DOI: 10.1111/j.1468-3083.2009.03150.

JEADV

CPD PAPER
Blackwell Publishing Ltd

Skin bleaching: highlighting the misuse of cutaneous depigmenting agents

OE Dadzie,* A Petit

Department of Dermatology, Chelsea and Westminster Hospital, London, UK Service de Dermatologie 1, Hpital Saint-Louis, Paris, France *Correspondence: OE Dadzie. E-mail: opheliadadzie@hotmail.com

Abstract
Hydroquinone and other cutaneous depigmenting agents are widely used by dermatologists to treat pigmentary disorders. On 29 August 2006, the US Food and Drug Administration (FDA) published a monograph in the US Federal Register proposing to ban all hydroquinone products that have not been approved via a New Drug Application process. Reports in the scientic literature on the occurrence of exogenous ochronosis, in relation to the use of hydroquinone, was one of the concerns expressed by the FDA in relation to this agent. However, a review of the English-language scientic literature reveals that most of the reported cases of hydroquinone-induced exogenous ochronosis occurs in Africa, where the cultural practice of skin bleaching is highly prevalent. Skin bleaching is the practice of applying hydroquinone and/or other depigmenting agents to specic or widespread areas of the body, the primary function being to lighten normally dark skin. This practice typically occurs in men and women with Fitzpatrick skin phototypes IV to VI. It is a dangerous practice associated with a diverse range of side-effects, including mercury poisoning. Thus, this current discussion within the dermatological community on the safety of hydroquinone provides a unique opportunity to raise awareness about skin bleaching.
Received: 20 September 2008; Accepted: 16 December 2008
DOI: 10.1111/j.1468-3083.2007.0@@@@.x

Keywords
corticosteroids, depigmentating agents, hydroquinone, skin bleaching

Introduction
The US Food and Drug Administration (FDA) Over-the-Counter Miscellaneous Panel had designated 2% as a safe concentration for hydroquinone products until 29 August 2006, when the FDA published a monograph in the US Federal Register proposing to ban all hydroquinone products that have not been approved via a New Drug Application process.1 This proposal arose following the failure of manufacturers to comply to a request by the FDA for safety studies on hydroquinone. In addition, the FDA has cited many safety concerns about this product, including the occurrence of hydroquinone-induced ochronosis. Nonetheless, hydroquinone remains a popular agent for the treatment of pigmentory disorders in people with skin phototypes IV to VI.2 Thus, the proposal to ban this agent has prompted many within the dermatological community to publish articles that address the concerns of the FDA. One important point highlighted in some of these published articles is that hydroquinone-induced ochronosis occurs typically in Africa, where the cultural practice of skin bleaching is prevalent.3,4 Thus, this current discussion within the dermatological community about the safety and regulation of hydroquinone is a perfect opportunity to present an overview of

the practice of skin bleaching, and to raise more awareness on the occurrence and dangers of this practice. Skin bleaching is the practice by which depigmenting agents are used typically by people with skin phototypes IV to VI on a cosmetic basis, primarily to lighten normally dark skin. The practice of skin bleaching dates back over many years in different communities around the world. In fact, in the early 1900s some US physicians advocated the use of radiation therapy as a skin bleaching agent.5,6 Despite the initial early enthusiasm for this treatment, the many undesirable side-effects of this therapy became apparent, leading to an end to this dangerous practice. Currently, skin bleaching remains a common part of life within some African communities, reflected even by the local vernacular. For example, in Mali and Senegal, the term caco and xeesal are, respectively, used to describe this practice,7 while in Ghana, the term nensoeben is used to describe the ochronosis that develops as a side-effect of this practice. Interviews conducted on skin bleachers in sub-Saharan African countries highlights many factors driving this practice. A desire to lighten skin colour is cited as a primary motivating factor for skin bleaching.8,9 This is because in some countries, white skin is still perceived to be associated with social privileges, including better

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology

742

Dadzie and Petit

Table 1 An overview of studies conducted worldwide on the cosmetic use of depigmenting agents (prevalence and types of agents used)
Reference (country of origin and type of study) Adebajo18 (Nigeria, community study) Ajose8 (Nigeria, hospital study) Prevalence of skin bleaching 77.3% (females, 72.4%; males, 27.6%) Females, 40%; males, 2% Type of depigmenting agents Site and frequency of use of depigmenting agents Not specied in study Duration of use

Hydroquinone; mercury; corticosteroids; locally concocted soaps/creams Hydroquinone; class I and II steroids; mercurials; phenolics caustics; unknown chemicals and plant derivatives; combinations Hydroquinone; steroids; mercurials; unknown composition Hydroquinone; corticosteroids; mercurials; detergents; hypochloride sodium; unknown composition Corticosteroids; hydroquinone; vegetable extracts; caustic products; unknown composition 48.7% hydroquinone; steroids; caustic agents; unknown composition; mercury iodide Hydroquinone; corticosteroids; mercurials Steroids; hydroquinone; mercurials; kojic acid; alpha hydroxyl acids; unknown composition Steroids; hydroquinone Mercurials; hydroquinone; steroids; unknown composition Phenolics; steroids; combination of agents; mercurials; unknown composition

13 years (46.3%)

Not specied in study

6 monthsover 20 years

Faye et al.7 (Mali, hospital study) Del Giudice et al.22 (Senegal, hospital study)

Not specied in study 27% active skin bleachers

Not specied in study Once to thrice per day

Not specied in study 50.5 months (mean), range 1240 months

Ly et al.34 (Senegal, hospital study) Mah et al.20 (Senegal, hospital study) Mah et al.23 (Senegal, maternity centre) Nnoruk et al.21 (Nigeria, hospital study)

Not specied in study

Not specied in study

6.7 5 years (mean), range 130 years 4 years (median)

52.7% ( 5)

Whole body; once or twice per day Whole body (85.2%); at least once per day Whole body; face; twice per day

68.7% 58.7%

5 year (mean), range 3 month24 years 5 years 1.3 years

Petit et al.27 (France, hospital study) Pitch19 et al. (Togo, community study) Traore et al.9 (Burkina Faso, community study)

80% 58.9% 44.3%

Entire body and face; at least once per day Not specied in study Not specied in study

14 years (mean), range 138 years Not specied in study 13 years

job and marital prospects. However, some skin bleachers may not desire white skin, but instead desire radiant skin.10 Up until recent years there was limited choice with regard to the types of cosmetic products available in Africa and Europe, especially for individuals with Fitzpatrick skin phototype VI.11 In absence of such products, bleaching the skin may be perceived as an alternative method of enhancing ones beauty, especially prior to important social events.8 Other reasons cited by individuals partaking in skin bleaching include imitation of others and dependency on the products.8,9 Finally, the higher prevalence of dyschromias in people with skin phototypes IV to VI may be another factor that initiates, promotes, and/or excuses this practice.12,13 As a result of a lack of understanding about the appropriate use of depigmenting agents, coupled with negative cultural perceptions about dark skin, these cutaneous depigmenting agents may be subsequently intentionally or inadvertently misused.14,15

North America, Europe, Asia and the Middle East practice skin bleaching. Evidence from the non-medical press further highlights the global burden of this practice. Thus, scientific studies conducted on the practice of skin bleaching, as summarized in Tables 1 and 2 and discussed in detail below, may only represent the clinical iceberg of a more widespread problem.
Africa

Prevalence of skin bleaching

A review of the scientific literature demonstrates that individuals from diverse communities around the world, including Africa,

The worldwide awareness of the cultural practice of skin bleaching originates from the work of Findlay et al.,16 who in 1975 first reported on the occurrence of exogenous ochronosis in South African women. These women had used high concentrations (3.57%) of hydroquinone-containing agents over the course of many years for bleaching their skin. Skin bleaching remained a problem in South Africa and by 1986 the total sales volume of skin lighteners was an estimated 30 million pounds.17 Currently, skin bleaching continues to have an impact on dermatological practice in many sub-Saharan African communities, with prevalence rates of this practice in community and clinic settings documented to be between 26% and 67%.79,1822 This estimate is based on descriptive

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology

Table 2 An overview of studies conducted worldwide on the cosmetic use of depigmenting agents (adverse reactions and motivation for skin bleaching)
Reference (country of origin and type of study) Adebajo18 (Nigeria, community study) Prevalence of adverse reactions 50% Infections Dyschromias Systemic side-effects Haematuria Other side-effects Motivation for skin bleaching (1) Treatment of skin blemishes. (2) To become more attractive and satisfy the desires of opposite sex. (3) Fashionable trend. (1) To even out skin tone. (2) To lighten complexion. (3) To improve appearance of skin prior to an event. (4) Dependency. Not specied in study Not specied in study

Skin bleaching

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology

Not specied

Yellowish brown discoloration of skin

Striae; hirsutism; oedema; thinning of the skin; easy bruising; body odour; weight gain

Ajose8 (Nigeria, hospital study)

69.2%

Mycoses; scabies; warts; erysipelas; pyodermas

Ochronosis; confetti-like hypomelanosis

Faye et al.7 (Mali, hospital study) Del Giudice et al.22 (Senegal, hospital study) Ly et al.34 (Senegal, hospital study)

Not specied in study Not specied in study

Mycoses; pyoderma; scabies Intertrigo; pyoderma; tinea corporis Cutaneous mycosis; scabies; erysipelas

Not specied in study Hyper- and hypopigmentation Peri-orbital hyperpigmentation; hyperpigmentation of joints; leucoderma; exogenous ochronosis; brownish nails

Cushings syndrome; renal impairment; immune suppression Not specied in study Not specied in study Not specied in study

Elastosis; sunburn; acne rosacea; striae; telangiectasia; hypertrichosis; body odour

Mah et al.20 (Senegal, hospital study)

Overall prevalence of adverse reactions not specied in study; however, specic prevalence date reported (e.g. hyperpigmentation of joint 85.4%, striae atrophicae 72%) Not specied in study

Striae atrophicae; acne vulgaris; irritant dermatitis Facial acne; facial hypertrichosis; cutaneous atrophy; stretch marks; purpura Striae atrophicae; telangiectasia; lichenication; skin atrophy; acne vulgaris; poikiloderma; scarring; pretibial ichthyosis; pigmented keratosis; pilaris; lilac erythema of eyelids

Not specied in study

Mah et al.23 (Senegal, hospital study) Nnoruka et al.21 (Nigeria, hospital study) Petit et al.27 (France, hospital study)

Not specied in study

Dermatophyte; candidiasis; nonspecic intertrigo; tinea versicolor; scabies; bacterial skin infections Not specied in study

Hyperchromia; hypochromia; ochronosis; blue ear

Not specied In study

Irritant dermatitis; eczema; acne; perioral dermatitis; striae; poikiloderma; facial hypertrichosis; xerosis/ichthyosis; isolated itching; keratosis pilaris Increased compared to non-steroid users; occurrence of mild vaginal bleeding; lower placental weight; lower plasma cortisol Acne vulgaris; striae; easy bruising; telangiectasia; hypertrichosis Skin atrophy; striae; acne; irritant or allergic contact; dermatitis; rosacea; acute caustic dermatitis

Not specied in study

Not specied in study

Not specied in study

Not specied in study

Not specied in study

Dermatophyte (atypical) Profuse tinea corporis; pyoderma

Not specied in study

Pitch et al.19 (Togo, community study) Traore et al.9 (Burkina Faso, community study)

Not specied in study

Nil

55.5%

Dermatophyte

Macular hyperpigmentation of face Hyperpigmentation dorsal aspects of interphalangeal joints; ochronosis; confetti-like hypopigmented spots Hypopigmentation; leucomelanoderma; hyperpigmentation Dyschromia; ochronosis

Diabetes; hypertension Biological signs of adrenal suppression

(1) Depigmentation; (2) For managing medical conditions (1) Beauty; (2) Dependency

Not specied in study Not specied in study

Acne; cutaneous atrophy

Not specied in study

Acne; cutaneous atrophy; vibices; telangiectasia eczema; burn; other

(1) Change skin colour. (2) Change skin texture. (3) Imitation of others. (4) No reason given. (5) Imperfections treatment.

743

744

Dadzie and Petit

studies and surveys on the cosmetic use of cutaneous depigmenting agents conducted in community- and/or hospital-based settings via questionnaires and/or interviews. In fact, most of the knowledge acquired about the practice and complications of skin bleaching originates primarily from such studies performed in sub-Saharan African countries. However, a review of some of these studies reveals inherent limitations. First, since most of the studies are based on interviews and/or questionnaires, the study subjects may have given inaccurate histories about their cosmetic use of cutaneous depigmenting agents. Second, studies in hospital-based settings may overestimate the prevalence of skin bleaching, as individuals attending dermatology clinics are more likely to have primary dermatological problems for which they would have sought out cutaneous depigmenting agents. Interestingly, studies also reveal that individuals often continue their practice of skin bleaching throughout pregnancy and lactation. For example, Mah et al.23 demonstrated that 68.7% of selected women between 6 and 9 months gestation, attending a maternity centre in Dakar, Senegal, used skin lighteners for cosmetic purpose during their pregnancy. This included agents containing hydroquinone, highly potent corticosteroids and products of unknown composition. Interestingly, some of the women in this study reported starting or increasing their use of skin lighteners because of their pregnancy.
North America

using this agent as a skin lightener, the results of this study do indicate that the practice of skin bleaching may be a problem in some communities within the USA. Thus, further studies to investigate the motivations for the cosmetic use of cutaneous depigmenting agents are warranted in the USA. This is of particular importance given the fact that the demographics of the USA is changing, with a higher proportion of the US population predicted to be of African and Hispanic descent in the future.12
Europe

The practice of skin bleaching has been reported in Africans and Afro-Caribbeans living in European countries, including the United Kingdom and France.14,26,27 In fact, the over-the-counter use of hydroquinone has now been banned in Europe, although this agent and various other depigmenting agents remain available illegally in many markets in Europe.15 In a multicentre study conducted in the Paris region, it has been estimated that 16% to 28% of adult African women seeking dermatological treatment in Paris are regular users of skin bleaching agents.26 Moreover, in a recent study by Petit et al.27 on 46 subjects from various African countries attending a dermatology clinic in Paris for side-effects of skin lighteners, 31% had begun their practice of skin bleaching in France.
Asia

To date, there have been no formal studies conducted in North America to assess the prevalence of skin bleaching. This indicates that either this practice is uncommon or it is under-recognized by practicing physicians in North America. Nonetheless, an insight on the cosmetic use of depigmenting agents in North America can be gained by reviewing case reports and other studies documenting adverse reactions to these agents. This review provides conflicting results. In a review of the 789 worldwide reported cases of exogenous ochronosis, only 22 cases (19832006) occurred in the USA.3 Subjects from the USA with hydroquinone-induced ochronosis had often self-medicated with these agents as a mode of therapy for their primary dyschromias. This indicates that the cultural practice of skin bleaching, as a mode of changing normal skin colour, is not very common in the USA. However, in the mid-1990s, following an index case of mercury poisoning associated with the use of a Mexican beauty cream containing high levels of mercury, a survey was conducted to describe the demographics and patterns of use of this cream in border communities of Arizona, California, New Mexico and Texas.24,25 The results of this study demonstrated that the majority of users of this beauty cream were Hispanic women, with 44% using this beauty cream as a skin lightener. Most cream users used this agent over a median of 4 years, with 52% applying this cream two to three times per day. Although most cream users had purchased the cream from Mexico, 21% purchased the cream in the USA, typically at flea markets or herb shops. Although cream users were not asked their motivation for

Ashikari28 when writing on the Japanese culture, states that since the late 1980s, consumption of whitening cosmetics has remained at consistently high levels and a white complexion has been considered trendy and desirable in Japan, being a symbolic physical characteristic for identifying Japanese people. Despite the popularity of skin bleaching in Japan, to date there have been no formal studies reported in the English-language scientific literature on the prevalence of this practice in this country. However, there are studies reported in the English-language scientific literature that gives an insight into the practice of skin bleaching in Hong Kong. Tang et al.29 reported the case of a woman who developed minimal change nephropathy as a complication of the use of mercury containing skin-lightening cream. Furthermore, following an index case of mercury poisoning, a survey was conducted in Hong Kong to describe the demographic characteristics, patterns of use and other laboratory parameters in people who had used the same skin whitening cream. Of note, among 314 cream users, 27% were using it as a skin whitening agent.30 The motivation for this behaviour was not discussed in this study.
The Middle East

To date, there are no formal studies documenting the prevalence of skin bleaching in this region of the world. However, in a study undertaken in Saudi Arabia to investigate the mercury content in skin-lightening creams, Al-Saleh et al.31 state that in Saudi markets a wide variety of different brands of skin-lightening

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology

Skin bleaching

745

creams are available, either being imported from overseas or being manufactured locally by traditional herbalists. This high supply indicates that there may be a high demand for such skinlightening products in this country.

Adverse effects of skin bleaching agents

A diverse range of products at various concentrations are used for skin bleaching. This includes hydroquinone, hydroquinone derivatives (hydroquinone monobenzylether and monomethylether), potent steroids2,22, mercurials (mercuric iodide 13% or mercuric chloride 68%), kojic acid, alpha hydroxyl acids, plant-derived products (that may contain active agents such as arbutin) and even hydrogen peroxide. Sometimes, various ingredients from the domestic environment (toothpaste, washing liquid, washing soda, hair straighteners, sand, cement and even battery fluid) may be mixed in homemade concoctions that are used once for their caustic effect. Skin bleaching agents are used in cream, lotion, oil, gel, soap or pomade formulations and are typically obtained from non-medical sources, including open markets and beauty stores.9,23 This unregulated trade in cutaneous depigmenting agents involving non-medically trained individuals has fuelled an international trafficking business, which needs to be curtailed. The risk of side-effects occurring with skin bleaching depends on the nature and concentration of products used.32,33 This is complicated by the fact that on occasion products used may contain a higher concentration of active agents than stated on their packages.34 Additional contributory factors for the development of side-effects with skin bleaching include the concurrent use of several depigmenting products, application of products over widespread areas of the body, application of products over prolonged periods (months to years) and lack of sunscreen usage. Table 1 lists some of the agents that have been used for skin bleaching, while Table 2 lists some of their associated adverse effects, which are discussed in detail below.
Hydroquinone

Figure 1 Hyperpigmented papules (conrmed on lesional biopsy to be consistent with exogenous ochronosis) on the back of a 36-year-old West African woman who practiced skin bleaching.

Hydroquinone, also chemically known as 1,4-dihydroxybenzene, is a ubiquitous chemical that occurs naturally in our environment.2 It is a strong oxidant that is rapidly converted to p-benzoquinone and hydroxybenzoquinone, both of which are melanocyte toxic. Hydroquinone is an effective inhibitor of melanogenesis in vitro and in vivo, inhibiting both DNA and RNA synthesis, as well as reducing tyrosinase activity primarily in melanocytes.35 In fact, it does affect other cell types, but because the dose required to inhibit their cellular metabolism is much higher than for melanocytes, it is primarily melanocyte specific. Irritant and allergic contact dermatitis, with subsequent post-inflammatory dyspigmentation, are potential side-effects that may occur with the use of hydroquinone during skin bleaching. However, the concomitant use of topical steroids may reduce this side-effect.20 Nail plate pigmentation36 and peripheral neuropathy37 have also been reported as a complication of hydroquinone usage.

In 2001, Karamagi et al.37 reported the case of a young black woman with chronic symmetrical sensorimotor polyneuropathy and autonomic neuropathy, which improved 4 months after she stopped the use of hydroquinone-based skin bleaching agents. Although most metabolic factors that may have accounted for her signs and symptoms were excluded, the authors did not perform HIV serological testing on their patient. Thus, the association of her symptoms and signs with her use of hydroquinone was circumstantial. Exogenous ochronosis (Fig. 1), characterized by progressive asymptomatic hyperpigmentation with associated papules on sun-exposed skin, is another reported side-effect of hydroquinone. Histology of lesional skin demonstrates collagen and elastic fibre degeneration and deposition of ochre-coloured fibres in the dermis.16 A total of 789 cases of exogenous ochronosis have been reported in the scientific literature, of which 756 occurred in Africa,3 where the practice of skin bleaching is highly prevalent, suggesting a link between skin bleaching and this side-effect.8,9,20,27 However, caution should be used when interpreting these data due to the presence of confounding factors that may account for higher levels of exogenous ochronosis in Africa. First, the concomitant use of antimalarials (which may also give rise to ochronosis) are frequently not cited in studies on the complications of skin bleaching. Second, in most studies in Africa on skin bleaching, the diagnosis of ochronosis is often based on clinical assessment, with no lesional biopsies undertaken to confirm these clinical findings. This is understandable in view of the limited resources in Africa, where most of these studies have been conducted. Finally, the lack of sunscreen use during skin bleaching, the use of higher concentrations of hydroquinone formulations,

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology

746

Dadzie and Petit

and the use of formulations containing resorcinol and other agents may all contribute to increase the risk of exogenous ochronosis in relation to the practice of skin bleaching. However, given that over the course of many years, many individuals have been exposed to hydroquinone (it has been available in over-thecounter formulation since about 1956 in the USA),2 the comparatively low rates of reported exogenous ochronosis, is somewhat reassuring, indicating that this may be an uncommon side-effect of hydroquinone. Alternatively, this low rate may also be a result of under-reporting of this complication in the scientific literature. Another important theoretical side-effect associated with skin bleaching with hydroquinone agents is the development of cutaneous and internal malignancies. Hydroquinone is a metabolite of benzene, a leukaemogenic agent. It is also associated with the development of mononuclear cell leukaemia in female rats exposed to oral hydroquinone over a 2-year period.3 Despite this theoretical risks, studies indicate that comparatively low levels of hydroquinone are absorbed with topical application of these agents.3 Moreover, hydroquinone and its derivative, arbutin (which is hydrolysed to hydroquinone in an acidic environment such as the stomach), are ubiquitous agents, such that humans are exposed to them from consumption of products such as tea, coffee, rice, onions, cranberries, blueberries and wheat. Furthermore, since hydroquinone is important in the development of black and white films, individuals working in this industry have high exposures to this agent. Nonetheless, studies that have assessed mortality rates and cancer prevalence in such individuals have not identified a higher-risk profile in this cohort.2 In light of the above, we can conclude that there remains a lack of conclusive evidence supporting a carcinogenic risk from the topical use of hydroquinone. Alternatively, since the practice of skin bleaching involves the application of high concentrations of hydroquinone over widespread areas of the body, it may be argued that this may represent a higher-risk profile for the development of malignancies. However, only two cases exist in the literature that documents the development of cutaneous malignancy in relation to skin bleaching.38 In these cases, spindle cell squamous cell carcinomas occurred in association with skin bleaching with hydroquinone agents. The mechanism for this observation is postulated to be through the pro-carcinogenic effect of hydroquinone or due to suppression of the natural photo-protection effect of melanin. Further studies are warranted in skin bleachers to accurately assess their risk of cutaneous malignancies.
Corticosteroids

Figure 2 Striae on the internal aspect of the arm of the woman shown in Fig. 1.

Topical steroids are anti-inflammatory agents used for the treatment of many inflammatory skin diseases. They are popular cutaneous depigmenting agents used for skin bleaching,21 and it is the present authors opinion that the extensive use of illegal clobetasol-containing agents is responsible for most of the severe side-effects associated with skin bleaching in Francophone countries. Their effect as depigmenting agents is mediated via the

initial local vasoconstriction occurring when applied to the skin, giving an impression of an immediate reduction in pigmentation of the skin.15 Eventually, topical steroids exert their depigmenting effect via an inhibitory effect on epidermic melanogenesis. Their prolonged use (> 3 weeks), especially on thin skin such as facial and flexural sites, is associated with a range of adverse effects.21,33,34 This includes the development of striae (Fig. 2), peri-oral dermatitis, rosacea-like eruption, acne vulgaris, telangiectasia, poor wound healing, easy bruising and hypertrichosis. Other side-effects include ophthalmic problems (cataracts, glaucoma, eye infections and blindness) associated with the application of topical steroids to the face, especially the eyelids and aseptic osteonecrosis (personal observations). Cutaneous infections (Fig. 3), such as dermatophytosis, cellulitis, erysipelas, scabies and warts, may also occur as a complication of the misuse of topical steroids. Often there is an atypical presentation or a masking of the clinical presentation of these cutaneous infections. For example, Mah et al.39 reported the case of a young black woman, who used 0.05% clobetasol propionate and hydroquinone on the peri-lesional skin of a hypochromic region on her cheek. Over time, this masked the hypochromic lesion on her cheek, which was one of the presenting features of her paucibacillary leprosy. Finally, the use of potent topical steroids is associated with systemic side-effects including diabetes and hypertension, Cushings syndrome, immunosuppression and adrenal insufficiency.27,4042
Mercury

Mercury salts produce their cutaneous depigmenting effect via inhibition of melanin formation. This occurs because mercury salts compete with copper in tyrosinase.43 Historically, chronic mercury poisoning has occurred in the context of industrial

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology

Skin bleaching

747

species, including Aspergillus and Penicillium. Side-effects observed with this agent include irritant contact dermatitis. Glycolic acids are alpha-hydroxyl acids derived from sugar cane. At low concentrations, it has an epidermal discohesive effect, while at high concentrations it results in epidermolysis. Both these actions lead to removal of the superficial layers of the epidermis and, hence, a depigmenting effect when used for skin lightening. Additional possible mechanisms for depigmentation include acceleration of keratinocytic turnover with a reduction in their melanosome loading time. Side-effects observed with this agent include irritant contact dermatitis, with the risk of postinflammatory hyperpigmentation.

Conclusion
The current focus within the dermatological community on the safety and regulation of hydroquinone presents a unique opportunity to raise awareness on the occurrence and dangers of skin bleaching. Aesthetic and systemic side-effects of skin bleaching not only remain a public health problem in most parts of sub-Saharan Africa, but also may increasingly impact many other communities around the world. It is important that we educate individuals with pigmentory problems to seek early dermatological care for their dermatoses, rather than to selfmedicate with over-the-counter or illegally obtained cutaneous depigmenting agents. However, this would not be enough to reduce the global burden of skin bleaching. Instead, a multifaceted approach is required, addressing several issues concurrently. First, more studies in the field of human sciences, to consider the sociological and psychological factors that are responsible for the search of a lighter complexion (which may vary among different communities) are required to guide the development and implementation of appropriate public health prevention campaigns. Second, international cooperation between governmental, nongovernmental and medical agencies is required to decrease the international trafficking of illegal depigmenting agents, especially clobetasol-containing products. Third, continued rigorous scientific studies, especially in Western, Arab and Asian countries where such studies remain scarce, are required to critically evaluate the global burden and adverse health effects associated with skin bleaching, Finally, more research directed towards the development of alternative safer agents for the inhibition of skin pigmentation is required.

Figure 3 Tinea inguinalis due to Trichophyton rubrum in a 40-year-old man from Central Africa. Note the surrounding hypopigmented skin, a result of the practice of skin bleaching.

exposure (felt hat industry) or during the use of mercurial medicinal preparations (used in the past to treat infectious skin disorders such as syphilis and impetigo).44 Currently, skin lightening is also a cause of mercury toxicity.24,25,29,30,4446 The features of mercury toxicity, also known as the hatters disease, as immortalized in Alice in Wonderland by Lewis Carroll, consists of psychiatric (disturbance of recent memory, impairment of intellectual function, inattention and depression) and neurological (irritability, memory loss and neuropathies) problems. 43 Other adverse reactions noted with mercury toxicity includes renal impairment (minimal change or membranous glomerulonephritis)29,30,45,46 and a paradoxical increase in skin pigmentation.44 The latter occurs either by an increase in melanin production (mechanism unknown) or via direct deposition of metallic mercury granules in the dermis. The percutaneous absorption of mercury occurs exclusively via cutaneous appendages and, hence, on lesional biopsy, peri-follicular accentuation of mercury deposition is observed in mercury-induced hyperpigmentation. Interestingly, the use of mercurial agents for skin lightening by pregnant and/or lactating women has also been associated with adverse effects in their neonates, including the development of anaemia, renal impairment and cataracts.47
Other depigmenting agents

Key points
Skin bleaching is the use/mis-use of depigmenting agents: the primary objective being to lighten normally pigmented skin Individuals from diverse communities around the world practise skin bleaching A wide range of agents such as hydroquinone and its derivatives, steroids, mercurials, kojic acid, alpha hydroxyl acids, plant-derived products and even hydrogen peroxide are used for skin bleaching

Other agents used during skin bleaching include kojic acid and glycolic acids.35 Kojic acid works primarily as a tyrosinase inhibitor and an antioxidant. It is derived from various fungal

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology

748

Dadzie and Petit

Many adverse effects have been reported in association with skin bleaching A multi-faceted approach is required to reduce the global burden of skin bleaching.

Questions and multiple choices

1. In 2006, the U.S. Food and Drug Administration (FDA) proposed (a) the banning of all hydroquinone products that have not been approved via a New Drug Application process (b) an increase in the concentration of over-the-counter hydroquinone products (c) the banning of all over-thecounter depigmenting agents (d) none of the above 2. Broadly speaking studies undertaken about skin bleaching in Africa are limited because of (a) recall bias of subjects (b) confounding factors e.g. the concurrent use of antimalarials (c) a higher prevalence of hospital based studies (d) all of the above 3. Which of the following has/have been used for skin bleaching? (a) radiation therapy (b) hydroquinone (c) corticosteroids (d) all of the above 4. Skin bleachers have cited the following motivating factors for their practice with the exception of: (a) lightening of skin colour (b) moisturising of skin (c) dependency (d) enhancement of beauty 5. Which of the following statement about skin bleaching is false? (a) it is practised by diverse communities around the world (b) it is more commonly undertaken by individuals with Fitzpatrick skin phototype I (c) some individuals continue this practice throughout their pregnancy (d) treatment of dyshcromias may be one reason that initiates and/or excuses this practice 6. The prevalence of skin bleaching in sub-Saharan African communities is between: (a) 26-67% (b) 2-7% (c) 1-25% (d) 22-97%. 7. Which of the following statement(s) is/are true? (a) the use of hydroquinone is banned throughout all of Europe (b) 2% hydroquinone can be purchased as an over-the-counter product legally in European countries such as the UK and France (c) hydroquinone is not available legally as an overthe-counter product in European countries such as UK and France (d) all of the above 8. Which of the following statement(s) about the practice of skin bleaching in Europe is/are true? (a) skin bleaching has been reported in Africans residing in Europe (b) skin bleaching has never been reported in Africans residing in Europe (c) In France, the majority of Africans who practice skin bleaching start this behaviour when they move to this country (d) none of the above 9. Which of the following agent(s) from the domestic environment may be used for skin bleaching? (a) toothpaste (b) battery fluid (c) cement (d) all of the above

10. The risk of side effects from skin bleaching is increased by all the following except: (a) the concurrent use of more than one depigmenting agent (b) the use of high concentrations of depigmenting agents (c) the concurrent use of sunscreens (d) the use of depigmenting agents over large body surface area and over a prolonged time course 11. Which of the following statement about hydroquinone is false? (a) it is also chemically known as 1,4 dihydroxybenzene (b) it occurs naturally in the environment (c) it is a strong oxidant (d) it increases the activity of tyrosinase 12. Recognised side effects of hydroquinone include all the following except: (a) nail plate pigmentation (b) nephrotoxicity (c) exogenous ochronosis (d) contact dermatitis (irritant and/ or allergic) 13. Which of the following statement(s) concerning the carcinogenic risk of hydroquinone is/are true? (a) benzene, a metabolite of hydroquinone is a carcinogen (b) mononuclear cell leukemia has been observed in female rats exposed to intravenous hydroquinone (c) the carcinogenic risk of hydroquinone accounts for the higher observed risk of cancer in individuals working in the photographic industry (d) all of the above 14. The observed skin lightening effects of topical corticosteroids occur initially via: (a) local vasoconstrictor effect (b) antiinflammatory properties (c) suppression of the hypothalamicpituitary axis (d) none of the above 15. Recognised side effects of topical corticosteroids used for skin bleaching include: (a) acne vulgaris (b) peri-oral dermatitis (c) cutaneous infections (d) all of the above 16. Historically exposure to mercury has been reported to occur as a result of: (a) working in the felt hat industry (b) treatment of syphilis (c) treatment of impetigo (d) all of the above 17. Characteristic features of mercury toxicity includes all the following except: (a) increased skin pigmentation (b) psychiatric problems (c) diabetes mellitus (d) nephrotoxicity 18. The use of mercurial products as skin bleaching agents: (a) has been associated with outbreaks of renal disease in Asian countries (b) is associated with an increased risk of cutaneous infections (c) does not cause adverse effects in neonates when used by pregnant and/or lactating mothers (d) is never associated with a paradoxical increase in skin pigmentation 19. Kojic acid is derived from: (a) bacteria (b) fungus (c) protozoa (d) none of the above 20. Possible interventions that can be undertaken to reduce the global burden of skin bleaching include: (a) education of at risk populations regarding the adverse effects associated with skin bleaching (b) co-operation between governmental and non-governmental agencies to help curb illegal trafficking of depigmenting agents (c) more research focused on the development of depigmenting agents with less adverse effects (d) all of the above

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology

Skin bleaching

749

Correct answers
1 2 3 4 5 (a) (d) (d) (b) (b) 6 7 8 9 10 (a) (c) (a) (d) (c) 11 12 13 14 15 (d) (b) (a) (a) (d) 16 17 18 19 20 (d) (c) (a) (b) (d)

References
1 U.S. Department of Health and Human Services, Food and Drug Administration. Skin bleaching drug products for over-the-counter human use; proposed rule. Federal Register 2006; 71: 5114651155 (codified at 21 CFR Part 310). 2 Nordlund JJ, Grimes PE, Ortonne JP. The safety of hydroquinone. J Eur Acad Dermatol Venereol 2006; 20: 781787. 3 Levitt J. The safety of hydroquinone: a dermatologists response to the 2006 Federal Register. J Am Acad Dermatol 2007; 57: 854872. 4 Toombs EL. Hydroquinone what is its future? Dermatol Ther 2007; 20: 149156. 5 Boston Globe. Can the Ethiopian change his skin or the leopard change his spots: radium light turns Negros skin white. 25 January 1904. 6 New York America. Burning out birthmarks, blemishes of the skin and even turning a Negro white with the magic rays of radium, the new mystery of science! 10 January 1904. 7 Faye O, Keita S, Diakit FS, Konar HD, Ndiaye HT. Side effects of de-pigmenting products in Bamako, Mali. Int J Dermatol 2005; 44: 3536. 8 Ajose FOA. Consequences of skin bleaching in Nigerian men and women. Int J Dermatol 2005; 44: 4143. 9 Traore A, Kadeba J-C, Niamba P, Barro F, Ouedraogo L. Use of cutaneous depigmenting products by women in two towns in Burkina Faso: epidemiologic data, motivations, products and side effects. Int J Dermatol 2005; 44: 3032. 10 Findlay GH. Ochronosis following skin bleaching with hydroquinone. J Am Acad Dermatol 1982; 6: 10921093. 11 de Souza MM. The concept of skin bleaching in Africa and its devastating health implications. Clin Dermatol 2008; 26: 2729. 12 Taylor S. Skin of color: biology, structure, function, and implications for dermatologic disease. J Am Acad Dermatol 2002; 46: S41S62. 13 Halder RM, Nootheti PK. Ethnic skin disorders overview. J Am Acad Dermatol 2003; 48: S143S148. 14 Bongiorno MR, Aric M. Exogenous ochronosis and striae atrophicae following the use of bleaching creams. Int J Dermatol 2005; 44: 112115. 15 Keane FM, Munn SE, Taylor NF, du Vivier AW. Unregulated use of clobetasol propionate. Br J Dermatol 2001; 144: 10951096. 16 Findlay GH, Morrison JGL, Simson IW. Exogenous ochronosis and pigmented colloid milium from hydroquinone bleaching creams. Br J Dermatol 1975; 93: 613622. 17 Hardwick N, van Gelder LW, van der Merwe CA, van der Merwe MP. Exogenous ochronosis: an epidemiological study. Br J Dermatol 1989; 120: 229238. Erratum in Br J Dermatol 1989; 121: 153. 18 Adebajo SB. An epidemiological survey of the use of cosmetic skin lightening cosmetics among traders in Lagos, Nigeria. West Afr J Med 2002; 21: 5155. 19 Pitch P, Kombat K, Tchangai-Walla K. Cosmetic use of skin-bleaching products and associated complications. Int J Dermatol 2005; 44: 3940. 20 Mah A, Ly F, Aymard G, Dangou JM. Skin diseases associated with the cosmetic use of bleaching products in women from Dakar, Senegal. Br J Dermatol 2003; 148: 493500. 21 Nnoruka E, Okoye O. Topical steroid abuse: its use as a depigmenting agent. J Natl Med Ass 2006; 98: 934939. 22 del Giudice P, Yves P. The widespread use of skin lightening creams in Senegal: a persistent public health problem in West Africa. Int J Dermatol 2002; 41: 6972.

23 Mah A, Perret JL, Ly F, Fall F, Rault JP, Dumont A. The cosmetic use of skin-lightening products during pregnancy in Dakar, Senegal: a common and potentially hazardous practice. Trans R Soc Trop Med Hyg 2007; 101: 183187. 24 Centers for Disease Control and Prevention. Mercury poisoning associated with beauty cream Texas, New Mexico, and California, 19951996. MMWR Morb Mortal Wkly Rep 1996; 45: 400403. 25 Weldon MM, Smolinski M, Maoufi A et al. Mercury poisoning associated with a Mexican beauty cream. West J Med 2000; 173: 1518. 26 Arsouze A, Fitoussi C, Cabotin P-P et al. [Presenting skin disorders in black Afro-Caribbean patients: a multicentre study conducted in the Paris region.] Ann Dermatol Venereol 2008; 135: 177182 (in French). 27 Petit A, Cohen-Ludman Clevenbergh P, Bergmann J-F, Dubertret L. Skin lightening and its complications among African people living in Paris. J Am Acad Dermatol 2006; 55: 873878. 28 Ashikari M. Cultivating Japanese whiteness: the whitening cosmetics boom and the Japanese identity. J Mat Cult 2005; 10: 7391. 29 Tang HL, Chu KH, Mak YF et al. Minimal change disease following exposure to mercury-containing skin lightening cream. Hong Kong Med J 2006; 12: 316318. 30 Sin KW, Tsang HF. Large-scale mercury exposure due to a cream cosmetic: community-wide case series. Hong Kong Med J 2003; 9: 329334. 31 Al-Saleh I, Al-Doush I. Mercury content in skin-lightening creams and potential hazards to the health of Saudi women. J Toxicol Environ Health 1997; 51: 123130. 32 Mah A, Ly F, Perret JL. Systemic complications of the cosmetic use of skin-bleaching products. Int J Dermatol 2005; 44: 3738. 33 Ly F, Soko AS, Dione DA et al. Aesthetic problems associated with the cosmetic use of bleaching products. Int J Dermatol 2007; 46: 1517. 34 Boyle J, Kennedy CT. Hydroquinone concentrations in skin lightening creams. Br J Dermatol 1986; 114: 501504. 35 Parvez S, Kang M, Chung H-S et al. Survey and mechanism of skin depigmenting and lightening agents. Phytother Res 2006; 20: 921934. 36 Mann RJ, Harman RR. Nail staining due to hydroquinone skin-lightening creams. Br J Dermatol 1983; 108: 363365. 37 Karamagi C, Owino E, Katabira ET. Hydroquinone neuropathy following use of skin bleaching creams: case report. East Afr Med J 2001; 78: 223224. 38 Kane A, Ly F, Dme A et al. Premiers cas de carcinomas pidermodes sur terrain de dpigmentation artificielle. Ann Dermatol Venereol 2007; 134: S57S58. 39 Mah A, Badiane C, Balde Y, Dangou JM. Irrational use of skin-bleaching products can delay the diagnosis of leprosy. Int J Lepr Other Mycobact Dis 2002; 70: 119121. 40 Raynaud E, Cellier C, Perret JL. Dpigmentation cutane vise cosmtique. Enqute de prvalence et effets indsirables dans une population fminine sngalaise. Ann Dermatol Venereol 2001; 128: 720724. 41 Bwomda P, Sermijin E, Lacor P, Velkeniers B. Glucocorticoid hypertension due to the use of bleaching skin cream, a case report. Acta Clin Belg 2005; 60: 146149. 42 Tobin AM, Barragry J, Kirby B, OShea L. Adrenal suppression following topical use of clobetasol propionate illegally supplied as a bleaching agent. Ir Med J 2005; 98: 118 Erratum. In: Ir Med J 2005; 98: 251. 43 Engler DE. Mercury bleaching creams. J Am Acad Dermatol 2005; 52: 11131114. 44 Dyall-Smith DJ, Scurry JP. Mercury pigmentation and high mercury levels from the use of a cosmetic cream. Med J Aust 1990; 53: 409415. 45 Oliveira DGB, Foster G, Savill J et al. Membranous nephropathy caused by mercury-containing skin lightening cream. Postgrad Med J 1987; 63: 303304. 46 Kibukamusoke JW, Davies DR, Hutt MSR. Membranous nephropathy due to skin-lightening cream. Br Med J 1974; 2: 646647. 47 Lauwerys R, Bonnier C, Evrard P et al. Prenatal and early postnatal intoxication by inorganic mercury resulting from the maternal use of mercury containing soap. Hum Toxicol 1987; 6: 253256.

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology

750

Dadzie and Petit

Information on authors
Dr. Petit was born in 1957. He is currently working as a Senior Physician at the Department of Dermatology, Hpital Saint-Louis, Paris, France. His main fields of interest are Skin of Color, Internal Medicine, Scleroderma and Keloids. He is also Copy Editor for the Annales de Dermatologie et de Vnrologie, which is the official organ of the Socit Franaise de Dermatologie.

Dr. Ophelia Dadzie was born on 16th October 1974 in Ghana, West Africa. She holds a first class degree in Biomedical Sciences and her MBBS degree from the University of London. She trained in internal medicine (and holds her MRCP, London) before embarking on her dermatology residency training in 2004. She has also undertaken a Dermatopathology Fellowship at Boston University, USA and she is now in her final year of dermatology residency training in London. Her special interest is in the fields of Dermatopathology and Skin of Colour.

JEADV 2009, 23, 741750

2009 The Authors Journal compilation 2009 European Academy of Dermatology and Venereology