Pre-emptive avoidance strategy 2016: update on pediatric contact dermatitis allergens

KEYWORDS:

• pediatric
• contact dermatitis
• dermatitis
• allergy
• allergen
• pre-emptive avoidance strategy

1. Introduction

While there are thousands of chemicals known to be skin sensitizers, it is notable that less than 100 account for the majority of reactions [1]. A significant proportion of these sensitization reactions in children are reported to occur in association with exposure to the haptens (allergens) contained in the everyday personal care products [2]. In a recent study by the Pediatric Contact Dermatitis Registry (PCDR), 48% of tested children were found to be contact sensitized (on par with the North American Contact Dermatitis Group (NACDG) overall patch test results). This was unexpected given that the adults had 30 more years of exposure to acquire sensitization, based on mean ages and demonstrates the impact of personal hygiene products and routine use items. Notably, 65% clinical relevance was found in both the PCDR and the NACDG data sets with the detection of a relevant contact allergen being identified as causing allergic contact dermatitis (ACD) [3].

1.1. Prior research – background

In 2015, we performed a systematic review of recent pediatric contact dermatitis studies reporting data on rates of positive patch tests in children referred for patch testing for suspected contact dermatitis. The five studies (Jacob et al. in 2008, Hammonds et al. in 2009, Fortina et al. in 2010, Jacob et al. in 2011, and Zug et al. in 2014) [4] were chosen based on four criteria: published within 5 years, reported only pediatric results, reported numerical rates of patch test results for specific allergens, and included results from children both with and without atopic dermatitis. In the original analysis, a total of 1,507 children aged 3 months to 18.9 years, with a mean age of 10.8 years, were tested across the five included studies between year and year [4].

2. Methods

Since the publication of the original Pre-Emptive Avoidance Strategy (P.E.A.S.) article, the PCDR has released its inaugural US-based pediatric patch test data [3]. Given that PCDR (2016) and NACDG [5] (2014) pediatric data [5] are independent databases, a meta-analysis of the two studies which met the prior P.E.A.S. analysis criteria was performed. There were a total of 2,025 children patch tested, aged 7 months to 18 years (with a mean age of 11.1 years in the PCDR and 13.3 years in the NACDG) [3,5].

We reproduced the methods of the initial P.E.A.S. study [4], and the tallied final prevalence results are reported as a ‘top twenty-five list’ of sensitizing allergens in children (see Table 1). This table compares these allergens to the top 10 allergens presented in the original P.E.A.S. study.

Table 1. Top 25 allergens in personal care products.

Allergen	Prevalence (%) 2016	Prevalence (%) 2000–2012 P.E.A.S.^a
1. Fragrance mix I 8% pet	8.34	4.56
2. Balsam of Peru (myroxylon pereirae) 25% pet	7.13	4.92
3. Neomycin sulfate 20% pet	7.05	5.77
4. Bacitracin 20% pet	5.67	N/C
5. Wool (wax) alcohols 30%	4.73	N/C
6. Formaldehyde 1% aq	4.43	2.89
7. Methylisothiazolinone 0.2% aq	4.29	N/R
8. Bronopol (2-bromo-2-nitropropane-1,3-diol) 0.5% pet	3.81	N/C
9. Propylene glycol 30% aq	3.77	2.03
10. Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) 0.01%	3.50	2.61
11. Quaternium-15 2% pet	3.42	N/C
12. Fragrance mix II 14% pet	3.30	N/C
13. Amerchol-L101-lanolin alcohol 50% pet	3.24	4.34
14. Cocamidopropyl betaine 1% aq	3.23	2.89
15. p-Phenylenediamine 1% pet	2.72	N/C
16. Decyl glucoside 5% pet	2.70	N/R
17. Propolis 10% pet	2.55	N/C
18. Compositae mix 6% pet	2.17	N/C
19. Colophony 20% pet	2.17	N/C
20. Iodopropynyl butylcarbamate 0.5% pet	1.95	N/C
21. Tixocortol-21-pivalate 1% pet	1.84	1.73
22. Sorbitan aesquioleate 5% pet	1.66	N/C
23. Cinnamic aldehyde 1% pet	1.60	N/C
24. Methyldibromoglutaronitrile (MDBGN)/phenoxyethanol 2% pet	1.59	N/C
25. Diazolidinyl urea 1% pet	1.42	N/C
Nickel sulfate	24.24	22.70
Cobalt chloride	10.40	8.57

While nickel and for the most part cobalt (with the exception of some cosmetics) are top sensitizers in children and generally not utilized in personal care products marketed to children, they should be considered for preemptive avoidance in children with eczema-related illness. Pet: petrolatum; N/C: not calculated; N/R: not reported.

^aOnly the top 10 allergens were calculated for P.E.A.S. 2015 publication.

3. Results

With the exception of Amerchol-L101-lanolin alcohol, all allergens were observed to have an increase in prevalence from the prior study period. Notably, wool (Wax) alcohols (a lanolin group substrate) were tested in the new study period and had a prevalence rate of 4.73%, underscoring the need to test for both wool wax alcohols and lanolin to increase detection rates [6].

Overall, the highest increases in the prevalence rates were seen for fragrance mix I (FM I) and balsam of Peru, which increased by 3.78 and 2.21 percentage points, respectively, to 8.34% and 7.13%. Fragrance mix II (FM II) was also included in the new study period and demonstrated a 3.30% prevalence rate. These trends may represent increasing sensitization rates, referral bias, or potentially an increase in testing pediatric patients with atopic dermatitis, where a significant frequency of fragrance allergy has been reported [7]. Propylene glycol was also noted to have a 1.74% increase to 3.77% from 2.03% and formaldehyde demonstrated a 1.54% increase from 2.89% to 4.43%. Cocamidopropyl betaine (2.89%–3.23%) and tixocortol (1.73%–1.84%) had slight increases in prevalence, but dropped off the top 10 allergen list, as methylisothiazolinone (MI) and bronopol emerged on the new analysis’s top 10. Importantly, the 2016 P.E.A.S. update reflects that the PCDR data specifically reported children tested with MI in addition to methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and found an increased detection rate of this problematic allergen. There was a 0.89% increase in the prevalence of MCI/MI detection from 2.61% to 3.50%, with the PCDR reporting a prevalence rate of MI of 4.4%. This high rate to MI suggests the epidemic sensitivity to MI that has been well documented around the globe is now also occurring in US children.

4. Discussion

The significant associations Ponten et al. have reported between contact allergy to MCI/MI and/or MI and FM I and/or FM II, and between formaldehyde and FM I and/or FM II, in the context of increased sensitization rates suggest that studies are needed to evaluate the sensitizing-potential relationship between these allergens and ACD [8]. Finally, new to the list are the glucosides, which are formed by reacting an alcohol with a cyclic form of the sugar, glucose or glucose polymers. Glucosides are found in a number of pediatric intended care products from shampoo to cleansing products to sunscreens [9].

Notable 10 of the top 25 allergens (40%) have the potential to go undetected if comprehensive testing is not performed, as these allergens are not included in the commercially available patch test screening kit (TRUE TEST^TM, Smartpractice, AZ). Adequate testing is needed to provide the correct confirmatory diagnosis and guide treatment. Table 1 reveals the top 25 allergens with high clinical relevance that can be used as a resource to direct patch test allergen selection or preemptive avoidance. Exposure history taking and allergen selection for children can be challenging due to the potential for them to be exposed in daycare-school, home, or indirectly from caregivers.

In the not too distant past, it was believed that ACD in children was uncommon. ‘It is clear that ACD in children (short of nickel allergy) is not very common’ [10]; we now have the evidence to prove that this notion is incorrect. Furthermore, it was believed that ‘Applying these proven allergens over and over to an infant’s occluded, wet, and often dermatitic skin should assure an ongoing collection of sensitized adults with allergic contact dermatitis (ACD) that we can evaluate and help for many years’ [10]. We now know that applying [these] proven allergens over and over leads to the same rates of sensitization in children as those seen in adults [3].

Limitations of this study include variability in allergens tested across multiple studies, protocol differences in final reading times, regional variations in exposure patterns, and referral bias to tertiary care centers.

5. Conclusion

It is vital that the true burden on pediatric contact dermatitis be recognized and that the known proven allergens either be removed from child-intended personal products, or preemptively avoided by the consumer. Table 1 can serve as a guide to providers and consumers who are looking to avoid the top sensitizing chemicals found in personal care products today.

Declaration of interest

SE Jacob received an American Contact Dermatitis Society Mid-Career Development award to support an education endeavor in information technology acquisition in association with this project. She was the Coordinating Principal Investigator on the PREA-1 and PREA-2 Trials. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.