Allergic Contact Dermatitis

to Fragrances
Margo J. Reeder, MD

KEYWORDS
 Fragrance  Perfume  Allergic contact dermatitis  Essential oils  Botanicals

KEY POINTS
 Allergic contact dermatitis to fragrance is common, and positive reaction rates range from 5% to
11% in patch-test populations.
 Fragrance allergy is more common in women and can present with dermatitis on the face, eyelids,
hands, or generalized.
 Supplementing fragrance screeners with additional fragrance chemicals can increase the diag-
nostic yield for detecting allergic contact dermatitis.

INTRODUCTION $8.2 billion, excluding sales in the United States

and Canada.1 The fragrance industry also contrib-
Allergic contact dermatitis (ACD) to fragrances re- utes 415,000 jobs to the workplace.1
mains a common cause of allergy. Patients are Fragrances can be characterized as natural or
exposed to fragrances through personal care synthetic. Natural fragrances are derived from
products, cleaning products, and aromatherapy. organic materials, including plants and flowers.
The popular trend of essential oils continues to Essential oils and botanicals are an example of
sensitize patients to fragrances. This review sum- natural fragrances. Synthetic fragrances are those
marizes ACD to fragrances, including positive re- created in a laboratory and may be produced to
action rates on patch testing, site-specific mimic a natural fragrance while using less organic
dermatitis related to fragrances, essential oils, resources.2
botanical ingredients, and challenges for the Fragrance can cause both allergic and irritant
fragrance-allergic patient. dermatitis. Irritant dermatitis from fragrances is
commonly seen in patients with atopic diathesis.
In general, patients with active dermatitis or a his-
CONTACT DERMATITIS TO FRAGRANCES
tory of “sensitive skin” are commonly advised to
Fragrances are chemicals added to products with avoid fragrances in care products, and patients
the usual intention of providing a pleasant scent. may seek out products that are labeled as
Fragrances can be encountered in all types of per- “fragrance free.” This review focuses on fragrance
sonal care products, such as shampoos, soaps, allergy.
lotions, makeup, and sunscreens. Fragrances
can also be added to products to mask an un- EPIDEMIOLOGY OF FRAGRANCE ALLERGY
pleasant scent, and they may be added to clean-
ing chemicals or industrial chemicals. The use of ACD from fragrances is common. In the general
masking fragrances is common in cleaning and in- population, the allergic reaction rate to fragrances
dustrial chemicals. Paper products, detergents, varies between 0.7% and 2.6%.3 A cross-
and medical products frequently contain additive sectional study of 5 European countries found
fragrances. In 2017, fragrance global sales topped the prevalence of fragrance allergy is 1.9% to
derm.theclinics.com

Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 1 South Park
Street, 7th Floor, Madison, WI 53715, USA
E-mail address: mreeder@dermatology.wisc.edu

Dermatol Clin 38 (2020) 371–377

https://doi.org/10.1016/j.det.2020.02.009
0733-8635/20/Ó 2020 Elsevier Inc. All rights reserved.
372 Reeder

2.6% among the general population.4 However, women than men. Despite the female predomi-
the rate of contact allergy to fragrances is much nance in studies, fragrance allergies tend to still
higher in a referral-based population. In the North disproportionately affect women, perhaps
American Contact Dermatitis Group (NACDG) because of increased use of cosmetics and
2015 to 2016 cycle, fragrances were among the perfumed products. Women allergic to fragrances
top positive allergens. Fragrance mix 1 (FM1), are most commonly in their 40s, whereas men
Fragrance mix 2 (FM2) (components are listed in allergic to fragrances tend to be 5 to 6 years older.7
Table 1), and Balsam of Peru are considered Fragrance allergy can be associated with all
markers for fragrance allergy, and reaction rates sites of dermatitis. An analysis from the European
range from 5.3% to 11.3%.5 Positive reaction Surveillance System on Contact Allergies found
rates from recent NACDG cycles to common that positive reactions to fragrance were associ-
fragrance chemicals are listed in Table 2.5 Howev- ated with all specific sites of dermatitis excluding
er, patch testing with FM1, FM2, and Balsam of the feet.8 Fragrance allergy has also been
Peru alone will not detect all fragrance-allergic pa- frequently associated with hand dermatitis. A
tients. Fragrance chemicals are often added to cross-sectional analysis of NACDG data from
baseline series in order to better detect fragrance 1994 to 2004 found that of patch tested patients
allergy. Hydroxyisohexyl 3-cyclohexene carboxal- with allergic hand dermatitis, 11.3% were positive
dehyde (HICC) is the most common allergen in to fragrance mix and 9.6% were positive to Bal-
FM2, and positive reaction rates to HICC range sam of Peru.9 Other common allergens included
from 1.5% to 3%. HICC alone was recommended nickel, preservatives, rubber, and antibiotics.9
to be added to the European Baseline Series in Eyelid dermatitis is another site where ACD to
2008.6 fragrances is a common culprit. For the eyelids,
ACD to fragrances is more commonly seen in fe- the exposure can be direct contact (such as prod-
male patients with women being 1.3 times more ucts applied to the hair or eyelids) and airborne
likely to be allergic to fragrances than men.7 In contact (including mists, sprays, and aerosols).
general, most large patch test studies have more Fragrances are a common cause of eyelid derma-
titis. In a single-center review of 100 consecutive
patients patch tested for eyelid dermatitis, 42%
Table 1 were positive to one or more fragrance chemical.10
Components of fragrance mixes commonly Fragrances may also be a source for occupa-
found in a standard tray of allergens tional dermatitis. Of reported occupational skin
disease in the United Kingdom between 1996
FM1, 8.0% Cinnamyl alcohol
and 2015, 6% were related to fragrance allergy
petrolatum* 1% pet
Cinnamal 1% pet
and were more commonly reported in women.
Hydroxycitronellal Hairdressers and beauticians were particularly
1% pet at risk, followed by therapists (including aroma-
Amyl cinnamal therapists) and those in the food preparation in-
1% pet dustry.11 Fragrances in the workplace may also
Geraniol be from exposure to essential oils. Diffusers are
1% pet more commonly used in shared office spaces
Eugenol 1% pet and represent an important exposure. Diffusion
Isoeugenol of essential oils can cause an airborne contact
1% pet
dermatitis leading to rash on exposed skin, such
Oakmoss Absolute 1% pet
*Contains 5% sorbitan
as the eyelids, face, and hands. Other important
sesquioleate as emulsifier occupation exposures include the addition of
masking fragrances to strongly scented chemi-
FM2, 14% Hexyl cinnamic aldehyde
petrolatum 5% pet cals. Fragrances are still added to industrial
Hydroxyisohexyl 3- chemicals, metalworking fluids, and cleaning
cyclohexene chemicals with the purpose of masking an un-
carboxaldehyde pleasant odor.
2.5% pet
Farnesol 2.5% pet
DETECTING FRAGRANCE ALLERGY
Coumarin
2.5% pet Patch testing with too few fragrance chemicals
Citral 1% pet may also miss fragrance-allergic patients. FM1,
Citronellol
FM2, and Balsam of Peru are considered the
0.5% pet
fragrance screening chemicals that are found on
 Fragrance Allergy 373

Table 2
Positive reaction rates based on previous North American Contact Dermatitis Group cycles

Allergen N 2015–2016 (%) 2013–2014 (%) 2011–2012 (%)

FM1, 8.0% petrolatum 5595 11.3 11.9 12.1
FM2, 14% petrolatum 5594 5.3 5.7 5.2
Balsam of Peru, 25% 5595 7.0 7.2 7.9
petrolatum
Ylang ylang oil, 2.0% 5594 1.3 1.2 0.7
petrolatum
Melaleuca alternifoilia (tea 5593 1.2 0.9 0.8
tree leaf oil), oxidized 5.0%
petrolatum
Mentha piperita oil 5591 0.6 0.6 0.4
(peppermint oil) 2.0%
petrolatum
Lavandula angustifolia oil 5594 0.5 0.3 0.4
(lavender oil), 2.0%
petrolatum
Data from DeKoven JG, Warshaw EM, Zug KA, et al. North American Contact Dermatitis Group Patch Test Results: 2015-
2016. Dermatitis 2018;29(6):297-309.

most standard trays. However, patch testing with performed. In a study of 62,354 patch-test pa-
just these 3 chemicals can miss a significant num- tients from North America and Europe, 1.4%
ber of fragrance-allergic patients. In a population (854) of patients reacted to an essential oil but
of 1951 eczema patients who underwent patch were negative to a fragrance marker.15 For the
testing with a standard and a fragrance tray, patients from North America, Melaluca (tea tree)
14.4% (281 patients) were allergic to a fragrance. and ylang ylang were common essential oils
However, only 57.6% (117 patients) reacted to a that would have been missed by testing with
fragrance in the screening series, meaning that fragrance markers alone.15
42.4% of patients would have been missed if the
supplemental tray was not added. The most PATCH TESTING PITFALLS: TECHNIQUE
commonly positive individual fragrances were cin-
namyl alcohol, Evernia furfuracea, isoeugenol, Fragrances are volatile chemicals and are prone to
Evernia prunastri, and cinnamal.12 degradation. A potential pitfall in patch testing,
Patch testing with limonene and linalool further false negative reactions to fragrances may occur
increases the ability to diagnose fragrance allergy. if trays are assembled ahead of time because aller-
In a study of 821 consecutively patch tested pa- gens may evaporate and degrade over time.16,17
tients, 9.4% were positive to hydroperoxide of Instead, fragrance allergens should be assembled
limonene and 11.7% were positive to linalool.13 on chambers directly before application to the pa-
Of all the fragrance-allergic patients in this series, tient. Patch test reactions to fragrances can also
10% were positive to limonene and/or linalool peak earlier than other allergens. Often, fragrance
but were negative to a fragrance marker on the chemicals can elicit a positive reaction at the 48-
standard series.13 In another single-institution hour reading.18 Delayed reactions done at
study of 103 patients who were tested to linalool, 120 hours or later may start to see a decline in
hydroperoxides of linalool, D-limonene, and/or hy- the degree of positive reactivity, and weak positive
droperoxides of D-limonene, 19% were positive to reactions may be missed if a delayed reading is
hydroperoxides of limonene and 7% were positive done only at 144 hours.
to hydroperoxides of linalool. Importantly, very few Differences also exist in the ability to detect
patients reacted to linalool (10%), and no fragrance allergy between patch testing systems.
patients were positive to D-limonene.14 This finding The TRUE test is a preloaded Food and Drug
suggests that patch testing with the hydroperox- Administration–approved commercially available
ides of limonene and hydroperoxides of linalool is patch test system that screens for 35 common al-
important in suspected fragrance-allergic patients. lergens plus a negative control.19 Although the
Patients allergic to essential oils may also be TRUE test can be an initial screen, it fails to detect
missed if expanded patch testing is not allergies in 25% to 40% of patients.5 In the
374 Reeder

chamber method, individual allergens are loaded derived from the fruit peels of orange, lime, lemon,
into either plastic or metal chambers and fixed to or tangerine through a mechanical cold press.25
the patient. Greater ability to customize allergens Although essential oils are often marketed as
to the patient’s dermatitis exists with the chamber “pure,” the plant-derived nature of essential oils
method. The chamber method is used by the means that the oils can often contain hundreds of
NACDG and the International Contact Dermatitis different compounds. Most essential oils upon
Research Group. mass spectrometry analysis contain between 100
The TRUE test may fail to detect patients with and 250 different chemicals, but some oils contain
fragrance allergies. In a comparative study of the up to 500 different chemicals.26 The variation in
TRUE test versus chamber method, the TRUE different batches of essential oils can be related
test failed to detect 50% of positive reactions to to the crop of plant or fruit, storage, temperature,
fragrance.20 Balsam of Peru in particular is and factors related to the products and produc-
frequently missed by TRUE testing.21 However, a tion.26 Certain chemical components have been
larger study examining FM1 reactions compared found to be dominant in essential oils. Limonene
with the TRUE test showed that although chamber is found in nearly all citrus-related oils. Anethole is
method produced more positive reactions, the re- found in most aniseed oils and eugenol is found in
actions found with the TRUE test had a larger 90% of clove oils. Other chemicals found in greater
percent of clinical relevance, calling for careful than 90% of essential oils include caryophyllene,
interpretation of weak positive reactions to fra- pinene, terpineol, cadinene, and myrcene.26
grances on chamber method.22 More than 80 essential oils have been described
in the literature as causes of ACD. The most com-
ESSENTIAL OILS mon essential oils known to cause ACD include tea
tree, turpentine, orange, citronella, ylang ylang,
The use of essential oils represents a popular sandalwood, and clove.27 Currently, the NACDG
trend, which is also exposing numerous patients includes 3 essential oils on the screening tray:
to concentrated chemicals known to elicit ACD. tea tree, ylang ylang, and peppermint. These
Essential oils are often seen by the public as a essential oils are in addition to FM1, FM2, Balsam
safe alternative to traditional medicine. Dermatolo- of Peru, hydroperoxides of limonene, and hydro-
gists likely encounter the use of essential oils when peroxides and linalool. Most patch testing hapten
they are used for medicinal purposes or aroma- companies have essential oil allergens available
therapy. Many essential oils have purported health for purchase for supplementing a standard tray
benefits, such as cleansing, detoxifying, awak- of chemicals.
ening, and healing. However, essential oils have
long been known to cause ACD. Many different NATURAL INGREDIENTS
methods of using essential oils are available.
Diffusing oils into the air in a mist is popular for Similar to essential oils, natural or botanical ingre-
bedrooms and home use, but increasingly, dif- dients are commonly found in cosmetic products
fusers may also be spotted at gyms and daycare and represent a potential source of exposure for
centers. Essential oils may also be applied directly fragrance-allergic patients. Plant-derived ingredi-
to the skin, either diluted in carrier oil or “as is.” ents are often used instead of fragrances. Ingredi-
Many essential oil companies warn of the sensi- ents such as aloe vera, chamomile, arnica,
tizing nature of essential oils given their high con- calendula, echinacea, and other plants are
centration, but consumers may not follow these increasingly added to personal care products. Pa-
recommendations. Information found on essential tients often gravitate toward products that contain
oil manufacturer Web sites can be misleading for natural ingredients because of a perceived safety
consumers, particularly statements that rashes associated with natural over synthetic ingredients.
from essential oils may be from “detoxification” A survey of 1274 users of botanical products cited
and not contact dermatitis.23 Essential oils are reasons for using natural products as curiosity
sometimes added to laundry or cosmetics and (52%), perceived safety (38%), failure of conven-
even may be ingested for dubious health benefits. tional therapy (7%), and mistrust in traditional
Aside from cosmetic use, essential oils may also topical products (3%).28 Medicinal uses of natural
be used as a flavoring for various foods, including products included moisturization, skin cleansing,
beverages, spices, and food preservation. Essen- itching, eczema, and antiaging among others.28
tial oils may be added to different household prod- In one retrospective study of 12529 patients with
ucts in place of other fragrances.24 contact allergy to an herbal preparation, most pa-
Most essential oils are created by the process of tients were using the natural product to treat
steam distillation. Essential oils that are citrus are another medical condition. Eczema, leg ulcers,
 Fragrance Allergy 375

wounds, and moisturizers were common condi- Box 1

tions that led to the use of botanical products. List of 26 fragrances that must be includes on
Implicated allergens included Balsam of Peru, com- labels in European Union
positae family plants, and tincture of benzoin.29
Products containing many botanical and plant- Amyl cinnamal
derived ingredients may frequently be listed as Amyl cinnamyl alcohol
“fragrance-free,” which is confusing for the con- Benzyl alcohol
sumer. These “natural” labeled products can still
lead to ACD for some fragrance-allergic patients Benzyl salicylate
and should be avoided. Botanical allergic patients Cinnamyl alcohol
should be certain to avoid related botanical ingredi- Cinnamal
ents in personal care products. In a study of 12 pa-
Citral
tients with known allergies to either chamomile or
arnica on previous patch testing, 8/12 of the cham- Coumarin
omile allergic and 5/6 of the arnica allergic reacted Eugenol
to botanical-containing products, respectively.30 Geraniol
The implications of natural ingredients for
Hydroxycitronellal
fragrance-allergic patients remain unclear. In gen-
eral, avoidance of fragrances includes botanical in- Hydroxymethylpentyl-
gredients. When in doubt, a repeat open cyclohexenecarboxaldehyde
application test is helpful. In this test, the product Isoeugenol
should be applied below the crease of the arm Anisyl alcohol
twice daily for 2 to 4 weeks. If a reaction does not
Benzyl benzoate
occur, the product will likely be tolerated. Impor-
tantly, with fragrance-allergic patients, it has been Benzyl cinnamate
shown that the repeat open application test must Citronellol
be done for up to 4 weeks to elicit a positive Farnesol
reaction.31
Hexyl cinnamaldehyde
Lilial
CHALLENGES FOR THE FRAGRANCE-
ALLERGIC PATIENT D-Limonene

Linalool
A unique challenge that fragrance-allergic patients
face in safe product selection primarily has to do Methyl heptine carbonate
with regulations on fragrance labeling in the United 3-Methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-
States. Fragrances are considered a “trade se- 3-buten-2-one
cret,” and individual components need not be fully Oak moss
disclosed on the ingredient label.32 In order to
Tree moss
avoid all potential exposure to a fragrance ingre-
dient, patients must choose products that are Adapted from Scientific Committee on Consumer
free of fragrances. Finding fragrance- free prod- Safety (SCCS). Opinion on Fragrance allergens in
cosmetic products. Brussels: European Union; 2011;
ucts is challenging given the ubiquitous nature of with permission.
fragrances as well as the use of masking fra-
grances in cosmetics. Products labeled as “un-
scented” may lead to inadvertent exposure to
fragrances given the product could contain a yet still label the product as fragrance free. A recent
masking fragrance to mask an unpleasant odor. review found that 45% (18/40) of best-selling mois-
To contrast, in the European Union, the top 26 turizers listed as “fragrance free” actually contained
fragrance chemicals known to cause ACD must a fragrance or botanical cross-reactor.34
be labeled on products (Box 1).33 Hair care products in general contain a signifi-
Because ingredients are characterized by their cant amount of fragrances. A recent query of the
function in the product, patients may also be inad- American Contact Dermatitis Society Contact Al-
vertently exposed to fragrances in a product that is lergy Management Program (CAMP) found that
listed as “fragrance free.” For example, benzyl of the 306 shampoos listed in CAMP, only 16
alcohol functions as a fragrance as well as a preser- were fragrance free. For styling products, only
vative. If it is used in a product as a preservative (and 2.8% (9/324) were free of fragrances.35 Education
not a fragrance), the company may list the ingredient on label reading as well as access to patient
376 Reeder

resources can greatly help those diagnosed with a 17-year period. Br J Dermatol 2000;142(2):
ACD to fragrances. 279–83.
8. Oosterhaven JAF, Uter W, Aberer W, et al. European
SUMMARY Surveillance System on Contact Allergies (ESSCA):
contact allergies in relation to body sites in patients
ACD to fragrances is common and is seen in 5% with allergic contact dermatitis. Contact Dermatitis
to 15% of patch tested patients. Patients are 2019;80:263–72.
exposed to fragrances through both household 9. Warshaw EM, Ahmed RL, Belsito DV, et al. Contact
and personal care products. Fragrance allergy dermatitis of the hands: cross-sectional analyses
commonly presents on the face, eyelids, and of North American Contact Dermatitis Group
hands, but other sites may be affected. Although data, 1994-2004. J Am Acad Dermatol 2007;57:
patch testing with FM1, FM2, and Balsam of 301–14.
Peru will screen for fragrance allergy, the diag- 10. Wenk KS, Ehrlich A. Fragrance series testing in
nostic yield is improved by the addition of the hy- eyelid dermatitis. Dermatitis 2012;23(1):22–6.
droperoxides of linalool, hydroperoxides of 11. Montgomery RL, Agius R, Wilkinson SM, et al. UK
limonene, and HICC. The popularity of essential trends of allergic occupational skin disease attrib-
oils represents an important source of fragrance uted to fragrances 1996–2015. Contact Dermatitis
allergy. The increasingly common use of botani- 2018;78(1):33–40.
cals in personal care products and incomplete 12. Mann J, McFadden JP, White JM, et al. Baseline se-
fragrance labeling by companies leads to addi- ries fragrance markers fail to predict contact allergy.
tional challenges for the fragrance-allergic patient. Contact Dermatitis 2014;70(5):276–81.
13. Dittmar D, Schuttelaar MLA. Contact sensitization to
DISCLOSURE hydroperoxides of limonene and linalool: results of
Nothing to disclose. consecutive patch testing and clinical relevance.
Contact Dermatitis 2019;80(2):101–9.
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