Trends in contact sensitization, results, and implications from a contact dermatitis clinic in Israel.

BACKGROUND: The baseline series includes common allergens, evolves over time, and differs by location. Our study aims to characterize allergen sensitization trends among the Israeli population during the last two decades, compare our results to American and European registries, as well as to highlight significant allergens in additional series outside the European baseline series (OEBS). METHODS: We analysed patch test results of 2086 patients from a designated contact dermatitis clinic in Tel Aviv between 2019 and 2022, compared them to European and North American registries and to 2156 patch test results conducted in Israel two decades ago. RESULTS: 38.6% of patients had at least one positive reaction to an allergen in the European baseline series (EBS), nickel sulphate (14.6%), fragrance mix I (4.6%), and Methylchloroisothiazolinone methylisothiazolinone (MCI/MI; 3.7%) were the most common among them. N-Isopropyl N-Phenyl-4-Phenylenediamine (NIPPD; 0%), Propolis (0.1%), Sesquiterpene lactone mix (0.1%), and Budesonide (0.1%) elicited a sensitization frequency significantly lower than the proposed threshold for baseline inclusion. Chi-square test revealed a statistically significant decrease (p < 0.05) in the sensitization frequency of fragrance mix I, Formaldehyde, Potassium dichromate, Neomycin sulphate, Myroxylon pereirae, Sesquiterpene lactone, and NIPPD during the last two decades. The overall sensitization frequency to the majority of allergens was lower in our cohort in comparison to the North American and European registries. CONCLUSIONS: MCI/MI and 2-hydroxyethyl methacrylate-2 (HEMA) are common, relevant allergens, with high SPIN (significance and prevalence index number) and should be better regulated by the authorities. While among the EBS, NIPPD, Propolis, Sesquiterpene lactone, and Budesonide usually do not elicit a positive reaction and therefore should be reconsidered in baseline series, among the OEBS, Chloramphenicol, Quaternium 15, Propyl gallate, and Amerchol L101 have elicited high SPIN values and should be vigilantly examined in the suitable clinical scenario. Significantly lower sensitization frequency to propolis raises the possibility of a protective effect due to early oral exposure among the Israeli population.

Fragrance- and Botanical-Related Allergy and Associated Concomitant Reactions: A Retrospective Analysis of the North American Contact Dermatitis Group Data 2007-2016.

IMPORTANCE: When fragrance- and botanical-related (F/BR) allergy is identified, concomitant reaction (CR) frequencies can help direct avoidance recommendations. OBJECTIVE: This study aimed to determine the CR rates for F/BR allergens. DESIGN: A retrospective cross-sectional analysis of the North American Contact Dermatitis Group data 2007-2016 was conducted. Frequencies of demographics, positive reactions, strength of reactions, trends, and CR rates were calculated. RESULTS: A total of 5504 (22.7%) of 24,246 patients had F/BR allergic reactions. The F/BR-sensitive patients were more likely to be female, older than age 40 years, and White and have face, leg, or anal/genital dermatitis. Top allergens included fragrance mix I (FMI, 10.6%), Myroxylon pereirae (balsam of Peru [BOP], 8%), and fragrance mix II (FMII, 4.9%). There were increasing trends for FMI, FMII, cinnamic aldehyde, and Compositae mix and decreasing trends for BOP and propolis. When patients were positive to any F/BR allergen, they were likely to be positive to FMI, FMII, and BOP. Concomitant reactions were bidirectional between multiple fragrance allergens and propolis, colophony, and Compositae mix. CONCLUSIONS: Concomitant reactions were identified between fragrances, between fragrances and BR allergens, and between BR allergens and fragrances. If CRs of greater than 10% suggest cross-reactivity, then all patients with fragrance sensitivity should avoid BR allergens and vice versa.

Sensitization to fragrances in Spain: A 5-year multicentre study (2011-2015).

BACKGROUND: Fragrance chemicals constitute the second most frequent cause of contact allergy in Spain. There are no data available concerning the individual fragrances that are most frequently involved. OBJECTIVES: To describe the diagnostic contribution provided by specific fragrance series to the results obtained with baseline series fragrance markers by correlating the results of both series. MATERIALS AND METHODS: We performed a 5-year retrospective study of fragrance marker-positive patients tested with specific fragrance series in 23 Spanish centres. We collected the demographic and clinical characteristics, and compared the results of patch tests obtained from different suppliers. RESULTS: Of 19 588 patients patch tested with the Spanish baseline series, 1590 (8.1%) reacted positively to a fragrance marker. Of these, 1013 (63.7%) were patch tested with a fragrance series, and 664 patients reacted positively to at least one individual fragrance other than hydroxyisohexyl 3-cyclohexene carboxaldehyde. Geraniol was the most frequent allergen. Positive reactions to substances not included in fragrance mix (FM) I or FM II were found in 230 patients. Of the 436 FM I-positive patients and the 419 FM II-positive patients, 184 (42%) and 64 (39.1%), respectively, had no positive reactions to fragrance series. In the case of FM I, negative results were more common when individual fragrances were patch tested at low concentrations. CONCLUSIONS: We recommend patch testing all patients positive for any fragrance marker with a specific fragrance series. The correlation between the results of baseline series and fragrance series could be improved by increasing the concentrations of individual fragrances.

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.

The current spectrum of contact sensitization in patients with chronic leg ulcers or stasis dermatitis - new data from the Information Network of Departments of Dermatology (IVDK).

BACKGROUND: Patients with lower leg dermatitis, chronic venous insufficiency or chronic leg ulcers have a high prevalence of contact sensitization. OBJECTIVES: To identify the current spectrum of contact allergens in these patients. PATIENTS AND METHODS: Data of the Information Network of Departments of Dermatology on 5264 patients with the above diagnoses from the years 2003 to 2014 (study group) were compared with data on 4881 corresponding patients from 1994 to 2003 (historical control group) and with a current control group without these diagnoses (n = 55 510). RESULTS: Allergic contact dermatitis was diagnosed less frequently in the study group than in the historical control group (25.9% versus 16.9%; p < 0.001), and contact sensitization to most allergens had declined. The allergen spectrum, however, was largely unchanged. Important allergens are Myroxylon pereirae (balsam of Peru) (14.8% positive reactions), fragrance mix I (11.4%), lanolin alcohol (7.8%), colophonium (6.6%), neomycin sulfate (5.0%), cetearyl alcohol (4.4%), oil of turpentine (3.1%), and paraben mix (2.6%). Patch testing with additional series showed sensitization to Amerchol L-101 (9.7%), tert-butyl hydroquinone (8.7%), framycetin sulfate (5.0%), and gentamicin sulfate (3.1%). CONCLUSIONS: Topical preparations for treating the above-mentioned conditions should not contain fragrances, Myroxylon pereirae, and colophonium. The special allergen spectrum has to be considered in patch testing.

Fragrance allergy could be missed without patch testing with 26 individual fragrance allergens.

BACKGROUND: In 2003, the EU Cosmetics Directive stated that 26 fragrance substances must be listed on the cosmetic product ingredient labels. Not all of these 26 fragrance substances are detected by the usual screening markers comprising fragrance mix I, fragrance mix II, and Myroxylon pereirae. OBJECTIVES: To evaluate the usefulness of testing with the 26 individual fragrance substances in addition to the standard fragrance screening markers. MATERIALS AND METHODS: Three hundred and twelve consecutive patients were patch tested with our baseline series and the 26 specific fragrance substances required to be declared on cosmetic product ingredient labels in accordance with the EU Cosmetics Directive. RESULTS: Positive reactions to at least either one of the 26 individual fragrance substances or the usual fragrance screening markers were seen in 84 of 312 patients (26.9%). Fifteen of these 84 patients (17.8%) reacted negatively to the fragrance screening markers. The most common individual fragrance allergens were cinnamyl alcohol (11.2%), cinnamal (9%), and hydroxycitronellal (3.8%). Sixty-two of 312 patients (19.8%) had at least one positive reaction to the fragrance screening markers. CONCLUSION: Additional patch testing with the 26 individual fragrance allergens, or with the commonest fragrance allergens identified within these 26, should be performed to optimize the detection of fragrance allergy. Cinnamyl alcohol and cinnamal are important fragrance allergens in Thailand.

Contact allergy to essential oils cannot always be predicted from allergy to fragrance markers in the baseline series.

BACKGROUND: Essential oils are fragrance substances that are labelled on cosmetic products by their INCI names, potentially confusing consumers. OBJECTIVES: To establish whether contact allergy to essential oils might be missed if not specifically tested for. METHODS: We tested 471 patients with 14 essential oils and 2104 patients with Melaleuca alternifolia oil between January 2008 and June 2014. All patients were tested with fragrance mix I, fragrance mix II, hydroxyisohexyl 3-cyclohexene carboxaldehyde, and Myroxylon pereirae. Three hundred and twenty-six patients were tested with hydroperoxides of limonene and linalool. RESULTS: Thirty-four patients had a +/++/+++ reaction to at least one essential oil. Eleven had no reaction to any of the six marker fragrance substances. Thus, 4 of 11 positive reactions to M. alternifolia oil, 2 of 7 reactions to Cymbopogon flexuosus oil, 1 of 5 reactions to Cananga odorata oil, 3 of 4 reactions to Santalum album oil and 2 of 3 reactions to Mentha piperita oil would have been missed without individual testing. CONCLUSION: A small number of patients who are allergic to essential oils could be missed if these are not specifically tested. Labelling by INCI names means that exposure may not be obvious. Careful inspection of so-called 'natural' products and targeted testing is recommended.

Multicenter Patch Testing With a Resol Resin Based on Phenol and Formaldehyde Within the International Contact Dermatitis Research Group.

BACKGROUND: Contact allergy to phenol-formaldehyde resins (PFRs) based on phenol and formaldehyde is not detected by a p-tertiary-butylphenol-formaldehyde resin included in most baseline patch test series. OBJECTIVE: The aims of this study were to investigate the contact allergy rate to PFR-2 in an international population and to investigate associated simultaneous allergic reactions. METHODS: Thirteen centers representing the International Contact Dermatitis Research Group included PFR-2 into their patch test baseline series during a period of 6 months in 2012. RESULTS: Of 2259 patients tested, 28 (1.2%) reacted to PFR-2. Of those 28 individuals, one had a positive reaction to formaldehyde and 2 to p-tertiary-butylphenol-formaldehyde resin. Simultaneous allergic reactions were noted to colophonium in 3, to Myroxylon pereirae in 5, and to fragrance mix I in 8. CONCLUSIONS: The contact allergy frequency in the tested population (1.2%) merits its inclusion into the international baseline series and possibly also into other baseline series after appropriate investigations. Significantly, overrepresented simultaneous allergic reactions were noted for M. pereirae and fragrance mix I.

Fragrance allergic contact dermatitis.

Fragrances are a common cause of allergic contact dermatitis in Europe and in North America. They can affect individuals at any age and elicit a spectrum of reactions from contact urticaria to systemic contact dermatitis. Growing recognition of the widespread use of fragrances in modern society has fueled attempts to prevent sensitization through improved allergen identification, labeling, and consumer education. This review provides an overview and update on fragrance allergy. Part 1 discusses the epidemiology and evaluation of suspected fragrance allergy. Part 2 reviews screening methods, emerging fragrance allergens, and management of patients with fragrance contact allergy. This review concludes by examining recent legislation on fragrances and suggesting potential additions to screening series to help prevent and detect fragrance allergy.

Results of patch testing with fragrance mix 1, fragrance mix 2, and their ingredients, and Myroxylon pereirae and colophonium, over a 21-year period.

BACKGROUND: The frequency of fragrance contact allergy has shown a fluctuating trend over the years. OBJECTIVES: To describe the frequency of positive reactions to the baseline screening agents and fragrance mix (FM) 1 and 2 components, to determine trends of the latter over the years, and to evaluate simultaneous reactions. PATIENTS AND METHODS: This was a cross-sectional study on patch test results of 13 332 patients from January 1990 to December 2011. RESULTS: Of the total population, 9.6% reacted positively to FM 1, and 6% of 3416 tested with FM 2 reacted positively. Of those tested with both, 30.4% of 349 FM 1-positive patients reacted to FM 2, and 51.7% of 205 FM 2-positive patients reacted to FM 1. Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) and FM 2 were tested simultaneously in 3401 patients: 6 reacted to HICC alone. Nine hundred and forty patients were tested with FM 1 ingredients and 205 with FM 2 ingredients; Evernia prunastri was the most frequent FM 1 allergen, and HICC was the most frequent FM 2 allergen. Simultaneous reactions were frequently observed. CONCLUSIONS: Fragrance-allergic subjects often show multiple positive reactions, some of which are highly significantly associated. Recently, there has been a decreasing trend in positivity for both Evernia prunastri and HICC, whereas a slight increase for cinnamyl alcohol has been observed.

Systemic contact dermatitis--kids and ketchup.

Systemic manifestations of allergic contact dermatitis due to consumption of foods containing balsam of Peru (Myroxylon pereirae)-associated chemicals have recently been reported in children. We present seven children with widespread, recalcitrant dermatitis who experienced 60-80% clearance after initiating a diet low in balsam of Peru, specifically the tomato product ketchup. Furthermore, because we have observed a high prevalence of ketchup in our pediatric patients' diets, we recommend consideration of moderate consumption of this product in patients with recalcitrant widespread dermatitis.

Fragrance mix II in the baseline series contributes significantly to detection of fragrance allergy.

BACKGROUND: Fragrance mix II (FM II) is a relatively new screening marker for fragrance contact allergy. It was introduced in the patch test baseline series in Denmark in 2005 and contains six different fragrance chemicals commonly present in cosmetic products and which are known allergens. AIM: To investigate the diagnostic contribution of including FM II in the baseline series by comparing it with other screening markers of fragrance allergy: fragrance mix I (FM I), Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC). METHOD: Retrospective study of 12 302 patients consecutively patch tested with FM II by members of the Danish Contact Dermatitis Group 2005-2008. RESULTS: FM II gave a positive patch test in 553 patients (4.5%), and in 72.2% of these patients the reaction was judged to be clinically relevant. FM II ranked second in detecting fragrance allergy, after FM I. If FM II had not been included as a screening marker in the baseline series, 15.6% (n = 202) of individuals with fragrance allergy would not have been identified by the other fragrance screening markers (FM I, M. pereirae or HICC). CONCLUSION: FM II contributes substantially to detecting fragrance allergy. It ranked second among the fragrance screening markers tested in the baseline series and detects individuals with an allergy who otherwise would not have been identified.

Changing delayed-type sensitizations to the baseline series allergens over a decade at the Zurich University Hospital.

BACKGROUND: Patch testing detects delayed-type sensitizations and may show changes in prevalence over time. OBJECTIVES: To compare sensitization prevalence to our baseline series allergens during the years 2000-2004 to results from 1990 to 1994. METHODS: We analysed baseline patch test series allergens from 2000 through 2004. RESULTS: 4094 individuals were patch tested to the baseline series (mean age 45.4 years, males 41.7%). The highest sensitization rates were found for nickel sulfate (19.3%), fragrance mix (10.4%) and Myroxylon pereirae (7.8%). Compared to 1990-1994, methylchloroisothiazolinone (and) methylisothiazoline (MCI/MI) and neomycin sulfate sensitization decreased and lanolin alcohol, thiuram mix and ammoniated mercury sensitization increased. CONCLUSIONS: Current sensitization rates are similar to those across Europe. Reduced sensitizations to MCI/MI and neomycin sulfate and increased sensitizations to thiuram mix and ammoniated mercury chloride may well be because of changes in exposure. The current group comprises a higher proportion affected by leg dermatitis and may thus explain the higher sensitization to lanolin alcohol. Comparing patch results over time shows important changes in sensitization prevalence.

Fragrance contact allergy: a 4-year retrospective study.

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.

The importance of propolis in patch testing--a multicentre survey.

BACKGROUND: Propolis is widely used in 'natural' cosmetics, remedies, and over-the-counter products. The incidence of propolis allergy is increasing, and cross-reaction with fragrance mix I (FMII), colophonium, and Myroxylon pereirae can occur. OBJECTIVES: To find out the prevalence and clinical relevance of positive patch tests to propolis and assess cross-reactions with Myroxylon pereirae, colophonium, FMI, and beeswax. METHODS: Two thousand eight hundred and twenty-eight subjects in 10 UK centres were patch tested with propolis and beeswax. Generic data were acquired from British Contact Dermatology Society (BCDS) database and further relevant information was requested by survey of participating centres. RESULTS: The prevalence of propolis allergy was 1.9% (55/2828). Out of these 55 subjects, only 4 (7.2%) were allergic to beeswax, 22 (40%) to Myroxylon pereirae, 15 (27.2%) to colophonium, and 6 (10.9%) to FMI. Additional data for 41 propolis allergic subjects were collected by questionnaire. Hands were the most common sites of involvement, and cosmetics were the most common source of contact. Eight out of 12 subjects reported improvement in eczema following avoidance of propolis. CONCLUSIONS: Propolis is an important allergen of increasing frequency and its inclusion in BCDS baseline series is appropriate. Cross-sensitivity to beeswax is rare.

The prevalence and morbidity of sensitization to fragrance mix I in the general population.

BACKGROUND: The prevalence of sensitization to fragrance mix (FM) I and Myroxylon pereirae (MP, balsam of Peru) has decreased in recent years among Danish women with dermatitis. OBJECTIVES: This study investigated whether the decrease could be confirmed among women in the general population. Furthermore, it addressed the morbidity of FM I sensitization. METHODS: In 1990, 1998 and 2006, 4299 individuals aged 18-69 years (18-41 years only in 1998) completed a premailed questionnaire and were patch tested to FM I and MP. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The prevalence of FM I and MP sensitization followed an inverted V-pattern among women aged 18-41 years (i.e. an increase from 1990 to 1998, followed by a decrease from 1998 to 2006). Logistic regression analyses showed that 'medical consultation due to cosmetic dermatitis' (OR 3.37, 95% CI 1.83-6.20) and 'cosmetic dermatitis within the past 12 months' (OR 3.53, CI 2.02-6.17) were significantly associated with sensitization to FM I. CONCLUSIONS: In line with trends observed in Danish patients with dermatitis, our results supported a recent decrease in the prevalence of FM I and MP sensitization in Denmark. The study also showed that fragrance sensitization was associated with self-reported cosmetic dermatitis and use of health care related to cosmetic dermatitis.

Contact sensitization to fragrances in the general population: a Koch's approach may reveal the burden of disease.

BACKGROUND: Contact sensitization to fragrance mix (FM) I and Myroxylon pereirae (MP) is common among European patients with dermatitis. Recently, FM II was included in the European baseline series as an additional marker of fragrance sensitization. OBJECTIVES: This literature review aims to assess the prevalence of fragrance sensitization in the general population, and to suggest how future population-based studies and questionnaires should be constructed, better to assess the prevalence and burden of fragrance sensitization. This is of relevance as it is often difficult to establish causality in biological systems. METHODS: A systematic review of the literature was carried out by searching Pubmed-Medline, Biosis and contact dermatitis textbooks. RESULTS: Nineteen studies were identified, of which 13 were performed among adults. Sample sizes varied between 82 and 2545 tested subjects, and 11 648 subjects were tested in total. The median prevalence of FM and MP sensitization among adults was 2.3% (women, 1.7%; men, 1.3%) and 1.1% (women, 1.4%; men, 0%), respectively. CONCLUSIONS: Based on the reliability of patch test data from the general population and exposure data obtained from patients with dermatitis, the prevalence and burden of fragrance sensitization in the general population is significant.