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Contact Dermatitis to Isothiazolinone Preservatives

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Abstract

Purpose of Review

Allergic contact dermatitis due to isothiazolinone derivatives is frequently observed both in consumers and in occupational exposures. In this article, we will review contact dermatitis to the most commonly used isothiazolinones, including trends in rates of allergy globally based on legislative changes, as well as looking at clinical presentation, diagnostic, and future considerations.

Recent Findings

Isothiazolinone derivatives are ubiquitous in cosmetic, cleaning, and industrial products and are a significant cause of allergic contact dermatitis as highlighted by the epidemic of allergy seen with methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and methylisothiazolinone (MI) which peaked in 2013–2014 in the EU. Changes in EU cosmetic legislation have led to a reduction in cases of allergic contact dermatitis from MCI/MI and MI. However, there is a degree of variability in legislation regarding permitted use in Europe and internationally, with cases in the USA and Canada still remaining high. We are also seeing an emergence of cases from other isothiazolinones, particularly benzisothiazolinone (BIT), increasingly being used by the chemical industry, resulting in not only occupational contact allergy but also an issue for consumers using non-cosmetic products such as in paints, detergents, and glues. The clinical presentation is variable and often reflected by the exposure pattern and isothiazolinone involved based on its permitted use in that particular part of the world. Patch testing is the gold standard for diagnosing allergic contact dermatitis and although generally accepted patch test concentrations for the isothiazolinones have been detailed, the appropriate patch test concentrations for BIT and octylisothiazolinone (OIT) may still need to be established.

Summary

Isothiazolinone contact dermatitis remains a significant issue despite legislative changes. Globally, a review of the regulations relating to use of these preservatives in cosmetic, detergent and industrial materials is required. Furthermore, issues with regard to accurate labelling and the presence of isothiazolinones in medical devices and the chemical industry require further legislation. There is a potential risk from newer and currently lesser known isothiazolinone derivatives causing contact allergy going forward.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Deza G, Gimenez-Arnau AM. Allergic contact dermatitis in preservatives: current standing and future options. Curr Opin Allergy Clin Immunol. 2017;17(4):263–8.

    Article  CAS  PubMed  Google Scholar 

  2. Williams T. The mechanism of action of isothiazolinone biocides. Powerplant Chem. 2007;9:14–22.

    CAS  Google Scholar 

  3. Schwensen JF, Menne Bonefeld C, Zachariae C, et al. Cross-reactivity between methylisothiazolinone, octylisothiazolinone and benzisothiazolinone using a modified local lymph node assay. Br J Dermatol. 2017;176:176–83.

    Article  CAS  PubMed  Google Scholar 

  4. Alexander BR. An assessment of the comparative sensitization potential of some common isothiazolinones. Contact Dermatitis. 2002;46:191–6.

    Article  CAS  PubMed  Google Scholar 

  5. de Groot AC, Liem DH, Weyland JW. Kathon CG: cosmetic allergy and patch test sensitization. Contact Dermatitis. 1985;12(2):76–80.

    Article  PubMed  Google Scholar 

  6. Wilkinson JD, Shaw S, Andersen KE, et al. Monitoring levels of preservative sensitivity in Europe. A 10-year overview (1991–2000). Contact Dermatitis. 2002;46(4):207–10.

    Article  CAS  PubMed  Google Scholar 

  7. Leiva-Salinas M, Frances L, Marin-Cabanas I, et al. Methylchloroisothiazolinone/methylisothiazolinone and methylisothiazolinone allergies can be detected by 200 ppm of methylchloroisothiazolinone/methylisothiazolinone patch test concentration. Dermatitis. 2014;25(3):130–4.

    Article  CAS  PubMed  Google Scholar 

  8. Leiva-Salinas M, Frances L, Silvestre JF. Update on allergic contact dermatitis due to methylchloroisothiazolinone/methylisothiazolinone and methylisothiazolinone. Actas Dermosifiliogr. 2014;105(9):840–6.

    Article  CAS  PubMed  Google Scholar 

  9. Latheef F, Wilkinson SM. Methylisothiazolinone outbreak in the European Union. Curr Opin Allergy Clin Immunol. 2015;15(5):461–6.

    Article  CAS  PubMed  Google Scholar 

  10. European Union Scientific Committee on Consumer Safety (SCCS). http://ec.europa.eu/health/archive/ph_risk/committees/04_sccp/docs/sccp_o_060.pdf. Accessed 6 Jan 2023.

  11. European Union Scientific Committee on Consumer Safety (SCCS). http://ec.europa.eu/health/ph_risk/committees/sccp/documents/out270_en.pdf. Accessed 6 Jan 2023.

  12. SCCS. Scientific committee on consumer safety, opinion on methylisothiazolinone (p 94) – submission ii, 12 December 2013, sccs/1521/13, revision of 27 march 2014. European Commission; 2014.

    Google Scholar 

  13. SCCS. Scientific committee on consumer safety, opinion on methylisothiazolinone (mi) (p 94) sensitisation only, 25 June 2015, sccs/1557/15, final opinion December 2015. European Commission; 2015.

    Google Scholar 

  14. Urwin R, Craig S, Latheef F, Wilkinson M. Methylisothiazolinone: the epidemic is declining – but not gone. Contact Dermatitis. 2017;76:301–2.

    Article  PubMed  Google Scholar 

  15. • Uter W, Aalto-Korte K, Agner T, Andersen K, Bircher A, et al. The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures. J Eur Acad Dermatol Venereol. 2020;34:333–9. Demonstrated that as a consequence of regulation, allergic contact dermatitis from MI in cosmetics (leave-on in particular) is decreasing.

  16. Herman A, Aerts O, de Montjoye L, et al. Isothiazolinone derivatives and allergic contact dermatitis: a review and update. J Eur Acad Dermatol Venereol. 2019;33:267–76.

    Article  CAS  PubMed  Google Scholar 

  17. Pedersen NB. Occupational allergy from 1,2-benzisothiazolin-3-one and other preservatives in plastic emulsions. Contact Dermatitis. 1976;2:340–2.

    Article  CAS  PubMed  Google Scholar 

  18. Thormann J. Contact dermatitis to a new fungicide, 2-n-octyl-4-isothiazolin-3-one. Contact Dermatitis. 1982;8:204.

    Article  CAS  PubMed  Google Scholar 

  19. Geier J, Lessmann H, Schnuch A, Uter W. Concomitant reactivity to methylisothiazolinone, benzisothiazolinone, and octylisothiazolinone. International Network of Departments of Dermatology data, 2009–2013. Contact Dermatitis. 2015;72(5):337–9.

    Article  CAS  PubMed  Google Scholar 

  20. Craig S, Urwin R, Latheef F, Wilkinson M. Patch test clinic experience of potential cross-reactivity of isothiazolinones. Contact Dermatitis. 2017;76(5):299–300.

    Article  PubMed  Google Scholar 

  21. •• Russo JP, Aerts O. In vivo demonstration of immunologic cross-reactivity to octylisothiazolinone in patients primarily and strongly sensitized to methylisothiazolinone. Contact Dermatitis. 2020;83(5):391–7. Established that patients primarily and strongly sensitized to MI may show immunologic cross-reactions to OIT, and to a lesser extent to BIT.

  22. Aalto-Korte K, Suuronen K. Patterns of concomitant allergic reactions in patients suggest cross-sensitization between octylisothiazolinone and methylisothiazolinone. Contact Dermatitis. 2017;77(6):385–9.

    Article  CAS  PubMed  Google Scholar 

  23. Holden C, Sabroe R. The frequency of contact allergy to four isothiazolinones in a general patch-test population, including a pilot study to determine the optimum patch test concentrations of benzisothiazolinone and octylisothiazolinone. Contact Dermatitis. 2016;75(suppl. 1):37–59.

    Google Scholar 

  24. Aerts O, Baeck M, Constandt L, et al. The dramatic increase in the rate of methylisothiazolinone contact allergy in Belgium: a multicentre study. Contact Dermatitis. 2014;71:41–8.

    Article  CAS  PubMed  Google Scholar 

  25. •• King N, Latheef F, Wilkinson M. Trends in preservative allergy: benzisothiazolinone emerges from the pack. Contact Dermatitis. 2021;85(6):637–42. Demonstrated a significant increase in the prevalence of contact allergy to BIT compared to other newer isothiazolinones, probably as a consequence of increased use in household products and highlighted BIT as the one to watch out for.

  26. DeKoven JG, Silverberg JI, Warshaw EM, Atwater AR, Reeder MJ, Sasseville D, et al. North American Contact Dermatitis Group Patch Test Results: 2017–2018. Dermatitis. 2021;32(2):111–23.

    Article  PubMed  Google Scholar 

  27. Bruze M, Goossens A, Isaksson M. Recommendation to increase the test concentration of methylchloroisothiazolinone/methylisothiazolinone in the European baseline patch test series - on behalf of the European Society of Contact Dermatitis and the European Environmental and Contact Dermatitis Research Group. Contact Dermatitis. 2014;71(1):35–40.

    Article  CAS  PubMed  Google Scholar 

  28. Isaksson M, Gruvberger B, Bruze M. Patch testing with serial dilutions of various isothiazolinones in patients hypersensitive to methylchloroisothiazolinone/methylisothiazolinone. Contact Dermatitis. 2014;70(5):270–5.

    Article  CAS  PubMed  Google Scholar 

  29. Lundov MD, Krongaard T, Menne TL, Johansen JD. Methylisothiazolinone contact allergy: a review. Br J Dermatol. 2011;165(6):1178–82.

    Article  CAS  PubMed  Google Scholar 

  30. Urwin R, Wilkinson M. Methylchloroisothiazolinone and methylisothiazolinone contact allergy: a new “epidemic.” Contact Dermatitis. 2013;68(4):253–5.

    Article  PubMed  Google Scholar 

  31. Isaksson M, Andersen KE, Goncalo M, et al. Multicentre patch testing with methylisothiazolinone by the European Environmental and Contact Dermatitis Research Group. Contact Dermatitis. 2014;70(5):317–20.

    Article  CAS  PubMed  Google Scholar 

  32. Bruze M, Engfeldt M, Goncalo M, Goossens A. Recommendation to include methylisothiazolinone in the European baseline patch test series–on behalf of the European Society of Contact Dermatitis and the European Environmental and Contact Dermatitis Research Group. Contact Dermatitis. 2013;69(5):263–70.

    Article  CAS  PubMed  Google Scholar 

  33. •• Isaksson M, Andersen KE, Elsner P, et al. Patch testing with methylchloroisothiazolinone/methylisothiazolinone using a new diagnostic mix: a multicenter study from the international contact dermatitis research group. Dermatitis. 2020;82(5):283–9. Showed that a new aqueous mix of MCI 0.015% and MI 0.2% detected significantly more patients with MCI/MI allergy than the currently used preparations baseline preparations of MCI/MI 0.02% and MI 0.2%.

  34. Wilkinson M, Gonçalo M, Aerts O, et al. The European baseline series and recommended additions: 2019. Contact Dermatitis. 2019;80(1):1–4.

    Article  PubMed  Google Scholar 

  35. • Herman A, Aerts O, Jacobs MC, et al. Evolution of methylisothiazolinone sensitization: a Belgian multicentric study from 2014 to 2019. Contact Dermatitis. 2021;85(6):643–9. Showed that contact allergy to MI in Belgium has reached a pre-epidemic level, as a result of regulatory measures. Also that leave-on cosmetics, in contrast to rinse-off products, have almost disappeared as sensitization sources in Europe and that paints and detergents remain problematic and a high number of patients (co)sensitized to BIT should be a focus of future research.

  36. Chew AL, Maibach HI. 1,2-Benzisothiazolin-3-one (Proxel): irritant or allergen? A clinical study and literature review. Contact Dermatitis. 1997;36(3):131–6.

    Article  CAS  PubMed  Google Scholar 

  37. Emmett EA, Ng SK, Levy MA, Moss JN, Morici IJ. The irritancy and allergenicity of 2-n-octyl-4-isothiazolin-3-one (Skane M-8), with recommendations for patch test concentration. Contact Dermatitis. 1989;20:21–6.

    Article  CAS  PubMed  Google Scholar 

  38. Uter W, Geier J, Bauer A, Schnuch A. Risk factors associated with methylisothiazolinone contact sensitization. Contact Dermatitis. 2013;69(4):231–8.

    Article  CAS  PubMed  Google Scholar 

  39. McFadden JP, Mann J, White JM, et al. Outbreak of methylisothiazolinone allergy targeting those aged >/=40 years. Contact Dermatitis. 2013;69(1):53–5.

    Article  CAS  PubMed  Google Scholar 

  40. Admani S, Matiz C, Jacob SE. Methylisothiazolinone: a case of perianal dermatitis caused by wet wipes and review of an emerging pediatric allergen. Pediatr Dermatol. 2014;31(3):350–2.

    Article  PubMed  Google Scholar 

  41. Salman A, Demir G, Apti Ö. “Slime”: a trending cause of isothiazolinone contact allergy in children. Contact Dermatitis. 2019;80(6):409–11.

    Article  PubMed  Google Scholar 

  42. Lundov MD, Kolarik B, Bossi R, Gunnarsen L, Johansen JD. Emission of isothiazolinones from water-based paints. Environ Sci Technol. 2014;48:6989–94.

    Article  CAS  PubMed  Google Scholar 

  43. Lundov MD, Friis UF, Menne T, Johansen JD. Methylisothiazolinone in paint forces a patient out of her apartment. Contact Dermatitis. 2013;69(4):252–3.

    Article  PubMed  Google Scholar 

  44. Lundov MD, Menne T. Airborne exposure to methylchloroisothiazolinone and methylisothiazolinone from a toilet cleaner. Contact Dermatitis. 2013;68(4):252–3.

    Article  PubMed  Google Scholar 

  45. Lundov MD, Mosbech H, Thyssen JP, et al. Two cases of airborne allergic contact dermatitis caused by methylisothiazolinone in paint. Contact Dermatitis. 2011;65(3):176–9.

    Article  PubMed  Google Scholar 

  46. Herry J, Esquirol Y, Giordano-Labadie F. An intriguing occupational atypical dermatitis with respiratory symptoms. Contact Dermatitis. 2016;75:322–3.

    Article  PubMed  Google Scholar 

  47. Aalto-Korte K, Ackermann L, Henriks-Eckerman M-L, et al. 1,2-Benzisothiazolin-3-one in disposable polyvinyl chloride gloves for medical use. Contact Dermatitis. 2007;57:365–70.

    Article  CAS  PubMed  Google Scholar 

  48. André R, Alipour Tehrany Y, Bugey A, et al. Hand dermatitis aggravated by contact allergy to methylisothiazolinone in protective nitrile gloves. Contact Dermatitis. 2022;87(4):383–4.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Amaro C, Santos R, Cardoso J. Contact allergy to methylisothiazolinone in a deodorant. Contact Dermatitis. 2011;64(5):298–9.

    Article  PubMed  Google Scholar 

  50. Vandevenne A, Vanden Broecke K, Goossens A. Sofa dermatitis caused by methylisothiazolinone in a leather-care product. Contact Dermatitis. 2014;71(2):111–3.

    Article  CAS  PubMed  Google Scholar 

  51. Raison-Peyron N, Amsler E, Pecquet C, et al. Severe allergic contact dermatitis caused by octylisothiazolinone in a leather sofa: two new cases. Contact Dermatitis. 2017;77(3):176–8.

    Article  PubMed  Google Scholar 

  52. Alipour Tehrany Y, Quenan S, Bugey A, Piletta P. Allergic contact dermatitis caused by octylisothiazolinone in a leather sofa. Contact Dermatitis. 2018;79(3):188–9.

    Article  PubMed  Google Scholar 

  53. Hunt WTN, Dunnill MG, Sansom JE. Sofa dermatitis again? A case report of allergic contact dermatitis to octylisothiazolinone from a leather reclining chair. Contact Dermatitis. 2019;82(3):161–2.

    Article  PubMed  Google Scholar 

  54. Van Steenkiste E, Goossens A, Meert H, et al. Airborne-induced lymphomatoid contact dermatitis caused by methylisothiazolinone. Contact Dermatitis. 2015;72(4):237–40.

    Article  PubMed  Google Scholar 

  55. Ezzelarab M, Hansson C, Wallengren J. Occupational allergy caused by 1,2-benzisothiazolin-3-one in water-based paints and glues. Am J Contact Dermat. 1994;5:165–7.

    Article  Google Scholar 

  56. Kaur-Knudsen D, Menne T, Christina CB. Systemic allergic dermatitis following airborne exposure to 1,2-benzisothiazolin-3-one. Contact Dermatitis. 2012;67:310–2.

    Article  PubMed  Google Scholar 

  57. Morren MA, Dooms-Goossens A, Delabie J, et al. Contact allergy to isothiazolinone derivatives: unusual clinical presentations. Dermatology. 1992;184:260–4.

    Article  CAS  PubMed  Google Scholar 

  58. Gebhardt M, Looks A, Hipler UC. Urticaria caused by type IV sensitization to isothiazolinones. Contact Dermatitis. 1997;36:314.

    Article  CAS  PubMed  Google Scholar 

  59. Pirmez R, Fernandes AL, Melo MG. Photoaggravated contact dermatitis to Kathon CG (methylchloroisothiazolinone/methylisothiazolinone): a novel pattern of involvement in a growing epidemic? Br J Dermatol. 2015;173:1343–4.

    Article  CAS  PubMed  Google Scholar 

  60. Trokoudes D, Banerjee P, Fityan A, et al. Photoaggravated contact dermatitis caused by methylisothiazolinone. Contact Dermatitis. 2017;76:303–4.

    Article  PubMed  Google Scholar 

  61. Gupta R, Kullberg SA, Warshaw EM. Relevant contact allergy to benzisothiazolinone in a personal care product. Dermatitis. 2020;31:e13–4.

    Article  CAS  PubMed  Google Scholar 

  62. Atkar R, Todd P. Four cases of allergic contact dermatitis caused by methylchloroisothiazolinone/methylisothiazolinone in ironing water. Contact Dermatitis. 2016;75(5):316–7.

    Article  PubMed  Google Scholar 

  63. Marrero-Alemán G, Borrego L, González Antuña A, Macías Montes A, Pérez LO. Persistence of Isothiazolinones in Clothes After Machine Washing. Dermatitis. 2021;32(5):298–300.

    Article  PubMed  Google Scholar 

  64. Hofmann MA, Giménez-Arnau A, Aberer W, Bindslev-Jensen C, Zuberbier T. MI (2-methyl-4-isothiazolin-3-one) contained in detergents is not detectable in machine washed textiles. Clin Transl Allergy. 2018;8:1.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Aerts O, Goossens A, Lambert J, Lepoittevin JP. Contact allergy caused by isothiazolinone derivatives: an overview of non-cosmetic and unusual cosmetic sources. Eur J Dermatol. 2017;27:115–22.

    Article  CAS  PubMed  Google Scholar 

  66. Horev L, Isaksson M, Engfeldt M, Persson L, Ingber A, Bruze M. Preservatives in cosmetics in the Israeli market conform well to the EU legislation. J Eur Acad Dermatol Venereol. 2015;29:761–6.

    Article  CAS  PubMed  Google Scholar 

  67. Isaksson M, Persson L. ‘Mislabelled’ make-up remover wet wipes as a cause of severe, recalcitrant facial eczema. Contact Dermatitis. 2015;73:56–9.

    Article  PubMed  Google Scholar 

  68. Aerts O, Meert H, Goossens A, Janssens S, Lambert J, Apers S. Methylisothiazolinone in selected consumer products in Belgium: adding fuel to the fire? Contact Dermatitis. 2015;73:142–9.

    Article  CAS  PubMed  Google Scholar 

  69. Santiago L, Goncalo M. Occupational allergic contact dermatitis caused by Acticide MV, a brand name for the mixture methylchloroisothiazolinone/methylisothiazolinone. Contact Dermatitis. 2018;79:46–7.

    Article  PubMed  Google Scholar 

  70. Madsen JT, Broesby-Olsen S, Andersen KE. Undisclosed methylisothiazolinone in an ultrasound gel causing occupational allergic contact dermatitis. Contact Dermatitis. 2014;71:312–3.

    Article  PubMed  Google Scholar 

  71. Changes to the Cosmetic Ingredient Hotlist. Government of Canada. https://www.canada.ca/en/health-canada/services/consumer-product-safety/cosmetics/cosmetic-ingredient-hotlist-prohibited-restricted-ingredients/changes.html. Accessed 6 Jan 2023.

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Acknowledgements

We acknowledge the help of Dr. Vikas Sharma (MD) in helping draw the chemical structures of isothiazolinones diagram and help with formatting for presentation.

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  1. Leeds Centre for Dermatology, Leeds Teaching Hospitals NHS Trust, Leeds, LS7 4SA, UK

    Faheem Latheef & Stephen Mark Wilkinson

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  1. Faheem Latheef
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Correspondence to Faheem Latheef.

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Latheef, F., Wilkinson, S.M. Contact Dermatitis to Isothiazolinone Preservatives. Curr Derm Rep 12, 38–44 (2023). https://doi.org/10.1007/s13671-023-00387-8

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