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. 2023 Mar 1;159(3):267-274.
doi: 10.1001/jamadermatol.2022.5991.

Trends in the Prevalence of Methylchloroisothiazolinone/Methylisothiazolinone Contact Allergy in North America and Europe

Margo J Reeder  1 , Erin Warshaw  2   3   4 , Srikanth Aravamuthan  1 , Donald V Belsito  5 , Johannes Geier  6 , Mark Wilkinson  7 , Amber Reck Atwater  8 , Ian R White  9 , Jonathan I Silverberg  10   11 , James S Taylor  12 , Joseph F Fowler Jr  13 , Howard I Maibach  14 , Joel G DeKoven  15 , Timo Buhl  16 , Nina Botto  14 , Ana Maria Giménez-Arnau  17 , Rosella Gallo  18 , Christen Mowad  19 , Claudia C V Lang  20 , Vincent A DeLeo  21 , Graham Johnston  22 , Melanie D Pratt  23 , Knut Brockow  24 , Brandon L Adler  21 , Marie-Claude Houle  25 , Heinrich Dickel  26 , Marie Louise A Schuttelaar  27 , JiaDe Yu  28 , Radoslaw Spiewak  29 , Cory Dunnick  30 , Francesca Larese Filon  31 , Skaidra Valiukeviciene  32 , Wolfgang Uter  33
Affiliations

Trends in the Prevalence of Methylchloroisothiazolinone/Methylisothiazolinone Contact Allergy in North America and Europe

Margo J Reeder et al. JAMA Dermatol. .

Abstract

Importance: The common use of isothiazolinones as preservatives is a global cause of allergic contact dermatitis. Differences in allowable concentrations of methylisothiazolinone (MI) exist in Europe, Canada, and the US.

Objective: To compare the prevalence of positive patch test reactions to the methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) combination and MI alone in North America and Europe from 2009 to 2018.

Design, setting, and participants: This retrospective analysis of North American Contact Dermatitis Group, European Surveillance System on Contact Allergies (ESSCA), and the Information Network of Departments of Dermatology (IVDK) databases included data from patients presenting for patch testing at referral patch test clinics in North America and Europe.

Exposures: Patch tests to MCI/MI and MI.

Main outcomes and measures: Prevalence of allergic contact dermatitis to MCI/MI and MI.

Results: From 2009 to 2018, participating sites in North America and Europe patch tested a total of 226 161 individuals to MCI/MI and 118 779 to MI. In Europe, positivity to MCI/MI peaked during 2013 and 2014 at 7.6% (ESSCA) and 5.4% (IVDK) before decreasing to 4.4% (ESSCA) and 3.2% (IVDK) during 2017 and 2018. Positive reactions to MI were 5.5% (ESSCA) and 3.4% (IVDK) during 2017 and 2018. In North America, the frequency of positivity to MCI/MI increased steadily through the study period, reaching 10.8% for MCI/MI during 2017 and 2018. Positive reactions to MI were 15.0% during 2017 and 2018.

Conclusions and relevance: The study results suggest that in contrast to the continued increase in North America, isothiazolinone allergy is decreasing in Europe. This trend may coincide with earlier and more stringent government regulation of MI in Europe.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Reeder reported personal fees from the American Contact Dermatitis Society and UpToDate outside the submitted work. Dr Warshaw reported grants and personal fees from Wen by Chaz Dean and personal fees from Noven Pharmaceuticals outside the submitted work. Dr Geier reported grants from VCI, the German Cosmetic, Toiletry, Perfumery and Detergent Association, and Schuelke during the conduct of the study and outside the submitted work. Dr Atwater reported employment with Eli Lilly and Company, grants from Pfizer, and personal fees from Henkel, Household & Commercial Products Assoc, and NC Derm Society outside the submitted work. Dr Taylor reported other noncontrolling stock and dividends from Cigna Health, Johnson and Johnson, AstraZeneca, Merck, and Opko Health, grants from Kao Corporation, and personal fees from Bayer Monsanto outside the submitted work; his child is a Pfizer employee. Dr Fowler reported personal fees from SmartPractice Inc outside the submitted work. Dr Giménez-Arnau reported grants from Uriach Pharma/Neucor, Novartis, Instituto Carlos III- FEDER and personal fees from Leo Pharma, Celldex, Thermo Fisher Scientific, GSK, Sanofi-Regeneron, Amgen, and Avene outside the submitted work. Dr Johnston reported personal fees from Sanofi and Canute outside the submitted work. Dr Pratt reported personal fees from AbbVie, Novartis, Leo, Sanofi, Janssen, Sun Pharma, and UCB outside the submitted work. Dr Adler reported grants from AbbVie and personal fees from Skin Research Institute, LLC outside the submitted work. Dr Spiewak reported personal fees from the Institute of Dermatology (Krakow, Poland) outside the submitted work. Dr Uter reported travel reimbursement and research funding from the International Fragrance Research Organisation. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Time Course of Sensitization to Combination Methylchloroisothiazolinone (MCI)/Methylisothiazolinone (MI) and MI Alone Diagnosed by Patch Testing Consecutive Patients in Context of Regulatory Timeline
A, The MCI/MI was tested at concentrations of 0.01%, 0.02%, or thin-layer rapid-use epicutaneous test. By US regulations, MCI/MI should not exceed 7.5 ppm in leave-on products or 15 ppm in rinse-off products. B, The MI was tested at concentrations of 0.01%, 0.02%, or 0.2%. Maximum recommended concentration for MI in rinse-off products is 100 ppm and is considered to be safe in leave-on products provided the concentration is nonsensitizing. ESSCA indicates European Surveillance System on Contact Allergies; IVDK, Information Network of Departments of Dermatology; NACDG, North American Contact Dermatitis Group; ppm, parts per million; SCCS, EU Scientific Committee on Consumer Safety.
Figure 2.
Figure 2.. Sensitization to Methylisothiazolinone (MI) From 2009 to 2018
Time course of sensitization to MI, diagnosed by patch testing consecutive patients with 0.02% aqueous (aq), 0.05% aq, and 0.2% aq, respectively, between 2009 and 2018 in the participating departments of the North American Contact Dermatitis Group (NACDG), European Surveillance System on Contact Allergies (ESSCA), and Information Network of Departments of Dermatology (IVDK). Results with fewer than 200 patients per 2-year interval were omitted; data from “West” during the final period were omitted owing to a substantial reduction of contributing UK departments from 4 to 1 during that period and freshly joined departments in the Netherlands; thus, there was no continuity.
Figure 3.
Figure 3.. Sensitization to Methylchloroisothiazolinone (MCI)/Methylisothiazolinone (MI) From 2009 to 2018
Time course of sensitization to MCI/MI, diagnosed by patch testing consecutive patients with 0.01% aqueous (aq) and 0.02% aq, respectively, between 2009 and 2018 in the participating departments of the North American Contact Dermatitis Group (NACDG), European Surveillance System on Contact Allergies (ESSCA), and Information Network of Departments of Dermatology (IVDK). Results with fewer than 200 patients per 2-year interval were omitted. Furthermore, 200 parts per million data from the “East” were omitted.
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