Fragrance contact allergy: a 4-year retrospective study

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Contact Dermatitis 2010: 63: 77–84 Printed in Singapore. All rights reserved © 2010 John Wiley & Sons A/S CONTACT DERMATITIS Fragrance contact allergy: a 4-year retrospective study Laura Cuesta, Juan Francisco Silvestre, Fernando Toledo, Ana Lucas, Mar´ ıa P´ erez-Crespo and Irene Ballester Department of Dermatology, Hospital General Universitario, 03010 Alicante, Spain Background: Fragrance chemicals are the second most frequent cause of contact allergy. The mandatory labelling of 26 fragrance chemicals when present in cosmetics has facilitated management of patients allergic to fragrances. Objectives: The study was aimed to define the characteristics of the population allergic to perfumes detected in our hospital district, to determine the usefulness of markers of fragrance allergy in the baseline GEIDAC series, and to describe the contribution made by the fragrance series to the data obtained with the baseline series. Material and methods: We performed a 4-year retrospective study of patients tested with the Spanish baseline series and/or fragrance series. There are four fragrance markers in the baseline series: fragrance mix I (FM I), Myroxylon pereirae, fragrance mix II (FM II), and hydroxyisohexyl 3-cyclohexene carboxaldehyde. Results: A total of 1253 patients were patch tested, 117 (9.3%) of whom were positive to a fragrance marker. FM I and M. pereirae detected 92.5% of the cases of fragrance contact allergy. FM II and hydroxyisohexyl 3-cyclohexene carboxaldehyde detected 6 additional cases and provided further information in 8, enabling improved management. A fragrance series was tested in a selected group of 86 patients and positive results were obtained in 45.3%. Geraniol was the allergen most frequently found in the group of patients tested with the fragrance series. Conclusions: Classic markers detect the majority of cases of fragrance contact allergy. We recommend incorporating FM II in the Spanish baseline series, as in the European baseline series, and using a specific fragrance series to study patients allergic to a fragrance marker. Key words: allergic contact dermatitis; epidemiology; fragrances; patch test. © John Wiley & Sons A/S, 2010. Conflict of interests: The authors have declared no conflicts. Accepted for publication 7 March 2010 There are about 3000 fragrance chemicals avail- able and a single perfume may contain 10–300 different fragrance chemicals (1, 2). They are also present in cosmetics, cleaning products, industrial products, and topical medicaments. Fragrances may be responsible for clinical conditions, including irri- tant contact dermatitis, allergic contact dermatitis, photosensitivity, immediate contact reactions (con- tact urticaria), and pigmented contact dermatitis (1). Fragrances are considered to be the second most frequent cause of contact allergy after metals (3). Furthermore, together with preservatives, they are the most important sensitizers in cosmetics. Fra- grance contact allergy affects approximately 1% of the general population, and 6–14% of patients with contact dermatitis (1–9). In recent years, there has been a greater aware- ness of the importance of fragrance contact allergy, as shown by the change made in the labelling of cosmetics in accordance with the seventh Amend- ment of the European Cosmetic Directive (10), which requires the labelling of 26 specific fragrance

Transcript of Fragrance contact allergy: a 4-year retrospective study

Page 1: Fragrance contact allergy: a 4-year retrospective study

Contact Dermatitis 2010: 63: 77–84Printed in Singapore. All rights reserved

© 2010 John Wiley & Sons A/S

CONTACT DERMATITIS

Fragrance contact allergy: a 4-yearretrospective study

Laura Cuesta, Juan Francisco Silvestre, Fernando Toledo, Ana Lucas,Marıa Perez-Crespo and Irene Ballester

Department of Dermatology, Hospital General Universitario, 03010 Alicante, Spain

Background: Fragrance chemicals are the second most frequent cause of contact allergy. The mandatorylabelling of 26 fragrance chemicals when present in cosmetics has facilitated management of patientsallergic to fragrances.

Objectives: The study was aimed to define the characteristics of the population allergic to perfumesdetected in our hospital district, to determine the usefulness of markers of fragrance allergy in thebaseline GEIDAC series, and to describe the contribution made by the fragrance series to the dataobtained with the baseline series.

Material and methods: We performed a 4-year retrospective study of patients tested with the Spanishbaseline series and/or fragrance series. There are four fragrance markers in the baseline series: fragrancemix I (FM I), Myroxylon pereirae, fragrance mix II (FM II), and hydroxyisohexyl 3-cyclohexenecarboxaldehyde.

Results: A total of 1253 patients were patch tested, 117 (9.3%) of whom were positive to a fragrancemarker. FM I and M. pereirae detected 92.5% of the cases of fragrance contact allergy. FM IIand hydroxyisohexyl 3-cyclohexene carboxaldehyde detected 6 additional cases and provided furtherinformation in 8, enabling improved management. A fragrance series was tested in a selected group of86 patients and positive results were obtained in 45.3%. Geraniol was the allergen most frequently foundin the group of patients tested with the fragrance series.

Conclusions: Classic markers detect the majority of cases of fragrance contact allergy. We recommendincorporating FM II in the Spanish baseline series, as in the European baseline series, and using a specificfragrance series to study patients allergic to a fragrance marker.

Key words: allergic contact dermatitis; epidemiology; fragrances; patch test. © John Wiley & Sons A/S,2010.

Conflict of interests: The authors have declared no conflicts.Accepted for publication 7 March 2010

There are about 3000 fragrance chemicals avail-able and a single perfume may contain 10–300different fragrance chemicals (1, 2). They are alsopresent in cosmetics, cleaning products, industrialproducts, and topical medicaments. Fragrances maybe responsible for clinical conditions, including irri-tant contact dermatitis, allergic contact dermatitis,photosensitivity, immediate contact reactions (con-tact urticaria), and pigmented contact dermatitis (1).

Fragrances are considered to be the second mostfrequent cause of contact allergy after metals (3).

Furthermore, together with preservatives, they arethe most important sensitizers in cosmetics. Fra-grance contact allergy affects approximately 1% ofthe general population, and 6–14% of patients withcontact dermatitis (1–9).

In recent years, there has been a greater aware-ness of the importance of fragrance contact allergy,as shown by the change made in the labelling ofcosmetics in accordance with the seventh Amend-ment of the European Cosmetic Directive (10),which requires the labelling of 26 specific fragrance

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Table 1. List of ingredients that must be declared on the labellingof cosmetics, according to the seventh Amendment of theCosmetics Directive

Cinnamala Farnesolb

Geraniola Benzyl alcoholc

Evernia prunastri a Benzyl salicylatec

Cinnamyl alcohola Linaloolc

Eugenola LimoneneHydroxycitronellala Butylphenyl methylpropionalIsoeugenola Anisyl alcoholα-Amyl cinnamala Benzyl cinnamateCitralb Benzyl benzoateCoumarinb Methyl-2-octynoatehydroxyisohexyl 3-cyclohexene

carboxaldehydebα-isomethyl ionone

Citronellolb Evernia fufuraceaα-Hexyl cinnamalb Amyl cinnamyl alcohol

We have marked the constituents analysed in our study.aConstituent of FM I.bConstituent of FM II.cPresent in fragrance series.

chemicals when present at ≥10 ppm in leave-on and≥100 ppm in rinse-off cosmetic products (Table 1).Previously, there was no obligation to specify thefragrance chemicals in the product; products weresimply said to contain ‘fragrance’ and patients withcontact allergy were obliged to use cosmetics with-out fragrance, which was difficult if not impossibleto do. More recently, household cleaning productshave carried similar labelling for the same chemicalswhen present at ≥100 ppm.

The baseline series of the Spanish Group forResearch into Contact Dermatitis and Skin Allergy(GEIDAC) contains various allergens that may beconsidered markers of fragrance allergy. Tradition-ally, these markers have been fragrance mix I (FMI), Myroxylon pereirae and colophonium. Fragrancemix II (FM II) and hydroxyisohexyl 3-cyclohexenecarboxaldehyde have recently been included(11–13). It is also possible to perform patchtests with a specific series of fragrance allergens(Chemotechnique Diagnostics®, Vellinge, Sweden).

Before the change in labelling of cosmetics andhousehold cleaning products came into effect, therewas limited use in knowing which specific fragrancechemical an individual was allergic to. Now, webelieve that using a fragrance series to test patientswho are positive for a fragrance marker in the base-line series may be of importance in the subsequentmanagement of these patients.

We performed a retrospective and descriptivestudy of all the patients seen by us in the last 4 yearswho were patch tested with the baseline and/orfragrance series (Chemotechnique®). The objectivesof this study were as follows:

(1) to define the characteristics of the populationallergic to perfumes detected in our hospitaldistrict;

(2) to determine the usefulness of markers offragrance allergy in the baseline GEIDACseries;

(3) to describe the contribution made by thefragrance series to the data obtained with thebaseline series.

Material and Methods

This is a retrospective and descriptive study carriedout at the Cutaneous Allergy Unit of a tertiaryreferral hospital, between October 2004 and June2008. All patients tested with the baseline SpanishGroup series were reviewed, as well as patientstested with the fragrance series either because theywere positive to the baseline series or because therewas clinical suspicion.

The clinical data recorded on each patient wereage, sex, profession, site of lesions, series tested,positive allergens and number of positive reactions,their relevance, origin of the sensitization, andpatient’s diagnosis.

The MOALFHA index was used to study thecharacteristics of the patients seen. This indexrecords the percentage of the following characteris-tics: male, occupational dermatitis, atopic dermatitis,leg dermatitis, face dermatitis, hand dermatitis, andage >40 years. A history of atopy was not ade-quately recorded and so it is not included in ourstudy.

The allergens used both in the standard series andin the fragrance series were supplied by Chemotech-nique Diagnostics®. The markers of the baselineSpanish Group series used in our study to detectfragrance allergic contact dermatitis were: the ‘tradi-tional’ markers (M. pereirae and FM I), hydroxyiso-hexyl 3-cyclohexene carboxaldehyde (included as ofOctober 2005), and FM II (included as of January2007). FM I consists of eight components: Ever-nia prunastri (1%), isoeugenol (1%), eugenol (1%),cinnamal (1%), hydroxycitronellal (1%), geraniol(1%), cinnamyl alcohol (1%), and α-amylcinnamal(1%). Both M. pereirae and FM I contain sorbi-tan sesquioleate as an emulsifying agent. FM IIis made up of six substances: hydroxyisohexyl3-cyclohexene carboxaldehyde (2.5%), citral (1%),farnesol (2.5%), citronellol (0.5%), α-hexyl cinna-mal (5%), and coumarin (2.5%) (12).

The fragrance series (Chemotechnique®) con-tains 30 substances (Table 2). We added sorbitansesquioleate to this series to detect false positives tofragrance chemical allergens prepared using this sus-btance. The individual components of FM II wereincluded in this series in January 2007.

The patches were prepared using FinnChambers® fixed with Scanpor® adhesive andremoved after 2D in contact with the skin. Readings

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Table 2. Constituents of the specific fragrance series(Chemotechnique®), concentration used in the patch test, andfrequency of reactions found in the population in whom this serieswas tested (86 patients tested)

Components of thefragrance series Concentrationa (%) Frequency n (%)

Geraniol 2.0 17 (19.7)Eugenol 2.0 12 (13.9)Ylang-ylang oilb 2.0 12 (13.9)Cinnamyl alcohol 2.0 12 (13.9)Isoeugenol 2.0 11 (12.8)Geranium oil

bourbonb2.0 8 (9.3)

Hydroxyisohexyl3-cyclohexenecarboxaldehyde

5.0 7 (8.1)

Cinnamal 2.0 7 (8.1)Rose oil absoluteb 2.0 6 (6.9)Hydroxycitronellalb 5.0 6 (6.9)Jasmine absolute,

Egyptian2.0 3 (3.5)

Cananga oil 2.0 3 (3.5)Jasmine synthetic 2.0 3 (3.5)Evernia prunastri 2.0 2 (2.3)Benzyl alcohol 1.0 2 (2.3)Benzyl salicylate 2.0 2 (2.3)Lavender absoluteb 2.0 2 (2.3)Sandalwood oil 2.0 2 (2.3)Citral 2.0 2 (2.3)Farnesol 5.0 1 (1.2)Coumarin 5.0 1 (1.2)α-Amyl cinnamal 2.0 0Narcissus absolute 2.0 0Musk xylene 1.0 0Musk moskene 1.0 0Musk ketone 1.0 0Vanillin 10 0Methyl anthranilate 5 0Citronellolb 1.0 0α-Hexyl cinnamal 10 0

aPetrolatum was used as the vehicle for all the constituents of thefragrance series.bFragrances that contain geraniol or that have cross reactions withgeraniol.

were taken at D2 and D4, with the evaluation criteria(+, ++, and +++) recommended by the ICDRG.If the result was doubtful, a late reading was takenat D7. The relevance was considered current if theclinical picture could be attributed totally or par-tially to the fragrance obtained, past if this positivityexplained only previous dermatitis, and unknownif the clinical picture could not be attributed to theuse of these fragrances.

Patients who were positive to any fragrancemarker in the GEIDAC baseline series (M. pereirae,FM I, hydroxyisohexyl 3-cyclohexene carboxalde-hyde, or FM II) were identified, and the percent-age of patients positive to each of the markers wasdetermined.

The characteristics of the population seen werecompared with those of the population with a

positive fragrance marker, according to theMOALFHA index (11).

We studied the relevance of the positivity toclassical markers of the baseline series.

In patients patch tested with a specific fragranceseries, the frequency of positive reactions to each ofthe fragrances present in the series was determined.We also studied the percentage of positivity inthe subgroup of patients negative to a classicalmarker of the standard series and in the subgroup ofpatients positive to a classical marker. Furthermore,in the latter subgroup we distinguished betweenwhether the marker was M. pereirae, FM I, or both,and studied which individual fragrances were mostfrequently positive in each subgroup.

Results

Between October 2004 and June 2008, patch testswere performed in a total of 1253 patients, allof whom were tested with the baseline SpanishGroup series. Of these patients, 852 were tested withhydroxyisohexyl 3-cyclohexene carboxaldehyde and450 with FM II. A total of 86 patients were testedwith the Chemotechnique® fragrance series.

Standard series markers

Frequencies. Of the 1253 patients, 117 (9.3%) hadat least one positive fragrance marker in the baselineSpanish Group series. In our population, the sumof these four markers represents the second mostfrequent cause of allergic contact eczema (9.3%)after metals.

M. pereirae was positive in 80 of 1253 patients(6.4%) and FM I was positive in 56 of 1253patients (4.5%), whereas FM II was positive in 7of 1253 patients (1.5%) and hydroxyisohexyl 3-cyclohexene carboxaldehyde in 9 of 1253 patients(1.1%). We found patients who were positive to var-ious markers – 29 patients (2.31%) were positive toM. pereirae and FM I. Only one patient (0.08%)was positive to M. pereirae and FM II. Two patients(0.16%) were positive to M. pereirae and hydroxy-isohexyl 3-cyclohexene carboxaldehyde, and threepatients (0.24%) were positive to hydroxyisohexyl3-cyclohexene carboxaldehyde and FM I. Threepatients (0.24%) were positive to FM I and FM II,and two of these were also positive to hydroxyiso-hexyl 3-cyclohexene carboxaldehyde (Fig. 1). It isremarkable that of the patients allergic to FM II,only three were positive to this marker alone. Sim-ilarly, of the patients allergic to hydroxyisohexyl3-cyclohexene carboxaldehyde, only three were pos-itive to this marker alone. Therefore, these twomarkers together detected six additional cases offragrance allergy.

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Fig. 1. Patients with more than one posi-tive fragrance marker in the standard series.Venn Diagram. A total of 1253 patients weretested. Fragrance mix I (FMI) = 56 patients,M. pereirae = 80 patients, fragrance mix II(FMII) = 7 patients, hydroxyisohexyl 3-cyclohexene carboxaldehyde = 9 patients.

Epidemiological data. The characteristics of thetotal patch test population studied using theMOALFHA index are shown in Table 3, togetherwith those of the population with a positivemarker; the differences were statistically significant(P < 0.05) for each index, except for occupationaldermatitis and hand dermatitis when we analysedwith Fisher’s exact test. The finding of higherpercentage of men (51.3 versus 38% in the generalpopulation) and of patients over 40 years old (74.4versus 56.4% in the general population) in patientswith a positive fragrance marker in the baselineseries is notable. The most frequent site was thehands, both in the population with a positive markerand in the general population studied (32.5 versus29.7%), but there was greater involvement of thelegs (12 versus 6.8%) and less involvement of theface (8.5 versus 16.4%) in the population with apositive marker.

Relevance. The relevance of positivity toM. pereirae was considered current in 53 (66.2%)cases, past in 6 (7.5%) cases, and unknown in21 (26.25%) cases. The relevance of FM I was

considered current in 52 (92.8%) cases and unknownin 4 (7.2%) cases.

Fragrance series

Of the 117 patients with a positive marker in thebaseline series, 54 were subsequently tested with thefragrance series. In addition, this series was used totest 32 patients with clinical symptoms compatiblewith fragrance contact dermatitis, despite not havingany positive fragrance marker in the baseline series.In total, 86 patients were tested with the fragranceseries.

Fragrance chemical frequencies. Of the 86 patientstested with the Chemotechnique® fragrance series,39 (45.3%) were positive to an allergen. Themost frequent allergens found in our population inthe fragrance series were geraniol, eugenol, ylang-ylang oil, cinnamyl alcohol, isoeugenol, geraniumoil bourbon, and hydroxyisohexyl 3-cyclohexenecarboxaldehyde. It should be mentioned that thefrequency of hydroxyisohexyl 3-cyclohexene car-boxaldehyde is probably underestimated, as it wasincluded in the baseline series 12 months after the

Table 3. Demographic description of the populations studied using the MOALFHA index (except for atopic dermatitis, which was notrecorded in our database)

Population treated in our unit Population with a positive fragrance marker

Total Percentage Total Percentage

Patients studied 1253 100 117 9.3M Men 476 38 60 51.3a

O Occupational dermatitis 175 14 12 10.3b

A Atopic dermatitis Not recorded in our databaseL Leg dermatitis 85 6.78 14 12a

F Face dermatitis 205 16.4 10 8.5a

H Hand dermatitis 372 29.7 38 32.5b

A >40 years 706 56.4 87 74.4a

aResults statistically significant (P < 0.05).bResults not statistically significant (P > 0.05).

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study was started. It is notable that we found onlytwo cases positive to Evernia prunastri (Table 2).

Patients with a positive fragrance marker in thestandard series. We used the specific fragranceseries to test 54 patients with a positive fragrancemarker (Fig. 2). In total, 17 patients were positive toM. pereirae and FM I, 12 to M. pereirae only, 19 toFM I only, and 6 to hydroxyisohexyl 3-cyclohexenecarboxaldehyde or FM II. Of the 54 patients, 39(72%) were positive to fragrances in the specificfragrance series.

Of the 17 patients positive to FM I andM. pereirae tested with the fragrance series, 11(64.7%) exhibited some positivity (Fig. 3). Themost frequent positive allergens in this group wereeugenol, isoeugenol (always in combination witheugenol), and ylang-ylang. Three patients (17.7%)were allergic to sorbitan sesquioleate and, therefore,were false negatives.

Of the 12 patients positive to M. pereirae alone,3 (25%) exhibited some positivity in the fragranceseries (Fig. 3). It is notable that in this group, therewas only one patient allergic to cinnamyl alcoholand none allergic to cinnamal.

Of the 19 patients who were positive to onlyFM I, 16 (84.2%) exhibited some positivity tothe fragrance series (Fig. 3). The main allergensdetected in these cases were geraniol, hydroxyc-itronellal, rose oil absolute, and geranium oil bour-bon (the latter two were almost always associatedwith geraniol).

In total, 36 patients were positive to FM I and 27of these (75%) were positive to some markers in thefragrance series.

Patients with negative fragrance markers in the stan-dard series. Of the 32 patients studied with nega-tive fragrance markers in the standard series, three(9.3%) exhibited some positivity in the fragranceseries (Fig. 2). Two of the patients were allergicto constituents of FM I (false negatives). There-fore, when we tested with the fragrance series based

Fig. 2. Percentage of patients with a reaction to at least onefragrance in the extended series in those with positive andnegative reactions to fragrance markers in the baseline series.

on the clinical symptoms, despite the fact that thebaseline series was negative, less than 10% werefound to be positive.

In total, 9 (3 hydroxyisohexyl 3-cyclohexene car-boxaldehyde, 3 FM II, and 3 fragrance series) of the120 patients (7.5%) with allergic contact dermatitisto perfumes were detected using markers other thanthose traditionally used (M. pereirae and FM I).

Discussion

The most frequent adverse reaction to fragrances isallergic contact dermatitis, although it is believedto be an underestimated problem as many individ-uals may be aware of the perfumed products theytolerate and those they do not, and rarely consult adermatologist about this problem.

In our study, fragrance contact allergy was secondonly to allergy caused by metals (9.3%), and thisis in agreement with the data in the literaturereviewed (6, 14, 15). In our population, M. pereiraeoccupied the sixth position of the allergens tested,with a frequency of 6.22%, and FM I occupiedthe seventh place, with a frequency of 4.46%.Our data are similar to those obtained by othergroups, such as the Portuguese group in which FM Iand M. pereirae occupy the fifth and sixth place,respectively, with a frequency of 7.6 and 6% (16). Inthe epidemiological study carried out by the SpanishGroup in 2001, similar results were found: FM Ioccupied the fifth place (5.03%) and M. pereirae theseventh (3.20%) (17).

If we compare the demographic characteristicsof our population allergic to fragrances with thoseof the general population, the high percentage ofmen (51.3 versus 38%) and an age of over 40 years(74.4% in those allergic to fragrances versus 56.4%in the general population) were found to be signifi-cant. This contrasts with the results obtained in stud-ies of most published series in which women werefound to be the most affected (18–20). The explana-tion for our findings remains unclear, although thereare other studies which reported no differences interms of gender (1, 21).

With regard to the distribution of eczema, thehands were most frequently affected in our study,which correlates with most of the data in theliterature (10, 20, 22–25). In our study, we foundgreater involvement of the legs and less of the face,compared with that in the general population (theseresults were statistically significant). However, inother studies, the face was found to be mostfrequently involved (1, 20, 21, 25). The greaterinvolvement of the legs may be attributed to thefact that among the population allergic to fragrances,many patients had vascular ulcers on the legs asa result of repeated exposure to topical drugs that

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Fig. 3. Results of testing the fragrance series in patients with a positive ‘classical marker’ in the baseline series.

frequently contained fragrance (18, 26–28). One ofthe most frequently used topical drugs for treatingleg ulcers in Spain is Blastoestimulina® (Almirall),which contains geraniol.

In our study, the markers FM I and M. pereiraeidentified more than 90% of our cases. In otherstudies, FM I and M. pereirae have been shownto detect 70–80% of the cases of allergic contactdermatitis to fragrances (4–6, 8). Some of thesestudies have used Trolab® (Hermal Almirall, Rein-beck, Germany) allergens, where the concentra-tion of some allergens varies from that used byChemotechnique®, which could explain this vari-ation. Some authors even detected 85% of the casesjust with FM I (12, 21).

FM II and hydroxyisohexyl 3-cyclohexene car-boxaldehyde have been used since 2005 as markersof fragrance allergy, although they are less power-ful markers than FM I. Nevertheless, in our study,hydroxyisohexyl 3-cyclohexene carboxaldehyde andFM II included in the baseline series identified sixnew patients allergic to fragrances. In addition, theywere concomitantly positive in nine patients whowere also allergic to M. pereirae and FM I, therebyallowing more comprehensive fragrance avoidanceinformation to be provided to these patients (29).We therefore consider that it would be advisable toinclude them in the baseline Spanish Group series,

as has occurred in other European countries such asGermany and UK (4, 12, 13, 30–33).

The current relevance found in our study was veryhigh, 92.8% for FM I and 66.2% for M. pereirae.Although this may seem excessive, according to DeGroot and Frosch (5, 33, 34), at least 55–65% ofthe cases with positive results have clinical rele-vance and in the latest epidemiological study of theSpanish Group, current relevance for M. pereiraewas found in 85.71% of the cases and for FM I in79.79% (19). We are convinced that very often fra-grance allergic contact dermatitis acts as an aggra-vating factor for atopic dermatitis, irritant dermatitis,and other previous cases of dermatosis, especially onthe hands, and unless personal hygiene and cleaningproducts containing fragrances are avoided, previ-ous dermatosis will not improve despite appropri-ate treatment and protective measures. De Grootand Frosch consider that a strong positive reac-tion is more likely to have clinical relevance than aweak positive reaction (5, 6). If there is high clin-ical suspicion and the results are not conclusive,many authors recommend using the standard seriesagain (35, 36).

The fragrance series has proved to be very usefulas we found positivity in 45.3% of the cases.We did not find any earlier studies that reviewedthe usefulness of applying a specific commercialfragrance series.

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The fragrance found most frequently was geran-iol, whereas Evernia prunastri absolute was rarelydetected. Other fragrances that contain geraniol,such as ylang-ylang oil, geranium oil bourbon, androse oil absolute, have also been frequently found.This differs from the European studies in whichthe most frequently detected individual fragranceswere Evernia prunastri, isoeugenol, and cinnamal,whereas geraniol was one of the less frequent (1,5, 11, 37). Some authors have suggested removinggeraniol and α-amyl-cinnamal from FM I, becauseof the small percentage of positivity (5, 21, 36, 38).We have not found any previous reports that supportour results and there seems to be no clear explana-tion. However, we believe that removing geraniolwould not be convenient in our region and probablyalso in most other areas of Spain (38, 39).

When we tested patients allergic to FM I with thefragrance series, we found positivity for some of theindividual components in 75% of the cases. Kiecet al. obtained similar results (72%) (40), althoughthey are high when compared with those found inmost studies, which vary from 40 to 60% (5, 8, 41).There may be three possible reasons for this discrep-ancy: (i) positivity to FM I may be false becauseof the irritative capacity of the mix. In our study,there is high concordance and this could be usedas a marker of the quality of our readings. (ii) Itcould be a false negative to the constituents of thefragrance series because of the fact that the concen-trations of the individual components are too low,or that absorption of FM I is increased by the emul-sifier sorbitan sesquioleate. In this case, it would benecessary to adjust the concentrations of the individ-ual fragrances used for patch testing. (iii) The otherpossibility is the existence of an allergy to a com-bination of two or more ingredients of FM I (42).

Patch testing a fragrance series in patients whoare allergic to only M. pereirae is not as worth-while as testing in patients allergic to FM I, aspositive results were obtained in only 25% of thecases. Therefore, from the practical point of view,we were obliged to recommend that patients useentirely unperfumed products in 75% of the cases,whereas in 25% we could be more specific. It isalso notable that of all the patients allergic to cin-namyl alcohol and/or cinnamal, only one was aller-gic to M. pereirae despite the fact that the formertwo were components of the latter (43); however,eugenol and isoeugenol, which were also compo-nents of M. pereirae, have been found quite fre-quently in patients who exhibited positivity to bothFMI and M. pereirae. There are probably multipleallergens present in M. pereirae and what appearsto be clear is that the constituents of the fra-grance series account for only a small percentageof them (41, 43).

Including sorbitan sesquioleate in the fragranceseries enabled us to find that 17.7% of patients withpositive patch test to both M. pereirae and FM I hada false positive, as they were in fact allergic to sorbi-tan sesquioleate. We, therefore, recommend includ-ing sorbitan sesquioleate in the fragrance series.

Using a fragrance series in patients with nofragrance marker but with a high clinical suspiciondetected positivity in only 9.3% of the cases. Thisindicates that there are good markers in our baselineseries with few false negatives.

Conclusions

The usual markers of the standard series, FM Iand M. pereirae, detected 90% of the cases, andso we believe them to be of great use. Addinghydroxyisohexyl 3-cyclohexene carboxaldehyde andFM II to the baseline series made it possible todiagnose new cases and study patients with knownfragrance allergy in more detail. We think that it isnecessary to include theses allergens in the Spanishbaseline series as in other national series and theEuropean baseline series.

Testing with a fragrance series proved to be ofgreat use as it was possible to identify more clearlywhich allergens were involved, mainly when thepositive marker in the baseline series was FM I.

The fragrance we found most frequently involvedwas geraniol, in contrast to the situation in mostEuropean countries.

We consider that identifying the fragrancesinvolved in a patient’s clinical condition enablesbetter treatment to be given, especially because ofthe change in legislation that makes it compulsoryto include a list of 26 fragrances in the labellingof cosmetics and because they became commer-cially available for patch testing (Trolab® andChemotechnique®).

References1. De Groot A C, Frosch P J. Adverse reaction to fragrances. A

clinical review. Contact Dermatitis 1997: 36: 57–86.2. Rastogi S C, Menne T, Johansen J D. The composition of fine

fragrances is changing. Contact Dermatitis 2003: 48: 130–132.3. Schnuch A, Uter W, Geier J et al. Epidemiology of contact

allergy: an estimation of morbidity employing the clinical epi-demiology and drug-utilization research (CE-DUR) approach.Contact Dermatitis 2002: 47: 32–39.

4. Thyssen J P, Menne T, Linneberg A et al. Contact sensitiza-tion to fragrances in the general population: a Koch’s approachmay reveal the burden of disease. British Journal of Dermatol-ogy 2009: 160: 29–35.

5. Wohrl S, Hemmer W, Focke M et al. The significance offragrance mix, balsam of Peru, colophony and propolis asscreening tools in the detection of fragrance allergy. BritishJournal of Dermatology 2001: 145: 268–273.

6. Trattner A, David M. Patch testing with fine fragrances: com-parison with fragrance mix, balsam of Peru and a fragranceseries. Contact Dermatitis 2004: 49: 287–289.

7. Johansen J D. Fragrance contact allergy: a clinical review.American Journal of Clinical Dermatology 2003: 4: 789–798.

Page 8: Fragrance contact allergy: a 4-year retrospective study

84 CUESTA ET AL. Contact Dermatitis 2010: 63: 77–84

8. Larsen W. Perfume dermatitis. Journal of the AmericanAcademy of Dermatology 1985: 12: 1–9.

9. Scheinman P L. Allergic contact dermatitis to fragrance: areview. American Journal of Contact Dermatitis 1996: 7:65–76.

10. Directive 2003/15/EC of the European Parliament and of theCouncil of 27 February 2003 amending Council Directiveof 27 July 1976 on the approximation of the laws of theMember States relating to cosmetic products(76/768/EEC).Official Journal of the European Union 2003: L66: 26–35.

11. Schnuch A, Wolfgang U, Johannes G et al. Sensitization to26 fragrances to be labelled according to current Europeanregulation. Results of the IVDK and review of the literature.Contact Dermatitis 2007: 57: 1–10.

12. Frosch P, Pirker C, Rastogi S et al. Patch testing with a newfragrance mix detects additional patients sensitive to perfumesand missed by the current fragrance mix. Contact Dermatitis2005: 52: 207–215.

13. Bruze M, Andersen K E, Goossens A, ESCD, EECDRG. Rec-ommendation to include fragrance mix 2 and hydroxyisohexyl3-ciclohexene carboxaldehyde (Lyral) in the European baselinepatch test series. Contact Dermatitis 2008: 58: 129–133.

14. Johansen J D, Menne T, Christophersen J et al. Changes inthe pattern of sensitization to common contact allergens inDenmark between 1985–86 and 1997–98, with a specialview to the effect of preventive strategies. British Journal ofDermatology 2000: 142: 490–495.

15. Freireich M, Trattner A, David M. Results of standard patchtests in Israeli patients with contact dermatitis. A review of943 patients between the years 1999–2000 (Abstract). 4th

International Symposium on Irritant Contact Dermatitis. 2003:Helsinki, Finland.

16. Grupo portugues de estudio de dermatitis de contacto.Estadıstica do GPEDC-2000.Boletim Informativo do GPEDC2001: 15: 52–53.

17. Garcıa-Bravo B, Conde-Salazar L, De la Cuadra J et al. Estu-dio epidemiologico de la dermatitis alergica de contacto enEspana (2001). Actas Dermosifiliogr 2004: 95: 14–24.

18. Larsen W, Nakayama H, Lindberg M et al. Fragrance contactdermatitis: a worldwide multicenter investigation (part I).American Journal of Contact Dermatitis 1996: 7: 77–83.

19. Katsarma G, Gawkrodger D J. Suspected fragrance allergyrequires extended patch testing to individual fragrance aller-gens. Contact Dermatitis 1999: 41: 193–197.

20. Johansen J D, Skov L, Volund A et al. Allergens in combina-tion have a synergistic effect on the elicitation response: a studyof fragrance-sensitized individuals. British Journal of Derma-tology 1998: 139: 264–270.

21. De Groot A C, van der Kley A M J, Bruynzeel D P et al.Frequency of false-negative reactions to the fragrance mix.Contact Dermatitis 1993: 28: 139–140.

22. Nardelli A, Carbonez A, Ottoy W et al. Frequency of andtrends in fragrance allergy over a 15-year period. ContactDermatitis 2008: 58: 134–141.

23. Malten K E, van Ketel W G, Nater J P et al. Reactions inselected patients to 22 fragrance materials. Contact Dermatitis1984: 11: 1–10.

24. Heydorn S, Menne T, Johansen J D. Fragrance allergy andhand eczema- a review. Contact Dermatitis 2003: 48: 59–66.

25. Schnuch A, Lessmann H, Geier J et al. Contact allergy tofragrances: frequencies of sensitization from 1996 to 2002.Results of the IVDK. Contact Dermatitis 2004: 50: 65–76.

26. Smart V, Alavi A, Coutts P et al. Contact allergens in personswith leg ulcers: a Canadian study in contact sensitization.

International Journal of Low Extremity Wounds 2008: 7:120–125.

27. Romaguera C, Grimalt F, Vilaplana J et al. Dermatitis de con-tacto por perfumes o esencias contenidos en diferentes prepara-ciones de uso topico. Medicina Cutanea Ibero Latino Ameri-cana 1987: 15: 367–370.

28. Guerra P, Aguilar A, Urbina F et al. Contact dermatitis togeraniol in a leg ulcer. Contact Dermatitis 1987: 16: 298–299.

29. Heras F, Dıaz-Recuero J L, Cabello M J et al. Sensitization toLyral. Actas Dermosifiliogr 2006: 97: 374–378.

30. Geier J, Brasch J, Schnuch A et al. For the Information Net-work of Departments of Dermatology (IVDK) and the GermanContact Dermatitis Research Group (DKG). Lyral has beenincluded in the patch test standard series in Germany. ContactDermatitis 2002: 46: 295–297.

31. Baxter K F, Wilkinson S M, Kirk S J. Hydroxymethylpentylcyclohexene-carboxaldehyde (Lyral) as a fragranceallergen in the UK. Contact Dermatitis 2003: 48: 117.

32. Geier J, Lessmann H, Uter W et al. Experiences with thefragrance mix II – the German perspective. Contact Dermatitis2006: 55: 12.

33. Santucci B, Cristaudo A, Cannistraci C et al. Contact Dermati-tis to fragrances. Contact Dermatitis 1987: 16: 93–95.

34. Frosch P J, Pilz B, Burrows D et al. Testing with fragrancemix- is the addition of sorbitan sesquioleate to the constituentsuseful? Contact Dermatitis 1995: 32: 266–272.

35. White J M, McFadden J P, White I R. A review of 241 sub-jects who were patch tested twice: could fragrance mix I causeactive sensitization? British Journal of Dermatology 2008: 158:518–521.

36. Johansen J D, Menne T. The fragrance mix and its constituents:a 14-year material. Contact Dermatitis 1995: 32: 18–23.

37. Buckley D A, Wakelin S H, Seed P T et al. The frequency offragrance allergy in a patch-test population over a 17-yearperiod. British Journal of Dermatology 2000: 142: 279–283.

38. Romaguera C, Grimalt F, Vilaplana J. Geraniol dermatitis.Contact Dermatitis 1986: 14: 185–186.

39. Vilaplana J, Romaguera C, Grimalt F. Contact dermatitis fromgeraniol in Bulgarian rose oil. Contact Dermatitis 1991: 24:301.

40. Kiec-Swierczynska M, Krecisz B, Swierczynska-Machura D.Contact allergy to fragrances. Medycyna Pracy 2006: 57:431–437.

41. Scheinman P. Exposing covert fragrance chemicals. AmericanJournal of Contact Dermatitis 2001: 12: 225–228.

42. Uter W, Schnuch A, Geier J et al. Association between occu-pation and contact allergy to the fragrance mix: a multifactorialanalysis of national surveillance data. Occupational and Envi-ronmental Medicine 2001: 58: 392–398.

43. Hausen B M, Simatupang T, Bryhn G et al. Identification ofnew allergenic constituents and proof of evidence of coniferylbenzoate in balsam of Peru. American Journal of ContactDermatitis 1995: 6: 199–208.

Address:Laura Cuesta MonteroDepartment of DermatologyHospital General UniversitarioPintor Baeza 1203010 AlicanteSpainTel: +34 965 937 873Fax: +34 965 937 853e-mail: [email protected]