skin bleaching- highlighting the misuse of cutaneous depigmenting

© 2009 The Authors

JEADV

2009,

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, 741–750 Journal compilation © 2009 European Academy of Dermatology and Venereology

DOI: 10.1111/j.1468-3083.2009.03150.x

JEADV

Blackwell Publishing Ltd

CPD PAPER

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, Hôpital Saint-Louis, Paris, France

*Correspondence:

OE Dadzie.

E-mail:

[email protected]

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 scientific 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 scientific

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 specific 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-CounterMiscellaneous Panel had designated 2% as a safe concentrationfor hydroquinone products until 29 August 2006, when the FDApublished a monograph in the US Federal Register proposing toban all hydroquinone products that have not been approved viaa New Drug Application process.

1

This proposal arose followingthe failure of manufacturers to comply to a request by the FDAfor safety studies on hydroquinone. In addition, the FDA hascited many safety concerns about this product, including theoccurrence of hydroquinone-induced ochronosis. Nonetheless,hydroquinone remains a popular agent for the treatment ofpigmentory disorders in people with skin phototypes IV to VI.

2

Thus, the proposal to ban this agent has prompted many withinthe dermatological community to publish articles that address theconcerns of the FDA. One important point highlighted in some ofthese published articles is that hydroquinone-induced ochronosisoccurs typically in Africa, where the cultural practice of skinbleaching is prevalent.

3,4

Thus, this current discussion within thedermatological community about the safety and regulation ofhydroquinone is a perfect opportunity to present an overview of

the practice of skin bleaching, and to raise more awareness on theoccurrence and dangers of this practice.

Skin bleaching is the practice by which depigmenting agents areused typically by people with skin phototypes IV to VI on a cosmeticbasis, primarily to lighten normally dark skin. The practice of skinbleaching dates back over many years in different communitiesaround the world. In fact, in the early 1900s some US physiciansadvocated the use of radiation therapy as a skin bleaching agent.

5,6

Despite the initial early enthusiasm for this treatment, the manyundesirable side-effects of this therapy became apparent, leadingto an end to this dangerous practice. Currently, skin bleachingremains a common part of life within some African communities,reflected even by the local vernacular. For example, in Mali andSenegal, the term

caco

and

xeesal

are, respectively, used to describethis practice,

7

while in Ghana, the term

nensoeben

is used to describethe ochronosis that develops as a side-effect of this practice.

Interviews conducted on skin bleachers in sub-Saharan Africancountries highlights many factors driving this practice. A desire tolighten skin colour is cited as a primary motivating factor for skinbleaching.

8,9

This is because in some countries, white skin is stillperceived to be associated with social privileges, including better

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job and marital prospects. However, some skin bleachers may notdesire white skin, but instead desire radiant skin.

10

Up until recentyears there was limited choice with regard to the types of cosmeticproducts available in Africa and Europe, especially for individualswith Fitzpatrick skin phototype VI.

11

In absence of such products,bleaching the skin may be perceived as an alternative method ofenhancing one’s beauty, especially prior to important social events.

8

Other reasons cited by individuals partaking in skin bleachinginclude imitation of others and dependency on the products.

8,9

Finally, the higher prevalence of dyschromias in people withskin phototypes IV to VI may be another factor that initiates,promotes, and/or excuses this practice.

12,13

As a result of a lack ofunderstanding about the appropriate use of depigmenting agents,coupled with negative cultural perceptions about dark skin, thesecutaneous depigmenting agents may be subsequently intentionallyor inadvertently misused.

14,15

Prevalence of skin bleaching

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

North America, Europe, Asia and the Middle East practice skinbleaching. Evidence from the non-medical press further highlightsthe global burden of this practice. Thus, scientific studies conductedon the practice of skin bleaching, as summarized in Tables 1 and2 and discussed in detail below, may only represent the clinicaliceberg of a more widespread problem.

Africa

The worldwide awareness of the cultural practice of skinbleaching originates from the work of Findlay

et al

.,

16

who in 1975first reported on the occurrence of exogenous ochronosis inSouth African women. These women had used high concentrations(3.5–7%) of hydroquinone-containing agents over the course ofmany years for bleaching their skin. Skin bleaching remained aproblem in South Africa and by 1986 the total sales volume of skinlighteners was an estimated 30 million pounds.

17

Currently, skinbleaching continues to have an impact on dermatological practicein many sub-Saharan African communities, with prevalence ratesof this practice in community and clinic settings documented tobe between 26% and 67%.

7–9,18–22

This estimate is based on descriptive

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)

Prevalence of skin bleaching

Type of depigmenting agents Site and frequency of use of depigmenting agents

Duration of use

Adebajo18 (Nigeria, community study)

77.3% (females, 72.4%; males, 27.6%)

Hydroquinone; mercury; corticosteroids; locally concocted soaps/creams

Not specified in study 1–3 years (46.3%)

Ajose8 (Nigeria, hospital study)

Females, 40%; males, 2% Hydroquinone; class I and II steroids; mercurials; phenolicscaustics; unknown chemicals and plant derivatives; combinations

Not specified in study 6 months–over 20 years

Faye et al.7 (Mali, hospital study)

Not specified in study Hydroquinone; steroids; mercurials; unknown composition

Not specified in study Not specified in study

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

27% active skin bleachers Hydroquinone; corticosteroids; mercurials; detergents; hypochloride sodium; unknown composition

Once to thrice per day 50.5 months (mean), range 1–240 months

Ly et al.34 (Senegal, hospital study)

Not specified in study Corticosteroids; hydroquinone; vegetable extracts; caustic products; unknown composition

Not specified in study 6.7 ± 5 years (mean), range 1–30 years

Mahé et al.20 (Senegal, hospital study)

52.7% (± 5) 4–8.7% hydroquinone; steroids; caustic agents; unknown composition; mercury iodide

Whole body; once or twice per day

4 years (median)

Mahé et al.23 (Senegal, maternity centre)

68.7% Hydroquinone; corticosteroids; mercurials

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

5 year (mean), range 3 month–24 years

Nnoruk et al.21 (Nigeria, hospital study)

58.7% Steroids; hydroquinone; mercurials; kojic acid; alpha hydroxyl acids; unknown composition

Whole body; face; twice per day

5 years ± 1.3 years

Petit et al.27 (France, hospital study)

80% Steroids; hydroquinone Entire body and face; at least once per day

14 years (mean), range 1–38 years

Pitché19 et al. (Togo, community study)

58.9% Mercurials; hydroquinone; steroids; unknown composition


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

44.3% Phenolics; steroids; combination of agents; mercurials; unknown composition

Not specified in study 1–3 years

Skin b

leaching

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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)

Prevalence of adverse reactions

Infections Dyschromias Systemic side-effects

Other side-effects Motivation for skin bleaching

Adebajo

18

(Nigeria, community study)

50% Not specified Yellowish brown discoloration of skin

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

(1) Treatment of skin blemishes. (2) To become more attractive and satisfy the desires of opposite sex. (3) Fashionable trend.

Ajose

8

(Nigeria, hospital study)

69.2% Mycoses; scabies; warts; erysipelas; pyodermas

Ochronosis; confetti-like hypomelanosis

Cushing’s syndrome; renal impairment; immune suppression

Elastosis; sunburn; acnerosacea; striae; telangiectasia; hypertrichosis; body odour

(1) To even out skin tone. (2) To lighten complexion. (3) To improve appearance of skin prior to an event. (4) Dependency.

Faye

et al

.

7

(Mali, hospital study)

Not specified in study Mycoses; pyoderma; scabies


Striae atrophicae; acne vulgaris; irritant dermatitis

Not specified in study

Del Giudice

et al

.

22

(Senegal, hospital study)

Not specified in study Intertrigo; pyoderma; tinea corporis

Hyper- and hypopigmentation


Facial acne; facial hypertrichosis; cutaneous atrophy; stretch marks; purpura


Ly

et al

.

34


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

Cutaneous mycosis; scabies; erysipelas

Peri-orbital hyperpigmentation; hyperpigmentation of joints; leucoderma; exogenous ochronosis; brownish nails


Striae atrophicae; telangiectasia; lichenification; skin atrophy; acne vulgaris; poikiloderma; scarring; pretibial ichthyosis; pigmented keratosis; pilaris; lilac erythema of eyelids


Mahé

et al

.

20


Not specified in study Dermatophyte; candidiasis; non-specific intertrigo; tinea versicolor; scabies; bacterial skin infections

Hyperchromia; hypochromia; ochronosis; blue ear

Not specified In study

Irritant dermatitis; eczema; acne; perioral dermatitis; striae; poikiloderma; facial hypertrichosis; xerosis/ichthyosis; isolated itching; keratosis pilaris


Mahé

et al

.

23


Not specified in study Not specified in study Not specified in study Not specified in study

Increased compared to non-steroid users; occurrence of mild vaginal bleeding; lower placental weight; lower plasma cortisol


Nnoruka

et al

.

21

(Nigeria, hospital study)

Not specified in study Dermatophyte (atypical)

Macular hyperpigmentation of face

Diabetes; hypertension

Acne vulgaris; striae; easy bruising; telangiectasia; hypertrichosis

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

Petit

et al

.

27

(France, hospital study)

Not specified in study Profuse tinea corporis; pyoderma

Hyperpigmentation dorsal aspects of interphalangeal joints; ochronosis; ‘confetti-like’ hypopigmented spots

Biological signs of adrenal suppression

Skin atrophy; striae; acne; irritant or allergic contact; dermatitis; rosacea; acute caustic dermatitis

(1) Beauty; (2) Dependency

Pitché

et al

.

19

(Togo, community study)

Not specified in study Nil Hypopigmentation; leucomelanoderma; hyperpigmentation


Acne; cutaneous atrophy Not specified in study

Traore

et al

.

9

(Burkina Faso, community study)

55.5% Dermatophyte Dyschromia; ochronosis Not specified 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.

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studies and surveys on the cosmetic use of cutaneous depigmentingagents conducted in community- and/or hospital-based settingsvia questionnaires and/or interviews. In fact, most of theknowledge acquired about the practice and complications of skinbleaching originates primarily from such studies performed insub-Saharan African countries. However, a review of some ofthese studies reveals inherent limitations. First, since most of thestudies are based on interviews and/or questionnaires, the studysubjects may have given inaccurate histories about their cosmeticuse of cutaneous depigmenting agents. Second, studies inhospital-based settings may overestimate the prevalence of skinbleaching, as individuals attending dermatology clinics aremore likely to have primary dermatological problems for whichthey would have sought out cutaneous depigmenting agents.Interestingly, studies also reveal that individuals often continuetheir practice of skin bleaching throughout pregnancy andlactation. For example, Mahé

et al

.

23

demonstrated that 68.7%of selected women between 6 and 9 months gestation, attendinga maternity centre in Dakar, Senegal, used skin lighteners forcosmetic purpose during their pregnancy. This included agentscontaining hydroquinone, highly potent corticosteroids andproducts of unknown composition. Interestingly, some of thewomen in this study reported starting or increasing their use ofskin lighteners because of their pregnancy.

North America

To date, there have been no formal studies conducted in NorthAmerica to assess the prevalence of skin bleaching. This indicatesthat either this practice is uncommon or it is under-recognized bypracticing physicians in North America. Nonetheless, an insight on thecosmetic use of depigmenting agents in North America can be gainedby reviewing case reports and other studies documenting adversereactions to these agents. This review provides conflicting results.

In a review of the 789 worldwide reported cases of exogenousochronosis, only 22 cases (1983–2006) occurred in the USA.

3

Subjects from the USA with hydroquinone-induced ochronosishad often self-medicated with these agents as a mode of therapyfor their primary dyschromias. This indicates that the culturalpractice of skin bleaching, as a mode of changing normal skincolour, is not very common in the USA. However, in the mid-1990s,following an index case of mercury poisoning associated with theuse of a Mexican ‘beauty cream’ containing high levels of mercury,a survey was conducted to describe the demographics and patterns ofuse of this cream in border communities of Arizona, California,New Mexico and Texas.

24,25

The results of this study demonstratedthat the majority of users of this ‘beauty cream’ were Hispanicwomen, with 44% using this ‘beauty cream’ as a skin lightener.Most cream users used this agent over a median of 4 years, with52% applying this cream two to three times per day. Althoughmost cream users had purchased the cream from Mexico, 21%purchased the cream in the USA, typically at flea markets or herbshops. Although cream users were not asked their motivation for

using this agent as a skin lightener, the results of this study doindicate that the practice of skin bleaching may be a problem insome communities within the USA. Thus, further studies toinvestigate the motivations for the cosmetic use of cutaneousdepigmenting agents are warranted in the USA. This is of particularimportance given the fact that the demographics of the USA ischanging, with a higher proportion of the US population predicted tobe of African and Hispanic descent in the future.

12

Europe

The practice of skin bleaching has been reported in Africans andAfro-Caribbeans living in European countries, including theUnited Kingdom and France.

14,26,27

In fact, the over-the-counteruse of hydroquinone has now been banned in Europe, althoughthis agent and various other depigmenting agents remainavailable illegally in many markets in Europe.

15

In a multicentrestudy conducted in the Paris region, it has been estimated that16% to 28% of adult African women seeking dermatologicaltreatment in Paris are regular users of skin bleaching agents.

26

Moreover, in a recent study by Petit

et al

.

27

on 46 subjects fromvarious African countries attending a dermatology clinic in Parisfor side-effects of skin lighteners, 31% had begun their practice ofskin bleaching in France.

Asia

Ashikari

28

when writing on the Japanese culture, states thatsince the late 1980s, consumption of ‘whitening’ cosmetics hasremained at consistently high levels and a ‘white’ complexion hasbeen considered trendy and desirable in Japan, being a symbolicphysical characteristic for identifying Japanese people. Despite thepopularity of skin bleaching in Japan, to date there have beenno formal studies reported in the English-language scientificliterature on the prevalence of this practice in this country.However, there are studies reported in the English-languagescientific literature that gives an insight into the practice ofskin bleaching in Hong Kong. Tang

et al

.

29

reported the case ofa woman who developed minimal change nephropathy as acomplication of the use of mercury containing skin-lighteningcream. Furthermore, following an index case of mercurypoisoning, a survey was conducted in Hong Kong to describe thedemographic characteristics, patterns of use and other laboratoryparameters in people who had used the same skin whiteningcream. Of note, among 314 cream users, 27% were using it as askin whitening agent.

30

The motivation for this behaviour was notdiscussed in this study.

The Middle East

To date, there are no formal studies documenting the prevalenceof skin bleaching in this region of the world. However, in a studyundertaken in Saudi Arabia to investigate the mercury contentin skin-lightening creams, Al-Saleh

et al

.

31

state that in Saudimarkets ‘a wide variety of different brands of skin-lightening

Skin bleaching

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creams are available, either being imported from overseas orbeing manufactured locally by traditional herbalists’. This highsupply indicates that there may be a high demand for such skin-lightening products in this country.

Adverse effects of skin bleaching agents

A diverse range of products at various concentrations are usedfor skin bleaching. This includes hydroquinone, hydroquinonederivatives (hydroquinone monobenzylether and monomethylether),potent steroids

2,22

, mercurials (mercuric iodide 1–3% or mercuricchloride 6–8%), kojic acid, alpha hydroxyl acids, plant-derivedproducts (that may contain active agents such as arbutin) andeven hydrogen peroxide. Sometimes, various ingredients from thedomestic environment (toothpaste, washing liquid, washing soda,hair straighteners, sand, cement and even battery fluid) may bemixed in homemade concoctions that are used once for theircaustic effect. Skin bleaching agents are used in cream, lotion, oil,gel, soap or pomade formulations and are typically obtained fromnon-medical sources, including open markets and beauty stores.

9,23

This unregulated trade in cutaneous depigmenting agents involvingnon-medically trained individuals has fuelled an internationaltrafficking business, which needs to be curtailed.

The risk of side-effects occurring with skin bleaching dependson the nature and concentration of products used.

32,33

This iscomplicated by the fact that on occasion products used maycontain a higher concentration of active agents than stated on theirpackages.

34

Additional contributory factors for the developmentof side-effects with skin bleaching include the concurrent use ofseveral depigmenting products, application of products overwidespread areas of the body, application of products overprolonged periods (months to years) and lack of sunscreen usage.Table 1 lists some of the agents that have been used for skinbleaching, while Table 2 lists some of their associated adverseeffects, which are discussed in detail below.

Hydroquinone

Hydroquinone, also chemically known as 1,4-dihydroxybenzene,is a ubiquitous chemical that occurs naturally in our environment.

2

Itis a strong oxidant that is rapidly converted to p-benzoquinoneand 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 asreducing tyrosinase activity primarily in melanocytes.

35

Infact, it does affect other cell types, but because the dose requiredto inhibit their cellular metabolism is much higher than formelanocytes, it is primarily melanocyte specific.

Irritant and allergic contact dermatitis, with subsequentpost-inflammatory dyspigmentation, are potential side-effectsthat may occur with the use of hydroquinone during skin bleaching.However, the concomitant use of topical steroids may reduce thisside-effect.

20

Nail plate pigmentation

36

and peripheral neuropathy

37

have also been reported as a complication of hydroquinone usage.

In 2001, Karamagi

et al

.

37

reported the case of a young blackwoman with chronic symmetrical sensorimotor polyneuropathyand autonomic neuropathy, which improved 4 months after shestopped the use of hydroquinone-based skin bleaching agents.Although most metabolic factors that may have accounted for hersigns and symptoms were excluded, the authors did not performHIV serological testing on their patient. Thus, the association ofher symptoms and signs with her use of hydroquinone wascircumstantial.

Exogenous ochronosis (Fig. 1), characterized by progressiveasymptomatic hyperpigmentation with associated papules onsun-exposed skin, is another reported side-effect of hydroquinone.Histology of lesional skin demonstrates collagen and elastic fibredegeneration and deposition of ochre-coloured fibres in thedermis.

16

A total of 789 cases of exogenous ochronosis have beenreported in the scientific literature, of which 756 occurred inAfrica,

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 datadue to the presence of confounding factors that may accountfor higher levels of exogenous ochronosis in Africa. First, theconcomitant use of antimalarials (which may also give rise toochronosis) are frequently not cited in studies on the complicationsof skin bleaching. Second, in most studies in Africa on skinbleaching, the diagnosis of ochronosis is often based on clinicalassessment, with no lesional biopsies undertaken to confirm theseclinical findings. This is understandable in view of the limitedresources in Africa, where most of these studies have been con-ducted. Finally, the lack of sunscreen use during skin bleaching,the use of higher concentrations of hydroquinone formulations,

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

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and the use of formulations containing resorcinol and otheragents may all contribute to increase the risk of exogenousochronosis in relation to the practice of skin bleaching. However,given that over the course of many years, many individuals havebeen exposed to hydroquinone (it has been available in over-the-counter formulation since about 1956 in the USA),

2

the compar-atively low rates of reported exogenous ochronosis, is somewhatreassuring, indicating that this may be an uncommon side-effectof hydroquinone. Alternatively, this low rate may also be a resultof under-reporting of this complication in the scientific literature.

Another important theoretical side-effect associated with skinbleaching with hydroquinone agents is the development of cuta-neous and internal malignancies. Hydroquinone is a metaboliteof benzene, a leukaemogenic agent. It is also associated withthe development of mononuclear cell leukaemia in female ratsexposed to oral hydroquinone over a 2-year period.

3

Despite thistheoretical risks, studies indicate that comparatively low levelsof hydroquinone are absorbed with topical application of theseagents.

3

Moreover, hydroquinone and its derivative, arbutin(which is hydrolysed to hydroquinone in an acidic environmentsuch as the stomach), are ubiquitous agents, such that humans areexposed 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 andwhite films, individuals working in this industry have high exposuresto this agent. Nonetheless, studies that have assessed mortalityrates and cancer prevalence in such individuals have not identifieda higher-risk profile in this cohort.

2

In light of the above, we canconclude that there remains a lack of conclusive evidence sup-porting a carcinogenic risk from the topical use of hydroquinone.Alternatively, since the practice of skin bleaching involves theapplication of high concentrations of hydroquinone overwidespread areas of the body, it may be argued that this mayrepresent a higher-risk profile for the development of malignancies.However, only two cases exist in the literature that documents thedevelopment of cutaneous malignancy in relation to skin bleaching.

38

In these cases, spindle cell squamous cell carcinomas occurred inassociation with skin bleaching with hydroquinone agents. Themechanism for this observation is postulated to be through thepro-carcinogenic effect of hydroquinone or due to suppression ofthe natural photo-protection effect of melanin. Further studiesare warranted in skin bleachers to accurately assess their risk ofcutaneous malignancies.

Corticosteroids

Topical steroids are anti-inflammatory agents used for thetreatment of many inflammatory skin diseases. They are popularcutaneous depigmenting agents used for skin bleaching,

21

and itis the present authors’ opinion that the extensive use of illegalclobetasol-containing agents is responsible for most of the severeside-effects associated with skin bleaching in Francophonecountries. 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 pigmentationof the skin.

15

Eventually, topical steroids exert their depigmentingeffect via an inhibitory effect on epidermic melanogenesis. Theirprolonged use (> 3 weeks), especially on thin skin such as facialand 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 woundhealing, easy bruising and hypertrichosis. Other side-effectsinclude ophthalmic problems (cataracts, glaucoma, eye infectionsand blindness) associated with the application of topical steroidsto the face, especially the eyelids and aseptic osteonecrosis(personal observations). Cutaneous infections (Fig. 3), such asdermatophytosis, cellulitis, erysipelas, scabies and warts, may alsooccur as a complication of the misuse of topical steroids. Oftenthere is an atypical presentation or a masking of the clinicalpresentation of these cutaneous infections. For example, Mahé

et al

.

39

reported the case of a young black woman, who used 0.05%clobetasol propionate and hydroquinone on the peri-lesional skinof a hypochromic region on her cheek. Over time, this masked thehypochromic lesion on her cheek, which was one of the presentingfeatures of her paucibacillary leprosy. Finally, the use of potenttopical steroids is associated with systemic side-effects includingdiabetes and hypertension, Cushing’s syndrome, immunosuppressionand adrenal insufficiency.

27,40–42

Mercury

Mercury salts produce their cutaneous depigmenting effect viainhibition of melanin formation. This occurs because mercurysalts compete with copper in tyrosinase.

43

Historically, chronicmercury poisoning has occurred in the context of industrial

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

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exposure (felt hat industry) or during the use of mercurialmedicinal preparations (used in the past to treat infectious skindisorders such as syphilis and impetigo).

44

Currently, skin lighteningis also a cause of mercury toxicity.24,25,29,30,44–46 The features ofmercury toxicity, also known as the ‘hatters disease’, asimmortalized in Alice in Wonderland by Lewis Carroll, consistsof psychiatric (disturbance of recent memory, impairment ofintellectual function, inattention and depression) and neurological(irritability, memory loss and neuropathies) problems.43

Other adverse reactions noted with mercury toxicity includesrenal impairment (minimal change or membranous glomeru-lonephritis)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 metallicmercury granules in the dermis. The percutaneous absorption ofmercury occurs exclusively via cutaneous appendages and, hence, onlesional biopsy, peri-follicular accentuation of mercury depositionis observed in mercury-induced hyperpigmentation. Interestingly,the use of mercurial agents for skin lightening by pregnant and/orlactating women has also been associated with adverse effectsin their neonates, including the development of anaemia, renalimpairment and cataracts.47

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

species, including Aspergillus and Penicillium. Side-effectsobserved 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 theseactions lead to removal of the superficial layers of the epidermisand, hence, a depigmenting effect when used for skin lightening.Additional possible mechanisms for depigmentation includeacceleration of keratinocytic turnover with a reduction in theirmelanosome loading time. Side-effects observed with this agentinclude irritant contact dermatitis, with the risk of post-inflammatory hyperpigmentation.

ConclusionThe current focus within the dermatological community onthe safety and regulation of hydroquinone presents a uniqueopportunity to raise awareness on the occurrence and dangersof skin bleaching. Aesthetic and systemic side-effects of skinbleaching not only remain a public health problem in most partsof sub-Saharan Africa, but also may increasingly impact manyother communities around the world. It is important that weeducate individuals with pigmentory problems to seek earlydermatological care for their dermatoses, rather than to self-medicate with over-the-counter or illegally obtained cutaneousdepigmenting agents. However, this would not be enough toreduce the global burden of skin bleaching. Instead, a multifacetedapproach is required, addressing several issues concurrently.First, more studies in the field of human sciences, to consider thesociological and psychological factors that are responsible for thesearch of a lighter complexion (which may vary among differentcommunities) are required to guide the development andimplementation of appropriate public health prevention campaigns.Second, international cooperation between governmental, non-governmental and medical agencies is required to decrease theinternational trafficking of illegal depigmenting agents, especiallyclobetasol-containing products. Third, continued rigorous scientificstudies, especially in Western, Arab and Asian countries wheresuch studies remain scarce, are required to critically evaluatethe global burden and adverse health effects associated withskin bleaching, Finally, more research directed towards thedevelopment of alternative safer agents for the inhibition of skinpigmentation is required.

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 hydroxylacids, plant-derived products and even hydrogen peroxide areused for skin bleaching

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.

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© 2009 The AuthorsJEADV 2009, 23, 741–750 Journal compilation © 2009 European Academy of Dermatology and Venereology

• Many adverse effects have been reported in association withskin bleaching

• A multi-faceted approach is required to reduce the globalburden of skin bleaching.

Questions and multiple choices1. In 2006, the U.S. Food and Drug Administration (FDA)

proposed (a) the banning of all hydroquinone products thathave not been approved via a New Drug Application process(b) an increase in the concentration of over-the-counterhydroquinone products (c) the banning of all over-the-counter depigmenting agents (d) none of the above

2. Broadly speaking studies undertaken about skin bleachingin 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 theabove

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 factorsfor their practice with the exception of: (a) lightening of skincolour (b) moisturising of skin (c) dependency (d) enhancementof beauty

5. Which of the following statement about skin bleaching isfalse? (a) it is practised by diverse communities around theworld (b) it is more commonly undertaken by individualswith Fitzpatrick skin phototype I (c) some individuals continuethis practice throughout their pregnancy (d) treatment ofdyshcromias may be one reason that initiates and/or excusesthis practice

6. The prevalence of skin bleaching in sub-Saharan Africancommunities 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 useof hydroquinone is banned throughout all of Europe (b) 2%hydroquinone can be purchased as an over-the-counterproduct legally in European countries such as the UK andFrance (c) hydroquinone is not available legally as an over-the-counter product in European countries such as UK andFrance (d) all of the above

8. Which of the following statement(s) about the practice of skinbleaching in Europe is/are true? (a) skin bleaching has beenreported in Africans residing in Europe (b) skin bleaching hasnever been reported in Africans residing in Europe (c) InFrance, the majority of Africans who practice skin bleachingstart this behaviour when they move to this country (d) noneof the above

9. Which of the following agent(s) from the domesticenvironment 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 byall the following except: (a) the concurrent use of more thanone depigmenting agent (b) the use of high concentrationsof depigmenting agents (c) the concurrent use of sunscreens(d) the use of depigmenting agents over large body surfacearea and over a prolonged time course

11. Which of the following statement about hydroquinone isfalse? (a) it is also chemically known as 1,4 dihydroxybenzene(b) it occurs naturally in the environment (c) it is a strongoxidant (d) it increases the activity of tyrosinase

12. Recognised side effects of hydroquinone include all thefollowing 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 thecarcinogenic risk of hydroquinone is/are true? (a) benzene, ametabolite of hydroquinone is a carcinogen (b) mononuclearcell leukemia has been observed in female rats exposed tointravenous hydroquinone (c) the carcinogenic risk ofhydroquinone accounts for the higher observed risk of cancerin individuals working in the photographic industry (d) all ofthe above

14. The observed skin lightening effects of topical corticosteroidsoccur initially via: (a) local vasoconstrictor effect (b) anti-inflammatory properties (c) suppression of the hypothalamic-pituitary axis (d) none of the above

15. Recognised side effects of topical corticosteroids used for skinbleaching 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 occuras a result of: (a) working in the felt hat industry (b) treatmentof syphilis (c) treatment of impetigo (d) all of the above

17. Characteristic features of mercury toxicity includes allthe 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 Asiancountries (b) is associated with an increased risk of cutaneousinfections (c) does not cause adverse effects in neonates whenused by pregnant and/or lactating mothers (d) is neverassociated 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 theglobal burden of skin bleaching include: (a) education of atrisk populations regarding the adverse effects associated withskin bleaching (b) co-operation between governmental andnon-governmental agencies to help curb illegal traffickingof depigmenting agents (c) more research focused on thedevelopment of depigmenting agents with less adverse effects(d) all of the above

Skin bleaching 749


Correct answers

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

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Information on authors

Dr. Petit was born in 1957. He is currently working as a Senior Physician at the Department ofDermatology, Hôpital 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 Dermatologieet de Vénéréologie, which is the official organ of the Société Française de Dermatologie.

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

skin bleaching- highlighting the misuse of cutaneous depigmenting

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