Contact sensitization to fragrance mix I and fragrance mix II among European dermatitis patients: A systematic review.

BACKGROUND: Fragrance substances are a frequent cause of contact allergy worldwide. Fragrance exposure varies by sex, age and possibly country, influenced by cosmetic availability, environmental conditions and cultural practices. OBJECTIVES: To systematically review and gather prevalence of sensitization to fragrance mix I (FM I) and fragrance mix II (FM II) in consecutively patch tested European dermatitis patients. METHOD: A total of 4134 publications on patch test results of European dermatitis patients, published from 1981 to 2022, were systematically reviewed according to a previously registered and published PROSPERO protocol. RESULTS: Eighty-four eligible original articles were analysed. Overall prevalence of sensitization to fragrance mix I (FM I) was 6.81% (95% CI: 6.37-7.28), and FM II was 3.64% (95% CI: 3.3-4.01). Sensitization to FM I was most prevalent in Central and Eastern Europe and to FM II in Western Europe. No clear time trends were observed. Among paediatric dermatitis patients, sensitization prevalence for FM I and FM II was 4.09% (95% CI: 3.37-4.96) and 2.17% (95% CI: 1.53-3.07). CONCLUSION: The frequency of positive patch test results for both FMI and FMII remains high. Sensitization is also prevalent among children. Enhanced regulation and labelling of cosmetic products play a vital role in averting exposure and sensitization to fragrance allergens.

Prevalence of contact allergy in the general population: A systematic review and meta-analysis.

BACKGROUND: Contact allergy and allergic contact dermatitis are frequent conditions in the general population. OBJECTIVES: To provide an updated estimate of the prevalence of contact allergy in the general population based on data from our previous review combined with new data from an updated search for relevant studies published between 2007 and 2017. METHODS: Two authors independently searched PubMed for studies reporting on the prevalence of contact allergy in samples of the general population. Proportion meta-analyses were performed to calculate the pooled prevalence estimates of contact allergy. RESULTS: A total of 28 studies were included in the analysis, covering 20 107 patch tested individuals from the general population. Overall, the pooled prevalence of contact allergy was 20.1% (95% confidence interval [CI]: 16.8%-23.7%). In children and adolescents (<18 years), the prevalence was 16.5% (95%CI: 13.6%-19.7%). The prevalence was significantly higher in women (27.9% [95%CI: 21.7%-34.5%]) than in men (13.2% [95%CI: 9.3%-17.6%]). The most common allergen was nickel (11.4% [95%CI: 9.4%-13.5%]), followed by fragrance mix I (3.5% [95%CI: 2.1%-5.4%]), cobalt (2.7% [95%CI: 2.1%-3.4%]), Myroxylon pereirae (1.8% [95%CI: 1.0%-2.7%]), chromium (1.8% [95%CI: 1.3%-2.6%]), p-phenylenediamine (1.5% [95%CI: 1.0%-2.1%]), methylchloroisothiazolinone/methylisothiazolinone (1.5% [95%CI: 0.8%-2.5%]), and colophonium (1.3% [95%CI: 1.0%-1.6%]). CONCLUSIONS: This meta-analysis confirmed that at least 20% of the general population are contact-allergic to common environmental allergens. It highlights the need for more effective preventive strategies for common allergens in consumer goods, cosmetics, and the workplace.

Allergic contact dermatitis caused by hydroperoxides of limonene and dose-response relationship-A repeated open application test (ROAT) study.

BACKGROUND: Contact allergy to oxidized limonene, with hydroperoxides of limonene (Lim-OOHs) as the main allergens, is common. However, high proportions of weak positive and doubtful patch test reactions have been reported. OBJECTIVES: To determine the clinical relevance, elicitation threshold and dose-response relationship of Lim-OOHs in individuals with a positive or doubtful patch test reaction to standard Lim-OOHs 0.3% pet. METHODS: A multicentre 3-week double-blind vehicle-controlled repeated open application test (ROAT) study with a simulated fine fragrance containing Lim-OOHs at 1260, 420 and 140 ppm, equal to a dose/area per application of Lim-OOHs of 3.0, 0.99 and 0.33 µg/cm2 , was performed. RESULTS: Among 11 subjects allergic to Lim-OOHs, 11 (100%), 7 (64%), and 3 (27%), respectively, reacted to the applied doses. No reactions were seen in 17 healthy controls exposed to the highest dose. This difference in reactivity was statistically significant (P < 0.0001). Among 13 subjects with doubtful patch test reactions to Lim-OOHs, two (15%) had positive ROAT reactions to the highest Lim-OOH dose applied (P = 0.36 as compared with controls). CONCLUSIONS: Contact allergy to Lim-OOHs is of clinical relevance in patients with positive patch test reactions. A doubtful patch test reaction to Lim-OOHs 0.3% pet. can be of clinical relevance.

Quality of life and disease severity in dermatitis patients with fragrance allergy-A cross-sectional European questionnaire study.

BACKGROUND: Fragrance contact allergy is common, but few studies on quality of life (QoL) in affected patients exist. Recently, the disease-specific Fragrance Quality of Life Index (FQLI) was developed. OBJECTIVES: To characterize QoL in European dermatitis patients with fragrance contact allergy at the time of diagnosis. METHODS: This was a cross-sectional study, in which 2011 Danish, British, Spanish and German adult consecutive dermatitis patients were invited to complete a questionnaire on self-reported disease severity, the Dermatology Life Quality Index (DLQI), and the FQLI immediately prior to being patch tested. RESULTS: One thousand seven hundred and fifty-eight patients responded, and 259 (14.7%; country range 11.7%-18.5%) were fragrance-positive. Among these, the total (SD) DLQI score was 6.2 (5.6) and the total (SD) FQLI score was 60 (25), with both estimates being comparable to those in fragrance-negative patients. Adjusting the total FQLI score for age, sex and self-rated disease severity showed a higher (ie, worse) score in fragrance-positive patients (3.6-point increase; 95% confidence interval: 0.30-6.8 points; P = 0.03). Specifically, contact allergy to oxidized linalool was associated with greater impairment in QoL. CONCLUSIONS: QoL in patients with fragrance contact allergy is impaired at a level comparable to that in other patch tested dermatitis patients, at the time of diagnosis, across several European countries.

Non-mix fragrances are top sensitizers in consecutive dermatitis patients - a cross-sectional study of the 26 EU-labelled fragrance allergens.

BACKGROUND: For cosmetics, it is mandatory to label 26 fragrance substances, including all constituents of fragrance mix I (FM I) and fragrance mix II (FM II). Earlier reports have not included oxidized R-limonene [hydroperoxides of R-limonene (Lim-OOH)] and oxidized linalool [hydroperoxides of linalool (Lin-OOH)], and breakdown testing of FM I and FM II has mainly been performed in selected, mix-positive patients. OBJECTIVES: To report the prevalence of sensitization to the 26 fragrances, and to assess concomitant reactivity to FM I and/or FM II. METHODS: A cross-sectional study on consecutive dermatitis patients patch tested with the 26 fragrances and the European baseline series from 2010 to 2015 at a single university clinic was performed. RESULTS: Of 6004 patients, 940 (15.7%, 95%CI: 14.7-16.6%) were fragrance-sensitized. Regarding the single fragrances, most patients were sensitized to Lin-OOH (3.9%), Evernia furfuracea (3.0%), Lim-OOH (2.5%), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (2.1%). Significantly fewer patients were 'FM I-positive and constituent-positive' than 'FM II-positive and constituent-positive' (32.7% versus 57.0%, p < 0.0001). Additionally, significantly more patients were 'FM II-negative but constituent-positive' than 'FM I-negative but constituent-positive' (12.4% versus 3.2%, p = 0.0008). CONCLUSIONS: Non-mix fragrances are the most important single fragrance allergens among consecutive patients. The test concentration of the single FM I constituents should be increased when possible.