Fragrances are a group of substances present in many cosmetic products, which are one of the most common sources of allergic contact dermatitis (ACD) in Europe. Their widespread distribution, the presence of these substances as combinations, their ability to transform into more reactive substances, and the relatively recent regulations regarding these products are the main reasons for this high prevalence. In the last few years, advances on knowledge about haptens in fragrances have made possible to discover new allergens, to state that current fragrance markers are not enough to detect most of fragrance ACD cases and to know the products that should be patched and their concentrations. In this review, we revise the mechanisms of sensitization to allergens that are not represented in baseline series and the concentrations at which they should be used, which should be included in specific series and the usefulness of baseline and fragrance specific series.
Purpose of review
To revise the most recent advances in knowledge about fragrance contact dermatitis, especially about sensitization mechanisms and effectivity of fragrance markers in baseline series and fragrances in essential oils.
Fragrance allergic contact dermatitis (ACD) is one of the most common sources of ACD only preceded by nickel sulfate. Many studies have shown that fragrance mix (FM)I, FMII, and colophonium, fragrance markers in baseline series, are not enough to screen for cases of ACD to fragrances. Some fragrances use limonene and linalool hydroperoxides, which have shown a high prevalence of sensitization and have been proposed as new allergens to include in the European Baseline Series, while other fragrances like Evernia furfuracea, which have also shown a high prevalence of sensitization, will not be included. Essential oils are obtained by distillation process and are widely used. In some cases, their allergenic components are not known. Co-sensitization to other fragrance components is frequent and they should be patch tested if allergic contact dermatitis to fragrances or cosmetics is suspected.
A more extensive group of fragrance markers should be included in the European Baseline Series, with at least limonene and linalool hydroperoxides and Evernia furfuracea. The use of products containing fragrances is very common and people sensitized to one of these substances should be suspected of multiple co-sensitizations.
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References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance
Heisterberg MV, Menne T, Johansen JD. Contact allergy to the 26 specific fragrance ingredients to be declared on cosmetic products in accordance with the EU cosmetics directive. Contact Dermatitis. 2011;65:266–75.
Diepgen TL, Ofenloch R, Bruze M, Cazzaniga S, Coenraads PJ, Elsner P, et al. Prevalence of fragrance contact allergy in the general population of five European countries: a cross-sectional study. Br J Dermatol. 2015;173:1411–9.
Schnuch A, Uter W, Geier J, Gefeller O. Epidemiology of contact allergy: an estimation of morbidity employing the clinical epidemiology and drug-utilization research (CE-DUR) approach. Contact Dermatitis. 2002;47:32–9.
Heisterberg MV, Andersen KE, Avnstorp C, Kristensen B, Kristensen O, Kaaber K, et al. Fragrance mix II in the baseline series contributes significantly to detection of fragrance allergy. Contact Dermatitis. 2010;63:270–6.
Paramasivan P, Lai C, Pickard C, Ardern-Jones M, Healy E, Friedmann PS. Repeated low-dose skin exposure is an effective sensitizing stimulus, a factor to be taken into account in predicting sensitization risk. Br J Dermatol. 2010;162:594–7.
Bonefeld CM, Nielsen MM, Rubin IMC, Vennegaard MT, Dabelsteen S, Gimenéz-Arnau E, et al. Enhanced sensitization and elicitation responses caused by mixtures of common fragrance allergens. Contact Dermatitis. 2011;65:336–42.
Uter W, Yazar K, Kratz EM, Mildau G, Liden C. Coupled exposure to ingredients of cosmetic products: I. Fragrances. Contact Dermatitis. 2013;69:335–41.
Karlberg AT, Bergstrom MA, Borje A, Luthman K, Nilsson JLG. Allergic contact dermatitis--formation, structural requirements, and reactivity of skin sensitizers. Chem Res Toxicol. 2008;21:53–69.
Liden C, Yazar K, Johansen JD, Karlberg AT, Uter W, White IR. Comparative sensitizing potencies of fragrances, preservatives, and hair dyes. Contact Dermatitis. 2016;75:265–75.
Kaplan DH, Igyarto BZ, Gaspari AA. Early immune events in the induction of allergic contact dermatitis. Nat Rev Immunol. 2012;12:114–24.
Brared Christensson J, Matura M, Backtorp C, Borje A, Nilsson JLG, Karlberg AT. Hydroperoxides form specific antigens in contact allergy. Contact Dermatitis. 2006;55:230–7.
Niklasson IB, Delaine T, Islam MN, Karlsson R, Luthman K, Karlberg AT. Cinnamyl alcohol oxidizes rapidly upon air exposure. Contact Dermatitis. 2013;68:129–38.
Rudback J, Bergstrom MA, Borje A, Nilsson U, Karlberg AT. alpha-Terpinene, an antioxidant in tea tree oil, autoxidizes rapidly to skin allergens on air exposure. Chem Res Toxicol. 2012;25:713–21.
Hagvall L, Backtorp C, Svensson S, Nyman G, Borje A, Karlberg AT. Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization. Chem Res Toxicol. 2007;20:807–14.
Karlberg AT, Borje A, Duus Johansen J, et al. Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers - prehaptens and prohaptens. Contact Dermatitis. 2013;69:323–34.
Smith C, Hotchkiss S. Enzymes and mechanisms of xenobiotic metabolism. In: allergic contact dermatitis chemical and metabolic mechanisms. London and New York, Taylor and Francis; 2001. p. 89–117.
Bergstrom MA, Luthman K, Nilsson JLG, Karlberg AT. Conjugated dienes as prohaptens in contact allergy: in vivo and in vitro studies of structure-activity relationships, sensitizing capacity, and metabolic activation. Chem Res Toxicol. 2006;19:760–9.
Basketter DA. Skin sensitization to cinnamic alcohol: the role of skin metabolism. Acta Derm Venereol. 1992;72:264–5.
Melles D, Vielhaber T, Baumann A, Zazzeroni R, Karst U. In chemico evaluation of skin metabolism: investigation of eugenol and isoeugenol by electrochemistry coupled to liquid chromatography and mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2013;913–914:106–12.
Schnuch A, Uter W, Geier J, Lessmann H, Frosch PJ. Sensitization to 26 fragrances to be labelled according to current European regulation. Results of the IVDK and review of the literature. Contact Dermatitis. 2007;57:1–10.
European Commission. Consolidated version of Cosmetics Directive 76/768/EEC, Cosmetic Restriction III/1,79, 2009. Available at: http://ec.europa.eu/enterprise/cosmetics/html/consolidated_dir.htm. Accessed Dec 2010.
Buckley DA. Fragrance ingredient labelling in products on sale in the U.K. Br J Dermatol. 2007;157:295–300.
Pongpairoj K, Puangpet P, Thaiwat S, McFadden JP. Should Evernia furfuracea be included in a baseline screening series of contact allergens? Contact Dermatitis. 2016;74:257–8.
Uter W, Schmidt E, Geier J, Lessmann H, Schnuch A, Frosch P. Contact allergy to essential oils: current patch test results (2000–2008) from the Information Network of Departments of Dermatology (IVDK). Contact Dermatitis. 2010;63:277–83.
van Oosten EJ, Schuttelaar MLA, Coenraads PJ. Clinical relevance of positive patch test reactions to the 26 EU-labelled fragrances. Contact Dermatitis. 2009;61:217–23.
Mann J, McFadden JP, White JML, White IR, Banerjee P. Baseline series fragrance markers fail to predict contact allergy. Contact Dermatitis. 2014;70:276–81.
Vejanurug P, Tresukosol P, Sajjachareonpong P, Puangpet P. Fragrance allergy could be missed without patch testing with 26 individual fragrance allergens. Contact Dermatitis. 2016;74:230–5.
Uter W, Schmidt E, Lessmann H, Schnuch A. Contact sensitization to tree moss (Evernia furfuracea extract, INCI) is heterogeneous. Contact Dermatitis. 2012;67:36–41.
Audrain H, Kenward C, Lovell CR, et al. Allergy to oxidized limonene and linalool is frequent in the U.K. Br J Dermatol. 2014;171:292–7.
Rudback J, Islam MN, Borje A, Nilsson U, Karlberg AT. Essential oils can contain allergenic hydroperoxides at eliciting levels, regardless of handling and storage. Contact Dermatitis. 2015;73:253–4.
Deza G, Garcia-Bravo B, Silvestre JF, et al. Contact sensitization to limonene and linalool hydroperoxides in Spain: a GEIDAC prospective study. Contact Dermatitis. 2017;76:74–80.
Brared Christensson J, Andersen KE, Bruze M, et al. An international multicentre study on the allergenic activity of air-oxidized R-limonene. Contact Dermatitis. 2013;68:214–23.
Brared Christensson J, Karlberg AT, Andersen KE, et al. Oxidized limonene and oxidized linalool - concomitant contact allergy to common fragrance terpenes. Contact Dermatitis. 2016;74:273–80.
Wilkinson M, Goncalo M, Aerts O et al. The European baseline series and recommended additions: 2019. Contact Dermatitis. 2018;80:1–4.
Heisterberg MV, Vigan M, Johansen JD. Active sensitization and contact allergy to methyl 2-octynoate. Contact Dermatitis. 2010;62:97–101.
Bennike NH, Zachariae C, Johansen JD. Non-mix fragrances are top sensitizers in consecutive dermatitis patients - a cross-sectional study of the 26 EU-labelled fragrance allergens. Contact Dermatitis. 2017;77:270–9.
Lauriola MM, De Bitonto A, Sena P. Allergic contact dermatitis due to cinnamon oil in galenic vaginal suppositories. Acta Derm Venereol. 2010;90:187–8.
Nardelli A, D’Hooghe E, Drieghe J, Dooms M, Goossens A. Allergic contact dermatitis from fragrance components in specific topical pharmaceutical products in Belgium. Contact Dermatitis. 2009;60:303–13.
Clayton R, Orton D. Contact allergy to spearmint oil in a patient with oral lichen planus. Contact Dermatitis. 2004;51:314–5.
de Groot AC, Schmidt E. Essential oils, part IV: contact allergy. Dermatitis. 2016;27:170–5.
de Groot AC, Schmidt E. Tea tree oil: contact allergy and chemical composition. Contact Dermatitis. 2016;75:129–43.
de Groot AC, Schmidt E. Essential oils, part VI: sandalwood oil, ylang-ylang oil, and jasmine absolute. Dermatitis. 2017;28:14–21.
Frosch PJ, Johansen JD, Menné T, et al. Further important sensitizers in patients sensitive to fragrances. Contact Dermatitis. 2003;47:279–87.
Wetter DA, Yiannias JA, Prakash AV, Davis MDP, Farmer SA, el-Azhary RA. Results of patch testing to personal care product allergens in a standard series and a supplemental cosmetic series: an analysis of 945 patients from the Mayo Clinic Contact Dermatitis Group, 2000–2007. J Am Acad Dermatol. 2010;63:789–98.
• Frosch PJ, Duus Johansen J, Schuttelaar MLA, et al. Patch test results with fragrance markers of the baseline series - analysis of the European Surveillance System on Contact Allergies (ESSCA) network 2009–2012. Contact Dermatitis. 2015;73:163–71 This study provides a thorough description of fragrance contact dermatitis in European countries.
Larsen W, Nakayama H, Fischer T, Elsner P, Frosch P, Burrows D, et al. A study of new fragrance mixtures. Am J Contact Dermat. 1998;9:202–6.
Frosch PJ, Pirker C, Rastogi SC, Andersen KE, Bruze M, Svedman C, et al. Patch testing with a new fragrance mix detects additional patients sensitive to perfumes and missed by the current fragrance mix. Contact Dermatitis. 2005;52:207–15.
Frosch PJ, Johansen JD, Menne T, Rastogi SC, Bruze M, Andersen KE, et al. Lyral is an important sensitizer in patients sensitive to fragrances. Br J Dermatol. 1999;141:1076–83.
Bruze M, Andersen KE, Goossens A. Recommendation to include fragrance mix 2 and hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral) in the European baseline patch test series. Contact Dermatitis. 2008;58:129–33.
Bruze M, Svedman C, Andersen KE, Bruynzeel D, Goossens A, Johansen JD, et al. Patch test concentrations (doses in mg/cm2 ) for the 12 non-mix fragrance substances regulated by European legislation. Contact Dermatitis. 2012;66:131–6.
Frosch PJ, Rastogi SC, Pirker C, Brinkmeier T, Andersen KE, Bruze M, et al. Patch testing with a new fragrance mix - reactivity to the individual constituents and chemical detection in relevant cosmetic products. Contact Dermatitis. 2005;52:216–25.
Krautheim A, Uter W, Frosch P, Schnuch A, Geier J. Patch testing with fragrance mix II: results of the IVDK 2005-2008. Contact Dermatitis. 2010;63:262–9.
Isaksson M, Inerot A, Liden C, et al. Multicentre patch testing with fragrance mix II and hydroxyisohexyl 3-cyclohexene carboxaldehyde by the Swedish Contact Dermatitis Research Group. Contact Dermatitis. 2014;70:187–9.
Rastogi SC, Johansen JD, Bossi R. Selected important fragrance sensitizers in perfumes--current exposures. Contact Dermatitis. 2007;56:201–4.
• Ung CY, White JML, White IR, Banerjee P, McFadden JP. Patch testing with the European baseline series fragrance markers: a 2016 update. Br J Dermatol. 2018;178:776–80 This study states that current fragrance markers in the European Baseline Series are not enough to detect fragrance sensitization.
Buckley DA. Advance preparation of some patch test series should be avoided. Br J Dermatol. 2012;167:708–9.
Silvestre JF, Mercader P, González-Pérez R et al. Sensitization to fragrances in Spain: a 5-year multicentre study (2011-2015). Contact Dermatitis. 2018;80:94–100.
Warshaw EM, Zug KA, Belsito DV, et al. Positive patch-test reactions to essential oils in consecutive patients from North America and Central Europe. Dermatitis. 2017;28:246–52.
• Wilkinson M, Gallo R, Goossens A, et al. A proposal to create an extension to the European baseline series. Contact Dermatitis. 2018;78:101–8. This article states that limonene and linalool hydroperoxides should be included in European baseline series.
Conflict of Interest
Luca Schneller-Pavelescu declares that he has no conflict of interest. Gemma Ochando-Ibernón declares that she has no conflict of interest. Juan Francisco Silvestre-Salvador has received grants as advisor and speaker for Novartis.
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Schneller-Pavelescu, L., Ochando-Ibernón, G. & Silvestre-Salvador, J.F. An Update on Fragrance Contact Dermatitis. Curr Treat Options Allergy 6, 92–102 (2019). https://doi.org/10.1007/s40521-019-0196-6
- Allergic contact dermatitis
- Baseline series
- Fragrance mix
- Fragrance markers