Contact Dermatitis • Original Article
`
`COD
`Contact Dermatitis
`
`Deodorants are the leading cause of allergic contact dermatitis to
`fragrance ingredients*
`Maria V. Heisterberg1, Torkil Menn ´e1, Klaus E. Andersen2, Christian Avnstorp3, Berit Kristensen4,
`Ove Kristensen4, Knud Kaaber5, Grete Laurberg6, Niels Henrik Nielsen7, Mette Sommerlund8, Jens
`Thormann9, Niels K. Veien6, Susanne Vissing10 and Jeanne D. Johansen1
`1Department of Dermato-allergology, National Allergy Research Centre, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark,
`2Department of Dermatology, Odense University Hospital, 5000 Odense, Denmark, 3Dermatology Clinic, 2610 Rødovre, Denmark, 4Dermatology Clinic,
`4400 Kalundborg, Denmark, 5Dermatology Clinic, 7400 Herning, Denmark, 6Dermatology Clinic, 9000 ˚Alborg, Denmark, 7Dermatology Clinic, 2880
`Bagsværd, Denmark, 8Department of Dermatology, 8000 ˚Arhus University Hospital, ˚Arhus, Denmark, 9Dermatology Clinic, 7100 Vejle, Denmark, and
`10Dermatology Clinic, 2970 Hørsholm, Denmark
`
`doi:10.1111/j.1600-0536.2011.01889.x
`
`Summary
`
`Background. Fragrances frequently cause contact allergy, and cosmetic products are
`the main causes of fragrance contact allergy. As the various products have distinctive
`forms of application and composition of ingredients, some product groups are potentially
`more likely to play a part in allergic reactions than others.
`Aim. To determine which cosmetic product groups cause fragrance allergy among
`Danish eczema patients.
`Method. This was a retrospective study based on data collected by members of the
`Danish Contact Dermatitis Group. Participants (N = 17 716) were consecutively patch
`tested with fragrance markers from the European baseline series (2005–2009).
`Results. Of the participants, 10.1% had fragrance allergy, of which 42.1% was caused
`by a cosmetic product: deodorants accounted for 25%, and scented lotions 24.4%. A sex
`difference was apparent, as deodorants were significantly more likely to be listed as the
`cause of fragrance allergy in men (odds ratio 2.2) than in women. Correlation was
`observed between deodorants listed as the cause of allergy and allergy detected with
`fragrance mix II (FM II) and hydroxyisohexyl 3-cyclohexene carboxaldehyde.
`Conclusion. Deodorants were the leading causes of fragrance allergy, especially among
`men. Seemingly, deodorants have an ‘unhealthy’ composition of the fragrance chemicals
`present in FM II.
`
`Key words: allergic contact dermatitis; clinically relevant patch tests; cosmetics;
`deodorants; fragrance.
`
`Cosmetic products cover wide range of different consumer
`products, and almost everyone has daily contact with a
`
`Correspondence: Maria Vølund Heisterberg, Department of Dermato-
`allergology, National Allergy Research Centre, Gentofte Hospital, University
`of Copenhagen, 2900 Hellerup, Denmark. Tel: +45 3977 7310; Fax: +45
`3997 7118. E-mail: mavohe01@geh.regionh.dk
`
`Conflicts of interest: The authors have declared no conflicts. Funding: The
`Danish Environmental Agency financed the study.
`∗Each author participated sufficiently to take responsibility for the work.
`
`Accepted for publication 15 January 2011
`
`cosmetic product. The EU Directive gives the following
`definition:
`‘A cosmetic product is any substance or
`preparation intended to be placed in contact with the
`various external parts of the human body or with the
`teeth and the mucous membranes of the oral cavity, with
`a view exclusively or mainly to cleaning them, perfuming
`them, changing their appearance, and/or correcting body
`odours, and/or protecting them or keeping them in good
`condition’ (1).
`Several aspects contribute to a cosmetic product’s
`ability to cause fragrance allergy (2). Foremost, a
`product must contain sensitizing fragrance ingredients.
`
`258
`
`© 2011 John Wiley & Sons A/S • Contact Dermatitis, 64, 258–264
`
`Petitioner Dr. Squatch
` Ex. 1031
`
`

`

`DEODORANTS AND FRAGRANCE ALLERGY • HEISTERBERG ET AL.
`
`Sensitization can occur after a single significant exposure
`or after multiple exposures (2, 3), and once sensitization
`has occurred, a lower dose can cause an elicitation
`response (4). In our study, we use the term fragrance
`allergy synonymously with allergic contact dermatitis.
`A wide range of fragrance ingredients exists, approx-
`imately 2500 different substances (5); many are known
`to be sensitizers in humans and are used in cosmetic
`products (6–8).
`fragrance ingredients are used in
`The individual
`various combinations, and some cosmetic products
`contain hundreds of individual fragrance ingredients (9).
`Other principal factors contributing to a product’s ability
`to cause allergy are related to its composition and
`intended use conditions. For example, the following
`may all play a role in a cosmetic product’s ability to
`elicit fragrance allergic contact dermatitis: the nature
`of fragrance ingredients, as some may have synergistic
`effects (10);
`the concentration and potency of
`the
`allergenic fragrance ingredients; the application site; the
`frequency of application; the duration of exposure; and
`the user’s skin barrier function (2, 11–13).
`The purpose of this study was to determine the
`distribution of cosmetic product groups listed as the cause
`of fragrance allergic contact dermatitis among Danish
`eczema patients. Furthermore, our aim was to investigate
`sex differences and to evaluate whether there was an
`association between the cosmetic product listed as having
`caused a fragrance allergy and the different fragrance
`markers detecting an allergy.
`
`Materials
`Data were retrieved from a clinical database containing
`patch test results, patient characteristics, and exposure
`sources. All patients were examined by members of the
`Danish Contact Dermatitis Group (DCDG). During the
`study period (January 2005 to June 2009) the DCDG
`comprised three dermatology departments (university
`hospitals in Gentofte, Odense, and ˚Arhus) and seven
`dermatology clinics (Rødovre, Aalborg, Herning, Vejle,
`Bagsværd, Hørsholm, and Kalundborg). All patients had
`been patch tested with fragrance markers included in the
`baseline series: fragrance mix I (FM I), fragrance mix II
`(FM II), hydroxyisohexyl 3-cyclohexene carboxaldehyde
`(HICC) 5%, and Myroxylon pereirae/balsam of Peru
`25% in petrolatum. FM I contains eight individual
`fragrance compounds: 1% cinnamal, 1% cinnamyl
`alcohol, 1% geraniol, 1% isoeugenol, 1% eugenol,
`1% hydroxycitronellal, 1% Evernia prunastri (oak moss
`absolute), 1% α-amyl cinnamal and an emulsifier 5%
`sorbitan sesquioleate. FM II is composed of six different
`
`© 2011 John Wiley & Sons A/S • Contact Dermatitis, 64, 258–264
`
`fragrances: 2.5% HICC, 1% citral, 2.5% farnesol, 2.5%
`coumarin, 0.5% citronellol and 5% α-hexyl cinnamal
`in pet.
`A total of 17 716 subjects were consecutively patch
`tested: 11 610 women and 6106 men. The mean age was
`44 years (standard deviation 18.3). Table 1 shows the
`study participants’ demographic characteristics.
`Relevant exposure sources causing a positive patch
`test reaction are registered in the database. The exposure
`sources are categorized as either ‘leave-on’ or ‘rinse-
`off’ products (Table 2) and further into specific cosmetic
`product groups (Table 3). If a cosmetic product could not
`be specified because it was unknown or did not fit any of the
`predetermined categories, it was registered as ‘unspecified
`leave-on’ or ‘unspecified rinse-off’. Patients could have
`more than one specific cosmetic product recorded.
`
`Methods
`The patients included had been patch tested with at
`least one of the fragrance markers from the European
`baseline series (FM I, FM II, M. pereirae and HICC). The
`
`Table 1. MOAHLFA index of consecutively patch tested eczema
`patients and patients with a fragrance allergy caused by a cosmetic
`product
`
`Tested subjects
`
`Cosmetic fragrance allergy
`
`Index
`
`No.
`
`M
`O
`A
`H
`L
`F
`AA
`Total
`
`6106
`2067
`3115
`6625
`815
`3370
`10465
`17716
`
`%
`
`34.5
`11.7
`17.6
`37.4
`4.6
`19.0
`59.1
`100
`
`No.
`190∗
`97
`137
`272
`23∗
`248∗
`488∗
`753
`
`%
`
`25.2
`12.9
`18.2
`36.1
`3.1
`32.9
`64.8
`100
`
`MOAHLFA index: M, male; O, occupational cause of dermatitis; A,
`atopy; H, hand dermatitis; L, leg dermatitis; F, facial dermatitis; and
`AA ≥ 40 years.
`∗
`χ 2-test, p < 0.05.
`
`Table 2. Leave-on or rinse-off cosmetic products listed as the
`exposure causing fragrance allergy
`
`Leave-on
`
`Rinse-off
`
`No.
`
`556
`162
`718
`
`%
`
`75.9
`69.2
`74.3
`
`No.
`
`176
`72
`248
`
`%
`
`24.1
`30.8
`25.7
`
`Women
`Men
`Total
`
`All
`
`No.
`
`732
`234
`966
`
`259
`
`

`

`DEODORANTS AND FRAGRANCE ALLERGY • HEISTERBERG ET AL.
`
`Table 3. The cosmetic product groups listed as having caused fragrance allergic contact dermatitis
`
`Cosmetic product categories
`
`Unspecified stay-on products
`Deodorant
`Scented lotion
`Unspecified rinse-off products
`Fine fragrances
`Shampoo
`Liquid soap
`Aftershave
`Lipstick
`Sun lotion
`Hairstyling product
`Shaving foam
`Mascara
`Hair dye
`Eyeshadow
`Makeup cream
`Sum of cosmetic product within each
`category listed as the cause of
`fragrance allergic contact dermatitis
`
`Men and women
`
`Women
`
`Men
`
`n
`
`286
`146
`142
`104
`93
`76
`63
`16
`11
`6
`6
`5
`4
`4
`2
`2
`966
`
`n
`
`224
`91
`123
`77
`85
`57
`41
`2
`9
`5
`5
`1
`4
`4
`2
`2
`732
`
`%
`
`29.8
`12.4
`16.8
`10.5
`11.6
`7.8
`5.6
`0.3
`1.2
`0.7
`0.7
`0.1
`0.5
`0.5
`0.3
`0.3
`
`n
`
`62
`55
`19
`27
`8
`19
`22
`14
`2
`1
`1
`4
`0
`0
`0
`0
`234
`
`%
`
`26.1
`23.5
`8.1
`11.5
`3.4
`8.1
`9.4
`6.0
`0.9
`0.4
`0.4
`1.7
`0.0
`0.0
`0.0
`0.0
`
`patch tests were performed according to international
`guidelines (14) with Finn Chambers® (8 mm; Epitest Ltd
`Oy, Tuusula, Finland) applied on the back with Scanpor
`tape® (Norgesplaster A/S, Alpharma, As, Norway) and
`kept
`in place for 2 days. Readings were performed
`on day 2, 3 or 4, and on day 7, according to the
`recommendations of the International Contact Dermatitis
`Research Group (15).
`Data administration and statistical analysis were per-
`fomed using SPSS version 15 and OPENEpi (www.openepi.
`com). Percentages of the cosmetic product groups listed
`as causing a positive patch test reaction to a fragrance
`marker were calculated. χ 2-tests for characteristic differ-
`ences were performed, and p < 0.05 was considered to
`be significant.
`
`Results
`Fragrance contact allergy to one or more of the fragrance
`markers was found in 1790 (10.1%) of the participants.
`Cosmetic products were the cause of fragrance allergic
`contact dermatitis in 753, comprising 42.1% of those with
`fragrance allergy, or 4.3% of the subjects consecutively
`examined for contact allergy. Some patients had more
`than one cosmetic product listed as causing their allergy;
`966 product groups were listed. The majority of cosmetic
`products listed were ‘leave-on’ products (74.3%) rather
`than ‘rinse-off’ products (25.7%).
`
`In general, many different cosmetic product categories
`were listed as causing fragrance allergic contact
`dermatitis (Table 3); 576 products had been listed as
`belonging to specific product categories. The commonest
`sources of allergic contact dermatitis were deodorants
`(25.3%), scented lotions (24.4%), fine fragrances (16.0%),
`shampoos (13.0%),
`liquid soaps (10.8%), aftershaves
`(2.7%), lipsticks (1.9%) and the remaining categories
`had frequencies of 1% or less (Fig. 1).
`A sex difference was apparent in the distribution of
`cosmetic products listed as causing fragrance allergic
`contact dermatitis (Fig. 2). Deodorants,
`in particular,
`played a large role in men, accounting for 37.9% of the
`145 products listed as causing fragrance allergic contact
`dermatitis among men, which was highly significant
`(p < 0.001). Scented lotions and fine fragrances played
`the largest role in women, accounting for 28.5% and
`19.7%, respectively, of the products listed (n = 436) and
`the sex difference was highly significant (p < 0.001).
`No sex difference was observed in the reporting of
`shampoo as the cause of
`fragrance allergic contact
`dermatitis.
`Figure 3 shows the role of the four most common
`products listed as having caused a positive patch test
`reaction to the different screening markers of
`the
`baseline series. There was a significant correlation
`between products listed as having caused allergy and
`the different markers (χ 2-test, p < 0.001). FM II and
`HICC were overrepresented in deodorants. Scented lotion
`
`260
`
`© 2011 John Wiley & Sons A/S • Contact Dermatitis, 64, 258–264
`
`

`

`DEODORANTS AND FRAGRANCE ALLERGY • HEISTERBERG ET AL.
`
`2.7
`
`1.9
`
`1.0
`
`1.0
`
`0.9
`
`0.7
`
`0.7
`
`0.3
`
`0.3
`
`25.3
`
`24.4
`
`16.0
`
`13.0
`
`10.8
`
`30
`
`25
`
`20
`
`15
`
`10
`
`05
`
`Percentages
`
`Fig. 1. Prevalence of specific cosmetic
`product groups listed as having caused
`fragrance allergy. The total number of
`specific products listed was 576.
`
`Shaving foam
`Sham poo
`Hairstyling product
`Scented lotion
`Aftershave
`Deodorant
`Sun lotion
`Lipstick
`Fine fragrances
`Liquid soap
`
`M akeup cream
`Eyeshadow
`M ascara
`Hair dye
`
`and shampoo were more likely to be associated with
`fragrance allergic contact dermatitis detected by FM I and
`M. pereirae.
`Among all the deodorants listed (n = 213) as having
`caused fragrance allergic contact dermatitis, an FM II
`allergy (34.3%) was more likely than an FM I (28.2%),
`HICC (24.9%) or M. pereirae (12.7%) allergy (Table 4).
`
`Discussion
`Adverse skin reactions caused by cosmetics are an
`increasing problem in the population of Denmark (16).
`The most frequent causes of cosmetic allergy have
`been shown to be fragrances (7, 11, 17, 18). Many
`different cosmetic product groups can cause allergic
`contact dermatitis; according to our study, it appears
`
`28.5
`
`19.7
`
`13.1
`
`13.1
`
`13.2
`
`5.5
`
`37.9
`
`21.1
`
`40
`35
`30
`25
`20
`15
`10
`
`05
`
`Percentages
`
`a n t
`
`D e o d o r
`
`i o n
`
`l o t
`
`e n t e d
`
`S c
`
`s
`
`e
`
`a n c
`
`a g r
`
`r
`
`f
`
`F i n e
`
`S h a m p o o
`
`Cosmetic products listed as having caused fragrance ACD in males n=145
`
`Cosmetic products listed as having caused fragrance ACD in females n=431
`
`Fig. 2. Sex distribution of the four most frequent cosmetic products listed as having caused fragrance allergic contact dermatitis (ACD).
`A statistical sex difference in deodorants listed as the cause of fragrance allergy was observed (p < 0.001). The odds ratio for a deodorant
`listed as the cause of fragrance allergy in men versus women was 2.3 [confidence interval (CI) 1.5–3.5]. Likewise, a statistical sex difference
`was seen for scented lotion and fine fragrances as the cause of fragrance allergic contact dermatitis (p < 0.001). They were more frequent
`among women: the odds ratio for a cream with a scent was 2.6 (CI 1.6–4.5), and the odds ratio for a fine fragrance was 4.2 (CI 2.0–9.4).
`No sex difference was observed for shampoo listed as the cause of fragrance allergic contact dermatitis.
`
`© 2011 John Wiley & Sons A/S • Contact Dermatitis, 64, 258–264
`
`261
`
`

`

`DEODORANTS AND FRAGRANCE ALLERGY • HEISTERBERG ET AL.
`
`34.3
`
`34.0
`
`29.8
`
`Fragrance mix I (n=306)
`Fragrance mix II (n=213)
`Hydroxyisohexyl 3-cyclohexene carboxaldehyde (n=156)
`Myroxylon pereirae (n=121)
`
`25.2
`
`22.3
`
`19.6
`
`21.2
`
`19.7
`
`20.5
`
`19.7
`
`19.0
`
`14.4
`
`15.7
`
`9.9
`
`9.9
`
`7.7
`
`40
`
`35
`
`30
`
`25
`
`20
`
`15
`
`10
`
`05
`
`Percentages
`
`Deodorant
`
`Scented lotion
`
`Fine fragrances
`
`Shampoo
`
`Fig. 3. The prevalence of each of the four most frequent cosmetic products responsible for fragrance allergy detected by different fragrance
`markers of the baseline series.
`
`that the use of deodorants is especially associated with an
`increased risk of fragrance allergic contact dermatitis.
`We found deodorants listed as the leading causes of
`fragrance allergic contact dermatitis among eczema
`patients. Likewise, a study of the general population in
`Denmark reported deodorants as the leading causes of
`allergic and irritant contact dermatitis (16).
`Deodorants are also related to first-time symptoms
`of fragrance allergy. A study of 925 eczema patients
`and a control group of 806 persons, randomly selected
`
`from the population, reported a statistically significant
`correlation between development of a rash resulting from
`a scented deodorant as a first-time symptom (odds ratio:
`2.3–2.9) and a later diagnosis of fragrance allergy (19).
`In a German study (20), eczema patients were patch tested
`with their own deodorants; 501 deodorants were tested,
`and 6.2% caused allergic reactions.
`The sex difference in the use of cosmetic products is
`obvious, and a difference was expected with regard to
`
`Table 4. The distribution of cosmetic product groups according to the fragrance screening markers that had a positive and clinically relevant
`patch test reaction (positive +, ++, +++)
`
`Fragrance screening markers of the baseline series
`
`Fragrance mix I
`
`Fragrance mix II
`
`Hydroxyisohexyl 3-cyclohexene carboxaldehyde
`
`Myroxylon pereirae
`
`Product
`
`Deodorant
`Scented lotion
`Fine fragrances
`Shampoo
`Liquid soap
`Aftershave
`Lipstick
`Sun lotion
`Hairstyling product
`Shaving foam
`Mascara
`Hair dye
`Eyeshadow
`Makeup cream
`
`n
`
`213
`188
`144
`96
`84
`23
`12
`10
`6
`6
`4
`4
`5
`3
`
`n
`
`60
`77
`58
`44
`37
`9
`4
`4
`3
`4
`2
`3
`2
`1
`
`%
`
`28.2
`41.0
`40.3
`45.8
`44.0
`39.1
`33.3
`40.0
`50.0
`66.7
`50.0
`75.0
`40.0
`33.3
`
`n
`
`73
`42
`42
`21
`17
`6
`5
`2
`2
`1
`0
`0
`1
`1
`
`%
`
`34.3
`22.3
`29.2
`21.9
`20.2
`26.1
`41.7
`20.0
`33.3
`16.7
`0.0
`0.0
`20.0
`33.3
`
`n
`
`53
`33
`32
`12
`16
`3
`0
`3
`1
`0
`1
`0
`1
`1
`
`%
`
`24.9
`17.6
`22.2
`12.5
`19.0
`13.0
`0.0
`30.0
`16.7
`0.0
`25.0
`0.0
`20.0
`33.3
`
`n
`
`27
`36
`12
`19
`14
`5
`3
`1
`0
`1
`1
`1
`1
`0
`
`%
`
`12.7
`19.1
`8.3
`19.8
`16.7
`21.7
`25.0
`10.0
`0.0
`16.7
`25.0
`25.0
`20.0
`0.0
`
`A cosmetic product could be listed as the cause of allergic contact dermatitis resulting from more than one fragrance marker.
`
`262
`
`© 2011 John Wiley & Sons A/S • Contact Dermatitis, 64, 258–264
`
`

`

`DEODORANTS AND FRAGRANCE ALLERGY • HEISTERBERG ET AL.
`
`which products were reported as having caused fragrance
`allergic contact dermatitis. Deodorants were significantly
`more likely to be listed as the cause of fragrance allergic
`contact dermatitis in men than in women (odds ratio 2.3),
`whereas women were significantly more likely to report a
`scented lotion or a fine fragrance as the cause of fragrance
`allergic contact dermatitis.
`Many factors may explain why deodorants in particular
`are associated with a high risk of developing a fragrance
`allergic contact dermatitis. The environment in the axil-
`lae is moist and occluded, and this, in combination with
`the presence of hair follicles, can increase the penetration
`of certain allergens (21, 22). Shaving also increases pene-
`tration, and thus the risk of contact allergy (23). In a case
`study, 14 fragrance-allergic patients were asked to use
`one of their own deodorants in both the axillae and on the
`upper arm for 1 week. Twenty deodorants were tested;
`12 of these (60%) caused eczema in the axillae, whereas
`only four (20%) caused eczema on the upper arm. The
`deodorants that caused eczema contained 1.3–8.6-fold
`higher concentrations of allergenic fragrance substances
`than those products that did not cause eczema (24). To
`provoke an allergic reaction, a lower concentration of a
`fragrance allergen is needed in the axillae than in other
`parts of the body. This could be explained by less fragrance
`evaporating than on non-occluded sites and the concen-
`tration of the fragrance substance remaining high for a
`longer time (25). As a lower concentration threshold is
`need in the axillae to provoke an elicitation response to an
`allergen (22), it could be argued that a lower concentra-
`tion of allergen can cause sensitization when administered
`in the axillae; the study on first-time symptoms previously
`mentioned could be an indication of this (19). Another
`reason why deodorants are responsible for allergic contact
`dermatitis caused by fragrances is that they may contain
`irritants that help to deliver a stronger danger signal (26),
`facilitating the sensitization response (27) to an allergen
`and the elicitation response (28, 29).
`The differences in formulation of deodorants (aerosol
`sprays, roll-ons, and sticks) also seem to play a role in the
`
`bioavailability of allergenic fragrance substances. One
`small study investigated a deodorant spray and a deostick
`with the same concentrations of allergenic fragrance sub-
`stances tested in the antecubital of 7 fragrance allergic
`patients. Five of these subjects reacted to the deodorant
`spray, whereas only 1 reacted to the deostick (30). The
`effects of using different deodorant formulations have not
`yet been systematically investigated.
`In our study, we identified a correlation between
`a deodorant being listed as the cause of allergy and
`a relevant, positive patch test reaction to HICC or
`FM II. This could be explained by frequent exposure
`to the single-compound fragrances of FM II used in
`deodorants (19, 31). A UK study on the labelling of cos-
`metic and household products revealed that deodorants
`had a mean of 7.8 (3–13) different fragrance ingredi-
`ents in each deodorant, and almost 30% of all products
`investigated (n = 300) contained HICC (32). Likewise, a
`study from Denmark reported that 50% of deodorants on
`the market contained HICC (31). It will be interesting to
`see whether HICC allergy will decrease after the recent
`reduction in the maximal concentration recommended
`by the International Fragrance Association (33).
`This study confirms that deodorants play a major
`role in allergic contact dermatitis caused by fragrances.
`Deodorants seem to have an unfortunate composition of
`FM II fragrance ingredients, leading to allergic contact
`dermatitis. As deodorants are used in sensitive areas of
`the body, it could be argued that these sensitizing fra-
`grance ingredients should either be avoided or used in
`lower concentrations in deodorants than in other types of
`product.
`
`Acknowledgements
`Our special thanks go to Søren Gade for assistance in
`retrieving data from the database, and to Fonden for
`Faglig Udvikling af Speciallægepraksis for financial sup-
`port of the database.
`
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