions.5,12 Conjunctival melanosis has also
been observed in some patients undergoing MBEH
therapy.13 Although depigmentation is permanent in most
cases, spontaneous and partial repigmentation can occur within
weeks to years after discontinuation of therapy.5,14
Exposure to ultraviolet light is the major reason for
repigmentation and often results in a freckle-like pigmentation
appearing in areas of previously depigmented skin owing to residual
melanocytes in follicles. Patients must be instructed to use
sunscreens and practice sun avoidance during and after MBEH use in
order to prevent this from occurring.
Other Depigmentation Agents
Although MBEH is the only FDA-approved therapy for
depigmentation in the US, alternative depigmentation therapies
being studied include other phenol derivatives, laser therapy, and
Mequinol is a phenol derivative thought to produce similar
results to MBEH but with a slower onset of
depigmentation.15 Mequinol therapy is currently used in
The Netherlands, where the use of MBEH has been restricted.
For rapid and selective depigmentation, laser therapy using a
Q-switched ruby laser has also been studied. Pain was reported as
the major side effect, and follicular depigmentation developed in
Finally, cryotherapy has recently been introduced as a
cost-effective method for depigmentation of pigmented macules in
vitiligo, but lentigo-like macules developed in sun-exposed areas
of some participants after treatment.17 Combination
therapy has also been studied; however, none of these methods has
been adopted as a mainstream therapy for depigmentation in patients
The desperation for treatment causes many patients suffering
from vitiligo to consider potentially harmful products marketed as
skin whiteners. For example, glutathione is marked as a skin
whitener in some countries such as the Philippines; however, the
Philippine government recently released a public warning on the
harmful effects of glutathione, including fatal skin rashes,
thyroid dysfunction, and potential kidney failure.19
Patients are often willing to purchase costly but ineffective
products in an attempt to improve the spotty appearance of
vitiligo. 97% of participants in one study reported that they would
give an entire year's salary in search of a cure.20 It
is important to discuss the ineffectiveness of many costly products
and the potential harmful side effects of over-the-counter products
The goal for depigmentation therapy is to obtain an even skin
appearance; however, it is important to consider the possible
disadvantages of permanent depigmentation. One such disadvantage is
the possibility of a vitiligo cure being found in the future. Major
discoveries have recently been made in the genetic causes and
pathogenesis of vitiligo, which might lead to breakthroughs in
future treatment options. Permanent depigmentation may not allow a
patient to take advantage of such future therapies. This is
especially important for younger patients. Additionally, the social
effects of vitiligo are psychologically and emotionally
distressing; however, depigmentation therapy in patients with
darker skin types can result in exacerbation of social and cultural
misunderstanding, as in the case of the African-American pop
superstar Michael Jackson, who sought out permanent depigmentation
of his skin.
Repigmentation is the optimal target for patients with vitiligo;
however, depigmentation therapy is the only current treatment
option for patients with severe, universal vitiligo. Research into
various depigmentation methods such as cryotherapy, laser therapy,
and combination therapy are on the horizon, but MBEH currently
remains the mainstay therapy for depigmentation in patients with
- Bolognia JL, Lapia K, Somma S. Depigmentation therapy.
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- Oliver EA, Schwartz L, Warren LH. Occupational leukoderma.
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- Mosher DB, Parrish JA, Fitzpatrick TB. Monobenzylether of
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- Oakley AM. Rapid repigmentation after depigmentation therapy:
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- Njoo MD, Vodegel RM, Westerhof W. Depigmentation therapy in
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- Radmanesh M. Depigmentation of the normally pigmented patches
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Philippines Department of Health Food and Drug Administration,
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- Ongenae K, Dierckxsens L, Brochez L, et al. Quality of
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