Complications of chronic use of skin lightening cosmetics
Yetunde M. Olumide, MD, Ayesha O. Akinkugbe, MD, Dan Altraide, MD, Tahir Mohammed, MD,
Ngozi Ahamefule, MD, Shola Ayanlowo MD, Chinwe Onyekonwu, MD, Nyomudim Essen, MD.
From the Dermatology Unit,
Department of Medicine
College of Medicine, Lagos, Nigeria
Professor Y. Mercy Olumide
Department of Medicine
College of Medicine of the
University of Lagos.
P M B 12003, Lagos, Nigeria
Skin lightening (bleaching) cosmetics and toiletries are widely used in most African countries. The active ingredients in these cosmetic
products are hydroquinone, mercury and corticosteroids. Several additives (conconctions) are used to enhance the bleaching effect. Since
these products are used for long duration, on a large body surface area, and under hot humid conditions, percutaneous absorption is
enhanced. The complications of these products are very serious and are sometimes fatal. Some of these complications are exogenous
ochronosis, impaired wound healing and wound dehiscence, the fish odour syndrome, nephropathy, steroid addiction syndrome,
predisposition to infections, a broad spectrum of cutaneous and endocrinologic complications of corticosteroids, including suppression of
hypothalamic-pituitary-adrenal axis. In this era of easy travels and migration, African patients with these complications can present to
physicians anywhere in the world. It is therefore critical for every practising physician to be aware of these complications.
A middle-aged Nigerian lady was recently brought home to die from a Western European country because she developed
an uncontrollable diabetes mellitus and evidence of hypothalamic-pituitary-adrenal axis suppression. On clinical
examination, the lady had dense stigmatas of chronic use of skin lightening creams, which was confirmed through history.
Majority of medical practitioners outside sub-saharan Africa may not be familiar with this habit of bleaching the skin nor
the cutaneous and extra-cutaneous complications of this widespread cosmetic habit of black Africans. Furthermore, these
cosmetics and toiletries are not sold in the regular departmental stores nor pharmacy shops in Europe and North America.
They are either manufactured purely for export to Africa or are exported from Africa to Europe and N. America so that
they are sold only in local shops in ghettoes patronized by the black Africans.
This paper sets out to give a brief review of this problem so that practitioners worldwide would be aware of these
complications which may atimes be fatal.
The use of skin bleaching agents or lighteners has been reported in many parts of the world, such as Kenya,1 Ghana,(2)
South Africa,(3, 4) Zimbabwe,(5) USA,(6, 7) Great Britain(8) and Saudi-Arabia.(9) Various chemicals have been used with
consequent undesirable side effects. While phenols were reported to have been associated with ochronosis,(10) the
mercurials were implicated in nephropathy.(1, 9) Addo in Ghana has also reported squamous cell carcinoma associated with
A survey done in Mali reported that 25% of two hundred and ten women developed seventy-four different side effects
from the use of bleaching creams.(12) Similarly, in a refugee camp in Balkan, 22.3% of the inhabitants including children
were found to have high concentrations of urinary mercury, which was traced to the use of mercury containing bleaching
Exogenous ochronosis was first reported in 1906.(14) It commonly presents as asymptomatic blue-black macules on the
malar areas, temples, inferior cheeks and necks.(15) This condition resembles endogenous ochronosis in the skin
histologically, but does not exhibit any systemic complications or the urinary abnormality. Hydroquinones are by far the
most common offending agents, but phenol, quinine injection and resorcinol have also been implicated.(16)
In South Africa, where the first reports of complications of hydroquinone abuse was reported, the government was
prevailed upon in 1980 to set an upper limit of 2% hydroquinone content in cosmetic products.(17) Britain and the United
States of America also limit the concentration of hydroquinone in cosmetic products to a maximum of 2%, and in
dermatological preparations to 4%. Although it was originally believed that only high concentrations of hydroquinone
were causal there have been reports of ochronosis after use of 2% hydroquinone preparations.(18, 19, 20) It has also been
suggested that the percentage of hydroquinone quoted by a manufacturer may not represent the true concentration of
hydroquinone in a product.(21) It may be that it is not the high concentration of hydroquinone, but rather, extended use of
this substance, which causes the disease. An analysis of 41 bleaching creams available over the counter in the UK in 1986
by Boyle and Kennedy revealed that eight contained more than 2% hydroquinone.(22)
The scenario in Nigeria (23-33)
The use of skin lightening creams has become a serious phenomenon widely practiced by both men and women in Nigeria.
In a study of four hundred and fifty Nigerians who confessed the use of bleaching creams, 73.3% were women and 27.6%
were men. The use of bleaching creams cuts across all sociodemographic characteristics. People of all religious groups,
single or married, rich and poor, literate and illiterate, low, middle and upper class use the products.
Various reasons were given for using the products. Some of these are to look more attractive; to go with existing
fashion trend; to treat skin blemishes like acne or melasma; to cleanse or ‘tone’ the face and body; or to satisfy the taste of
ones spouse. Although the men also use the products for the above reasons, some of them claimed they use the creams
because their wives use them; and some male marketers of female cosmetics and toiletries claim they use the products to
advertise their wares. Some of the men are homosexuals. The habit of bleaching the skin is most rampant among
commercial sex workers who camouflage their occupation in the clinic data as “fashion designer” because of the
opprobium attached to prostitution. It is noteworthy that even some people who are naturally fair in complexion, still use
the bleaching creams to “maintain” the light skin colour and prevent tanning or blotches from sunlight.
As a result of both medical and public outcry against the damaging effects of the skin lightening creams, the National
Food and Drug Agency of Nigeria (NAFDAC) had initially allowed a maximum of 2% hydroquinone in bleaching creams.
However, due to the adverse side effects associated with long term hydroquinone use and also lack of compliance with
content and labelling requirements, all forms of bleaching agents were prohibited in cosmetics and toiletries. However, in
spite of the ban on these products, both the importation and manufacture of the products have continued unabated. This
situation has been fostered largely by the vulnerability of the consumers, the inexpensive nature of some of these products,
and the advertising agencies, who use light-complexioned ladies to advertise most consumer products (e.g. alcoholic and
non-alcoholic beverages, toiletries, cosmetics, textiles, telephone handsets etc.) both on the electronic and print media.
Hence, the dominant signal being sent to an undiscerning mind is that light complexioned people are the beautiful ones.
As regards ingredient labelling of cosmetics and toiletries in Nigeria, most products are not registered by NAFDAC,
and bear no ingredient labelling nor address of manufacturers. Some are even misbranded, e.g. a product which was
labelled as “Betnovate-N” was found to contain Mercury. Furthermore, the concentrations of chemicals on the labelled
products were largely found to be inaccurate on analysis as most products exceeded the concentrations displayed on the
products. Since hydroquinone and mercury in cosmetics and toiletries have been prohibited and have gained some
notoriety, manufacturers have now resorted to using synonyms of hydroquinone to camouflage the products. Some of
these synonyms include 1, 4-Benzenediol, Quinol, Benzene-1, 4-diol, p-Diphenol, p-Dihydroxyl benzene, Hydrochinone, p-
hydroxylphenol, Hydrochinonium, Hydroquinol, and Tequinol. All corticosteroid preparations can be purchased over-the-
counter in Nigeria. Hence, these products are readily available not only in the pharmacy shops but also among drug
vendors in the open market place.
Chemicals often used and methods of use
The list of some of the bleaching creams used are given in Table 1, and the contents of some analysed products are on
Table 2. The same products are largely available in the African countries mentioned above because of easy cross country
trade links. The active ingredients commonly used are hydroquinone, mercury, and a broad spectrum of the very potent
corticosteroid preparations containing e.g. Betamethasone valerate and Clobetasol propionate.
Furthermore, the products are hardly used as marketed and various additives are used to ‘enhance’ the bleaching
effect. Some of the additives (concoction) are lemon juice, potash, tooth paste, liquid milk, pulverized Naphthalene
(camphor) balls — a mothproofing agent, Vitamin C, peroxides and chlorates used in hair dyes. Atimes detergents are
added to the concoction. Some of the creams have equivalent soaps with same chemicals incorporated. Indeed, the above
listed additives are not exhaustive.
At the initiation of the bleaching habit, a total body surface immersion “bath” is often used for maximum effect. The
bleaching is then maintained with daily applications of the creams. Most of the creams are very cheap so it is possible to
spend as little as 2 US dollars (about 300 Nigerian Naira) a month on the bleaching creams to maintain the light
complexion. Continuous use of the chemical is mandatory so that the skin does not repigment. Even when the
complications appear, the bleachers often intensify the use of the chemicals with the hope that the skin complications
would eventually be bleached away. Multiple products containing different chemicals may be used concurrently or
The duration of use of the bleaching creams before the onset of complications vary from 6-60 months. However,
history from patients is often inaccurate, and some even deny use of the bleaching creams, or pretend not to know their
functions due to a guilt complex, because various religious groups and the press continue to condemn the practice of
changing the colour of the natural skin.
Table 1 A list of some of the bleaching creams used by patients in Nigeria and ingredients as labelled
Crusader Vitamed B3 toner 2%, Escalol UV 507, Vit E Allantoin
Looking Good2% hydroquinone, Allantoin, Sunscreen, Vit E
Peauclair Hydroquinone, Clobetasol propionate
Mic Hydroquinone, Dimethicone, D-methyl-PABA
Tura Octyl- Dimethyl PABA, Dimethicone, Aqua glyceryl, propylene glycol mubbery
A3A-hydroxyl acids, methyl p-ben
Ultra Vitamed B3 toner 2%, Escalol UV 507, Vit E Allantoin
VenusBenzophone 3-Dimethicone, Cyclomethicone
Swiss collagen Triethanolamine, Carbomer, Dimethicone
Fashion FairBetamethasone dipropionate
ShirleyNatural Essences from botany
Ambi2% hydroquinone padimate
Skin Success2% hydroquinone Octisalate
Sivoclaire2% hydroquinone, Vit E 1.0
Fashoin Fair Clobetasol propionate 0,05
Tony Montana Stearic Acid, MPG, Sorbitol Jelly, Fragrance
Table 2 Contents of some creams analysed( 25 )
Cream Hydroquinone (mg%)
Pathogenesis and complications
Hydroquinone is a dihydric phenol that has two important derivatives viz monobenzyl and monomethyl ether of
hydroquinone. Hydroquinone is known to competitively inhibit melanin production by inhibiting sulfhydryl groups and
acting as a substrate for tyrosinase. The melanosomes and ultimately the melanocytes are damaged by semiquinone free
radicals released during the above reaction.(34, 35, 36)
With prolonged application and sun stimulation, the melanocytes recover from the damaging effect of the
hydroquinone which passes down into the papillary dermis of the skin. Hence they are actively taken up by fibroblasts and
lead to altered elastic fibre production and excretion of abnormal material into new fibre bundles.(37) Furthermore,
benzoquinone acetic acid formed during the oxidative processes in which hydroquinone is involved, bind and cross link
collagen fibres leading to degenerative changes due to altered physico-chemical bonds.
Histologic examination of exogenous ochronotic lesions reveals yellow-brown banana-shaped fibers in the papillary
dermis. Homogenization and swelling of the collagen bundles is noted and a moderate histiocytic infiltrate may be present.
Sarcoid-like granulomas with multinucleated giant cells engulfing ochronotic particles have been noted.(38) Transfollicular
elimination of ochronotic fibers has also been described.(39) Fibers stain black with Fontana stain and blue-black with
methylene blue stain.(18, 40) Ultrastructural examination reveals homogenous electron-dense, irregular structures embedded
in an amorphous granular material infiltrating adjacent collagen fibril bundles.(41, 42) The source of these ochronotic fibers is
not clear. Topical hydroquinones may inhibit homogentisic acid oxidase in the skin, resulting in the local accumulation of
homogentisic acid that then polymerizes to form ochronotic pigment.(37, 43, 44) Pigmented particles may be elastic or collagen
fibers.(19, 45) Melanocytes may be involved; most cases involve sun-exposed sites and one case is reported of ochronosis that
avoided areas of vitiligo.(19, 46) The changes in the collagen bundles may be responsible for the loss of elasticity and poor
Complications of hydroquinone use that have been reported are dermatitis, exogenous ochronosis, cataract, pigmented
colloid milia, scleral and nail pigmentation and patchy depigmentation.(3,4,15,20,26) The pigmented exogenous ochronotic
lesions are most marked on sun-exposed areas of the body viz, face, upper chest and upper back. Dogliotte,(47) described 3
stages of this condition: (1) Erythema and mild pigmentation; (2) hyperpigmentation, black colloid milia and scanty
atrophy; and (3) papulonodules with or without surrounding inflammation. Figures 1-3 show exogenous ochronosis. Since
most commercial sex workers use these skin lightening creams, some of them are HIV positive; and in an attempt to bleach
away the pruritic papular eruption (PPE) commonly seen in HIV/AIDS patients, the skin of the extremities appear scruffy
with the excoriated papules on a background of ochronotic pigmentation on bleached skin as shown in Figures 4 and 5. A
patient developed squamous cell carcinoma on the site of chronic exogenous ochronosis (Fig. 6). It is not clear if this is a
chance finding or an expected sequelae of hydroquinone induced exogenous ochronosis with superimposed chronic sun
damage on the vulnerable skin. Coalescence of multiple colloid milia may give rise to big nodular lesions particularly on
the upper back. The fawn colored pigmentation of all the twenty nails may mimic the yellow nail syndrome—hence the
authors call the phenomenon “pseudo yellow-nail syndrome.” Abnormal repigmentation of depigmented skin has also
been reported on discontinuing therapy. This abnormal repigmentation has been attributed to the Meirowsky effect of long
wavelengths of ultraviolet light darkening melanin already present in the skin and leading to a skin color darker than that
prior to bleaching. Because of this repigmentation, users find it compelling to continue to use the bleaching creams to
maintain the newly acquired light colored skin. Hence, the inevitable complications from prolonged use. A more serious
complication is loss of elasticity of the skin and impaired wound healing. When cutting through the skin, either for
incisional biopsy or other surgical procedures, it is as if one was cutting through the skin of a cadaver. There is difficulty
in apposing the edges of the wounds when stitching, hence the skin often tears through the suture material. Furthermore,
there is often delayed wound healing. After major abdominal surgeries like Caesarian section, myomectomy, hysterectomy
etc, there may be catastrophic wound dehiscence, burst abdomen, and death from overwhelming infection.
The chronic bleachers also exude an offensive fish odour in the sweat like the ‘fish odour syndrome.’(39, 40 ) The ‘fish
odour syndrome,’ also known as trimethylaminuria, is characterised by body odour of rotten fish. This is due to excretion
of a chemical, trimethylamine in the breath, urine, sweat, saliva, and vaginal secretions.
Trimethylamine (TMA) is produced in the gut mainly by bacterial degradation of choline and lecithin-rich foods, such
as salt water fish, eggs, offals (such as intestines, liver, and kidney), and leguminous vegetables such as soya beans.
Normally, this compound is converted by TMA oxidase into a stable non-odorous trimethylamine N-oxide (TMA-oxide)
that is then excreted in the urine. In the presence of a defective TMA oxidase activity, the accumulated TMA is eliminated
as a volatile product in the urine, sweat, and breath, giving the affected individual the characteristic fishy smell.
The TMA oxidase activity may be defective because of a congenital, inherited impairment of N-oxidation (primary
trimethylaminuria) or for other acquired reasons that interfere with the action of the enzyme (secondary
trimethylaminurias). Some of these causes are: (1) overload with TMA precursors, such as choline and lecithin, leading to
the formation of an increased burden of TMA through enterobacterial degradation; (2) intake of inhibitors of TMA
oxidase, both dietary (e.g., Brussels sprouts) and pharmacologic (e.g. thiourea), and (3) liver and kidney diseases. In all
these cases, the causative agent may act rather as an inducing, precipitating factor in predisposed subjects, who are carriers
of the potential defect as heterozygotes. Other causes of fish odour are bacterial vaginosis, and pemphigus vulgaris or
foliaceus due to muco-cutaneous bacterial degradation of body fluids.
Hydroquinone is an antioxidant, it may cause the fish odour by reducing the ability to oxidise trimethylamine in
chronic bleachers, or hydroquinone may act rather as an inducing, precipitating factor in predisposed subjects, who are
carriers of the potential defect as heterozygotes.
Treatment of exogenous ochronosis has been disappointing. Tretinoin gel, cryotherapy, and trichloroacetic acid have
been tried without benefit. Cases of exogenous ochronosis successfully treated with dermabrasion and CO2 laser(16) and Q-
switched ruby laser(50) have been reported.
Mercury exists in three forms viz, organic, inorganic and elemental. Mercury is a protoplasmic poison, which can be
absorbed by the respiratory tract as vapour or through the skin and gastrointestinal tract as finely dispersed granules, and
excreted through the kidneys and colon. Cole(51) observed that the amount of mercury excreted by the kidneys was
proportional to the quantity applied on the skin. Until some decades ago, mercury was ubiquitous in medicinal products
such as those used for treating syphilis, psoriasis, ringworm, ophthalmic solutions, teething powders, and diuretics.
Though it is no longer commonly used in medications.
Mercury toxicity after topical applications was noted in 1923.(52) Mercury toxicity may manifest in an acute or chronic
form. Acute toxicity usually manifests as a pneumonitis and gastric discomfort. Chronic toxicity may be evidenced by
neurological manifestations and nephrotoxicity. Both organic and inorganic preparations of mercury have been associated
with acute and chronic toxicity. Nephrotic syndrome due to topical or systemic use of mercury has been well documented.
(1, 53) Both membranous glomerulonephritis and proliferative glomerulonephritis were found in patients who had used
mercury containing skin lightening creams.
Mercurious chloride, oxide and ammoniated mercury were first introduced into the market during the first decade of
the 20th century as the active ingredient in cosmetics and toiletries. They eventually became popular as skin lighteners.
Following studies with electron microscope, mercury bleaches the skin by probably inactivating the sulfhydryl enzymes.
(54,55) These enzymes, which are called mercaptans due to their ability to capture mercurial ions, then replace copper by
competitive inhibition leading to inactivation of the tyrosinase molecule and interrupting melanin production.
Paradoxically, chronic use of mercury can also lead to increased pigmentation, due to accumulation of mercury granules in
the dermis. These granules are absorbed via the skin appendages such as the hair follicles and sebaceous glands into the
dermis. Deposition of mercury in keratin also leads to discoloration and brittleness of the nails.(52) Goeckermann(56) noted
that a brown-grey discoloration of the face and neck (especially the skin folds and eyelids) was associated with prolonged
use of mercury containing creams.
Fig. 1Exogenous ochronosis (EO) Fig. 2Exogenous ochronosis in man
Fig. 3 Exogenous ochronosis (EO)Fig. 4 Exogenous ochronosis in a patient with PPE
Fig. 5 Exogenous ochronosis in a patient with PPEFig. 6 Squamous cell epithelioma on EO
Corticosteroids bleach the skin. It is believed that they lighten the skin due to inhibition of endogenous steroid production
and thus a decrease in precursor hormone levels. This precursor hormone, propiocortin is also the precursor for
melanocyte stimulating hormone and thus, such negative feedback will lead to decreased amounts of the hormone. Topical
steroids are also cytostatic to the epidermis. When used over a prolonged period, they decrease the rate of epidermal
turnover, with fewer, abnormal, and less pigmented melanocytes on histology. The skin lightening properties of these
preparations have been found to be directly proportional to their vasoconstrictor (blanching) effect.
Fluocinonide (Topsyn gel), Betamethasone dipropionate (Diprosone), and Clobetasol propionate (Temovate) rate as
some of the strongest topical corticoids, and are among the commonly used bleaching agents in Nigeria. They are readily
available in the market place among the battery of bleaching creams. When used as cosmetics, they are applied over a
large surface area for prolonged periods—several months to years. This factor, coupled with the occlusive effect of
environmental heat and humidity, promote percutaneous absorption, and hence, complications. The possible complications
of chronic corticosteroid use are shown in Table 3. All these complications have been observed among chronic bleachers
in Nigeria.(23, 24, 31-35) Figures 7-14 show some of the complications of long-team use of topical corticosteroids as skin
lightening cosmetics. The lower part of the axilla is a favored site for steroid folliculitis (Fig. 7) and both sides are usually
symmetrically affected. The striae are often very wide (gaping) and erythematous (Figs. 8-10). Overt features of
Cushing’s syndrome — ‘mooning’ of the face and truncal obesity (Fig. 10) are frequently seen. Some of them, at the time
of presentation, have already developed systemic manifestations like glucose intolerance and hypertension.
Fig. 7 Steroid folliculitisFig. 8 Steroid folliculitis
Fig. 9 Steroid striae
Fig. 10 Cushion’s syndrome
Steroid addiction syndrome
The steroid addiction syndrome is the result of chronic daily application for greater than a 1-month period of a potent or
moderately potent glucocorticosteroid preparation to the facial skin, neck, scrotum or vulva. These tissues become
“addicted” to the topical steroid, so that withdrawing the topical steroid results in severe burning which is only relieved by
further steroid applications. As application continues, the patient experiences a rebound vasodilatation. Permanent redness
of the facial skin eventuates, with thinning and fine wrinkling of the skin. Indeed the redness is so striking that the authors
call the phenomenon “L’homme rouge.” For unexplainable reason, this permanent redness is more pronounced on male
bleachers. Furthermore, the thinning and wrinkling of the skin on the neck gives a rippling pattern like the neck of a
plucked chicken, rather reminiscent of pseudoxanthoma elasticum—hence, the authors code this complication of steroid as
“pseudo-pseudoxanthoma elasticum.”(Fig. 11) Some bleachers claim that they developed the habit of chronic steroid use
while trying to treat acne. They experienced good response initially due to the anti-inflammatory effect of the steroids.
Abruptly stopping the topical steroids preparation will result in increased numbers of papules and pustules over the
subsequent days—a “rebound phenomenon.” The patient soon finds it difficult to stop the steroid and the facial skin then
develops persistent redness, and acneiform papules and pustules located on the nose, chin, cheeks, and lower eyelids—acne
Table 3 Complications of topical steroids(57, 58)
Atrophy of the skin (thinning and fine wrinkling)
Telangiectasia, purpura, persistent erythema
Pustular acneiform eruption (face)—steroid rosacea
Steroid addiction syndrome
Predisposition and masking of cutaneous infection
(e.g. Tinea incognito, multiple filiform warts)
Allergic contact dermatitis
Cushingoid syndrome with moon facies, buffalo
humps, supraclavicular fat pads
Hyperglycaemia and diabetes mellitus
Suppression of hypothalamic-pituitary-adrenal axis
Suppression of growth in children
Aseptic necrosis of the head of femur
Predisposition to infection
Protein catabolism with negative nitrogen balance
Predisposition to infections
A very common observed complication of steroid on chronic bleachers is dermatophyte infection. Tinea faciei (Fig. 11) is
common in these patients and may mimic cutaneous lupus erythematosus or rosacea.(59-61) Very bizarre and extensive Tinea
corposis and cruris (Figs.12) are often seen , which are readily transmitted to the spouse and baby. Hence, it is common to
find the trio of wife, husband and baby with Tinea incognito. Older children are not part of this phenomenon. The wife
often transmits the fungal infection to husband and baby because of close body contact. Figure 13 shows a child with
Tinea incognito on the forehead, acquired from the infected skin of the mother while feeding on her breast. The clinical
presentation of these steroid induced dermatophyte infections are often atypical — hence the term Tinea incognito. Tinea
versicolor could also be very extensive, and is usually pigmented with dirty brown scales.
Also, multiple histologically proven viral warts are frequently found on these chronic bleachers. They often appear in
an eruptive manner—rather reminiscent of eruptive seborrheic keratosis (Leser-Trélat sign). Hence the authors call this
complication “pseudo-Leser-Trelat sign.” They are multiple tiny filiform warts, common on the neck and upper trunk (Fig.
Paradoxically, topical corticosteroid preparations may induce allergic contact dermatitis.(48) This complication should
be considered in any patient with an eczematous dermatitis who becomes worse or is refractory to topical steroid treatment.
Fig. 11 Tinea faciei and“Pseudo-pseudo xanthoma
elasticum” on the neck
Fig. 12 Tinea corporis
Fig. 13 Tinea incognito in a child Fig. 14 Eruptive filiform wart (“Pseudo Lesser-Trélat sign”) note gaping striae
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