Contact Allergy in Children in Europe: A Proposal for a Paediatric European Baseline Series.

Contact allergy to hydroperoxides of limonene and linalool in a pediatric population

Cross-sectional evaluation of the pediatric baseline series in detection of contact sensitization in children

Evaluating the inclusiveness of common allergens in expanded series patch tests for children in the pediatric allergic contact dermatitis registry

BackgroundHydroperoxides of limonene and linalool are potent sensitizers.ObjectivesTo investigate the prevalence of contact allergy to both hydroperoxides of limonene and hydroperoxides of linalool, to report clinical relevance, and to investigate patient demographics.MethodsA total of 821 patients (35.6% male, mean age 42.4 years ± 17.8 years) were consecutively patch tested with our departmental baseline series and our fragrance series, including hydroperoxides of limonene 0.3% pet. and hydroperoxides of linalool 1.0% pet. The clinical relevance was assessed for all positive reactions.ResultsPositive patch test reactions to hydroperoxides of limonene and to hydroperoxides of linalool were observed in 77 patients (9.4%, 95% confidence interval [CI]: 7.4%‐11.4%) and in 96 patients (11.7%, 95%CI: 9.5%‐13.9%), respectively; 38 of these patients (4.6%, 95%CI: 3.2%‐6.0%) reacted to both. Most reactions were considered to be possibly or probably clinically relevant (66.3% and 68.8%, respectively), and a small proportion were deemed to be of certain clinical relevance (18.2% and 19.8%, respectively).ConclusionAs compared with previous studies, high numbers of positive reactions to both hydroperoxides of limonene and hydroperoxides of linalool were observed, the majority of which were clinically relevant, supporting their inclusion in the European baseline series.

Pigmented contact dermatitis in the axillae caused by hydroperoxides of limonene

Contact allergy rates of linalool and limonene hydroperoxides (HPs) have increased. 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. A retrospective analysis of consecutive dermatitis patients in 2015-2020 was performed. 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. 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 is increasingly recognized as being important in children with eczema. To retrospectively analyse the patch test results in children over the past 10 years, aiming to (1) evaluate demographic characteristics and lesion locations, (2) describe frequencies of positive patch test reactions, and (3) investigate the relationship with atopic dermatitis (AD). A total of 329 children were patch tested between January 2010 and December 2019 with the European (children) baseline series and/or other series, and the personal product(s) used. A total of 119 (36%) children presented with at least one positive reaction. Children with AD had a higher prevalence of positive reactions compared with the non-AD group (P=.002), but without statistically significant difference regarding sensitization to more than one hapten (P=.39). The face (20.2%), hands (19.3%), feet (16.8%), arms (12.6%), and body folds (10.9%) were the most common sites of primary localizations. The most frequent contact allergens were nickel sulfate and linalool hydroperoxide (both 16%), limonene hydroperoxide (13.5%), and para-phenylenediamine (10.9%). No statistically significant difference for nickel sulfate was found between the AD and non-AD group (P=.20). Contact allergy in children with eczema was frequently observed in our tertiary referral centre in Belgium as well, confirming the need for patch testing.

A Patch Testing Initiative for the Investigation of Allergic Contact Dermatitis in a UK Allergy Practice: A Retrospective Study

Background: Data on contact allergies in children are conflicting. This study aims to identify frequent contact allergens and their relevance in children with and without atopic dermatitis (AD). This will allow better identification of potential sensitizers and improve patients' care in children. Methods: We conducted a retrospective study of 1083 patient records of children aged 0-18 years suspected of having contact dermatitis. Children were patch tested between 1996-2013 in 3 University Hospitals in the Netherlands. Patch testing was performed using the Chamber technique and the TRUE test. Patients were excluded (n = 71) when not tested with at minimum the European Baseline Series. Results of additional patch tested series, tested “on indication” according to the patient history, were also evaluated. The primary analysis was performed on routinely tested allergens, while the secondary analysis was performed on the combined data from routinely tested allergens plus allergens tested “on indication”. Provided relevance scores are the current “certain” and “probable” relevance scores combined. Statistical analysis was performed with Chi-square or Fisher's exact test. Results: 1012 children (female 63%, mean age 13 years) were included, and 469 (46%) of children developed ≥1 positive reaction. The most frequent reactions were to nickel (16,4%: 164/998), cocamidopropyl betaine (CAPB) (15,9%: 54/339), fragrance mix I (9,9%: 100/1008), Amerchol L-101 (8,8%: 30/339) and wool alcohols (6,2%: 63/1009). 52% of children had AD, 39% did not have AD and in 9% had an unknown atopic status. Sensitization rates for children with and without AD were similar (48% vs. 47%). In children with AD, CAPB was the most frequent allergen (19%; 33/174). Compared to children without AD, the primary analysis showed no significant difference. However, when analyzing all reactions to CAPB found in the routinely tested series plus the “on indication” tested series together, a significant difference between children with and without AD was seen for CAPB (17% vs. 9%; p <0.02). Reactions to CAPB were considered relevant in the majority of cases (56%). Reactions to wool alcohols (p <0.04) and fragrances (p <0.05) were found significantly more often in children with AD vs. children without AD, with relevance scores of at least 59% and 63%, respectively. Surprisingly, less positive reactions to wool alcohols and fragrances were found with the TRUE test as compared to the Chamber technique. Conclusion: Sensitisation rates in children with and without AD were similar, but significant differences were found in the reacting allergens between these 2 groups. Reactions to CAPB, fragrances and wool alcohols are more common in children with AD, and these should be tested when a contact dermatitis is suspected in this population. The difference in positive reactions to wool alcohols and fragrances between TRUE test and Chamber technique is striking and needs further investigation.

Contact allergy in children was previously considered to be uncommon. However, data from the last decades have shown an increase in its prevalence, which is thought to result from more frequent exposure to allergens at a younger age, new trends in body piercing, use of cosmetic and pharmaceutical products, and participation in sports and hobbies. Factors that may influence the onset of sensitization in children are atopic dermatitis, skin barrier defects, and intense or repetitive contact with allergens. Although there are many similarities between adult and children with contact allergy, the patch test results obtained in adults cannot always be applied to children. Moreover, the notion of an association between atopy and contact allergy in children has been challenged. Experimental studies have shown that individuals with atopic dermatitis (AD) have suppressed contact sensitivity due to their disease. Patch testing should be considered at early stages in patients with AD; it is indicated not only when contact allergy is suspected but also in cases of persistent eczema on specific localizations, such as on the hands and the feet, around the mouth, and also in the umbilical region. Patients with AD should be tested when multiple exacerbations occur, even when they are treated, or when the dermatitis is asymmetrical. The most frequent contact allergens in children are metals, fragrances, hair dyes, adhesive and rubber chemicals, preservatives, and topical pharmaceutical products. Toys and portable electronic devices are another potential source of hapten exposure in children. Positive reactions in atopic children must be interpreted carefully, as atopic skin is readily irritated; this is specially the case for metals. Patch testing in children is safe, but false-positive reactions can occur. In addition, an abbreviated baseline series, supplemented with allergens suggested by the child’s history, should be tested. The fundamental relationship between atopic disease and environmental chemical exposure in children is complex and occurs more tightly than previously supposed.

To determine the frequency of positive and relevant patch tests in children referred for patch testing in North America; to compare results of patch testing children and adults; and to compare our results with international data on contact allergy in children. Retrospective cross-sectional analyses of North American Contact Dermatitis Group (NACDG) data from January 1, 2001, through December 31, 2004. Patch test reactions for allergens that were positive and considered of clinical importance to the patient's eczematous problem were defined as being of current or past relevance. Clinical patch test data from 13 NACDG members, primarily a referral population. The pediatric population (hereafter referred to as "children") was defined as patients aged 0 to 18 years (n = 391). Patients 19 years and older constituted the comparison adult group (n = 9670). The frequency of positive patch test reactions and number of relevant ones. Secondary measures included the association of atopic markers, frequency of irritant reactions, and sources of relevant supplementary allergens. No significant difference in the overall frequency of at least 1 relevant positive patch test reaction was noted in children (51.2%) compared with adults (54.1%). The most frequent positive reactions in children were to nickel (28.3%), cobalt chloride (17.9%), thimerosal (15.3%), neomycin sulfate (8.0%), gold sodium thiosulfate (7.7%), and fragrance mix (5.1%). For children aged 0 to 18 the most frequent relevant positive reactions were to nickel sulfate (26.0%), cobalt (12.4%), neomycin (4.4%), fragrance mix (4.1%), gold (3.6%), and quaternium 15 (3.6%). The frequency of irritant reactions in adults and children was similar. Of the children with a relevant positive reaction, 34.0% had atopic dermatitis included as one of their final diagnoses, compared with 11.2% of adults (P < .001). Fifteen percent and 39% of children had relevant allergens not included in the NACDG series and a commercially available skin patch test (T.R.U.E. TEST [thin-layer rapid use epicutaneous test], panel 1.1 and 2.1; Allerderm, Phoenix, Arizona), respectively. Adults and children in this group are equally likely to have allergic contact dermatitis; frequency of relevant allergen reactions differs.

The oxidized forms of the fragrance terpenes limonene and linalool are known to cause allergic contact dermatitis. Significant rates of contact allergy to these fragrances have been reported in European studies and in a recent worldwide study. Patch testing to oxidized terpenes is not routinely carried out either in the U.K. or in other centres internationally. To investigate the prevalence of contact allergy to oxidized limonene and linalool in the U.K. Between 1 August 2011 and 31 December 2012, 4731 consecutive patients in 13 U.K. dermatology departments were tested for hydroperoxides of limonene 0·3% pet., hydroperoxides of linalool 1·0% pet., stabilized limonene 10·0% pet. and stabilized linalool 10·0% pet. Doubtful (?+) and equivocal (±) reactions were grouped together as irritant reactions. Two hundred and thirty-seven patients (5·0%) had a positive patch test reaction to hydroperoxides of limonene 0·3% pet. and 281 (5·9%) to hydroperoxides of linalool 1·0% pet. Irritant reactions to one or both oxidized terpenes were found in 242 patients (7·3%). Eleven patients (0·2%) had a positive patch test reaction to the stabilized terpenes alone. This large, multicentre U.K. audit shows a significant rate of allergy to the hydroperoxides of limonene and linalool plus a high rate of irritant reactions. Testing to the oxidized forms alone captures the majority (97·0%; 411 of 422) of positive reactions; testing to nonoxidized terpenes appears to be less useful. We recommend that the hydroperoxides of limonene and linalool be added to an extended baseline patch test series.

Background: Patch testing to a standard series is used to identify culprit allergens in patients with contact dermatitis. The reaction rates evolve over time based on trends in cutaneous exposures by the general population. Objective: The aim of this study was to analyze the patch test results of the Mayo Clinic standard series in patients tested from 2017 to 2021. Methods: The patch test reactions of standard series allergens tested from 2017 to 2021 were retrospectively reviewed and compared with the results of our prior report from 2011 to 2015 as well as the North American Contact Dermatitis Group (NACDG) report from 2017 to 2018. Results: Of 2667 patients tested, 1683 (63.1%) had at least 1 positive reaction. The 15 allergens with the highest reaction rates were hydroperoxides of linalool 1%, nickel (II) sulfate hexahydrate, methylisothiazolinone, Myroxylon pereirae resin, hydroperoxides of linalool 0.5%, methyldibromo glutaronitrile, neomycin sulfate, cobalt (II) chloride hexahydrate, fragrance mix I, benzalkonium chloride, bacitracin, hydroperoxides of limonene, methylchloroisothiazolinone/methylisothiazolinone, p-phenylenediamine, and textile dye mix. Twelve (80%) of these allergens were also in the top 15 of the most recent NACDG report. Conclusions: Hydroperoxides of linalool and hydroperoxides of limonene are new allergens that have been added to our standard series. These are associated with high reaction rates.

Background: Allergic contact Dermatitis (ACD) is a common condition within the pediatric population. Patch testing is an important way to identify relevant allergens. Objective: To provide an update of the common contact allergens seen in children based on patch testing data at our institution from 2016 to 2020. Methods: We performed a retrospective analysis of patch test data from children aged 1-18 years from 2016 to 2020 at Mayo Clinic. Reaction rates were compared to the rates reported by the Pediatric Contact Dermatitis Registry (PCDR). Results: One hundred ninety-two children aged 1-18 were patch tested to various allergens. A total of 15,457 allergens were tested, with 291 positive tests. The top 5 allergens with highest positive reaction rates were hydroperoxides of linalool, hydroperoxides of limonene, methylisothiazolinone, nickel, and cobalt. Seven of the top 38 allergens with the highest reaction rates are not currently included in the Mayo Clinic Pediatric Patch Test Series, and 11 are not currently included in the Pediatric Baseline Series (as developed by the Pediatric Contact Dermatitis Workgroup). Conclusions: Patch testing is a useful tool to diagnose children with ACD. With new products and exposures, there is an opportunity to expand current pediatric patch testing series.

Whether children with atopic dermatitis have an altered risk of contact allergy than children without atopic dermatitis is frequently debated and studies have been conflicting. Theoretically, the impaired skin barrier in atopic dermatitis (AD) facilitates the penetration of potential allergens and several authors have highlighted the risk of underestimating and overlooking contact allergy in children with atopic dermatitis. To determine the prevalence of contact allergy in Danish children with atopic dermatitis and explore the problem of unacknowledged allergies maintaining or aggravating the skin symptoms. In a cross-sectional study, 100 children and adolescents aged 5-17years with a diagnosis of atopic dermatitis were patch tested with a paediatric series of 31 allergens. Thirty per cent of the children had at least one positive patch test reaction, and 17% had at least one contact allergy that was relevant to the current skin symptoms. The risk of contact allergy was significantly correlated to the severity of atopic dermatitis. Metals and components of topical skincare products were the most frequent sensitizers. Patch testing is relevant as a screening tool in the management of children with atopic dermatitis as they may have unacknowledged contact allergies contributing to or maintaining their skin symptoms. Children with atopic dermatitis seem to be at greater risk of sensitization to certain allergens including metals and components of skincare products.