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Dermatol Clin 24 (2006) 215 – 232

Allergic Contact Dermatitis to Cosmetics


Katherine A. Biebl, BS, Erin M. Warshaw, MD, MST
Department of Dermatology, University of Minnesota School of Medicine, Veterans Affairs Medical Center,
Department 111 K VAMC, 1 Veterans Drive, Minneapolis, MN 55417, USA

The US Food and Drug Administration defines the irritant reactions [7]. The prevalence of allergic reac-
term ‘‘cosmetic’’ as ‘‘articles intended to be rubbed, tions to cosmetics in the general population is rela-
poured, sprinkled, or sprayed on, introduced into, or tively low but, nevertheless, is significant because the
otherwise applied to the human body or any part diagnosis is often not suspected [8 – 10]. Skin care
thereof for cleansing, beautifying, promoting attrac- products have been responsible for most cases of cos-
tiveness, or altering the appearance, and articles metic allergy followed by hair care preparations or
intended for use as a component of any such articles; nail cosmetics [8,10 – 13]. The most common respon-
except that such term shall not include soap’’ [1]. The sible allergens are fragrances and preservatives [8,
broad category of cosmetics includes skin care prod- 10 – 14]. This article specifically focuses on allergic
ucts, facial makeups, personal cleanliness products, contact dermatitis to skin care products and facial
nail and hair care products, perfumes, and shaving makeup. Medline was used to search published ar-
preparations. It has been estimated that over $800 mil- ticles in English using the terms ‘‘allergy,’’ ‘‘cos-
lion is spent on over-the-counter moisturizers alone metics,’’ and ‘‘contact dermatitis.’’ In addition, hand
[2]. Precautions have been taken to ensure the safety searching of published manuscripts was performed.
of the ingredients used. The Cosmetic Ingredient
Review was established in 1976 by the Cosmetic,
Toiletry and Fragrance Association to document the Spectrum of adverse cutaneous reactions
safety of ingredients used in cosmetics [3]. The Cos-
metic Ingredient Review Expert Panel reviews ingre- Cosmetics may cause many types of adverse re-
dients that are used in at least 20 or more cosmetic actions. Most reactions are irritant in nature, but
formulations that are not otherwise regulated by the cosmetics also cause contact urticaria; delayed-type
Food and Drug Administration [4]. hypersensitivity; photosensitization (either phototoxic
Given the widespread use of cosmetics, it is im- or photoallergic); pigmentary disorders; damage of
portant to monitor their adverse effects. DeGroot and hair and nails; paronychia; acneiform eruptions; fol-
coworkers [5] interviewed female clients of beau- liculitis; and worsening of pre-existing dermatoses
ticians and found that 254 (26%) of 982 women in- [15]. The primary differential diagnoses for allergic
terviewed claimed to have experienced adverse contact dermatitis include irritant contact dermatitis,
reactions to cosmetics and toiletries in the preceding photoallergic reactions, and contact urticaria. There
5 years. It has been estimated that adverse reactions are two types of irritation: subjective and objective.
to cosmetics occur, on average, once every 13.3 years Subjective irritation consists of the sensation of burn-
per person [6]. Adverse effects are most commonly ing or stinging on the application of cosmetics that is
not accompanied by visible changes [15,16]. Often,
patients do not seek medical care for such reactions,
T Corresponding author. yet they may be the most common source of dis-
E-mail address: erin.warshaw@med.va.gov satisfaction with cosmetics [17]. Objective irritation
(E.M. Warshaw). is defined as nonimmunologically mediated skin in-

0733-8635/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.det.2006.01.006 derm.theclinics.com
216 biebl & warshaw

flammation with visible changes [17]. Both contact tested for suspected contact dermatitis in seven
urticaria (type I or immediate hypersensitivity) and different studies, the pooled prevalence rate of aller-
allergic contact dermatitis (type IV or delayed hyper- gic contact dermatitis to cosmetics was 9.8% (see
sensitivity) are immunologically mediated reac- Table 1) [8 – 11,14,24,25]. Rates of cosmetic allergy
tions [16]. Allergic contact dermatitis is much less vary with time and geographic location [18]. Nielsen
common than irritant reactions to cosmetics [12,18]. and coworkers [25] patch tested patients in Denmark
The development of sensitization depends on sev- in both 1990 and 1998 and reported that contact sen-
eral factors: product composition and concentration sitization to cosmetic-related allergens had doubled.
of ingredients, application site, skin barrier integrity, The increased prevalence of cosmetic allergy may be
contact time, and frequency of application [19,20]. caused by increased consumer use of cosmetics, use
Sensitization often occurs after repeated applications of more allergenic ingredients, or enhanced accessi-
or application to damaged skin. Photoallergy is a type bility of allergens for patch testing [14]. Risk factors
of delayed hypersensitivity in which ultraviolet radia- for allergic contact dermatitis seem to be related to
tion converts a chemical into an allergen and evokes populations with increased exposure to cosmetic prod-
dermatitis on sun-exposed skin [17]. In the past, most ucts. Most patients with cosmetic sensitivity are
cases of photoallergy caused by cosmetics were the between the ages of 20 and 55 [1,8 – 10] and are fe-
result of halogenated salicylanilides in soaps [21] and male [8,10,11,14,26].
musk ambrette, a fragrance ingredient often found
in men’s after-shave products [22]. Currently, most
cases of photoallergy are caused by sunscreen ingre- Clinical features of allergic contact dermatitis
dients [18].
Allergic contact dermatitis occurs at the site of
contact with an allergen. It may acutely present
Epidemiology with pruritic papules, vesicles, or bullae [16]. Chronic
exposure may result in eczematous dermatitis. Be-
Despite the widespread use of cosmetic products, cause most cosmetic ingredients are relatively weak
the rates of allergic reactions to cosmetic ingredients allergens, chronic eczematous dermatitis is more com-
are relatively low. Several studies in Europe and the mon than acute vesicular eruptions [27]. More than
United States have found a prevalence of cosmetic half of the reported cases of cosmetic sensitivity oc-
allergy of less than 1% in the general population, as cur on the face and the periocular area [8,11,12,14]. It
shown in Table 1 [8 – 11,14,23 – 25]. The actual rate is possible that a product applied to the entire face
of allergic reactions to cosmetics is likely higher, may only affect the eyelids because this thin skin is
however, because most people do not seek medi- very vulnerable [19]. The site of eruption usually
cal care for mild reactions and simply discontinue indicates the causative agent. The offending product
the offending product [17]. Of 30,207 patients patch may not be obvious, however, because surfaces con-

Table 1
Proportions of patients with cosmetic allergic contact dermatitis in general and patch tested populations
No. with cosmetic Total No. No. with cosmetic No. patients
Investigators ACD (% of patch tested) patients evaluated ACD (% of patch tested) patch tested
Europe
Skog 1980 [23] — 70,126 41 (0.06) —
Romaguera et al 1983 [9] 460 (8.3) 58,128 460 (0.8) 5539
DeGroot 1987 [11] 75 (4.2) 18,747 75 (0.4) 1781
Nielsen and Menné 1992 [24] 7a (2.4) — — 290
Nielsen et al 2001 [25] 27a (5.8) — — 469
Kohl 2002 [14] 297 (36.3) — — 819
United States
Eiermann et al 1982 [8] 487 (6) 179,800 487 (0.3) 8093
Adams and Maibach 1985 [10] 713 (5.4) 281,100 713 (0.3) 13,216

Pooled prevalence 9.8% 607,901 0.4% 30,207


ACD, allergic contact dermatitis.
a
Estimated numbers of patients calculated from reported percentages.
allergic contact dermatitis to cosmetics 217

Table 2 (continued)
Patch test
Table 2 concentration
Allergens recommended for patch testing in suspected cos- Function and vehicle
metic contact dermatitis (excluding hair and nail cosmetics) Antigen [32,33] [34,35]

Patch test Other antigens


concentration Abietic acid Plasticizer 5% pet
Function and vehicle Abitol (dihydroabietyl Plasticizer 10% pet
Antigen [32,33] [34,35] alcohol)
Amerchol L-101 Emollient, 50% pet
Standard seriesa emulsifier
Alpha tocopherol Antioxidant 100%
Benzyl alcohol Preservative, 1% pet
Amidoamine Surfactant 0.1% aq fragrance
Balsam of Peru, Fragrance 25% pet Butylated hydroxyanisole Antioxidant 2% pet
Myroxylon pereira b Butylated hydroxytoluene Antioxidant 2% pet
Benzalkonium chloride Preservative, 0.1% aq
Captan Preservative 0.1% pet
disinfectant Castor oil Emollient 100%
Benzophenone-3, Ultraviolet 3% pet Cetylstearyl alcohol Emulsifier 20% pet
oxybenzone absorber 2-Chloracetamide Preservative 0.2% pet
2-Bromo-2-nitropropane- Preservative 0.5% pet
4-Chloro-3-cresol Preservative 1% pet
1,3-diol Cinnamic aldehyde Fragrance 1% pet
Chloroxylenol Preservative 1% pet Cocamide DEA Emulsifier 0.5% pet
Cocamidopropyl betaine Surfactant 0.5% pet, 3-(Dimethylamino) Surfactant 1% aq
1% aq
propylamine
Colophony, rosin Plasticizer 20% pet Dodecyl gallate Antioxidant 0.25% pet
Compositae mix Fragrance 6% pet Ethylenediaminetetraacetic Antioxidant 1% pet
Diazolidinyl urea Preservative 1% pet,
acid
1% aq Hydroquinone Antioxidant, 1% pet
DMDM hydantoin Preservative 1% pet, bleaching
1% aq agent
Ethylenediamine Emulsifier 1% pet
Isopropyl myristate Emulsifier 20% pet
dihydrochlorideb Lemon grass oil Fragrance/ 2% pet
Formaldehydeb Preservative 1% aq botanical
Fragrance mixb Fragrance 8% pet Octyl gallate Antioxidant 1% pet
Glutaraldehyde Preservative 1% pet
Oleamidopropyl Emulsifier 0.1% aq
Imidazolidinyl urea Preservative 2% pet, dimethylamine
2% aq Polyethylene glycol Solvent 100%
Iodopropynyl Preservative 0.1% pet
Propolis Emulsifier 10% pet
butylcarbamate Propyl gallate Antioxidant 1% pet
Jasmine absolute Fragrance 2% pet Sodium benzoate Preservative 5% pet
Lanolin alcoholb Emollient, 30% pet Sorbic acid Preservative 2% pet
emulsifier
Sorbitan sesquioleate Emulsifier 20% pet
Methylchloroiso- Preservative 100 ppm aq Tea tree oil Fragrance/ 1% pet
thiazolinone, botanical
methyliso- Triclosan Preservative 2% pet
thiazolinoneb
Triethanolamine Emulsifier 2.5% pet
Methyldibromo- Preservative 4% pet Vanillin Fragrance 10% pet
glutaronitrile,
phenoxyethanol Abbreviations: Aq, aqueous; pet, petrolatum.
a
Paraben mixb Preservative 1% pet Selected cosmetic-related allergens from the 65 aller-
Phenoxyethanol Preservative 1% pet gens of the 2006 NACDG Standard Screening Series [33].
b
Propylene glycol Solvent, 30% aq Allergens present on TRUE test (Allerderm, Peta-
humectant, luma, California).
preservative
Quaternium-15b Preservative 2% pet
Sesquiterpene Fragrance, 0.1% pet
lactone mix botanical
Thimerosalb Preservative 0.1% pet
Ylang-ylang oil Fragrance 2% pet
218 biebl & warshaw

taminated with cosmetic products, such as towels, allergy [8]. Aromatic compounds can also be used
pillows, or telephones, can induce contact dermatitis as flavorings in cosmetics. Taylor and coworkers
[19]. Allergens may even be transmitted by sexual [45] reported a case of perioral eczema caused by
partners, friends, or coworkers causing ‘‘connubial’’ maltol, a flavor enhancer and component of the
[28] or ‘‘consort’’ [29] dermatitis [30]. strawberry flavor present in the patient’s lip salve.
The diagnosis of allergic contact dermatitis is Buckley and coworkers [37] found that females were
made by a thorough history and physical examination 1.3 times more likely to be allergic to fragrance than
and patch testing to commercial allergens and per- males (P < .001, 95% confidence interval 1.17 – 1.41).
sonal products. For most leave-on cosmetic products, This likely reflects the more frequent exposure of
such as creams and foundation makeup, patch testing women to fragrances in cosmetics and household
can be performed with the product as is. Some prod- products [17].
ucts must be allowed to dry before occlusion. These Determining the optimal patch testing method for
include mascara, liquid eyeliner, and nail polish [31]. detecting fragrance allergy has been debated. In 1976,
For rinse-off products, such as facial cleansers, dilu- Larsen [46] designed a fragrance mixture to screen for
tions of 1% should be used for patch testing [31]. fragrance allergy. The 16% fragrance mix consisted
Recommended allergens and the appropriate concen- of a concentration of 2% each of eugenol, isoeugenol,
trations and vehicles for patch testing in patients with cinnamic aldehyde, cinnamic alcohol, oak moss, ge-
suspected cosmetic-related facial contact dermatitis raniol, hydroxycitronella, and a-amylcinnamic al-
are listed in Table 2 [32 – 35]. dehyde. Later, the concentration of the constituents
was decreased to 1% each and the emulsifier sorbitan
sesquioleate was added at 5%, creating the 8% fra-
Responsible allergens grance mix that is currently widely used [36,37]. This
mix commonly results in irritant reactions, so patch
Fragrances test results must be interpreted with caution.
Initial studies indicated that the fragrance mix
In patch-tested patients, the frequency of positive was a good reflection of exposure because up to six
reactions to fragrance mix (8% petrolatum) is high. constituents of the fragrance mix were detected in
Recent European studies have found relatively con- most perfumes and scented cosmetic products inves-
stant rates of fragrance sensitivity in patch-tested pa- tigated [17,47 – 49]. Larsen’s 8% fragrance mix was
tients: 6.2% from 1988 to 1992 in Denmark [36], estimated to identify 70% to 80% of fragrance-
6.7% in males and 8.5% in females from 1980 to sensitive patients [42]. In the early 1990s, however,
1996 in the United Kingdom [37], and 7% from DeGroot and coworkers [50] found that 6.2% of
1995 to 2002 in Finland [38]. The North American 65 patients allergic to fragrances had false-negative
Contact Dermatitis Group (NACDG) has reported reactions to the 8% mix. The percentage of false-
higher, but decreasing, rates in the United States: negative reactions to fragrance mix may be increasing
14% during 1994 to 1996 [39] and 10.4% during with time because exposure to fragrances is changing.
2001 to 2002 (relevance rates are much lower) [33]. It has been shown that, as compared with older per-
Fragrances have consistently proved to be the fumes, newer perfumes contain fewer of the com-
most common cause of cosmetic allergic contact der- pounds included in the 8% mix [51]. Also, with the
matitis [8,10,12,14]. Positive reactions to fragrances popularity of ‘‘natural’’ products, there has been in-
were found in 42% to 54% of patch-tested patients creased use of plant extracts as fragrance ingredients
with suspected cosmetic dermatitis [11,14,40]. The [52]. Many investigators have evaluated other screen-
high frequency of sensitization to fragrance ingre- ing allergens to enhance the detection of fragrance
dients relates to the widespread presence of fra- allergy. In a multicenter study, Larsen and coworkers
grances in commercial products. Besides perfumes [53] reviewed the patch test results of 167 fragrance-
and colognes, fragrance allergens are encountered in sensitive patients and found that the 8% fragrance
cosmetics, soaps, toothpastes, household cleaning mix correlated with 85.6% of positive responses to
products, medications, and even perfumed products fragrance ingredients. This was improved by simul-
worn by other people [37,41 – 43]. Additionally, prod- taneously testing with ylang-ylang oil, narcissus oil,
ucts marketed as ‘‘unscented’’ are not ‘‘fragrance- sandalwood oil, and balsam of Peru, the combination
free’’ and may contain a masking fragrance [17,44]. of which detected 96% of fragrance-sensitive pa-
Most reactions occur from sensitization to fragranced tients. A new fragrance mix, fragrance mix II, was
skin care products. Actual fragrance products, such as shown to have a lower number of false-positive reac-
perfumes, toilet water, and colognes, rarely cause tions and to detect additional patients sensitive to
allergic contact dermatitis to cosmetics 219

fragrances missed by Larsen’s 8% mix [54]. Fra- thimerosal had the highest sensitization rates of
grance mix II consists of 2.5% hydroxyisohexyl 13 preservatives tested [59]. The chemicals with the
3-cyclohexene carboxaldehyde, 1% citral, 2.5% far- lowest rates of sensitization included three form-
nesol, 2.5% coumarin, 0.5% citronellol, and 5% aldehyde-releasers: (1) quaternium-15, (2) imidaz-
a-hexylcinnamic aldehyde [54]. olidnyl urea, and (3) 2-bromo-2-nitropropane-1,3-diol
Although sensitivity rates to fragrance mix in [59]. Wilkinson and coworkers [60] studied patch test
Europe have stabilized, there has been an increase in results of over 70,000 patients evaluated at 16 dif-
the rate of sensitivity to another marker of fragrance ferent centers in 11 countries in the European Union
allergy, balsam of Peru. This may indicate changing from 1991 to 2000 and found the highest rates of
compositions of fragrances and the resulting insuffi- sensitization to formaldehyde and MCI-MI and the
ciency of fragrance mix to reveal fragrance sensitivity lowest rates of sensitization to parabens.
[38]. Balsam of Peru is a natural mixture of aromatic
chemicals produced from the Myroxilon pereirae tree Formaldehyde
in Central America [43] and contains the following Formaldehyde is an inexpensive preservative
chemicals: cinnamic acid, cinnamic aldehyde, methyl with good antimicrobial activity [61], yet it is rarely
cinnamate, benzyl cinnamate, benzyl benzoate, ben- used in cosmetics because it is a frequent sensitizer.
zoic acid, benzyl alcohol, and vanillin [55]. It is used Despite decreased use in cosmetics, formaldehyde
as a screening agent for detection of fragrance allergy sensitivity levels remain high because of continued
but is not as sensitive as the fragrance mix. It has use of formaldehyde in cleaning products and from
been estimated that balsam of Peru detects approxi- exposure to formaldehyde-releasing biocides [60].
mately 50% of fragrance-sensitive patients [12,18]. NACDG patch test results show an increasing rate
The prevalence of allergy to balsam of Peru has of allergic reactions to formaldehyde 1% aqueous
recently exceeded that of fragrance mix. In the ranging from 6.8% of 3290 patients in the late 1980s
NACDG report from 1994 to 1996 evaluating the to 9.2% of 5830 patients in the late 1990s and 8.4%
patch test results of approximately 3000 patients, of 4909 patients tested from 2000 to 2001 [33,62].
10.4% reacted to balsam of Peru, whereas 14% re- Wilkinson and coworkers [60] found lower and stable
acted to the 8% fragrance mix [39]. From 2001 to levels of sensitivity to formaldehyde 1% aqueous in
2002 close to 5000 patients were evaluated and 11.6% Europe, between 2% and 2.5% from 1991 to 2000.
reacted to balsam of Peru compared with 10.4% re- Formaldehyde is one of the most ubiquitous con-
acting to the 8% fragrance mix [33]. tact allergens [18,58]. The presence of formaldehyde
in a product may not always be documented because
Preservatives of the presence of formaldehyde-releasers, the deg-
radation of other ingredients to formaldehyde during
Preservatives are used in cosmetics to prevent the storage and use, or because of its unidentified pres-
overgrowth of microorganisms. Prevention of con- ence in raw materials [19,63]. Agner and coworkers
tamination is essential because many cosmetics are [63] evaluated 57 patients with formaldehyde allergy
designed as multiuse products and come into repeated several years after initial diagnosis and found that
contact with the environment and human skin [18,56]. 77% were still exposed to formaldehyde. Because
Preservatives fall into three categories: (1) antimicro- 65% of the formaldehyde-allergic patients reported
bials, (2) antioxidants, and (3) ultraviolet light ab- avoidance behavior, it was concluded that the avoid-
sorbers [15,57]. The antimicrobials can be further ance of formaldehyde is difficult. Thus, formaldehyde-
categorized as formaldehyde, formaldehyde-releasers, sensitive patients often have chronic contact dermatitis
and non – formaldehyde-releasing preservatives. Of [64]. Agner and coworkers [63] also found, however,
the antimicrobials, it has been reported that the most that patients with formaldehyde allergy who ac-
frequently used preservatives in cosmetics and toilet- tively engaged in avoidance practices had statistically
ries include parabens, imidazolidinyl urea, quater- significantly fewer eruptions than those who did not
nium-15, formaldehyde, and isothiazolinones [17,58]. engage in avoidance practices [63].
Studies have repeatedly shown preservatives to
be one of the two most common classes of cosmetic Formaldehyde releasers
allergens [10 – 13,26]. A 1-year study (1989 – 1990) Formaldehyde-releasing preservatives include
by the Swiss Contact Dermatitis Research Group 2-bromo-2-nitropropane-1,3-diol, DMDM hydantoin,
involving 2295 patch test patients found that form- diazolidinyl urea, imidazolidinyl urea, and quater-
aldehyde, benzalkonium chloride, methylchloroiso- nium-15. These preservatives are inherently antibac-
thiazolinone-methylisothiazolinone (MCI-MI), and terial and antifungal but also act by formaldehyde
220 biebl & warshaw

release because of an easily detachable formaldehyde [72]. It is found in many cosmetic products, most
moiety [17,19,65]. The amount of formaldehyde frequently in shampoos, followed by skin care prepa-
produced by these chemicals depends on temperature rations, hair conditioners, makeup foundations and
and pH [65]. Allergic reactions to formaldehyde re- bases, and personal cleanliness products [72]. The
leasers may be caused by the preservative, formal- NACDG reported increasing sensitivity rates from
dehyde, or both [65,66]. 0.5% of approximately 3000 patients in 1985 to
The rate of cross-reactivity between formaldehyde- 1990 to 3.3% of almost 5000 patients in 2001 to 2002
releasers and formaldehyde varies. Herbert and [33,39]. Rates seem lower in Europe and may be
Rietschel [67] reviewed patch test reactions of related to less exposure to this preservative [73]. In a
219 patients who reacted to either formaldehyde study of patch test results of 67,915 patients in Ger-
or five different formaldehyde-releasing preserva- many from 1995 to 2000 the proportion of positive
tives from 1996 to 2002. Of these patients, over half reactions ranged from 0.39% to 0.65% [73].
only reacted to one or two of these allergens and less
than 1% reacted to all six [67]. Allergy to one Diazolidinyl urea
formaldehyde-releasing preservative may not neces- Diazolidinyl urea was first introduced in 1982
sitate a restriction of the entire class [67]. (Sutton Labs, Chatham, New Jersey) [66,74]. It is a
colorless, odorless, stable, and water-soluble preser-
2-Bromo-2-nitropropane-1,3-diol vative [74,75]. It is reported to have a wider anti-
The preservative 2-bromo-2-nitropropane-1,3-diol microbial spectrum than imidazolidinyl urea [75], to
has been used in a wide variety of cosmetic and phar- which it is structurally related. It is effective against
maceutical preparations including shampoos, creams, gram-negative and gram-positive bacteria, molds, and
lotions, cleansers, and eye makeup [68]. It is water yeast, but has limited activity against fungi [74].
soluble with antimicrobial activity against bacteria, Allergy to diazolidinyl urea was first reported in 1985
fungi, and yeast [61,68]. Since the early 1980s, how- in a man who reacted to this preservative in a hair gel
ever, its use has declined [15,57]. This is because at but did not react to formaldehyde alone [75]. There
alkaline pHs it breaks down into formaldehyde and were also several reports of women with facial and
bromo compounds, which develop a yellow or brown eyelid dermatitis that was determined by patch testing
color on exposure to light [61]. Additionally, it can to be caused by diazolidinyl urea in hypoallergenic
react with amines or amides to produce potentially day and night creams [76]. Formaldehyde release is
carcinogenic nitrosamines or nitrosamides [57]. the main mode of sensitization to diazolidinyl urea
2-Bromo-2-nitropropane-1,3-diol can be allergenic but primary sensitization also occurs [74]. From the
itself or can cause allergy by its formaldehyde- late 1980s to the first part of this decade, the NACDG
releasing properties [69,70]. Also, it is a frequent cause found a rate of positive reactions of 2.7% to 3.7% for
of irritant reactions at concentrations as low as 0.25% 1% diazolidinyl urea in petrolatum and 2.9% to 3.9%
aqueous and 1% in petrolatum [68]. Studies have for 1% diazolidinyl urea aqueous [33,62]. In a study
shown that 2-bromo-2-nitropropane-1,3-diol is a rela- of patch test reactions to cosmetic allergens, diazo-
tively rare sensitizer with positive patch tests rates as lidinyl urea was responsible for only 0.9% of al-
low as 0.47% of 8149 patients in Europe [70]. In the lergic reactions in 6539 patients in Finland from
early 1980s, Adams and Maibach [10] found that 2000 to 2002 [38]. Additionally, diazolidinyl urea has
2-bromo-2-nitropropane-1,3-diol was the fourth most been reported to cross-react with imidazolidinyl urea
common implicated preservative in 713 cases of cos- because of their structural similarity [75].
metic allergy in the United States. The NACDG has
reported increasing sensitivity rates ranging from Imidazolidinyl urea
0.7% in the late 1980s to approximately 3% of 3000 Imidazolidinyl urea is a widely used preservative
to 5000 patients tested during the late 1990s and first in cosmetics because of several desirable features. It is
few years of this decade [33,39,71]. 2-Bromo-2-nitro- compatible with almost all cosmetic ingredients and
propane-1,3-diol was responsible for numerous cases is colorless, odorless, tasteless, and not pH-dependent
of allergic contact dermatitis caused by Eucerin cream [61]. It is more active against bacteria than against
(Beiersdorf, Wilton, Connecticut) in the early 1980s yeast and molds [61]. An important feature of this
until it was replaced by a different preservative [68]. preservative is that it acts synergistically with other
preservatives, especially parabens [61]. It is not sur-
DMDM hydantoin prising that imidazolidinyl urea has been reported to
DMDM hydantoin is active against fungi, yeast, be the second most commonly used preservative in
gram-positive bacteria, and gram-negative bacteria cosmetics, after parabens [17,57].
allergic contact dermatitis to cosmetics 221

In 1974, the first case of cosmetic allergy caused Nonformaldehyde preservatives


by imidazolidinyl urea was described in a woman Parabens. Parabens are esters of 4-hydroxy ben-
with facial dermatitis proven by patch testing to be zoic acid. The five commonly used parabens are:
caused by imidazolidinyl urea in her facial mois- (1) methylparaben, (2) ethylparaben, (3) propylparaben,
turizing lotion and liquid eyeliner [77]. Adams and (4) butylparaben, and (5) benzylparaben [58,81,82].
Maibach [10] subsequently found that imidazolidinyl Parabens have a broad spectrum of activity against
urea was the second most common preservative re- yeasts and molds but are less active against bacteria
sponsible for cases of cosmetic allergy in 13,216 pa- [61]. Two or more parabens are often combined be-
tients evaluated from 1977 to 1983. The role of cause they have a synergistic preservative effect [81].
imidazolidinyl urea in allergy to cosmetics seems, Parabens are also usually combined with other preser-
however, to have decreased. More recent studies have vatives, such as formaldehyde releasers [56,61].
shown that it ranks fifth or lower as a cause of cos- Parabens are popular because of their broad anti-
metic allergy [12,14,38]. microbial activity; low rate of allergenicity; effec-
Despite its frequency of use, imidazolidinyl tiveness over a wide pH range; and because they
urea seems to be the least common sensitizer of the are colorless, odorless, nontoxic, and inexpensive
formaldehyde-releasing preservatives [18]. Guinea [82 – 84]. Because of these characteristics, they are
pig sensitization tests showed that the lowest con- the most widely used preservatives. It has been re-
centration that induced contact hypersensitivity was ported that 87% to 93% of investigated cosmetic
10 times higher than concentrations used in cosmetic products contain one or more of the parabens [58,83].
preparations (0.02% – 0.5%) [78]. Human patch test They are found in facial makeup (especially mascara
results parallel the low rate of sensitivity found in and eye shadow); skin care products; and medicinal
animal testing. A Belgian study detected only three creams and lotions [81].
allergic reactions to 2% aqueous imidazolidinyl urea Despite the widespread use of parabens in cos-
in 279 patients with cosmetic allergy of a total of metics, these compounds are rare causes of allergic
1175 patients patch tested [79]. Wilkinson and co- contact dermatitis. Mowad [84] reported a case of a
workers [60] found that levels of sensitivity of Euro- 76-year-old woman with an extremely pruritic face
pean patients to imidazolidinyl urea remained stable and neck dermatitis that coincided with usage of an
at around 1% during the 1990s. Sensitivity rates increased number of cosmetic products. Patch testing
have been higher in the United States according to with an expanded series, including preservatives,
the NACDG, who reported reactions in 2.5% to 3.2% vehicles, and corticosteroids revealed a positive reac-
of patients patch tested [33,62]. tion to paraben mix, which was found in her cos-
metics. Wilkinson’s and coworkers [60] analysis of a
Quaternium-15 decade of patch test results (1991 – 2000) in the
Quaternium-15 is an odorless, colorless, water- European Union found that the parabens had the
soluble, antimicrobial agent that is active against lowest level of sensitivity, approximately 0.5% to
bacteria more so than yeast and molds [61,67]. It is a 1%. Similarly, the NACDG reported that only 0.6% of
widely used preservative in cosmetics and toiletries 4898 patients patch tested reacted to parabens
and has been shown to be the most common cosmetic [33,62]. Patch testing is performed with a paraben
preservative allergen [8,10]. Positive patch test mix (methylparaben, ethylparaben, propylparaben,
reactions have increased from 6.2% of 3994 patients and butylparaben) in petrolatum with subsequent
to 9.3% of 4910 patients according to NACDG re- testing of the individual esters if there is a positive
sults from 1985 to 2002 [33,62]. Compared with the reaction to the mix [82].
NACDG results, European studies have found lower Fisher [85] first described a ‘‘parabens paradox’’
rates of sensitivity to quaternium-15 [11,12,14,38]. in 1973, referring to observations that paraben-
Wilkinson and coworkers [60] found that rates of sensitive patients can often tolerate paraben-containing
sensitivity in the European Union were stable during products on normal skin. Several hypotheses for
the 1990s, at about 1%. Quaternium-15 has proved to this phenomenon have been suggested [85], includ-
be more than eight times as sensitizing as imidazo- ing the ‘‘esterase’’ and ‘‘microbial metabolism’’ hy-
lidinyl urea [61]. Most sensitization to quaternium-15 potheses [82]. Although parabens have generally
is caused by formaldehyde release. Most patients been regarded as safe in cosmetics, the Cosmetic
who are allergic to quaternium-15 are also allergic Ingredient Review Expert Panel recently elected to
to formaldehyde [39,80]. Conversely, it is the most review data suggesting that parabens may act as
common coallergen in formaldehyde-sensitive pa- reproductive toxins and disregulators of endocrine
tients [80]. function [86].
222 biebl & warshaw

Methylchloroisothiazolinone-methylisothiazolinone. sitizing potential and a substitute for MCI-MI was


MCI-MI is the active ingredient of a commonly used needed [96]. It was introduced in Europe in 1985
preservative system. It consists of a mixture of two [66,97,98] and in the United States approximately
isothiazolinones, 1.15% MCI and 0.35% MI, in water 5 years later [98]. It is equally effective against bacteria,
with 23% magnesium chloride and nitrate as stabilizers yeasts, and fungi at a low concentration of 0.1%
[66,87,88]. It is a broad-spectrum antimicrobial active [66,97]. MDBGN-PE is used as a preservative in cos-
against bacteria, yeasts, and fungi, and is effective in metics, predominantly in creams and lotions [98–100].
low concentrations [88 – 92]. It was introduced in Eu- It is commonly referred to in the literature as Euxyl
rope in the mid-1970s and into the United States in the K400 [101].
early 1980s [87,88]. MCI-MI can be found in many Contrary to the initial animal studies, MDBGN-PE
cosmetic products, including rinse-off and leave-on has shown to be a sensitizing agent in humans,
products [88 – 90]. predominantly in Europe where it was first introduced
The first cases of allergic contact dermatitis to [98,100]. The principal allergen has been shown to be
MCI-MI were reported in Europe [88] and many MDBGN [97,102]. Before its use in cosmetics, there
resulted from the use of moisturizing creams on com- were numerous cases of perianal allergic contact
promised skin [93]. MCI-MI was the most important dermatitis reported from this preservative in moist
cosmetic allergen in a study from The Netherlands in toilet tissue [100]. The first case of cosmetic allergy
1986 to 1987, causing reactions in 27.7% of 119 pa- was reported in 1989 caused by MDBGN in an
tients with cosmetic allergy [12]. Hannuksela [85] antiwrinkle cream [103]. Now, most reported cases of
reported that the proportion of positive patch tests to MDBGN allergy result from exposure to cosmetics
MCI-MI 100 ppm in 167 unselected eczema patients [98,104]. As the rate of allergy to MCI-MI has
increased from 0% in 1983 to 0.7% in the first half of decreased [99], the rate of allergy to MDBGN has
1985 and to 4.6% in late 1985 and early 1986 [94]. increased, corresponding to the replacement of the
Because of the rapidly increasing sensitivity, the use former by the latter as a preferred preservative system.
of MCI-MI in Europe, and later in the United States, In The Netherlands, 0.3% of 281 patch-tested patients
was limited to concentrations of 7.5 ppm in leave-on were found to be positive to MDBGN during the first
products and 15 ppm in rinse-off products [38,88]. half of 1993. Prevalence rapidly increased to 3.2% of
Subsequently, throughout the 1990s, the frequency of 281 patients in the second half of 1993 and 2.4% of
MCI-MI sensitivity in the European Union remained 247 patients in the first half of 1994 [100]. In 1996,
high, but stable, around 2% to 2.5% [59,60]. In 2005, DeGroot and coworkers [105] reported that MDGBN
Hasan and coworkers [38] reported that sensitivity was the most common preservative allergen in The
rates to MCI-MI in Finland had fallen from 2.4% in Netherlands, surpassing MCI-MI (4% versus 3.2%).
1995 to 1996 to 1.3% in 2000 to 2002. The decrease The frequency of MDBGN allergy increased in the
is likely due to the restriction of MCI-MI use and United Kingdom in the late 1990s and in Finland in
the replacement with newer, more popular preserva- the late 1990s to 2002 [38,104]. Wilkinson’s and
tives, such as MDBGN [38,59]. In the United States, coworkers [60] multicountry study in the European
sensitivity patterns have followed that of Europe. Union from 1991 to 2000 reported that reactions to
NACDG patch testing results show that positive MDBGN increased from 0.7% in 1991 to 3.5% in
patch test reactions to 100 ppm MCI-MI increased 2001. Two recent studies in Denmark showed that
from 1.8% in the late 1980s to 2.9% to 3% in the MDBGN was the third most common allergen, after
mid-1990s but then decreased in the first part of nickel and fragrance allergy [99,106]. In the United
this decade to 2.3% [33,62]. MCI-MI is patch tested States, MDBGN allergy is also increasing [62,71,107]
at 100 ppm aqueous but the amount actually used albeit at a slower rate and with lower prevalence than
in products is much lower. Patients sensitized to in Europe, likely because of its later introduction into
MCI-MI may often have false-negative reactions to the American market.
MCI-MI – containing products [12,19,95]. Interpretation of sensitivity rates is affected by
a debate over proper patch test concentrations for
Methyldibromoglutaronitrile-phenoxyethanol. The MDBGN [38,60,101,108]. Additionally, patch tests
methyldibromoglutaronitrile-phenoxyethanol (MDBGN- with the incriminated products often give false-
PE) preservative system is a combination of two active negative reactions because of the low concentration
ingredients, 2-phenoxyethanol and 1,2-dibromo-2, of the preservative in the product [98]. Nevertheless,
4-dicyanobutane, in a ratio of 4:1 [17,66]. Manu- because of the rapidly increasing sensitization, its use
facturers began using this preservative system in in Europe in leave-on products was banned in 2003
cosmetics because guinea pig testing showed no sen- [108]. A recent study aimed at determining the maxi-
allergic contact dermatitis to cosmetics 223

mum noneliciting concentration for leave-on products rancid odor and oxidation-based discoloration [15,18,
in MDBGN-PE – sensitized patients was unable to 34,57,115]. The most commonly used antioxidants
find a concentration that was safe and still micro- include butylhydroxyanisole; butylated hydoxy-
bicidal [108]. toluene; tertiary butylhydroquinone; the gallate esters
(propylgallate, octylgallate, and dodecylgallate); nor-
Iodopropynyl butylcarbamate. Iodopropynyl butyl- hydroguaiaretic acid; a-tocopherol (vitamin E); and
carbamate is a relatively new preservative in cos- ascorbic acid (vitamin C). Allergic contact dermati-
metics. It is used in shampoos, lotions, powders, tis has been reported to butylhydroxyanisole, butyl-
makeup, and creams [109 – 111]. Iodopropynyl butyl- ated hydoxytoluene, and tertiary butylhydroquinone,
carbamate is a known irritant at concentrations of which often cross-react with each other because of
0.5% but was not recognized as a cosmetic allergen structural similarity [115,116]. Norhydroguaiaretic
until this past decade [109]. It is permitted for use in acid has also been reported as a sensitizer, most of-
cosmetics in the European Union in concentrations ten in creams [115]. There are numerous reports of
up to 0.1% [109,110]. Interestingly, industrial prod- sensitization to gallate esters. These antioxidants are
ucts in Europe containing a concentration greater frequently used in lip products, such as lipsticks, lip
than 0.01% are labeled as ‘‘irritant’’ but this same balm, and salves, but are also present in creams and
requirement does not apply to cosmetics [109]. lotions [117]. Most cases of cosmetic allergy caused
There have only been three case reports of iodo- by gallates result in cheilitis from lip care products
propynyl butylcarbamate allergy related to cosmetics [117 – 119]. The first case of lipstick dermatitis from
[109,110]. In 1999, the first case described a 29-year- propylgallate was reported by Cronin in 1980 [120].
old woman with a recurrent, pruritic, papular facial Although other topical products contain gallate esters,
dermatitis that was determined by patch testing to be the concentration may be too low to induce sensiti-
caused by iodopropynyl butylcarbamate in her facial zation [115]. a-Tocopherol has caused relatively fre-
cosmetic cream [112]. Subsequently, Bryld and co- quent cases of allergic contact dermatitis [121,122].
workers [110] reported two cases in 2001 caused by In contrast, ascorbic acid is a rare cause of cosmetic
a moisturizer, which caused severe contact dermatitis, allergy [123].
necessitating one of the patients to be hospitalized
with erythroderma. The data on sensitivity to iodo-
propynyl butylcarbamate are limited because it has UV absorbers
not routinely been evaluated in the past. Reported Chemicals that absorb ultraviolet radiation are
rates have been low: 0.02% of 3168 [110], 0.3% of added to cosmetics to prevent deterioration of the
approximately 5000 [33,113], and 0.32% of 312 product and to function as a sunscreen. Sunscreens
[112] patch-tested patients, respectively. can cause both photocontact and contact allergy [34].
The sensitivity rates of iodopropynyl butylcarba- In cosmetics, benzophenones have replaced the use of
mate must be interpreted carefully because the proper p-aminobenzoic acid, which was a commonly re-
patch test concentration has not been determined. ported sensitizer in the past [43,124]. Because of its
Most studies have used a concentration of 0.1% iodo- increased usage, oxybenzone, or benzophenone-3,
propynyl butylcarbamate [109 – 113], although the has become the most commonly reported sunscreen
Information Network of Departments of Dermatol- sensitizer, present in 0.6% of NACDG patients patch
ogy in Germany recently suggested 0.2% may be the tested [71].
optimal patch test concentration [113,114]. The dif-
ficulty in determining proper patch test concentration
results from the scarcity of patients with proven and Vehicles, emulsifier, and other base ingredients
clinically relevant contact allergy to this allergen
[114]. Also, it is a newer preservative in cosmetics Vehicles of topically applied preparations used
and may have lower rates of usage and exposure. The to be considered inert ingredients [125]. They are
experiences with MCI-MI and then with MDBGN-PE potential sensitizers, however, and have been reported
have shown there is often a lag time between intro- to cause allergic contact dermatitis [125,126]. Even
duction of a new preservative and overt clinical prob- petrolatum, which has classically been considered
lems [114]. harmless [126], has been reported to cause allergic
contact dermatitis [127], although this is rare. Surface
Antioxidants active agents can also cause cosmetic contact der-
Antioxidants protect products from the deterio- matitis [128]. Emulsifiers are present in creams and
ration of unsaturated fatty acids, which can cause a lotions to facilitate the combination of water and ole-
224 biebl & warshaw

aginous materials [57]. They are analogous to sur- wool [18,134,135]. It is used in cosmetic products as
factants present in soaps and detergents, which build an emollient and emulsifier [18]. Sensitization rates
viscosity and foaming of cleansing products [15,129]. to lanolin are high from topical therapeutics used
Emulsifiers can be mild irritants but are infrequent on patients with stasis dermatitis but it is rarely a
sensitizers [57]. sensitizer in cosmetics [18]. Analogous to the ‘‘para-
bens paradoxes’’ described by Fisher [85], Wolf [135]
described two paradoxes related to the use of lanolin.
Glycerin and glycols Lanolin in topical therapeutic agents sensitizes a high
Glycerin is a nonirritating humectant that is stable, proportion of patients [134] but is relatively safe in
nontoxic, and imparts smoothness to cosmetics [130]. cosmetics; patients with lanolin-allergy can often use
It is a rare sensitizer [131], especially when compared lanolin-containing cosmetics [135].
with other vehicles, such as propylene glycol [130]. The allergenic component of lanolin is thought to
Preston and Finch [131] reported a 29-year-old be wool-wax alcohols [19,43,135 – 137]. Sensitiza-
woman with a 7-month history of patchy eyelid, fa- tion rates to lanolin alcohol in patients with suspected
cial, neck, scalp, and axillary eczema. Patch testing contact dermatitis were 1.2% to 3.3% [62,71,126].
showed a positive reaction to a hand cream and, sub- From 1977 to 1983, Adams and Maibach [10] re-
sequently, to glycerin that was present in this hand ported that allergy to lanolin was the fourth most
cream. Despite its desirable nonirritating and non- common allergen causing cosmetic reactions (after
allergenic qualities, glycerin has largely been replaced fragrances, preservatives, and p-phenylenediamine).
by the glycols (propylene, 1,3-butylene, hexylene, DeGroot [11] reported that lanolin derivatives were
pentylene, and polyethylene glycol) because it is an responsible for 6.1% of 82 reactions to cosmetic
inferior solvent [131]. allergens in 75 patients with allergic contact derma-
Of the glycols, propylene glycol and 1,3-butylene titis to cosmetics.
glycol are most frequently discussed in cases of cos-
metic contact dermatitis. Propylene glycol has been
Castor oil-ricinoleic acid
widely used in cosmetics. It is a solvent and humec-
Castor oil is extracted from the seeds of Ricinus
tant, and has antimicrobial properties [57]. Propylene
communis and used in cosmetics as an emollient in
glycol is a frequent cause of irritant and allergic
lipsticks, makeup removers, and moisturizers [138,
contact dermatitis, with irritation being particularly
139]. Allergic contact dermatitis to castor oil has been
common [126,131]. The NACDG found that sensi-
reported, most commonly from lipsticks [139,140].
tivity to 30% propylene glycol aqueous was 1.1% in
Brandle and coworkers [141] reported a case of acute
3077 patients from 1994 to 1996 and increased to
facial dermatitis in a 23-year-old woman caused by
4.2% of 4899 patients tested from 2001 to 2002 [33].
castor oil in a makeup remover. Ricinoleic acid is
1,3-Butylene glycol is also widely used in cosmetics
the sensitizer in castor oil [140] and metal salts of
because it has desirable humectant and antibacterial
ricinoleic acid, known as rincinoleates, are also com-
effects, good solubility, and low irritant potential
mon causes of allergic cosmetic cheilitis [139].
[132]. Unfortunately, there are frequent cases of cos-
metic allergy caused by this vehicle, many occurring
in Japan [133]. Suguira and Hayakawa [133] re- Cocamidopropyl betaine
ported a patient with a history of cosmetic dermatitis Cocamidopropyl betaine is a surfactant that is
who presented with facial erythema that appeared widely used in cosmetics, especially in shampoos, but
1 day after using a foundation cream containing also in liquid soaps; skin care products (moisturizers
1,3-butylene glycol. These investigators subsequently and cleansers); deodorants; shower gels; and bath
evaluated 18 ‘‘hypoirritant’’ cosmetics marketed for foams [129,142,143]. Of the numerous case reports
sensitive skin and found that 1,3-butylene glycol was of allergy to cocamidopropyl betaine, most are caused
present in all the investigated products. Diegenant by cocamidopropyl betaine in shampoos and shower
and coworkers [132] reported two Belgian patients gels [129,143]. Ross and White [142], however,
with generalized dermatitis who, on patch testing, reported a 60-year-old woman with a 2-month history
had positive reactions to a ‘‘supertanner’’ cream and of eyelid eczema, which was caused by an oil-free
one of its ingredients, 1,3-butylene glycol. lotion makeup remover containing cocamidopropyl
betaine. It is broadly accepted that cocamidopropyl
Lanolin betaine itself is not allergenic [144]. Rather, impu-
Lanolin is a variable mixture of fatty acids esteri- rities remaining from the synthesis of cocamidopro-
fied with monohydric alcohols derived from sheep’s pyl betaine are thought to be the actual allergens.
allergic contact dermatitis to cosmetics 225

Cocamidopropyl betaine is formed by reacting fatty plasticizer and as a pigment-grinding medium in


acids extracted from coconut oil with dimethyl- cosmetics [154].
aminopropylamine, yielding cocamidopropyl di-
methylamine (also known as ‘‘amidoamine’’ or
‘‘cocamidoamine’’), which then reacts with sodium Pigments
monochloroacetate to produce cocamidopropyl beta- Agents used to impart colors to cosmetics can also
ine [143,144]. Amdioamine [145 – 147] and dimethyl- be responsible for allergic cosmetic reactions. They
aminopropylamine are thought to be the primary are referred to as ‘‘D&C’’ colors, indicating usage in
allergens [147 – 149]. drugs and cosmetics [57], and are carefully monitored
by the federal government. In the 1950s, D&C red
21 (eosin) used in lipsticks caused many adverse
Other cosmetic allergens reactions and was reported to be the most common
cause of cosmetic allergy at that time [27]. The al-
Propolis lergen was thought to result from an impurity, and the
Propolis, also known as ‘‘bee-glue’’ [27], is made incidence of sensitivity decreased with improved
by bees from the resinous exudates of plants, es- purification processes [27]. Several other D&C pig-
pecially poplar trees [150,151]. It can be found in ments have been reported to be sensitizers including
many natural cosmetics, such as lotions, lip care D&C red 7 [159], D&C red 36 [160], and D&C
products, and shampoos, and pharmaceutical and yellow 11 [161,162]. Iron oxides are pigments
dental products [27,152]. Rates of sensitization vary used in eye makeup and lipsticks that have rarely
from 1.2% to 6.2% [38,152]. A Finnish study of been reported to cause allergic contact dermatitis
cosmetic allergens found a significant increase in the [163,164]. Saxena and coworkers [164] reported a
rate of patch test sensitivity to propolis, rising from 44-year-old woman with chronic periorbital and
1.4% of 3885 patients during 1995 to 1997 to 6.2% of eyelid dermatitis that was determined by patch test-
5130 patients during 2000 to 2002 [38]. The authors ing to be caused by black iron oxide in the pa-
hypothesized that one reason for the drastic increase tient’s mascara.
in propolis sensitivity is the popularity of natural
cosmetics containing this substance [38]. The main Other
allergen in propolis is LB-1, which consists primarily
of 3-methyl-2-butenyl caffeate and phenylethyl caf- Case reports of cosmetic allergy have been
feate [27,150,152,153]. One interesting case report of reported to many other chemicals used in cosmetics.
cosmetic propolis allergy described erosive dermatitis These include, but are not limited to, the allergens
of the lips and oral mucosa, which mimicked pem- listed in Table 3 [138,165 – 194].
phigus vulgaris but was determined by patch testing
to be allergic contact dermatitis to propolis in a lip
balm [151]. Pertinent noncosmetic allergens

In the evaluation of suspected allergic reactions to


Colophony cosmetics, it is important to consider three major
Colophony, or rosin, is obtained from the tree noncosmetic allergens that may mimic cosmetic al-
species Pinaceae and consists of resin acids and lergy: (1) gold, (2) nickel, and (3) rubber. Gold is a
neutral matter [15,154,155]. In cosmetics, it is used common allergen that often presents as a patchy
primarily in lipsticks and eye makeups, including facial or eyelid dermatitis in sensitized patients
mascaras, eye shadow, and eyeliners [15,156]. Sen- [195,196]. Nickel has been reported as a contaminant
sitization is not common, but has been reported in in eye cosmetics, such as eye shadow and eyeliner,
cases of eyelid and periorbital dermatitis [154,157] possibly because of container leaching [197,198].
and with chelitis and perioral dermatitis [158]. Two Also, it has been reported to cause eyelid dermatitis
substances from colophony have been determined to from nickel-plated eyelash curlers [199]. Rubber used
be allergens: abietic acid and dihyroabeityl alcohol. in cosmetic applicators and sponges can produce an
Abietic acid is a major component of colophony and eczematous reaction in the same distribution in which
it, or its oxidation products, has been considered to be the associated makeup product is used. Fisher [200]
the main allergen [15,155]. It serves as a binder or described a 29-year-old woman with facial dermatitis
plasticizer in cosmetics [15]. Dihydroabietyl alcohol who did not react to any cosmetics or standard
is produced from rosin acids and is used as a resinous allergens on patch testing but did react to tetramethyl-
226 biebl & warshaw

Table 3
Rarer allergens in facial cosmetic products
Allergen Product Reference
Preservatives
Chlorphenesin Face cream, foundation make-up Wakelin and White [165],
Brown and Orton [166]
Potassium sorbate Face powder Fisher [167]
Vehicles, active ingredients
C12 – 16 (medium chain) triglyceride Face cream Laube et al [168]
C18 – 36 acid triglyceride Lip gloss Kimura et al [169]
C18 aliphatic compounds Lipstick Hayakawa et al [170]
DEA-dihydroxypalmityl phosphate, Face lotion Dooms-Goossens et al [171]
isopropyl hydroxypalmityl ether mixture
Di-isostearyl malate Lipstick Guin [172]
Glyceryl monoisostearate monomyristate Lipstick Asai et al [173]
2-Hexyldecanoic acid Lipstick Kimura and Kawada [174]
Hydroxy stearic acid Lip gloss Kimura et al [169]
Isohexadecane Sunscreen lotion Bharati and King [175]
Isopalmityl diglyceryl sebacate Lipstick Suzuki et al [176], Shono [177]
Isopropyl myristate Sunscreen Bharati and King [175]
Lanpol 5 Lipstick Rademaker et al [178]
Monotertiary butyl hydroquinone Lipstick Calnan [179]
Oleyl alcohol Face cleanser, lipstick Guidetti et al [180], Tan et al [138]
Polyoxyethylene laurylether Foundation make-up Kimura and Kawada [181]
Sodium dihydroxycetyl phosphate Face cream Lomholt et al [182]
Sodium myristoyl sarcosinate, Face cleanser Malanin [183]
sodium myristoate
Stearic acid Face cream De Groot et al [184]
Other
Coathylene Mascara Chowdhury [185]
Ethylenediaminetetraacetic acid Face lotion, face cream Kimura and Kawada [186],
Soga et al [187]
Para-tertiary-butylphenol Lip liner Angelini et al [188]
Prime yellow carnuba wax Mascara Chowdhury [185]
Pyrocatechol Eyelash, eyebrow cream dye Andersen and Carlsen [189]
Sesquiterpene lactone Facial make-up Bernedo et al [190]
Shellac Lipstick, mascara Rademaker et al [178],
Orton et al [191],
LeCoz et al [192]
Tetrahydrocurcumin Sunblock cream Lamb and Wilkinson [193]
Vanilla Lipsalve Ferguson and Beck [194]

thiuram, an accelerator present in the rubber sponge [201]. This allowed consumers to avoid allergens by
used for applying her cosmetics. reading cosmetic labels. The individual components
of fragrances are rarely listed, however, because these
are regarded as trade secrets [201]. Fragrances are
Management also very difficult to avoid given their ubiquitous
presence in many common products and because of
The key tenet in management of allergic contact the presence of unlabeled fragrances in some prod-
dermatitis is avoidance of the offending allergen. The ucts, even in products labeled as ‘‘fragrance-free’’
prevalence of the allergen and availability of sub- [44]. Fragrances that have more than one function,
stitutes are important for successful avoidance. The such as those that act as preservatives or fixatives,
first step in facilitating avoidance was taken in 1976 can be included in but not listed as an ingredient of
when the US Food and Drug Administration required fragrance-free cosmetics [17]. Additionally, natural
ingredients be listed on all direct consumer cosmetics products, such as essential oils and botanical ex-
allergic contact dermatitis to cosmetics 227

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cause problems for the fragrance-allergic patient reactions to cosmetic ingredients. Contact Dermatitis
and should be avoided [52]. Similarly, avoidance of 1985;13:258 – 65.
[8] Eiermann HJ, Larsen W, Maibach HI, et al. Prospec-
formaldehyde-containing products can also be very
tive study of cosmetic reactions: 1977 – 1980. J Am
difficult [63]. Rastogi [58] found that 23% to 33% of
Acad Dermatol 1982;6:909 – 17.
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