Allergic Contact Dermatitis from Ethylhexyl Salicylate ...

CASE REPORT

Allergic Contact Dermatitis from Ethylhexyl Salicylate and Other Salicylates Charlotte Gotthard Mortz, Henrik Thormann, An Goossens, and Klaus Ejner Andersen Allergic contact dermatitis from salicylates present in topical products is uncommon. Most publications are case reports describing only a few patients. Cross-reactivity between salicylates is not commonly reported. This article describes allergic contact dermatitis from ethylhexyl salicylate used as an ultraviolet filter and fragrance compound and reviews the published literature on contact allergy to salicylates.

LLERGIC CONTACT DERMATITIS from the topical use of salicylates is uncommon. However, case reports and patch-test studies document its occurrence.1–25 The European Commission database on cosmetic ingredients (CosIng, available at: http://ec.europa.eu/enterprise/ cosmetics/html/cosm_inci_index.htm) lists 48 International Nomenclature Cosmetic Ingredient (INCI) or substance names when ‘‘salicylate’’ is entered as the search term. The various salicylates have different functions, termed as perfuming, ultraviolet (UV) absorber, UV filter, skin conditioning, denaturant, preservative, soothing, keratolytic, antioxidant, antiinflammatory, and analgetic (Table 1). Salicylic acid is a white crystalline powder. The sodium salt contains both a hydroxyl group and a carboxyl group and forms the basis for many derivatives. For example, the carboxyl group forms esters with alcohols (eg, methyl salicylate with methanol, phenol salicylate with phenol), and the hydroxyl group reacts with acetic acid to form acetylsalicylic acid (aspirin). Ethylhexyl salicylate (its INCI name),—also called octyl salicylate, octisalate, 2-ethylhexyl salicylate, or CAS 11860-5—is a cosmetic ingredient used both as a UV absorber

A

From the Department of Dermatology and Allergy Centre, Odense University Hospital, University of Southern Denmark, DK-5000 Odense C, Denmark, and the Department of Dermatology, University Hospital KU Leuven, B3000 Leuven, Belgium. Address reprint requests to Charlotte Gotthard Mortz, Department of Dermatology and Allergy Centre, Odense University Hospital, University of Southern Denmark, Sdr. Boulevard 29, DK-5000 Odense C, Denmark. E-mail: [email protected] Klaus Ejner Andersen is advisor to Mekos A/S. Charlotte Gotthard Mortz is an investigator for Mekos A/S. DOI 10.2310/6620.2010.09090 #

2010 American Contact Dermatitis Society. All Rights Reserved.

and UV filter with an absorption spectrum ranging from 280 to 320 nm (ultraviolet B). It is also a fragrance compound. We report on a patient with allergic contact dermatitis from ethylhexyl salicylate in a sunscreen and review published data on allergic reactions to different salicylates.

Case Report A 48-year-old woman with a 12-year history of rosacea was advised to use a sunscreen during several months prior to IPL (intense pulsed light) treatment for facial telangiectasia. A sample of Anthelios dermo-pediatrics SPF 50+ lotion (La Roche-Posay, Asnie`res Cedex, France) was given to the patient. Half a year later, the patient developed facial dermatitis. She was tested with the European baseline series using panels 1, 2, and 3 of the Thin-Layer Rapid Use Epicutaneous Test (T.R.U.E. Test) (Mekos Laboratories A/S, Hillerød, Denmark) supplemented with petrolatum-based allergens in Finn Chambers (Epitest Ltd Oy, Tuusula, Finland) on Scanpor tape (Norgesplaster A/S, Vennesla, Norway) and with her own topical products, including Anthelios dermo-pediatrics SPF 50+ lotion. The tests were occluded for 2 days and read according to the International Contact Dermatitis Research Group scoring scale on day 3 and day 7. A positive nickel patch-test result was without current relevance, and there was a positive (+) reaction to Anthelios dermo-pediatrics SPF 50+ lotion. The patient was subsequently patch-tested with individual components of Anthelios dermo-pediatrics SPF 50+ lotion which were provided by the manufacturer (L’Oreál Denmark A/S , Glostrup, Denmark). The patient reacted to ethylhexyl salicylate 2% in petrolatum (pet) (++), butyl methoxydibenzoylmethane 2% pet (+), and Anthelios

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Table 1 Chemical Abstracts Service Number, Test Concentration, and Function of Different Salicylates Test Compound

CAS No.

Function{

Day 3 Reading{

Day 7 Reading{

Perfuming, skin conditioning Perfuming, UV absorber Perfuming UV absorber, antiinflammatory Perfuming, denaturant, soothing, antiinflammatory Perfuming, UV absorber, UV filter Antimicrobial, denaturant, perfuming, UV absorber Analgesic, antipyretic, antidandruff, hair conditioning, keratolytic, masking, preservative, skin conditioning Keratolytic Denaturant, preservative Antioxidant, keratolytic, reducing

2 +? 2 2 2

2 +? 2 2 2

+ 2

++ 2

2

2

2 2 2

2 2 2

Drug Drug, antiacid, antiinflammatory Perfuming Drug, antiinflammatory, analgesic Drug, antiinflammatory, analgesic Drug Drug, eyedrops Drug, tuberculostatic Drug, analgesic Drug

2 2 2 2 2 2 2 2 +? follicular 2

2 2 2 2 2 2 2 2 +? 2

2

2

Test Concentration

Compounds listed as cosmetics ingredients* Amyl salicylate 2050-08-0 Benzyl salicylate 118-58-1 Ethyl salicylate1 118-61-6 Glycol salicylate 87-28-5 Methyl salicylate 119-36-8

5% 2% 2% 10% 2%

pet pet pet ethanol pet

Ethylhexyl salicylate Phenyl salicylate

118-60-5 118-55-8

2% pet 1% pet

Salicylic acid

69-72-7

2% pet

Salicylamide Sodium salicylate Thiosalicylic acid Other compounds Bamipine salicylate Bismuth subsalicylate Bornyl salicylate Choline salicylate Diethylamine salicylate Dithiosalicylic acid Eserine salicylate para-Aminosalicylic acid Phenazone salicylate Pheniramine aminosalicylate Phenyl propyl salicylate

65-45-2 54-21-7 147-93-3

2% pet 2% pet 0.1% pet

14882-18-19 560-88-3 2016-36-6 4419-92-5 119-80-2 57-64-7 65-49-6 520-07-0 2508-73-8

2% 2% 2% 4% 2% 2% 2% 2% 2% 2%

pet pet pet pet pet pet pet pet pet pet

24781-13-3

2% pet

Drug, antiinflammatory

CAS 5 Chemical Abstracts Service; INCI 5 International Nomenclature Cosmetic Ingredient; pet 5 in petrolatum; UV 5 ultraviolet. *INCI name, unless otherwise noted. { Functions of compounds as listed in CosIng (the European Commission database with information on cosmetic ingredients [http://ec.europa.eu/enterprise/ cosmetics/cosing/index.cfm?fuseaction5search.simple]), supplemented with information from Google Scholar. { Readings are for the patient in the case report. 1 Not the official INCI name but perfuming name.

dermo-pediatrics SPF 50+ lotion (++). She also reacted to octyl salicylate 5% pet (Chemotechnique, Malmo¨ , Sweden) (+), which is synonymous with ethylhexyl salicylate. The patch-test reaction to butyl methoxydibenzoylmethane 10% pet (Chemotechnique) was doubtful (+?). Results of repeated open application tests (ROATs) with ethylhexyl salicylate 2% and 5% were positive from day 4 on. Results of patch tests with the patient’s other personal products were negative. A total of 29 consecutive eczema patients acting as controls were negative to ethylhexyl salicylate 5% pet and 2% pet. The dermatitis cleared after the elimination of exposure.

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The patient was retested after 1 year, and the + reaction to ethylhexyl salicylate was reproduced. There was no reaction to other allergens in the sunscreen series, and the results of photopatch tests were negative. Results of patch tests with 21 other salicylates (see Table 1) and phenolformaldehyde resin were also negative.

Discussion Contact allergy to ethylhexyl salicylate has been described.1–3 In a retrospective study on allergic contact cheilitis, one of 146 patients had a clinically relevant positive patch-test reaction to octyl salicylate.1 Two further

Allergic Contact Dermatitis from Ethylhexyl Salicylate

cases were caused by sunscreens and anti-aging creams.2,3 cis-3-Hexenyl salicylate is chemically similar to octyl salicylate and may give rise to cross-reactivity.2,4 In the study reported by Shaw,2 the patch-test result was supported by patch testing with octyl salicylate 5% pet (with negative results in 35 controls) and by ROAT. To increase the accuracy of an evaluation of the relevance of a positive patch-test reaction, it is important to include additional procedures such as retests and serial dilution patch tests with the allergen in question, ROAT, or a use test. For new allergens, testing of controls is recommended to exclude irritancy. Amyl salicylate was included in a multicenter study on fragrance sensitization. Only one allergic reaction was found, and it appeared to be irrelevant.5 Benzyl salicylate is a fragrance allergen and may cause allergic contact dermatitis, more commonly among Japanese eczema patients than in Europe and the United States (11.9% vs 1.1% vs 2.8%).6 Benzyl salicylate is a component of propolis, and propolis-sensitive patients should be informed about potential cross-reactions to cosmetics.7 Benzyl salicylate is a moderate sensitizer in guinea pigs.8 However, in a recent European review, it was found to be an very rare allergen in humans.9 Phenyl salicylate (salol) is found in lip salves,10,11 safety spectacle frames,12 and cosmetic creams.13 It has a pleasant odor somewhat similar to that of oil of wintergreen. It is also included in mouthwashes and some sunscreen preparations. It absorbs UV radiation in the 290-to-330 nm range and is used in plastics to prevent their deterioration by sunlight. Sonnex and Rycroft reported negative patch-test results for 20 controls.12 Homomenthyl salicylate in a sunscreen lotion was reported to cause contact dermatitis in two patients. However, these two patients presented a follicular dermatitis pattern, and four controls had negative results.14 Salicylates are widely used in many topical analgesics. Patients have benefited from their analgetic, antithrombotic, and anti-inflammatory effects for many years, and they are used by the general population, especially in Mediterranean countries. Hydroxyethyl salicylate (glycol salicylate) in antiinflammatory gels,15,16 methyl salicylate,17,18 methyl butetisalicylate,19 and picolinamine salicylate (3-(aminomethyl)-pyridyl salicylate, pyridyl-3methylamine salicylate)20,21 in topical analgesics have also caused allergic reactions. One report described patch testing with hydroxyethyl salicylate in different concentrations,16 and a few investigators have performed patch tests in 3 to 35 controls, with negative results.17,19–21


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Contact sensitization to salicylic acid is rare.22 Rudzki and Koslowska described five cases caused by salicylic spirit and unguentum salicylicum.23 Warts and calluses are sometimes treated with salicylic acid plaster because of the keratolytic action, and a few cases of allergic contact dermatitis have been described.24 Gonçalo and colleagues described three cases of occupational contact dermatitis due to the bush Salix viminalis, the branches of which are used in basket manufacture or for packing glass bottles. The bark contains salicin or salicoside, which can be converted by oxidation into salicylic acid.25 Our patient did not react to other salicylates. The degree of cross-reactivity among salicylates is unknown, and only a few patients have been patch-tested with other salicylates.2,4,16 Testing with the individual salicylates according to a list of products’ ingredients is recommended. Hindson and colleagues17described a flare-up of dermatitis after oral ingestion of acetylsalicylic acid (aspirin) in a patient with previous allergic contact dermatitis from methyl salicylate. However, this has not been reproduced by others.2,16,19,20

Conclusion Most studies on allergic contact dermatitis from salicylates are case reports with a small number of patients and varying use of additional test procedures (retests, serial dilution patch tests, repeated open application tests, and the inclusion of controls in testing) to increase the accuracy of the evaluation of the relevance of a positive patch-test result. Salicylates are mainly used in topical products and drugs. Allergic contact dermatitis from salicylates in topical products is uncommon, and the degree of cross-reactivity among salicylates is unknown. in the case of allergens as rare as salicylates, it is important to test with the patients’ own products and the individual ingredients to obtain clues. We recommend testing with the individual salicylates shown on the list of the product’s ingredients.

Acknowledgment Financial disclosures of authors: Klaus Ejner Andersen is an advisor and Charlotte Gotthard Mortz is an investigator for Mekos A/S. Financial disclosure of reviewers: None reported.

References 1. Strauss RM, Orton DI. Allergic contact cheilitis in the United Kingdom: a retrospective study. Am J Contact Dermat 2003;14: 75–7.

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2. Shaw DW. Allergic contact dermatitis from octisalate and cis-3hexenyl salicylate. Dermatitis 2006;17:152–5. 3. Singh M, Beck MH. Octyl salicylate: a new contact sensitivity. Contact Dermatitis 2007;56:48. 4. Van Ketel WG. Sensitization to cis-3-hexenyl salicylate. Contact Dermatitis 1983;9:154. 5. Frosch PJ, Pilz B, Andersen KE, et al. Patch testing with fragrances: results of a multicenter study of the European Environmental and Contact Dermatitis Research Group with 48 frequently used constituents of perfume. Contact Dermatitis 1995;33:333–42. 6. Larsen W, Nakayama H, Lindberg M, et al. Fragrance contact dermatitis: a worldwide multicenter investigation (part 1). Am J Contact Dermat 1996;7:77–83. 7. Walgrave SE, Warshaw EM, Glesne LA. Allergic contact dermatitis from propolis. Dermatitis 2005;16:209–15. 8. Hausen BM, Wollenweber E. Propolis allergy (III). Sensitization studies with minor constituents. Contact Dermatitis 1988;19:296– 303. 9. Schnuch A, Uter W, Geier J, et al. 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. 10. Hindson C. Phenyl salicylate (salol) in a lip salve. Contact Dermatitis 1980;6:216. 11. Calnan CD, Cronin E, Rycroft RJG. Allergy to phenyl salicylate. Contact Dermatitis 1981. 208–11. 12. Sonnex TS, Rycroft RJG. Dermatitis from phenyl salicylate in safety spectacle frames. Contact Dermatitis 1986;14:268–70.


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13. Fimiani M, Casini L, Bocci S. Contact dermatitis from phenyl salicylate in a galenic cream. Contact Dermatitis 1990;22:239. 14. Rietschel RL, Lewis CCW. Contact dermatitis to homomenthyl salicylate. Arch Dermatol 1978;114:442–3. 15. Horak J, Hemmer M, Focke M, et al. Contact dermatitis from antiinflammatory gel containing hydroxyethyl salicylate. Contact Dermatitis 2002;47:120–1. 16. Reichert C, Gall H. Contact dermatitis from hydroxyethyl salicylate. Contact Dermatitis 1995;33:275–6. 17. Hindson C. Contact eczema from methyl salicylate reproduced by oral aspirin (acetyl salicylic acid). Contact Dermatitis 1977;3:348–9. 18. Oiso N, Fukai K, Ishii M. Allergic contact dermatitis due to methyl salicylate in a compress. Contact Dermatitis 2004;51:34–42. 19. Valsecchi R, Aiolfi M, Leghissa P, et al. Contact dermatitis from methyl butetisalicylate. Contact Dermatitis 1998;38:360–1. 20. Gamboa P, Jaúregui I, Fernańdez JC, et al. Contact sensitization to topical salicylate. Contact Dermatitis 1995;33:52. 21. Camarasa JG, Lluch M, Serra-Baldrich E, et al. Allergic contact dermatitis from 3-(aminomethyl)-pyridyl salicylate. Contact Dermatitis 1989;20:347–51. 22. Goh CL, Ng SK. Contact allergy to salicylic acid. Contact Dermatitis 1986;14:114. 23. Rudzki E, Koslowska A. Sensitivity to salicylic acid. Contact Dermatitis 1976;2:178–82. 24. Rasmussen JE, Fisher A. Allergic contact dermatitis to a salicylic acid plaster. Contact Dermatitis 1976;2:237–8. 25. Gonçalo S, Sousa I, Moreno A, Leitao A. Occupational dermatitis from Salix vimminalis. Contact Dermatitis 1986;14:188–9.