Fragrance Contact Allergy - A Review Focusing on Patch Testing.

Fragrance materials are widely used in various types of products in daily life and many of them can be contact sensitizers. Contact allergy to fragrances has been reported to be common worldwide. Unlike other groups of contact allergens such as metals and preservatives, fragrance materials in consumer products can be present as single fragrance chemicals or in the form of mixtures known as natural complex substances. Due to the complexity of the fragrance materials and the high number of fragrance substances known to cause contact sensitization, selecting suitable materials for patch testing is challenging. Emerging fragrance markers have been additionally introduced in different baseline series for screening to enhance the rate of fragrance contact allergy detection. Moreover, there have been continual updates on basic knowledge, clinical perspectives, sources of exposure, and regulations on the use of fragrance materials. Avoiding pitfalls while performing patch testing with fragrance test materials is also crucial and should not be overlooked. Therefore, this review aims to update knowledge to provide a high-quality holistic approach to fragrance contact allergy diagnosis and management.

Contact Allergy to Allergens in the Swedish Baseline Series Overrepresented in Diabetes Patients with Skin Reactions to Medical Devices - A Retrospective Study from Southern Sweden.

Allergic contact dermatitis is reported among individuals using continuous glucose monitoring systems and insulin pumps. The aim of this study was to describe contact allergy patterns for allergens in the Swedish baseline series and medical device-related allergens among users. Contact allergy to baseline series allergens and isobornyl acrylate was compared between diabetes patients and dermatitis patients patch-tested at the Department of Occupational and Environmental Dermatology during 2017 to 2020. Fifty- four diabetes patients and 2,567 dermatitis patients were included. The prevalence of contact allergy to fragrance mix II and sesquiterpene lactone mix was significantly higher in diabetes patients compared with dermatitis patients. Of the diabetes patients 13.0% and of the dermatitis patients 0.5% tested positive to sesquiterpene lactone mix (p < 0.001). Of the diabetes patients 7.4% and of the dermatitis patients 2.3% tested positive to fragrance mix II (p = 0.041). Of the diabetes patients 70.4% tested positive to medical device-related allergens. Of the diabetes patients 63.0% and of the dermatitis patients 0.2% were allergic to isobornyl acrylate (p < 0.001). In conclusion, not only medical device-related contact allergies, but also contact allergy to baseline series allergens (fragrance mix II and sesquiterpene lactone mix), is overrepresented in diabetes patients who use medical devices.

Comparison of Perceptions of Skin Condition, Product Use and Allergen Reactivity Between People with Psoriasis and Controls in the European Dermato-Epidemiology Network (EDEN) Fragrance Study.

Psoriasis, a chronic inflammatory skin disease, goes beyond visible symptoms and affects the general well-being of patients. The aim of this study is to understand how patients with psoriasis perceive their skin characteristics and reactivity to allergens. The study population includes 11,283 participants within the European Dermato-Epidemiology Network (EDEN) Fragrance study, covering several European regions. The study compared perceptions of skin dryness, sensitivity, product avoidance and reactivity to allergens between patients with psoriasis and controls, evaluating the potential influence of psoriasis severity. The results showed that subjects with psoriasis reported dry skin (71.1%) and sensitive skin (49.4%) more often than did controls (51.6% and 38.5%, respectively). Psoriasis patients were more likely to avoid specific products. Interestingly, there were no significant differences in patch-test results between the 2 groups and the severity of psoriasis did not have a consistent impact on these perceptions. In conclusion, people with psoriasis tend to perceive their skin as drier and more sensitive. Notably, the severity of psoriasis did not consistently influence these perceptions and objective reactivity to allergens did not align with subjective perception. Understanding these aspects is crucial for tailoring treatments to improve the well-being of patients with psoriasis, which warrants further research to explore subjective perceptions of skin well-being in patients with psoriasis.

Patterns of simultaneous contact allergies in patients with contact sensitization to oxidised linalool and oxidised limonene.

BACKGROUND: Contact allergy rates of linalool and limonene hydroperoxides (HPs) have increased. OBJECTIVES: To demonstrate the patterns of simultaneous positive patch test (PT) reactions and prevalences of multiple contact allergies (MCAs) in patients with contact allergy to linalool and/or limonene HPs. METHODS: A retrospective analysis of consecutive dermatitis patients in 2015-2020 was performed. RESULTS: Of all 4192 patients, 1851 had at least one positive PT reaction. Of these, 410 (22.2%) had MCAs, significantly related to a higher age (p-value = 0.003). Patients with an exclusively positive reaction to linalool HPs but not limonene HPs were shown to have MCAs (p-value <0.001, odds ratio (95% confidence interval) = 4.15 (3.01-5.73)). Patients with simultaneous contact allergies to both linalool and limonene HPs had contact allergies to many other screening and fragrance allergens. CONCLUSIONS: Simultaneous positive PT reactions to allergens in baseline series and fragrances are common in patients with the HPs contact allergy, especially linalool HPs. The pattern of simultaneous PT reactions principally suggested the co-sensitization of the cosmetic allergens.

Contact allergy to oxidised geraniol may be over-represented in individuals with photocontact allergy to ketoprofen.

BACKGROUND: Simultaneous overrepresentations of contact allergies and photocontact allergies are common in individuals with photocontact allergy to ketoprofen. AIMS: To investigate whether contact allergy to oxidised (ox.) geraniol, geraniol, geranial, neral and citral is overrepresented in individuals with photocontact allergy to ketoprofen. METHODS: The contact allergy rates to ox. geraniol, geraniol, geranial, neral and citral in routinely patch tested dermatitis patients were compared with the corresponding rates in individuals with photocontact allergy to ketoprofen. RESULTS: Allergic patch test reactions were noted to ox. geraniol 11% (n = 39, 5.8%), ox. geraniol 6% (n = 12, 1.8%), geraniol 6% (n = 2, 0.3%), geranial (n = 18, 2.7%), neral (n = 7, 1.0%) and citral (n = 15, 2.2%). In those four patients who were diagnosed with photocontact allergy to ketoprofen during the test period, a significant overrepresentation (p = 0.020) of simultaneous contact allergy to ox. geraniol 11% was demonstrated. Overrepresentation of simultaneous contact allergy to various combinations of ox. geraniol, ox. limonene and ox. linalool was also noted in ketoprofen-photoallergic patients. CONCLUSIONS: Contact allergy to ox. geraniol, geranial and citral is common in routinely tested dermatitis patients. There is an overrepresentation of simultaneous contact allergy to ox. geraniol, ox. limonene and ox. linalool in patients with photocontact allergy to ketoprofen.

Oral lichenoid lesions in two snuff users with contact allergy to carvone.

BACKGROUND: Contact allergy to the mint-tasting flavour carvone has been observed in patients with oral lichenoid lesions (OLL). Mint-flavoured products such as toothpaste frequently contain carvone. Snuff is a smokeless tobacco product that is chewed or placed in the mouth rather than smoked. In Sweden, the use of snuff and its flavoured versions is extremely common. OBJECTIVES: To investigate whether the consumption of mint-flavoured snuff is associated with contact allergy to carvone and subsequently plays a role in the aetiology of OLL. METHODS: Regarding the two patients, patch testing with snuff pouches was performed. High-performance liquid chromatography and gas chromatography-mass spectrometry analysis were used for identification of carvone in different snuff samples. RESULTS: Two patients with OLL were contacted allergic to carvone when patch tested. Both were using mint-flavoured snuffs several hours a day for many years. One patient was contacted allergic to the snuff pouch tested as is. Carvone was detected in the snuff samples of both patients. CONCLUSIONS: The patients were recommended to avoid the use of mint-flavoured snuffs, toothpaste and foodstuffs. At follow-up 3 months later, the patients had a dramatic clinical improvement of the OLL and oral symptoms. Exposure to mint-flavoured snuffs can be overlooked as a possible aggravating/provoking factor in OLL.

Contact allergy in Swedish professional ice hockey players.

BACKGROUND: Professional ice hockey players may contract irritant and allergic contact dermatitis. AIMS: To investigate the presence of contact allergy (CA) in professional ice hockey players in Sweden. METHODS: Ten teams from the two top leagues were assessed for potential occupational exposure to sensitizers. Exactly 107 players were patch tested with an extended baseline series and a working series, in total 74 test preparations. The CA rates were compared between the ice hockey players and controls from the general population and dermatitis patients. RESULTS: One out of 4 players had at least one contact allergy. The most common sensitizers were Amerchol L 101, nickel and oxidized limonene. CA was as common in the ice hockey players as in dermatitis patients and significantly more common than in the general population. Fragrances and combined sensitizers in cosmetic products (fragrances + preservatives + emulsifier) were significantly more common in ice hockey players compared with the general population. CONCLUSION: The possible relationship between CA to fragrances and cosmetic products on the one hand and the presence of dermatitis on the other should be explored further.

Current frequency of contact allergy to isothiazolinones (methyl-, benz- and octylisothiazolinone) across Europe.

BACKGROUND: The use of methylisothiazolinone (MI) as a preservative in cosmetic products caused an alarming increase in MI contact allergy across Europe in the 2010s. This was followed by regulations of use with a total ban on leave-on (implemented in 2017) and reduced use concentrations in rinse-off cosmetics (2018). OBJECTIVE: To follow-up on the prevalence of contact allergy to MI and the related benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in consecutively patch-tested patients in Europe. METHODS: A cross-sectional audit following the design of two previous audits on MI contact allergy from 1 May 2022 to 31 October 2022 included all patients patch tested with the European baseline series, including or supplemented with MI, BIT and OIT across 10 departments in eight European countries. RESULTS: A total of 2554 patients were consecutively patch tested with the three isothiazolinones during the study period. The prevalence of MI and BIT contact allergy was 2.9% (95% confidence interval [CI]: 2.3%-3.7%; range 1.1%-5.8%) and 3.1% (95% CI: 2.4%-3.9%; range 0.0%-6.6%), respectively; that of OIT was 0.7% (95% CI: 0.4%-1.1%; range 0%-3.2%). Rinse-off cosmetic (73.3%) and leave-on cosmetic products (13.3%) were still associated with eliciting allergic contact dermatitis to MI. CONCLUSION: We confirmed a positive impact of regulatory measures on the prevalence of MI contact allergy in Europe, which halved compared to 2015. However, our data suggest that consumers may still be exposed to older cosmetic products containing MI. BIT has superseded MI in causing contact allergy, despite not being allowed for use in cosmetic products.

Results of patch testing with five fragrance materials hitherto not tested: A dose-finding study in the clinical population.

BACKGROUND: Quantitative risk assessment (QRA) for skin sensitization is used to derive safe use levels of sensitising fragrance ingredients in products. Post-marketing surveillance of the prevalence of contact allergy to these ingredients provides relevant data to help evaluate the performance of these measures. OBJECTIVES: To determine a suitable patch test concentration for five fragrance materials that had hitherto not been tested on a regular basis. These concentrations are then to be used in a surveillance study with patch testing consecutive patients over an extended monitoring period. MATERIALS AND METHODS: Furaneol, CAS.3658-77-3; trans-2-hexenal, CAS.6728-26-3; 4,8-dimethyl-4,9-decadienal, CAS.71077-31-1; longifolene, CAS.475-20-7; benzaldehyde, CAS.10052-7, were patch tested with other fragrance allergens in four clinics. Patch testing was conducted in three rounds, starting with the lowest concentrations of the five ingredients. The doses were increased in the subsequent rounds if no late-appearing positive reactions and virtually no irritant reactions were reported. RESULTS: Overall, 373 patients were tested. No positive allergic reaction was reported to the five ingredients. Patch test results of other fragrance allergens are reported. CONCLUSIONS: The highest test concentrations are each considered safe for patch testing consecutive patients. Further surveillance based on these preparations will evaluate the hypothesis that QRA-driven consumer product levels of these fragrances can prevent sensitization.

T-Helper 22 Cell Type Responses to Nickel in Contact Allergic Subjects Are Associated with T-Helper 1, T-Helper 2, and T-Helper 17 Cell Cytokine Profile Responses and Patch Test Reactivity.

INTRODUCTION: Contact allergy to nickel (Ni) is a delayed-type hypersensitivity reaction mediated by Ni-reactive T cells producing the hallmark cytokines of several T-helper cell (Th) populations including IFN-γ (Th1), IL-4, IL-5 and IL-13 (Th2), and IL-17A (Th17). IL-22-expressing CD4+ cells, which could be either Th17 co-expressing IL-22 or Th22, expressing IL-22 in the absence of IL-17A, have also been found in Ni-provoked skin of allergic subjects. It has been unclear if Ni-reactive T cells consist of distinct Th cell type populations or if they secrete a mix of Th cell hallmark cytokines. The aim herein was to assess if cellular cytokine responses to Ni, in ex vivo-stimulated peripheral blood mononuclear cells (PBMCs) from Ni-allergic subjects, include not only Th1, Th2, and Th17 but also Th22 hallmark cytokines and to define if the cytokines are produced by distinct cell populations representing different Th profiles. METHODS: PBMC from Ni-allergic subjects (n = 15) with different degrees of patch test reactivity and non-allergic controls (n = 5) were in vitro stimulated with Ni. Cytokine levels in PBMC supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA) (IFN-γ, IL-2, IL-3, IL-5, IL-6, IL-13, IL-17A, IL-22, and IL-31). FluoroSpot was used to assess if individual Ni-reactive cells produced single, or combinations of, cytokines representing different Th profiles. Cytokine combinations analyzed were IL-17A/IL-22/IFN-γ, IL-5/IL-17A/IFN-γ, IL-13/IL-22/IFN-γ, and IL-5/IL-13. RESULTS: IL-22 as well as all other cytokines measured by ELISA were induced by Ni at higher levels in PBMC from allergic versus non-allergic subjects, with higher levels being associated with stronger patch test reactivity. The levels of most Ni-induced cytokines were positively correlated with each other; IL-2 displayed the highest correlation with other cytokines and IL-6 the lowest. FluoroSpot analysis showed that Th signature cytokines, IFN-γ (Th1), IL-5 and IL-13 (Th2), IL-17A (Th17), and IL-22 (Th22), were almost exclusively produced by distinct cell populations. CONCLUSION: Distinct Th cell populations, including Ni-reactive cells displaying Th1, Th2, Th17, and Th22 cytokine profiles, are all increased in PBMC from Ni-allergic subjects and positively associated with patch test reactivity. The relevance of these different Th profile populations for the up- or down-regulation of inflammatory reactions in the skin of Ni-allergic subjects remains to be clarified.

Colophonium-related Allergic Contact Dermatitis Caused by Medical Adhesive Tape Used to Prevent Skin Lesions in Soldiers.

Medical adhesive tapes are commonly recommended for the prevention of friction blisters during hiking and military marches. The aim of this paper is to report on the results of investigations into an outbreak of tape-related foot dermatitis in 26 military conscripts following continuous use of medical adhesive tapes for several days during a field exercise. Patch tests were performed using baseline series and aimed testing was performed with colophonium-related substances and different medical adhesive tapes. Contact allergy to the adhesive tapes used was found in 20 (77%) subjects, and contact allergy to colophonium in 16 (61%). Chemical analysis detected colophonium-related substances in the culprit tapes. Compared with consecutive dermatitis patients investigated at our Department of Occupational and Environmental Dermatology in the previous 10 years, conscripts with colophonium allergy had increased odds ratios for concomitant contact allergy to phenol formaldehyde resins and fragrance substances including hydroperoxides of limonene and linalool. The results show that prolonged use of medical adhesive tapes on intact skin carries a high risk for allergic contact dermatitis. Prior to their introduction on the market, medical devices should be assessed for possible side-effects.

Increased Rates of Gold and Acrylate Allergy in Individuals with Fibromyalgia Tested with an Extended Dental Patch Test Series.

Fibromyalgia is a common chronic pain condition. Rates of contact allergy in individuals with fibromyalgia have not been widely studied. Systemic contact allergy can present with muscle and joint pain and general malaise. The aim of this study is to investigate contact allergy rates in individuals with fibromyalgia to the sensitizers in an extended dental series and compare with control groups. Contact allergy to gold was significantly more common in the fibromyalgia group than the dermatitis control group. When corrected for patch test system, contact allergy to gold was significantly more common in the fibromyalgia group than the dental control group. Contact allergy to hydroxyethyl methacrylate and grouped acrylates and methacrylates was significantly more common in the fibromyalgia group than the dental control group. In conclusion, individuals with fibromyalgia may have a propensity to sensitization to gold, either via an increased exposure or an alteration in the oral environment. Gold is also implicated in systemic contact dermatitis and may be a factor in elicitation of symptoms in individuals with fibromyalgia. Acrylate allergy is also common in the fibromyalgia population and may be a consequence of occupational exposure or dental treatment.

Increased rates of fragrance allergy in fibromyalgia individuals tested with the Swedish baseline patch test series.

BACKGROUND: Contact allergy can manifest in a variety of ways clinically. Systemic contact allergy may occasionally present with pain in muscles and joints. Fibromyalgia is a chronic rheumatic disease characterized by pain and with virtually unknown aetiology. OBJECTIVES: The aim of this study was to investigate the contact allergy rates to the sensitizers in a baseline series and compare with corresponding rates in dermatitis patients and the general population. METHODS: Patch testing with the Swedish baseline series was performed in 120 individuals with fibromyalgia. Fisher's exact test was used for pair-wise comparisons of contact allergy rates between the fibromyalgia group and two control groups, dermatitis patients and individuals in the general population. RESULTS: Contact allergy was significantly more common in the fibromyalgia group compared to the general population concerning nickel and the fragrance markers Myroxolon pereirae and fragrance mix I. There were fewer allergic reactions to preservatives in the fibromyalgia group compared with the dermatitis group. CONCLUSIONS: Myroxolon pereirae and fragrance mix I represent besides fragrance allergy also allergy to flavouring substances which indicate that oral exposure to flavouring substances and hygiene products might be important for sensitization and possibly elicitation of systemic contact allergy symptoms in fibromyalgia individuals.

Use of sorbitan sesquioleate in patch test preparations and patch testing with the substance-What do our results mean?

BACKGROUND: Sorbitan sesquioleate (SSO) is a sorbitan fatty acid ester, an emulsifier used in topical products and certain patch test preparations. SSO may affect the patch test results. It has been debated whether to include the substance in the baseline series to avoid misinterpretation of the results. OBJECTIVES: To report the prevalence and simultaneous reactions of SSO with other patch test preparations containing SSO as an emulsifier. MATERIALS AND METHODS: A retrospective analysis of 3539 dermatitis patients who underwent patch testing from 2016 to 2020 was performed. RESULTS: The 5-year SSO contact allergy prevalence was 0.48%, and 1.3% had a doubtful reaction. Patients with a stronger positive reaction (2+, 3+) were more likely to react simultaneously to other allergen preparations containing SSO (p value = 0.018). One patient with a strong reaction to SSO reacted positively to all SSO-containing patch test preparations. Definite fragrance allergens could not be identified in the patients who had simultaneous reactions to SSO and fragrance mix (FM) I. CONCLUSIONS: Patch testing with allergen preparations containing SSO affected the patch test interpretation. Fragrance contact allergy could not be ruled out when a patient simultaneously reacted to SSO and FM I. Changing emulsifiers in patch test preparations would be advantageous.

Effects of aluminium chloride added to common patch test substances.

BACKGROUND: A modulating effect of aluminium regarding type IV reactions might exist but has not been further investigated. OBJECTIVES: The aim of this study was to investigate the effect on patch test reactions when adding aluminium chloride hexahydrate (Al-Cl) to common test preparations. MATERIALS AND METHODS: Al-Cl in different concentrations was added to nickel sulphate 15.0% aqua (Ni), methylisothiazolinone 0.2% aqua (MI) and fragrance mix I 10.0% aqua/ethanol (FM I). The Ni preparations were tested in 120 consecutive patients. MI and FM I were tested in participants known to have contact allergy to the respective allergen. McNemar's test was used to decide which Ni preparation had the highest sensitivity. Wilcoxon signed-rank test was used to calculate pairwise comparison in summarized test score for the preparations with MI and FM I. RESULTS: Adding Al-Cl 20.0%/30.0% to Ni identified twice as many patients with contact allergy to nickel compared to Ni without Al-Cl. Adding Al-Cl 20.0%/10.0% to MI, decreased the patch test reactivity compared to MI without Al-Cl. No differences in patch reactivity were noticed when adding Al-Cl to FM I. CONCLUSION: Al-Cl 20.0% or 30.0% seems to enhance the patch test reactivity to Ni 15.0% aqua.

Use test with l-carvone in toothpaste on sensitized individuals.

BACKGROUND: The mint flavour carvone (l-carvone) is considered a weak contact allergen. However, contact allergy to carvone is more prevalent in patients with oral lichen planus or oral lichenoid lesions (OLP/OLL). OBJECTIVE: Our aim was to investigate how carvone affects sensitized individuals through a use test with toothpaste containing carvone. Non-flavoured toothpaste served as control. METHODS: Subjects were patch tested prior to the use test-14 subjects allergic to carvone (11 with OLP/OLL), 20 subjects with OLP/OLL and 3 healthy controls. The month-long use test comprised of using toothpaste twice daily. Subjects were examined fortnightly. Clinical signs were assessed with a mucosal scoring system. The subjects' oral health-related quality of life was measured with the oral health impact profile (OHIP-49). RESULTS: Local reactions to the carvone toothpaste presented as aggravated OLL (7/10) and peri-oral eczema (2/10) in allergic subjects. They also had significantly higher mucosal and OHIP scores compared with those receiving non-flavoured toothpaste. CONCLUSION: In sensitized individuals, oral exposure to carvone gives aggravated oral lesions and/or peri-oral eczema. The lesions mimic OLP and allergic individuals are therefore at risk of not being assessed with regard to flavour contact allergy.

Epoxy allergy, investigation of a modern industry.

BACKGROUND: Five workers from an industry manufacturing various articles from carbon fibre reinforced epoxy plastics were referred to our department because of suspected occupational allergic contact dermatitis (OACD). When patch tested, four of them had positive reactions to components of epoxy resin systems (ERSs) that could explain their current skin problems. All of them had been working at the same workstation at a specially designed pressing machine, with operations including manually mixing epoxy resin with hardener. Multiple cases of OACD in the plant prompted an investigation including all workers with possible risk exposures at the plant. OBJECTIVES: To investigate the prevalence of occupational dermatoses and contact allergies among the workers at the plant. MATERIALS AND METHODS: Totally 25 workers underwent investigation that included a brief consultation with a standardized anamnesis and clinical examination followed by patch testing. RESULTS: ERSs-related reactions were found in 7 of the 25 investigated workers. None of the seven had a history of previous exposure to ERSs and they are regarded as sensitized through work. CONCLUSIONS: Twenty-eight percent of investigated workers showed reactions to ERSs. Of these the majority would have been missed if supplementary testing would not have been added to testing with the Swedish base line series.

4,4'-Thiobis(2-tert-butyl-5-methylphenol), an antioxidant in medical devices that may cause allergic contact dermatitis.

BACKGROUND: Antioxidants in medical devices, added to protect polymers or adhesives, may also cause contact dermatitis in some individuals. OBJECTIVES: To present data on sensitization to 4,4'-thiobis(2-tert-butyl-5-methylphenol), an antioxidant detected in some types of medical devices, for six patients that experienced eczematous reactions to different medical devices. METHODS: Patch testing with 4,4'-thiobis(2-tert-butyl-5-methylphenol), 1% pet was performed. Gas chromatography-mass spectrometry (GC-MS) was used for identification of 4,4'-thiobis(2-tert-butyl-5-methylphenol) in different medical device products. RESULTS: Six patients with contact allergy to 4,4'-thiobis(2-tert-butyl-5-methylphenol) also had relevant contact allergic reactions to medical devices containing the antioxidant. The presence of the antioxidant in products was detected using GC-MS analysis. CONCLUSIONS: The antioxidant 4,4'-thiobis(2-tert-butyl-5-methylphenol) may cause allergic contact dermatitis after exposure to different medical devices.

Active sensitization to dimethylthiocarbamylbenzothiazol sulphide: An unexpectedly strong rubber contact allergen.

BACKGROUND: The two dialkylthiocarbamyl benzothiazole sulphides, dimethyl-thiocarbamylbenzothiazole sulphide (DMTBS) and diethylthio-carbamylbenzothiazole sulphide (DETBS) were shown to be good markers of both thiuram and mercaptobenzothiazole sensitivity. OBJECTIVES: To investigate if DMTBS and/or DETBS could be better markers of contact allergy to common rubber additives than the ones currently used. METHODS: Sixty-eight dermatitis patients were patch tested with DMTBS and DETBS, both at 1% in petrolatum (pet). Because of late reactions in 10 patients, these were retested to DMTBS and DETBS in serial dilutions. Tetramethylthiuram monosulphide (TMTM) 1.0% pet was also tested. RESULTS: At the initial reading Days 3 and 7, no reactions were noted to DMTBS or DETBS. At retesting, 10 of the 68 (15%) patients reacted positively to lower concentrations of DMTBS than the initial test concentration. Seven of 8 also reacted to TMTM. Three of them had positive reactions to DEBTS. All 10 patients had reactions to more diluted solutions to DMBTS than to DEBTS (p = 0.0077; Mc-Nemar test, two-sided). CONCLUSIONS: Results speak for patch test sensitization to DMTBS with cross-reactivity to TMTM and also DEBTS. DMTBS and DEBTS could be new markers of rubber allergy but a safe test concentration must be found.

Allergic reactivity for different dilutions of eugenol in repeated open application test and patch testing.

BACKGROUND: Eugenol is a known contact sensitiser included in fragrance mix I. OBJECTIVE: To assess the allergic reactivity to eugenol in different concentrations using patch test as well as repeated open application test (ROAT). METHODS: Overall 67 subjects from 6 European dermatology clinics participated in the study. The ROAT was performed for 21 days twice a day, applying 3 dilutions of eugenol (2.7%-0.5%) and a control. Before and after the ROAT, patch testing with 17 dilutions of eugenol (2.0%-0.00006%) and controls was performed. RESULTS: Out of the 34 subjects with contact allergy to eugenol, 21 (61.8%) showed a positive patch test before ROAT was performed, the lowest positive concentration was 0.031%. The ROAT was positive in 19 (55.9%) of the 34 subjects, the time until a positive reaction occurred was negatively associated with the concentration of the ROAT solution, as well as with the allergic reactivity of the subjects as defined by patch testing. In the patch test after ROAT, 20 of the 34 test subjects (58.8%) showed a positive reaction. In 13 (38.2%) of the 34 test subjects, the patch test result was not reproduceable, still 4 (31.0%) of these 13 subjects developed a positive ROAT. CONCLUSION: Eugenol can provoke a positive patch test reaction in a very low dose; besides, this hypersensitivity may persist even if a former positive patch test is not reproduceable.