Background: Essential oils (EOs) are widely used in cosmetics, perfumes, massage fluids, aroma therapy and natural medicine. Some EOs contain contact sensitizers. Objectives: To describe the frequency of sensitization to EOs in dermatitis patients presenting in skin clinics including concomitant reactions, to evaluate the EO patch test preparations and to identify patient groups with an increased risk of EO sensitization. Patients and methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010–2019. Results: Twelve EOs were patch tested in an aimed manner in 10 930 patients, of whom 908 (8.3%) reacted to at least 1 EO. Only 6 EOs elicited more than 1% positive patch test reactions: ylang ylang (I + II) oil (3.9%), lemongrass oil (2.6%), jasmine absolute (1.8%), sandalwood oil (1.8%), clove oil (1.6%) and neroli oil (1.1%). Concomitant reactions among EOs or to EOs and fragrances were frequent. Among EO‐positive patients, women, leg dermatitis patients, patients aged 40 years or more, masseurs and cosmeticians were over‐represented. Conclusions: Sensitization to EOs occurs, albeit infrequently in most cases. Masseurs and cosmeticians have an increased risk of sensitization to EOs.
Keywords: clinical epidemiology; contact allergy; essential oils; fragrances; patch testing
Allergic reactions to most EOs mostly cannot be traced back to single fragrance components, are often accompanied by contact allergy to other fragrances/EOs, and occur preferably in women, patients aged 40+, leg dermatitis patients, masseurs and cosmeticians.
Essential oils (EOs) are widely used in cosmetics, massage oils/fluids, perfumes, aroma therapy and natural medicine. Some EOs contain well‐known contact sensitizers.1‐4 Contact sensitization to EOs has been reported in massage therapists,5‐8 aromatherapists,9,10 their patients11 or from private use.12
Few large‐scale data on contact sensitization to EOs have been published.13,14 An analysis of data from the Information Network of Departments of Dermatology (IVDK) of the years 2000 to 2008 revealed that sensitization to EOs occurred in a substantial number of patients. When patch tested in special fragrance test series, that is, in aimed testing, ylang ylang (I + II) oil elicited positive reactions in 4.2% of the patients tested, followed by lemongrass oil (2.5%), sandalwood oil (1.8%), clove oil (1.5%), patchouli oil (1.3%) and jasmine absolute (1.2%).13 A substantial concomitant reactivity between lemongrass oil and citral, and clove oil and eugenol, respectively, was noted. Among patients sensitized to at least one EO, the share of masseurs and physiotherapists was significantly increased.13
The objective of our current study was to comprehensively analyse recent patch test results with EOs and clinical data from the IVDK database in order to examine EO patch test preparations and to better understand contact sensitization to EOs. Two absolutes (jasmine and narcissus absolute) are also included and are subsumed under "EOs" in this paper, although they are not really EOs.
In detail, we calculated percentages of positive reactions to EOs patch tested in a special series, described the reaction patterns and determined the "Reaction Indices" and "Positivity Ratios,"15‐17 evaluated concomitant reactivity to the irritant control sodium lauryl sulfate (SLS), analysed concomitant reactions between EOs and other fragrances, and compared population characteristics of patients with and without positive patch test reactions to EOs, respectively.
The IVDK (
All IVDK members are also members of the German Contact Dermatitis Research Group (DKG). Patch testing and evaluation of reactions is performed according to DKG guidelines.19,20 For the present data analysis, patch test reactions at Day 3 (D3) were considered. In a few exceptional cases, when a patch test reading was performed at D4 instead of D3, this reading was selected. Readings coded as +, ++ or +++, that is, positive reactions with erythema, infiltration, papules and/or (coalescing) vesicles were rated as positive.
Departments of dermatology participating in the IVDK use the test series recommended by the DKG for patch testing. The DKG test series no. 44 "additional fragrances and essential oils" contains 14 EOs.
Percentages of proportions of items from the patients' medical histories and of reaction frequencies in subgroups of patients are presented together with exact 95% confidence intervals (CIs). Besides non‐adjusted reaction frequencies, age‐ and sex‐standardized proportions of positive test reactions are presented. Age‐ and sex‐standardization is performed according to published approaches.21 Statistical significance of differences on a 5% level was concluded from non‐overlapping 95% CIs.
Data was managed and analysed using the statistical analysis software SAS, version 9.4 (SAS Institute, Cary, NC, USA).
In the years 2010 to 2019, altogether 117 279 patients have been patch tested in the departments of dermatology joining the IVDK. EOs of the DKG patch test series "additional fragrances and essential oils" were patch tested in 10 930 patients. Of these, 908 (8.3%) had a positive reaction to at least 1 of the 14 EOs. Patch test results are presented in detail in Table 1. Of the 908 patients reacting to at least 1 EO, 823 (90.6%) also reacted to at least 1 of the fragrance sensitivity markers of the baseline series, that is, fragrance mix I or II or balsam of Peru. Only 6 EOs yielded more than 1% positive patch test reactions. These were ylang ylang (I + II) oil (3.9% positive reactions), lemongrass oil (2.6%), jasmine absolute (1.8%), sandalwood oil (1.8%), clove oil (1.6%) and neroli oil (1.1%); for INCI names see Table 1.
1 TABLEIVDK, 2010–2019: Patch test results with essential oils. Numbers of patients tested and of patients with doubtful or irritant (?, f, ir), weak positive (+) and strong positive (++/+++) test reactions, respectively. Percentages of positive reactions (% pos.), age‐ and sex‐standardized proportions of positive reactions (std. % pos.), reaction index (RI) and positivity ratio (PR) are presented together with 95% confidence intervals [in brackets]. Vehicle was petrolatum throughout.
Essential oil INCI name Conc. Tested ?, f, ir + ++/+++ % Pos. Std. % pos. RI PR Cedarwood oil Juniperus virginiana wood oil 10% 10 820 130 80 30 1.0 [0.8 to 1.2] 1.0 [0.8 to 1.2] −0.1 [−0.2 to 0.0] 72.7 [63.4 to 80.8] Clove oil Eugenia caryophyllus leaf or stem oil 2% 7059 79 77 33 1.6 [1.3 to 1.9] 1.5 [1.2 to 1.9] 0.2 [0.0 to 0.3] 70.0 [60.5 to 78.4] Eucalyptus oil Eucalyptus globulus leaf or twig oil 2% 10 820 77 25 5 0.3 [0.2 to 0.4] 0.3 [0.2 to 0.4] −0.4 [−0.6 to −0.3] 83.3 [65.3 to 94.4] Jasmine absolute Jasminum grandiflorum or sambac flower extract 5% 10 799 210 163 32 1.8 [1.6 to 2.1] 1.6 [1.3 to 1.8] 0.0 [−0.1 to 0.1] 83.6 [77.6 to 88.5] Laurel leaf essential oil Laurus nobilis leaf oil 2% 10 824 102 60 8 0.6 [0.5 to 0.8] 0.6 [0.4 to 0.7] −0.2 [−0.3 to −0.1] 88.2 [78.1 to 94.8] Lemon oil Citrus Limon peel oil 2% 10 830 104 37 7 0.4 [0.3 to 0.5] 0.4 [0.2 to 0.5] −0.4 [−0.6 to −0.3] 84.1 [69.9 to 93.4] Lemongrass oil Cymbopogon flexousos or citratus leaf oil 2% 10 826 221 193 92 2.6 [2.3 to 3.0] 2.4 [2.1 to 2.7] 0.1 [0.0 to 0.2] 67.7 [62.0 to 73.1] Narcissus absolute Narcissus flower extract 2% 8930 131 79 9 1.0 [0.8 to 1.2] 1.1 [0.9 to 1.4] −0.2 [−0.3 to −0.1] 89.8 [81.5 to 95.2] Narcissus poeticus absolute Narcissus poeticus flower extract 2% 1879 16 10 1 0.6 [0.3 to 1.0] 0.6 [0.2 to 0.9] −0.2 [−0.6 to 0.2] 90.9 [58.7 to 99.8] Neroli oil Citrus aurantium Amara flower oil 2% 7007 55 57 23 1.1 [0.9 to 1.4] 1.0 [0.7 to 1.2] 0.2 [0.0 to 0.4] 71.3 [60.0 to 80.8] Neroli oil Citrus aurantium Amara flower oil 5% 3876 63 32 10 1.1 [0.8 to 1.5] 0.9 [0.6 to 1.2] −0.2 [−0.4 to 0.0] 76.2 [60.5 to 87.9] Orange oil Citrus aurantium Amara peel oil 2% 10 832 95 16 1 0.2 [0.1 to 0.3] 0.2 [0.1 to 0.2] −0.7 [−0.8 to −0.6] 94.1 [71.3 to 99.9] Patchouli oil Pogostemon cablin leaf oil 10% 8954 103 58 27 0.9 [0.8 to 1.2] 0.9 [0.7 to 1.1] −0.1 [−0.2 to 0.0] 68.2 [57.2 to 77.9] Patchouli oil (Chemotechnique) Pogostemon cablin leaf oil 10% 1874 25 11 3 0.7 [0.4 to 1.3] 0.7 [0.3 to 1.0] −0.3 [−0.6 to 0.0] 78.6 [49.2 to 95.3] Peppermint oil Mentha piperita oil 2% 10 824 131 48 12 0.6 [0.4 to 0.7] 0.5 [0.3 to 0.6] −0.4 [−0.5 to −0.2] 80.0 [67.7 to 89.2] Sandalwood oil Santalum album oil 10% 10 802 168 161 31 1.8 [1.5 to 2.0] 1.7 [1.5 to 2.0] 0.1 [−0.0 to 0.2] 83.9 [77.9 to 88.8] Ylang ylang (I + II) oil Cananga odorata flower oil 10% 10 797 230 258 168 3.9 [3.6 to 4.3] 3.7 [3.3 to 4.1] 0.3 [0.2 to 0.4] 60.6 [55.7 to 65.2]
1 Note: Most EO patch test preparations were purchased from Almirall Hermal, Reinbek, Germany, until 2013, and from SmartPractice Europe, Greven, Germany, from 2014 on (exceptions see below).
- 2 Abbreviation: Conc., test concentration.
- 3 a Reaction indices (RIs) and positivity ratios (PRs) were calculated according to the published formulae.15‐17 The proportion of doubtful or irritant patch test reactions, in relation to allergic positive reactions, varies between allergen preparations. The reaction index (RI) is defined as the quotient RI = (a − [q + i])/(a + [q + i]), where the number of positive, allergic reactions is "a," of doubtful reactions is "q," and of irritant reactions is "i." Thus, the RI ranges from +1, when all observed non‐negative test reactions are positive (allergic) to −1, when only doubtful and/or irritant test reactions occur.15 The higher the RI, the better is the diagnostic discriminatory power of the patch test preparation. The positivity ratio (PR) is an additional measure of the diagnostic quality of a patch test preparation. It is defined as the percentage of weak positive (+) reactions among the total of positive reactions (i.e., +, ++ and +++).16 Most of the routinely tested baseline series allergen preparations have a positive RI (0.2–0.5) and a PR of <75%, indicating a good diagnostic discriminatory power.22
- 4 b Clove oil was only available until March 2016.
- 5 c Narcissus absolute from SmartPractice Europe was replaced by Narcissus poeticus absolute from Chemotechnique from April 2016 to December 2017.
- 6 d Neroli oil 2% pet. was replaced by neroli oil 5% pet. from April 2016 on.
- 7 e Patchouli oil 10% pet. from SmartPractice Europe was replaced by Patchouli oil 10% pet. from Chemotechnique from April 2016 to December 2017.
Most of the EO test preparations elicited more doubtful and irritant reactions than clear‐cut positive reactions, resulting in negative reaction indices. The only test preparations with a positive, that is, desirable, reaction index (RI) were again ylang ylang (I + II) oil (RI = 0.3), neroli oil 2% pet. (0.2), clove oil (0.2), lemongrass oil (0.1) and sandalwood oil (0.1). Raising the test concentration of neroli oil from 2% pet. to 5% pet. (in April 2016) resulted in a significant increase in doubtful and irritant reactions from 55/7007 (0.8%) to 63/3876 (1.6%), while the percentage of positive reactions including the distribution of weak versus strong positive reactions (+ vs. ++ and +++) remained stable. This caused a decline of the reaction index from +0.2 to −0.2, while the positivity ratio did not change significantly (see Table 1). The vast majority of the EO patch test preparations had a positivity ratio of more than 80%, which is not satisfying. Exceptions were ylang ylang (I + II) oil (positivity ratio [PR] = 60.6%), lemongrass oil (67.7%), clove oil (70.0%), patchouli oil (68.2% and 78.6%), neroli oil (71.3% and 76.2%) and cedarwood oil (72.7%).
By patch testing with SLS 0.25% in water (aq.), it can be determined if the patient's skin is irritable at the time and in the region of the allergen patch test. According to DKG studies, doubtful reactions are more likely irritant than allergic if the SLS test is "positive" (i.e., if an irritant reaction occurs),.22,23 Therefore, it is of interest if the reaction pattern to a particular allergen preparation differs between those with a positive SLS reaction and those with a negative SLS patch test. SLS 0.25% aq. was patch tested in 10 376 of the 10 930 patients (95% of the study group). Of these, 3155 (30.4%) had an irritant reaction, while 7221 (69.6%) remained negative. Frequencies of (
According to recent textbooks,1,2 11 of the 14 EOs investigated in our study contain fragrance components which are also available as standardized patch test preparations. In Table S2, the ranges of the contents of these fragrances in those 11 EOs are listed. Ingredients of cedarwood oil and sandalwood oil1,2 are not commercially available as standardized patch test preparations and have hence not been tested.
In Table S3, we give a general overview of positive test reactions to these fragrance allergens. Comparing percentages of positive reactions to the fragrances, it shows that there were significantly more positive reactions to all fragrance materials (except for D‐limonene) among patients sensitized to at least one EO. The most impressive differences were noted with citral (22.4% vs. 0.8%), geraniol (11.5% vs. 0.5%), eugenol (9.1% vs. 0.5%), isoeugenol (23.1% vs. 1.5%), cinnamyl alcohol (9.3% vs. 0.7%), farnesol (7.0% vs. 1.1%) and menthol (1.6% vs. 0.1%).
In a next step, we analysed reaction frequencies to the specific fragrance materials contained in the single EOs (as listed in Table S2). Results are presented in Table 2. Frequencies of sensitization to all fragrance components contained in the respective EO were higher among those reacting positively to the corresponding EO. We excluded d‐limonene from this data analysis because there was only one positive patch test reaction to it among 3508 patients tested (see Table S3), and this reaction was seen in a patient who did not react to any of the EOs tested.
2 TABLEIVDK, 2010–2019, patients tested with essential oils: Patch test results with fragrance materials contained in the respective essential oil and available as standardized patch test preparations. For each essential oil, percentages of positive reactions (% pos.) in three subgroups of patients are presented together with 95% confidence intervals [in brackets]: Patients with positive reactions, patients with doubtful or irritant reactions, and patients with negative reactions to the respective essential oils. The total sizes of these subgroups of patients are noted; however, not every fragrance was tested in all of these patients. Vehicle was petrolatum throughout.
Patients tested with clove oil 2% pet. Pos (n = 110) ?, f, ir (n = 79) Neg (n = 6870) Eugenol 1% 50.0 [38.7 – 61.3] 4.3 [0.5 – 14.8] 0.6 [0.4 – 0.9] Patients tested with eucalyptus oil 2% pet. Pos (n = 30) ?, f, ir (n = 77) Neg (n = 10 713) Citronellol 1% 16.7 [3.6 – 41.4] 0.0 [0.0 – 9.3] 0.6 [0.4 – 0.8] Patients tested with jasmine absolute 5% pet. Pos (n = 195) ?, f, ir (n = 210) Neg (n = 10 394) Benzyl alcohol 1% 2.7 [0.9 – 6.1] 0.5 [0.0 – 2.7] 0.1 [0.1 – 0.2] Benzyl benzoate 1% 0.6 [0.0 – 3.5] 0.5 [0.0 – 2.9] 0.1 [0.0 – 0.1] Eugenol 1% 13.3 [7.6 – 20.9] 4.2 [1.4 – 9.5] 1.0 [0.7 – 1.3] Linalool (stabilized) 10% 1.5 [0.2 – 5.2] 0.0 [0.0 – 2.4] 0.3 [0.2 – 0.5] Patients tested with laurel leaf essential oil 2% pet. Pos (n = 68) ?, f, ir (n = 102) Neg (n = 10 654) Eugenol 1% 15.8 [6.0 – 31.3] 5.6 [1.2 – 15.4] 1.2 [0.9 – 1.5] Linalool (stabilized) 10% 14.3 [5.9 – 27.2] 4.2 [0.9 – 11.7] 0.2 [0.1 – 0.3] Patients tested with lemon oil 2% pet. Pos (n = 44) ?, f, ir (n = 104) Neg (n = 10 682) Citral 2% 75.0 [53.3 – 90.2] 12.2 [4.1 – 26.2] 2.4 [2.0 – 2.8] Patients tested with lemongrass oil 2% pet. Pos (n = 285) ?, f, ir (n = 221) Neg (n = 10 320) Citral 2% 58.4 [50.5 – 66.0] 12.8 [7.4 – 20.3] 0.7 [0.5 – 1.0] Geraniol 1% 29.2 [22.4 – 36.7] 4.1 [1.3 – 3.9] 0.6 [0.4 – 0.9] Linalool (stabilized) 10% 5.0 [2.4 – 9.0] 1.1 [0.1 – 3.9] 0.2 [0.1 – 0.3] Patients tested with narcissus absolute 2% pet. or Narcissus poeticus absolute 2% pet. Pos (n = 99) ?, f, ir (n = 147) Neg (n = 10 563) Benzyl alcohol 1% 0.0 [0.0 – 4.7] 0.0 [0.0 – 2.5] 0.2 [0.1 – 0.3] Benzyl benzoate 1% 1.6 [0.0 – 8.8] 0.7 [0.0 – 4.0] 0.1 [0.0 – 0.1] Cinnamyl alcohol 1% 10.6 [3.5 – 23.1] 1.4 [0.0 – 7.6] 1.4 [1.1 – 1.8] Coumarin 5% 0.0 [0.0 – 7.9] 1.5 [0.0 – 8.3] 0.4 [0.2 – 0.6] Patients tested with neroli oil 2% pet. or 5% pet. Pos (n = 122) ?, f, ir (n = 118) Neg (n = 10 643) Farnesol 5% 11.8 [5.2 – 21.9] 8.2 [2.3 – 19.6] 1.4 [1.1 – 1.8] Geraniol 1% 32.8 [21.3 – 46.0] 15.4 [6.9 – 28.1] 1.1 [0.8 – 1.4] Linalool (stabilized) 10% 17.7 [10.0 – 27.9] 1.2 [0.0 – 6.5] 0.1 [0.1 – 0.2] Patients tested with peppermint oil 2% pet. Pos (n = 60) ?, f, ir (n = 131) Neg (n = 10 633) Menthol 1% 16.7 [8.3 – 28.5] 0.0 [0.0 – 2.3] 0.1 [0.1 – 0.2] Patients tested with ylang ylang (I + II) oil 10% pet. Pos (n = 426) ?, f, ir (n = 230) Neg (n = 10 141) Benzyl benzoate 1% 0.6 [0.1 – 2.1] 0.0 [0.0 – 1.9] 0.1 [0.0 – 0.1] Benzyl salicylate 1% 0.9 [0.2 – 2.6] 0.0 [0.0 – 1.8] 0.1 [0.1 – 0.2] Eugenol 1% 12.9 [9.1 – 17.6] 0.9 [0.0 – 4.9] 0.7 [0.5 – 1.0] Farnesol 5% 11.0 [7.4 – 15.6] 1.9 [0.2 – 6.7] 1.2 [0.9 – 1.5] Geraniol 1% 14.5 [10.5 – 19.4] 2.7 [0.6 – 7.8] 0.8 [0.6 – 1.1] Isoeugenol 1% 33.6 [27.9 – 39.7] 7.3 [3.2 – 14.0] 1.9 [1.5 – 2.3] Linalool (stabilized) 10% 5.1 [2.9 – 8.2] 0.0 [0.0 – 2.2] 0.1 [0.1 – 0.2]
Concomitant reactivity to EOs and fragrances also may indicate co‐sensitization acquired from different sources, including other EOs. Therefore, we analysed how many patients reacted to how many of the EOs tested. Of the 908 patients reacting to EOs, 493 (54.3%; 95% CI 51.0–57.6) reacted to 1 EO, 183 (20.2%; 95% CI 17.6–22.9) to 2 EOs, 112 (12.3%, 95% CI 10.3–14.7) to 3 EOs and 120 (13.2%; 95% CI 11.1–15.6) to more than 3 EOs.
In the next step, we analysed separately for each EO, how many patients reacted to this oil only, but not to any other of the EOs tested. Results are shown in Table 3. The highest percentages of "isolated" positive reactions to the respective EO were noted for jasmine absolute (51.3%), narcissus (poeticus) absolute (40.4%) and sandalwood oil (37.0%). With all the other EOs, "isolated" reactions were seen in 30% of the positive reactions or less. In other words: Apart from the three EOs mentioned, the proportions of patients reacting to more than the respective EO ranged from 69.7% (ylang‐ylang [I + II] oil) to 92.6% (neroli oil).
3 TABLEIVDK, 2010–2019, patients tested with essential oils: Numbers of patients with positive reactions to the respective essential oil, and numbers and percentages [with 95% confidence intervals in brackets] of patients reacting to the respective essential oil, but not to any of the other essential oils listed ("isolated" positive reactions).
Essential oil % Positive "isolated"/total Cedarwood oil 110 16 14.5 [8.5–22.5] Clove oil 110 20 18.2 [11.5–26.7] Eucalyptus oil 30 6 20.0 [7.7–38.6] Jasmine absolute 195 100 51.3 [44.0–58.5] Laurel leaf essential oil 68 16 23.5 [14.1–35.4] Lemon oil 44 4 9.1 [2.5–21.7] Lemongrass oil 285 53 18.6 [14.3–23.6] Narcissus absolute or Narcissus poeticus absolute 99 40 40.4 [30.7–50.7] Neroli oil (2% or 5% pet.) 122 9 7.4 [3.4–13.5] Orange oil 17 5 29.4 [10.3–56.0] Patchouli oil (SmartPractice or Chemotechnique) 99 13 13.1 [7.2–21.4] Peppermint oil 60 11 18.3 [9.5–30.4] Sandalwood oil 192 71 37.0 [30.1–44.2] Ylang ylang (I + II) oil 426 129 30.3 [26.0–34.9]
The great overlap of sensitization to different EOs, and to EOs and fragrances, that is, the large proportion of patients with multiple fragrance sensitizations, makes it almost impossible to identify groups of patients at risk of sensitization to one particular EO. Therefore we limited analyses of patient characteristics to two subgroups of patients, that is, those with a positive reaction to at least one of the EOs (n = 908), and those who did not react to any of the EOs (n = 10 022). Results are presented in Table 4. Among patients sensitized to at least one EO, there were significantly more women (76.6 vs. 70.1%), more patients aged 40 years or more (73.9 vs. 68.5%) and more patients with leg dermatitis (6.1 vs. 3.1%), while the other parameters of the MOAHLFA index did not differ significantly. Axillae were affected in 1.4% [95% CI 0.8–2.4] of the EO positive patients, and in 0.8% [95% CI 0.7–1.0] of the patients not reacting positively to any EO (no significant difference). Concerning current occupations, proportions of masseurs and physiotherapists (who have not been coded separately during most of the study period) and cosmeticians were almost three times as high among those reacting to at least one EO compared to those who did not (8.9 vs. 3.0% and 1.7 vs. 0.6%, respectively). Patients sensitized to at least one EO, compared to those negative to the EOs, were significantly more often tested because of suspected intolerance of cosmetics (57.5 vs. 48.2%), perfume, deodorant, etc. (16.3 vs. 11.1%) and topical medications (14.5 vs. 10.6%). Conversely, soap, shower gel, shampoos, etc. were significantly less often suspected as allergen sources (11.6 vs. 15.1%).
4 TABLESelected population characteristics of patients reacting to at least one essential oil (n = 908), and those who did not (n = 10 022). Proportions are presented as percentages, together with the corresponding 95% confidence intervals [in brackets]. Items with significantly higher values in the positive group are highlighted in bold.
Patients with at least one positive reaction to an essential oil ( Patients not reacting positively to any essential oil ( MOAHLFA‐index Males 24.4 [21.7–27.4] 29.9 [29.0–30.8] Occupational dermatitis 32.3 [29.2–35.4] 30.4 [29.5–31.3] Atopic dermatitis (past or present) 34.7 [31.6–37.9] 34.3 [33.4–35.2] Hand dermatitis 42.2 [38.9–45.5] 45.5 [44.6–46.5] Leg dermatitis 6.1 [4.6–7.8] 3.1 [2.8–3.5] Face dermatitis 21.1 [18.5–23.9] 22.0 [21.2–22.8] Age ≥ 40 years 73.9 [70.9–76.7] 68.5 [67.6–69.4] Current occupations Jobs with undetermined exposure (e.g., pensioners) 26.7 [23.8–29.7] 21.9 [21.1–22.7] Masseurs/physiotherapists 8.9 [7.1–11.0] 3.0 [2.7–3.4] Geriatric nurses 4.5 [3.3–6.1] 5.4 [4.9–5.8] Nurses 3.9 [2.7–5.3] 4.5 [4.1–4.9] Cosmeticians 1.7 [0.9–2.7] 0.6 [0.5–0.8] Suspected cause of dermatitis Cosmetics 57.5 [54.2–60.7] 48.2 [47.3–49.2] Perfume, deodorant, etc. 16.3 [14.0–18.9] 11.1 [10.5–11.7] Gloves 15.6 [13.3–18.2] 21.1 [20.3–21.9] Topical medications 14.5 [12.3–17.0] 10.6 [10.0–11.2] Disinfectants 14.2 [12.0–16.6] 16.4 [15.7–17.1] Soap, shower gel, shampoo 11.6 [9.6–13.8] 15.1 [14.4–15.8]
The frequency and pattern of contact sensitization to EOs (Table 1) remained largely unchanged, compared to our earlier IVDK data analysis.13 When tested as part of a special EO test series, ylang ylang (I + II) oil elicited positive patch test reactions most frequently. The crude reaction frequency was 3.9% in the years 2010 to 2019, compared to 4.2% in the years 2000 to 2008. Lemongrass oil ranked second with 2.6% (2000–2008: 2.5%), followed by jasmine absolute (1.8%; 2000–2008: 1.2%), sandalwood oil (1.8%; 2000–2008: 1.8%) and clove oil (1.6%; 2000–2008: 1.5%). All other EOs elicited positive reactions in 1.1% or less of the patients tested. When interpreting this data, it has to be considered that it is based on aimed patch testing in dermatitis patients with suspected contact allergy to cosmetics, body care products or perfumes, and not on patch testing of consecutive, that is, unselectively tested, contact dermatitis patients.
The lowest frequencies of sensitization were noted to eucalyptus oil, laurel leaf oil, lemon oil, orange oil and peppermint oil. These have in common that they are also found in food and/or are used as food aromas. It may thus be hypothesized that (early in life) oral exposure leads to tolerance induction. Similar mechanisms are discussed to explain the low rate of sensitization to sesquiterpene lactones in countries where chrysanthemum teas are common.24
From the patch test data presented in Table 1, it can be concluded that the patch test preparations ylang ylang (I + II) oil 10% pet., lemongrass oil 2% pet., sandalwood oil 10% pet., clove oil 2% pet. and neroli oil 2% pet. can be regarded as useful patch test preparations. Cedarwood oil 10% pet. and patchouli oil 10% pet. are acceptable, despite their negative reaction indices. Based on reaction characteristics summarized in the reaction index and the positivity ratio, orange oil 2% pet., eucalyptus oil 2% pet., lemon oil 2% pet., peppermint oil 2% pet. and both Narcissus absolute test preparations (2% pet.) appear to be unfavourable test preparations. Verification tests such as a repeated open application test (ROAT) and reliable information on clinical relevance (see also discussion below) are needed. Corresponding studies should be performed to determine whether the patch test concentrations need to be adapted (increased or decreased).
The observation of positive test reactions to EOs being far less influenced by skin irritability (as shown by the SLS patch test; Table S1) than doubtful test reactions suggests the interpretation that the majority of the positive patch test reactions indicates true contact sensitization. Hence, despite the suboptimal test preparation characteristics of most EO test preparations as expressed by RI and PR, it can be assumed that percentages of positive test reactions largely reflect sensitization frequencies.
From the data presented in Table 2, it is evident that there is a correlation between positive reactions to EOs and to important fragrance constituents in these EOs (see Table S2). For instance, 50 % of the patients sensitized to clove oil also reacted to eugenol. Similar findings were made with lemongrass oil and citral, confirming previous findings.13 Second, it can be concluded that not every allergic reaction to an EO can be explained by sensitization to one or more of the patch tested fragrances. This is not unexpected because in many cases, the major constituents of the tested EOs are not available as patch test preparations. Third, we see unexpectedly high percentages of positive reactions to fragrances which are only contained in a small proportion by weight in the respective EO. An additional analysis revealed that patients reacting to lemon oil also frequently reacted to eugenol and isoeugenol which are not contained at all in lemon oil (data not shown in detail). The latter finding points to a general issue. According to Table S3, fragrances which elicited positive patch test reactions most frequently among EO positive patients were isoeugenol (23.1%), citral (22.4%), geraniol (11.5%), cinnamyl alcohol (9.3%), eugenol (9.1%) and farnesol (7.0%). However, reactions to these fragrances did not only occur in patients sensitized to EOs containing these fragrances. Hence, concomitant reactivity to EOs and fragrances also may indicate co‐sensitization acquired from different sources, including other EOs or synthetic fragrance compounds.
EOs are complex mixtures, containing known fragrance allergens, compounds which are not associated with a known sensitization hazard, and compounds with unknown allergenic potential. Unfortunately, only a very limited set of fragrances which are contained in EOs is commercially available as standardized patch test preparations. Hence, our analysis of concomitant reactions to EOs and their single components can only give limited information on the allergens responsible for positive reactions to EOs.
However, some of the results presented in Table 2 are plausible in this concern. We found that 50.0% of the patients reacting to clove oil also reacted to eugenol, which is a major component of clove oil (Table S2). While clove oil is patch tested at 2% pet. (containing 1.44–1.8% eugenol), the routinely used test concentration of eugenol is only 1% pet. Hence, it is no surprise that there is no higher concordance of positive test reactions. Patients with a low degree of sensitization, that is, with a higher elicitation threshold, may react to the higher eugenol concentration in the clove oil patch test, but not to the lower one in eugenol 1% pet.25
Of those patients reacting to lemongrass oil, 58.4% also reacted to citral, and 29.2% to geraniol (Table 2). Lemongrass oil contains citral and geraniol (Table S2),1,2 and citral is a mixture of the stereoisomers geranial and neral.1,2,26 Geraniol acts as a prehapten and prohapten and is oxidized to geranial and neral.26 These relationships explain the high degree of concomitant reactivity to lemongrass oil, citral and geraniol. A recent Swedish study showed that patch testing with oxidized geraniol may pick up more sensitized patients than patch testing with pure geraniol.27 However, for the time being, no patch test preparation with oxidized geraniol is commercially available.
In other cases, we noted only few positive reactions to fragrance compounds among patients reacting to EOs containing these fragrances (Table 2). This lack of concomitant reactivity may have various reasons.
- The fragrance concerned is not an important sensitizer. This, for instance, is true for benzyl alcohol, benzyl benzoate or benzyl salicylate. In all corresponding IVDK data analyses since 2003, sensitization frequencies to these fragrances were 0.3% or less. 28‐30 Similar results were obtained with limonene and linalool. 28‐30 However, it is known that not limonene and linalool, but their oxidation products, in particular their hydroperoxides, are relevant contact sensitizers. 31‐35 In several European studies, it has been shown that limonene hydroperoxides (lim‐OOH) 0.3% pet. and linalool hydroperoxides (lin‐OOH) 1.0% pet. elicited positive reactions quite frequently. 35‐41 However, clinical relevance of these reactions remains a matter of some speculation, because consumers' exposure to hydroperoxides of limonene and/or linalool has not been sufficiently demonstrated yet. 42,43 On the other hand, ROAT studies with lim‐OOH involving a dose per area of 0.33 μg/cm
2 have shown that some patients patch test positive to lim‐OOH 0.3% pet. will be elicited upon open, repeated application, 44 similarly with lin‐OOHs. 45 However, the test preparations we have used in the study period contain the non‐oxidized forms of the molecules, and hence cannot detect sensitization to limonene or linalool hydroperoxides. - Concentration of the fragrance compound in the EO is too low to induce sensitization or to elicit a patch test reaction.
- The fragrance patch test preparation is not sufficiently suitable to detect contact sensitization. This may be the case with eugenol 1% pet. or geraniol 1% pet. 25
Generally, it has to be emphasized that concomitant reactions to an EO and its single fragrance compounds do not unravel the primary source of sensitization. The patient may have acquired sensitization to a fragrance material by contact with an EO, and subsequently reacts to the fragrance compound during patch testing. Or she or he has acquired sensitization to a fragrance in another context, and shows a positive patch test reaction to an EO containing this fragrance, although exposure to this EO did not cause sensitization—however, elicitation not being unlikely, given sufficient contact with the EO.
Data presented in Table S3 show increased frequencies of sensitization to fragrances among patients sensitized to EOs. A more extended data analysis (not shown in detail) revealed that sensitization to several of these fragrances did not correspond to the ingredients of the EOs these patients reacted to. This means that, in these cases, we have "independent" sensitizations to the fragrance compound(s) and the EO(s). Such a constellation may arise from co‐exposure to both in one product or in several products used by the patient at the same time, or in metachronous exposure in the course of years. The same applies to cases of sensitization to two or more EOs which do not share common ingredients.
Sensitization to more than one EO is a frequent event. Hence, we saw no sense in trying to analyse particular patient characteristics to identify risk factors for sensitization to one particular EO. Instead, we analysed population characteristics of patients with sensitization to any of the EOs tested (n = 908) and compared to patients without EO sensitization (n = 10 022). Results presented in Table 4 reflected the known pattern of patients with fragrance allergy28,46‐49 and confirmed the plausibility of our data. Predominance of women, aged patients, and leg dermatitis patients among those sensitized to fragrances is a constellation which was noted several times (with some slight variation) during the last decades.50 Increased proportions of masseurs and physiotherapists as well as cosmeticians are plausible because these occupations are more frequently and more intensely exposed to scented products and/or products containing EOs, and thus are at higher risk of sensitization. Corresponding case reports are cited in the introduction. Remarkably, geriatric nurses, whom we have found to be frequently occupationally sensitized to fragrances,51 were not overrepresented among the EO positive patients. However, we did not differentiate occupational from non‐occupational cases in this analysis. Rinse‐off products such as shower gel, liquid soap or shampoo are apparently not associated with a particular risk of sensitization to EOs in the consumer, as this suspected allergen source was not overrepresented among those reacting to an EO in patch testing.
As a limitation, our analysis of clinical routine data could not address clinical relevance of positive reactions, because contrary to all other cosmetic ingredients, labelling of fragrances is still limited to 26 fragrances (Annex III of the Cosmetics Regulation, by the 7th amendment [2003/15/EC]), and these 26 do not include EOs (only Evernia prunastri and E. furfuracea, respectively, as natural extracts/mixtures). Moreover, while in some types of products, like massage oils or aroma liquids, the EO(s) may be indicated, there is no standard, including terminology, for this.
Sensitization to most of the tested EOs (or their ingredients) is infrequent. Fragrance labelling of cosmetics should be extended to cover also EOs, at least to those mentioned in Annex I of the SSCS Opinion on Fragrance allergens in cosmetic products of 26–27 June 2012 (SCCS/1459/11).
Composition of EOs may vary in a certain range. It is unknown whether the patch tested EOs indeed represent those used by consumers. Hence, a study correlating patch test results and use test with consumer products would be worthwhile.
Second, for the time being, we cannot identify causative allergens in EO sensitization in most cases because by far not every EO component is commercially available as standardized patch test preparation. It would be highly desirable to develop such test preparations at least for those constituents with a non‐negligible sensitization hazard.
The IVDK, maintained by the IVDK e.V., of which Johannes Geier and Steffen Schubert are employees, is sponsored by the chemical, cosmetic and fragrance industry (associations) as well as by public funds. For details, see
Johannes Geier: Conceptualization; investigation; methodology; validation; formal analysis; project administration; data curation; supervision; writing—original draft. Steffen Schubert: Investigation; validation; writing—review and editing; data curation; formal analysis. Kristian Reich: writing—review and editing; validation. Christoph Skudlik: Writing—review and editing; validation; investigation. Barbara Ballmer‐Weber: Investigation; validation; writing—review and editing. Randolf Brehler: Investigation; validation; writing—review and editing. Elke Weisshaar: Investigation; validation; writing—review and editing. Wolfgang Uter: Conceptualization; investigation; writing—review and editing; formal analysis; supervision.
Data are not available due to European and German data protection regulations.
GRAPH: Table S1 IVDK, 2010–2019: Percentages of patients with doubtful or irritant reactions (% ?, f, ir) and of patients with positive reactions (% pos) to essential oils among patients with and without irritant reaction to sodium lauryl sulphate (SLS) 0.25% in water (SLS pos and SLS neg), respectively. Percentages are presented together with 95% confidence intervals [in brackets]. Vehicle of the allergen test preparations was petrolatum throughout. Significant differences are highlighted in bold.Table S2. Ranges of contents of fragrance materials available as standardized patch test preparations in the tested essential oils, according to [
By Johannes Geier; Steffen Schubert; Kristian Reich; Christoph Skudlik; Barbara Ballmer‐Weber; Randolf Brehler; Elke Weisshaar and Wolfgang Uter
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