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Contact dermatitis

Nature Reviews Disease Primers volume 7, Article number: 38 (2021) Cite this article

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Abstract

Contact dermatitis (CD) is among the most common inflammatory dermatological conditions and includes allergic CD, photoallergic CD, irritant CD, photoirritant CD (also called phototoxic CD) and protein CD. Occupational CD can be of any type and is the most prevalent occupational skin disease. Each CD type is characterized by different immunological mechanisms and/or requisite exposures. Clinical manifestations of CD vary widely and multiple subtypes may occur simultaneously. The diagnosis relies on clinical presentation, thorough exposure assessment and evaluation with techniques such as patch testing and skin-prick testing. Management is based on patient education, avoidance strategies of specific substances, and topical treatments; in severe or recalcitrant cases, which can negatively affect the quality of life of patients, systemic medications may be needed.

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Fig. 1: Top sensitizers in various regions worldwide.
Fig. 2: Schematic representation of the pathophysiology of ICD and ACD.
Fig. 3: Recognition of haptens and metal allergens by the innate immune system.
Fig. 4: Typical CD reactions to various chemicals.
Fig. 5: Diagnostic algorithms for contact dermatitis.
Fig. 6: Grading system for patch test reactions.
Fig. 7: Suggested algorithm for the treatment of allergic contact dermatitis.

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References

  1. Alinaghi, F., Bennike, N. H., Egeberg, A., Thyssen, J. P. & Johansen, J. D. Prevalence of contact allergy in the general population: A systematic review and meta-analysis. Contact Dermatitis 80, 77–85 (2019). This review and meta-analysis provides extensive information on contact allergy prevalence in the general population, including data from 28 studies between 2007 and 2017, and over 20,000 individuals from multiple continents who underwent patch testing.

    Article  CAS  PubMed  Google Scholar 

  2. Diepgen, T. L. et al. Prevalence of contact allergy in the general population in different European regions. Br. J. Dermatol. 174, 319–329 (2016).

    Article  CAS  PubMed  Google Scholar 

  3. Bains, S. N., Nash, P. & Fonacier, L. Irritant contact dermatitis. Clin. Rev. Allergy Immunol. 56, 99–109 (2019).

    Article  CAS  PubMed  Google Scholar 

  4. DeKoven, J. G. et al. North American Contact dermatitis group patch test results: 2015-2016. Dermatitis 29, 297–309 (2018).

    Article  PubMed  Google Scholar 

  5. Zug, K. A. et al. Patch testing in children from 2005 to 2012: results from the North American contact dermatitis group. Dermatitis 25, 345–355 (2014).

    Article  PubMed  Google Scholar 

  6. Goldenberg, A. et al. Pediatric contact dermatitis registry inaugural case data. Dermatitis 27, 293–302 (2016).

    Article  PubMed  Google Scholar 

  7. Ortiz Salvador, J. M. et al. Pediatric allergic contact dermatitis: clinical and epidemiological study in a Tertiary Hospital. Actas Dermosifiliogr. 108, 571–578 (2017).

    Article  CAS  PubMed  Google Scholar 

  8. Hinton, A. N. & Goldminz, A. M. Feeling the burn: phototoxicity and photoallergy. Dermatol. Clin. 38, 165–175 (2020).

    Article  CAS  PubMed  Google Scholar 

  9. Pongpairoj, K. et al. Proposed ICDRG classification of the clinical presentation of contact allergy. Dermatitis 27, 248–258 (2016).

    Article  CAS  PubMed  Google Scholar 

  10. Pesonen, M., Koskela, K. & Aalto-Korte, K. Contact urticaria and protein contact dermatitis in the Finnish register of occupational diseases in a period of 12 years. Contact Dermatitis 83, 1–7 (2020).

    Article  CAS  PubMed  Google Scholar 

  11. Pesonen, M. et al. Patch test results of the European baseline series among patients with occupational contact dermatitis across Europe-analyses of the European Surveillance System on Contact Allergy network, 2002-2010. Contact Dermatitis 72, 154–163 (2015).

    Article  CAS  PubMed  Google Scholar 

  12. Wiszniewska, M. & Walusiak-Skorupa, J. Recent trends in occupational contact dermatitis. Curr. Allergy Asthma Rep. 15, 43 (2015).

    Article  PubMed  Google Scholar 

  13. Meyer, J. D., Chen, Y., Holt, D. L., Beck, M. H. & Cherry, N. M. Occupational contact dermatitis in the UK: a surveillance report from EPIDERM and OPRA. Occup. Med. 50, 265–273 (2000).

    Article  CAS  Google Scholar 

  14. Turner, S. et al. The incidence of occupational skin disease as reported to The Health and Occupation Reporting (THOR) network between 2002 and 2005. Br. J. Dermatol. 157, 713–722 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Bhatia, R. & Sharma, V. K. Occupational dermatoses: An Asian perspective. Indian J. Dermatol. Venereol. Leprol. 83, 525–535 (2017).

    Article  PubMed  Google Scholar 

  16. Cahill, J. L. et al. Occupational skin disease in Victoria, Australia. Australas. J. Dermatol. 57, 108–114 (2016).

    Article  PubMed  Google Scholar 

  17. Melo, M., Villarinho, A. & Leite, I. D. C. Sociodemographic and clinical profile of patients with occupational contact dermatitis seen at a work-related dermatology service, 2000 - 2014. Bras. Dermatol. 94, 147–156 (2019).

    Article  Google Scholar 

  18. Peiser, M. et al. Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. Cell. Mol. Life Sci. 69, 763–781 (2012).

    Article  CAS  PubMed  Google Scholar 

  19. Nassau, S. & Fonacier, L. Allergic contact dermatitis. Med. Clin. North Am. 104, 61–76 (2020).

    Article  PubMed  Google Scholar 

  20. Cashman, M. W., Reutemann, P. A. & Ehrlich, A. Contact dermatitis in the United States: epidemiology, economic impact, and workplace prevention. Dermatol. Clin. 30, 87–98 (2012).

    Article  CAS  PubMed  Google Scholar 

  21. Agner, T. Noninvasive measuring methods for the investigation of irritant patch test reactions. A study of patients with hand eczema, atopic dermatitis and controls. Acta Derm. Venereol. Suppl. 173, 1–26 (1992).

    CAS  Google Scholar 

  22. Thyssen, J. P., McFadden, J. P. & Kimber, I. The multiple factors affecting the association between atopic dermatitis and contact sensitization. Allergy 69, 28–36 (2014).

    Article  CAS  PubMed  Google Scholar 

  23. Milam, E. C., Jacob, S. E. & Cohen, D. E. Contact dermatitis in the patient with atopic dermatitis. J. Allergy Clin. Immunol. Pract. 7, 18–26 (2019).

    Article  PubMed  Google Scholar 

  24. Uehara, M. & Sawai, T. A longitudinal study of contact sensitivity in patients with atopic dermatitis. Arch. Dermatol. 125, 366–368 (1989).

    Article  CAS  PubMed  Google Scholar 

  25. Teo, Y., McFadden, J. P., White, I. R., Lynch, M. & Banerjee, P. Allergic contact dermatitis in atopic individuals: results of a 30-year retrospective study. Contact Dermatitis 81, 409–416 (2019).

    Article  PubMed  Google Scholar 

  26. Hegewald, J., Uter, W., Pfahlberg, A., Geier, J. & Schnuch, A. A multifactorial analysis of concurrent patch-test reactions to nickel, cobalt, and chromate. Allergy 60, 372–378 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Malajian, D. & Belsito, D. V. Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis. J. Am. Acad. Dermatol. 69, 232–237 (2013).

    Article  CAS  PubMed  Google Scholar 

  28. Ross-Hansen, K. et al. Filaggrin is a predominant member of the denaturation-resistant nickel-binding proteome of human epidermis. J. Invest. Dermatol. 134, 1164–1166 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Hamann, C. R. et al. Association between atopic dermatitis and contact sensitization: a systematic review and meta-analysis. J. Am. Acad. Dermatol. 77, 70–78 (2017).

    Article  PubMed  Google Scholar 

  30. Vester, L., Thyssen, J. P., Menné, T. & Johansen, J. D. Occupational food-related hand dermatoses seen over a 10-year period. Contact Dermatitis 66, 264–270 (2012).

    Article  CAS  PubMed  Google Scholar 

  31. Barbaud, A., Poreaux, C., Penven, E. & Waton, J. Occupational protein contact dermatitis. Eur. J. Dermatol. 25, 527–534 (2015).

    Article  CAS  PubMed  Google Scholar 

  32. Lertphanichkul, C. & Scheinman, P. L. Occupational allergic contact dermatitis (OACD) in a cohort of 458 consecutive dermatitis patients; A case series of 17 patients with OACD. J. Am. Acad. Dermatol. 84, 798–804 (2020).

    Article  PubMed  Google Scholar 

  33. Johnston, G. A. et al. British Association of Dermatologists’ guidelines for the management of contact dermatitis 2017. Br. J. Dermatol. 176, 317–329 (2017).

    Article  CAS  PubMed  Google Scholar 

  34. Goldminz, A. M. & Scheinman, P. L. Comparison of nickel sulfate 2.5% and nickel sulfate 5% for detecting nickel contact allergy. Dermatitis 29, 321–323 (2018).

    Article  CAS  PubMed  Google Scholar 

  35. Ahlström, M., Thyssen, J. & Wennervalft, M. Nickel allergy and allergic contact dermatitis: a clinical review of immunology, epidemiology, exposure, and treatment. Contact Dermatitis 81, 227–241 (2019).

    Article  PubMed  Google Scholar 

  36. Thyssen, J. P., Linneberg, A., Menné, T., Nielsen, N. H. & Johansen, J. D. The association between hand eczema and nickel allergy has weakened among young women in the general population following the Danish nickel regulation: results from two cross-sectional studies. Contact Dermatitis 61, 342–348 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Uter, W. et al. ESSCA results with nickel, cobalt and chromium, 2009-2012. Contact Dermatitis 75, 117–121 (2016).

    Article  PubMed  Google Scholar 

  38. Ahlström, M. G., Thyssen, J. P., Menné, T. & Johansen, J. D. Prevalence of nickel allergy in Europe following the EU Nickel Directive - a review. Contact Dermatitis 77, 193–200 (2017). This review investigates the prevalence of nickel allergy in Europe following the highly effective EU Nickel Directive, an important public health initiative that has successfully reduced rates of nickel contact allergy among the European population.

    Article  CAS  PubMed  Google Scholar 

  39. Bregnbak, D. et al. Chromium allergy and dermatitis: Prevalence and main findings. Contact Dermatitis 73, 261–280 (2015).

    Article  CAS  PubMed  Google Scholar 

  40. Warshaw, E. M. et al. Epidemiology of nickel sensitivity: Retrospective cross-sectional analysis of North American Contact Dermatitis Group data 1994-2014. J. Am. Acad. Dermatol. 80, 701–713 (2019).

    Article  PubMed  Google Scholar 

  41. Cheng, T. Y., Tseng, Y. H., Sun, C. C. & Chu, C. Y. Contact sensitization to metals in Taiwan. Contact Dermatitis 59, 353–360 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Goon, A. T. & Goh, C. L. Metal allergy in Singapore. Contact Dermatitis 52, 130–132 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Dou, X., Zhao, Y., Ni, C., Zhu, X. & Liu, L. Prevalence of contact allergy at a dermatology clinic in China from 1990-2009. Dermatitis 22, 324–331 (2011).

    PubMed  Google Scholar 

  44. Uter, W. et al. European Surveillance System on Contact Allergies (ESSCA): results with the European baseline series, 2013/14. J. Eur. Acad. Dermatol. Venereol. 31, 1516–1525 (2017).

    Article  CAS  PubMed  Google Scholar 

  45. Kirchlechner, S., Hübner, A. & Uter, W. Survey of sensitizing components of oxidative hair dyes (retail and professional products) in Germany. J. Dtsch. Dermatol. Ges. 14, 707–715 (2016).

    PubMed  Google Scholar 

  46. Uter, W. et al. The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures. J. Eur. Acad. Dermatol. Venereol. 34, 333–339 (2020). This survey study assessed changes in isothiazolinone contact allergy following regulations implemented for isothiazolinones in skin-care products, another important example of an effective public health initiative in the area of contact dermatitis.

    Article  CAS  PubMed  Google Scholar 

  47. Rolls, S. et al. Recommendation to include hydroxyethyl (meth)acrylate in the British baseline patch test series. Br. J. Dermatol. 181, 811–817 (2019).

    Article  CAS  PubMed  Google Scholar 

  48. Toholka, R. et al. The first Australian Baseline Series: Recommendations for patch testing in suspected contact dermatitis. Australas. J. Dermatol. 56, 107–115 (2015).

    Article  PubMed  Google Scholar 

  49. Lee, H. Y., Stieger, M., Yawalkar, N. & Kakeda, M. Cytokines and chemokines in irritant contact dermatitis. Mediators Inflamm. 2013, 916497 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Nosbaum, A., Vocanson, M., Rozieres, A., Hennino, A. & Nicolas, J. F. Allergic and irritant contact dermatitis. EJD 19, 325–332 (2009).

    CAS  PubMed  Google Scholar 

  51. Vocanson, M., Hennino, A., Rozieres, A., Poyet, G. & Nicolas, J. F. Effector and regulatory mechanisms in allergic contact dermatitis. Allergy 64, 1699–1714 (2009).

    Article  CAS  PubMed  Google Scholar 

  52. Kaplan, D. H., Igyarto, B. Z. & Gaspari, A. A. Early immune events in the induction of allergic contact dermatitis. Nat. Rev. Immunol. 12, 114–124 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Honda, T., Egawa, G., Grabbe, S. & Kabashima, K. Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis. J. Invest. Dermatol. 133, 303–315 (2013).

    Article  CAS  PubMed  Google Scholar 

  54. Martin S. F., Rustemeyer T., Thyssen J. P. Recent advances in understanding and managing contact dermatitis. F1000Res. 2018;https://doi.org/10.12688/f1000research.13499.1

  55. Basketter, D. A., Kan-King-Yu, D., Dierkes, P. & Jowsey, I. R. Does irritation potency contribute to the skin sensitization potency of contact allergens? Cutan. Ocul. Toxicol. 26, 279–286 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Lepoittevin, J. & Leblond, I. Hapten-peptide T cell receptor interactions: molecular basis for the recognition of haptens by T lymphocytes. EJD 7, 151–154 (1997).

    CAS  Google Scholar 

  57. Karlberg, A. T., Bergstrom, M. A., Borje, A., Luthman, K. & Nilsson, J. L. Allergic contact dermatitis–formation, structural requirements, and reactivity of skin sensitizers. Chem. Res. Toxicol. 21, 53–69 (2008).

    Article  PubMed  Google Scholar 

  58. Barbaud, A. Mechanism and diagnosis of protein contact dermatitis. Curr. Opin. Allergy Clin. Immunol. 20, 117–121 (2020).

    Article  CAS  PubMed  Google Scholar 

  59. Hannuksela, M. Protein Contact Dermatitis 345–348 (Springer, 2006).

  60. Fartasch, M. Ultrastructure of the epidermal barrier after irritation. Microsc. Res. Tech. 37, 193–199 (1997).

    Article  CAS  PubMed  Google Scholar 

  61. Angelova-Fischer, I. Irritants and skin barrier function. Curr. Probl. Dermatol. 49, 80–89 (2016).

    Article  PubMed  Google Scholar 

  62. Eskes, C. et al. Regulatory assessment of in vitro skin corrosion and irritation data within the European framework: Workshop recommendations. Regul. Toxicol. Pharmacol. 62, 393–403 (2012).

    Article  PubMed  Google Scholar 

  63. Patel, S. Danger-associated molecular patterns (DAMPs): the derivatives and triggers of inflammation. Curr. Allergy Asthma Rep. 18, 63 (2018).

    Article  CAS  PubMed  Google Scholar 

  64. Gibbs, S. In vitro irritation models and immune reactions. Skin. Pharmacol. Physiol. 22, 103–113 (2009).

    Article  CAS  PubMed  Google Scholar 

  65. Kumari, V., Babina, M., Hazzan, T. & Worm, M. Thymic stromal lymphopoietin induction by skin irritation is independent of tumour necrosis factor-alpha, but supported by interleukin-1. Br. J. Dermatol. 172, 951–960 (2015).

    Article  CAS  PubMed  Google Scholar 

  66. Kendall, A. C., Pilkington, S. M., Sassano, G., Rhodes, L. E. & Nicolaou, A. N-Acyl ethanolamide and eicosanoid involvement in irritant dermatitis. Br. J. Dermatol. 175, 163–171 (2016).

    Article  CAS  PubMed  Google Scholar 

  67. Clemmensen, A. et al. Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid. J. Invest. Dermatol. 130, 2201–2210 (2010).

    Article  CAS  PubMed  Google Scholar 

  68. Fulzele, S. V., Babu, R. J., Ahaghotu, E. & Singh, M. Estimation of proinflammatory biomarkers of skin irritation by dermal microdialysis following exposure with irritant chemicals. Toxicology 237, 77–88 (2007).

    Article  CAS  PubMed  Google Scholar 

  69. Calhoun, K. N., Luckett-Chastain, L. R., Frempah, B. & Gallucci, R. M. Associations Between Immune Phenotype and Inflammation in Murine Models of Irritant Contact Dermatitis. Toxicol. Sci. 168, 179–189 (2019).

    Article  CAS  PubMed  Google Scholar 

  70. Willis, C. M., Stephens, C. J. & Wilkinson, J. D. Differential patterns of epidermal leukocyte infiltration in patch test reactions to structurally unrelated chemical irritants. J. Invest. Dermatol. 101, 364–370 (1993).

    Article  CAS  PubMed  Google Scholar 

  71. Landsteiner, K. & Jacobs, J. Studies on the sensitization of animals with simple chemical compounds. Ii. J. Exp. Med. 64, 625–639 (1936).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Esser, P. R. & Martin, S. F. Pathomechanisms of contact sensitization. Curr. Allergy Asthma Rep. 17, 83 (2017).

    Article  PubMed  Google Scholar 

  73. Aptula, A. O. & Roberts, D. W. Mechanistic applicability domains for nonanimal-based prediction of toxicological end points: general principles and application to reactive toxicity. Chem. Res. Toxicol. 19, 1097–1105 (2006).

    Article  CAS  PubMed  Google Scholar 

  74. Karlberg, A. T. et al. Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers - prehaptens and prohaptens. Contact Dermatitis 69, 323–334 (2013).

    Article  CAS  PubMed  Google Scholar 

  75. Schmidt, M. & Goebeler, M. Immunology of metal allergies. J. Dtsch. Dermatol. Ges. 13, 653–660 (2015).

    PubMed  Google Scholar 

  76. Fitzpatrick, J. M., Roberts, D. W. & Patlewicz, G. What determines skin sensitization potency: Myths, maybes and realities. The 500 molecular weight cut-off: An updated analysis. J. Appl. Toxicol. 37, 105–116 (2017).

    Article  CAS  PubMed  Google Scholar 

  77. Fitzpatrick, J. M., Roberts, D. W. & Patlewicz, G. Is skin penetration a determining factor in skin sensitization potential and potency? Refuting the notion of a LogKow threshold for skin sensitization. J. Appl. Toxicol. 37, 117–127 (2017).

    Article  CAS  PubMed  Google Scholar 

  78. Paramasivan, P. et al. Repeated low-dose skin exposure is an effective sensitizing stimulus, a factor to be taken into account in predicting sensitization risk. Br. J. Dermatol. 162, 594–597 (2010).

    Article  CAS  PubMed  Google Scholar 

  79. van Och, F. M., Vandebriel, R. J., De Jong, W. H. & van Loveren, H. Effect of prolonged exposure to low antigen concentration for sensitization. Toxicology 184, 23–30 (2003).

    Article  PubMed  Google Scholar 

  80. Sekiguchi, K. et al. Enhancement of mouse contact hypersensitivity appears with a short chain triacylglycerol but not with a long chain one. Toxicology 412, 48–54 (2019).

    Article  CAS  PubMed  Google Scholar 

  81. Pickard, C. et al. The cutaneous biochemical redox barrier: a component of the innate immune defenses against sensitization by highly reactive environmental xenobiotics. J. Immunol. 183, 7576–7584 (2009).

    Article  CAS  PubMed  Google Scholar 

  82. Aleksic, M. et al. Mass spectrometric identification of covalent adducts of the skin allergen 2,4-dinitro-1-chlorobenzene and model skin proteins. Toxicol. Vitr. 22, 1169–1176 (2008).

    Article  CAS  Google Scholar 

  83. Doi, T., Mizukawa, Y., Shimoda, Y., Yamazaki, Y. & Shiohara, T. Importance of water content of the stratum corneum in mouse models for contact hypersensitivity. J. Invest. Dermatol. 137, 151–158 (2017).

    Article  CAS  PubMed  Google Scholar 

  84. Friedmann, P. S., Sanchez-Elsner, T. & Schnuch, A. Genetic factors in susceptibility to contact sensitivity. Contact Dermatitis.72, 263–274 (2015).

    Article  PubMed  Google Scholar 

  85. Schnuch, A., Westphal, G., Mossner, R., Uter, W. & Reich, K. Genetic factors in contact allergy–review and future goals. Contact Dermatitis 64, 2–23 (2011).

    Article  CAS  PubMed  Google Scholar 

  86. Gomez de Aguero, M. et al. Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells. J. Clin. Invest. 122, 1700–1711 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Cavani, A. et al. Human CD25+regulatory T cells maintain immune tolerance to nickel in healthy, nonallergic individuals. J. Immunol. 171, 5760–5768 (2003).

    Article  CAS  PubMed  Google Scholar 

  88. Luckey, U. et al. Crosstalk of regulatory T cells and tolerogenic dendritic cells prevents contact allergy in subjects with low zone tolerance. J. Allergy Clin. Immunol. 130, 781–797.e711 (2012).

    Article  CAS  PubMed  Google Scholar 

  89. Vocanson, M. et al. CD8+ T cells are effector cells of contact dermatitis to common skin allergens in mice. J. Invest. Dermatol. 126, 815–820 (2006).

    Article  CAS  PubMed  Google Scholar 

  90. Rozieres, A. et al. CD8+ T cells mediate skin allergy to amoxicillin in a mouse model. Allergy 65, 996–1003 (2010).

    Article  CAS  PubMed  Google Scholar 

  91. Watanabe, H. et al. Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization. J. Immunol. 180, 5826–5832 (2008).

    Article  CAS  PubMed  Google Scholar 

  92. Riemann, H. et al. IL-12 breaks dinitrothiocyanobenzene (DNTB)-mediated tolerance and converts the tolerogen DNTB into an immunogen. J. Immunol. 175, 5866–5874 (2005).

    Article  CAS  PubMed  Google Scholar 

  93. Kimber, I., Dearman, R. J., Basketter, D. A., Ryan, C. A. & Gerberick, G. F. The local lymph node assay: past, present and future. Contact Dermatitis 47, 315–328 (2002).

    Article  CAS  PubMed  Google Scholar 

  94. Wang, Y. & Dai, S. Structural basis of metal hypersensitivity. Immunol. Res. 55, 83–90 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Bonefeld, C. M. et al. Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens. Contact Dermatitis 77, 133–142 (2017).

    Article  PubMed  Google Scholar 

  96. Saint-Mezard, P. et al. Psychological stress exerts an adjuvant effect on skin dendritic cell functions in vivo. J. Immunol. 171, 4073–4080 (2003).

    Article  CAS  PubMed  Google Scholar 

  97. Martin, S. F. et al. Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity. J. Exp. Med. 205, 2151–2162 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Esser, P. R. et al. Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation. PLoS ONE 7, e41340 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Migdal, C. et al. Sensitization effect of thimerosal is mediated in vitro via reactive oxygen species and calcium signaling. Toxicology 274, 1–9 (2010).

    Article  CAS  PubMed  Google Scholar 

  100. Muto, J. et al. Hyaluronan digestion controls DC migration from the skin. J. Clin. Invest. 124, 1309–1319 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Galbiati, V., Papale, A., Galli, C. L., Marinovich, M. & Corsini, E. Role of ROS and HMGB1 in contact allergen-induced IL-18 production in human keratinocytes. J. Invest. Dermatol. 134, 2719–2727 (2014).

    Article  CAS  PubMed  Google Scholar 

  102. Klekotka, P. A., Yang, L. & Yokoyama, W. M. Contrasting roles of the IL-1 and IL-18 receptors in MyD88-dependent contact hypersensitivity. J. Invest. Dermatol. 130, 184–191 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yasukawa, S. et al. An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells. Nat. Commun. 5, 3755 (2014).

    Article  CAS  PubMed  Google Scholar 

  104. Enk A. H. in Immune Mechanisms in Allergic Cotact Dermatitis. 76-80 (Springer, 2005).

  105. Sutterwala, F. S. et al. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity 24, 317–327 (2006).

    Article  CAS  PubMed  Google Scholar 

  106. Antonopoulos, C. et al. IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis. J. Leukoc. Biol. 83, 361–367 (2008).

    Article  CAS  PubMed  Google Scholar 

  107. Weber, F. C. et al. Lack of the purinergic receptor P2X(7) results in resistance to contact hypersensitivity. J. Exp. Med. 207, 2609–2619 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kostarnoy, A. V. et al. Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate. Proc. Natl Acad. Sci. USA 114, E2758–E2765 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Luis, A. et al. Oxidative stress-dependent activation of the eIF2alpha-ATF4 unfolded protein response branch by skin sensitizer 1-fluoro-2,4-dinitrobenzene modulates dendritic-like cell maturation and inflammatory status in a biphasic manner [corrected]. Free Radic. Biol. Med. 77, 217–229 (2014).

    Article  CAS  PubMed  Google Scholar 

  110. Schmidt, M. et al. Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat. Immunol. 11, 814–819 (2010).

    Article  CAS  PubMed  Google Scholar 

  111. Adam, C. et al. Allergy-inducing chromium compounds trigger potent innate immune stimulation Via ROS-dependent inflammasome Activation. J. Invest. Dermatol. 137, 367–376 (2017).

    Article  CAS  PubMed  Google Scholar 

  112. Li, X. & Zhong, F. Nickel induces interleukin-1beta secretion via the NLRP3-ASC-caspase-1 pathway. Inflammation 37, 457–466 (2014).

    Article  CAS  PubMed  Google Scholar 

  113. El Ali, Z. et al. Allergic skin inflammation induced by chemical sensitizers is controlled by the transcription factor Nrf2. Toxicol. Sci. 134, 39–48 (2013).

    Article  CAS  PubMed  Google Scholar 

  114. Helou, D. G., Martin, S. F., Pallardy, M., Chollet-Martin, S. & Kerdine-Römer, S. Nrf2 involvement in chemical-induced skin innate immunity. Front. Immunol. 10, 1004 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Eaton, L. H., Roberts, R. A., Kimber, I., Dearman, R. J. & Metryka, A. Skin sensitization induced Langerhans’ cell mobilization: variable requirements for tumour necrosis factor-alpha. Immunology 144, 139–148 (2015).

    Article  CAS  PubMed  Google Scholar 

  116. Peng, B. et al. Thimerosal induces skin pseudo-allergic reaction via Mas-related G-protein coupled receptor B2. J. Dermatol. Sci. 95, 99–106 (2019).

    Article  CAS  PubMed  Google Scholar 

  117. Meixiong, J. et al. Activation of mast-cell-expressed Mas-related G-protein-coupled receptors drives non-histaminergic itch. Immunity 50, 1163–1171.e5 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Dudeck, A. et al. Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens. Immunity 34, 973–984 (2011).

    Article  CAS  PubMed  Google Scholar 

  119. Dudeck, J. et al. Mast-cell-derived TNF amplifies CD8+ dendritic cell functionality and CD8+ T cell priming. Cell Rep. 13, 399–411 (2015).

    Article  CAS  PubMed  Google Scholar 

  120. Biedermann, T. et al. Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2. J. Exp. Med. 192, 1441–1452 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Weber, F. C. et al. Neutrophils are required for both the sensitization and elicitation phase of contact hypersensitivity. J. Exp. Med. 212, 15–22 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Tamoutounour, S. et al. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39, 925–938 (2013).

    Article  CAS  PubMed  Google Scholar 

  123. Clausen, B. E. & Stoitzner, P. Functional specialization of skin dendritic cell subsets in regulating T cell responses. Front. Immunol. 6, 534 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Bacci, S., Alard, P., Dai, R., Nakamura, T. & Streilein, J. W. High and low doses of haptens dictate whether dermal or epidermal antigen-presenting cells promote contact hypersensitivity. Eur. J. Immunol. 27, 442–448 (1997).

    Article  CAS  PubMed  Google Scholar 

  125. Edelson, B. T. et al. Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells. J. Exp. Med. 207, 823–836 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Honda, T. et al. Compensatory role of Langerhans cells and langerin-positive dermal dendritic cells in the sensitization phase of murine contact hypersensitivity. J. Allergy Clin. Immunol. 125, 1154–1156.e2 (2010).

    Article  PubMed  Google Scholar 

  127. Noordegraaf, M., Flacher, V., Stoitzner, P. & Clausen, B. E. Functional redundancy of Langerhans cells and Langerin+ dermal dendritic cells in contact hypersensitivity. J. Invest. Dermatol. 130, 2752–2759 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Cho, Y., Kwon, D. & Kang, S. J. The Cooperative Role of CD326+ and CD11b+ dendritic cell subsets for a hapten-induced Th2 differentiation. J. Immunol. 199, 3137–3146 (2017).

    Article  CAS  PubMed  Google Scholar 

  129. Le Borgne, M. et al. Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo. Immunity 24, 191–201 (2006).

    Article  CAS  PubMed  Google Scholar 

  130. Micosse, C. et al. Human “TH9” cells are a subpopulation of PPAR-γ+ TH2 cells. Sci. Immunol. 4, eaat5943 (2019).

    Article  CAS  PubMed  Google Scholar 

  131. Gibson, A. et al. In Vitro Priming of Naive T-cells with p-Phenylenediamine and Bandrowski’s Base. Chem. Res. Toxicol. 28, 2069–2077 (2015).

    Article  CAS  PubMed  Google Scholar 

  132. Bechara, R., Antonios, D., Azouri, H. & Pallardy, M. Nickel sulfate promotes IL-17A producing CD4+ T cells by an IL-23-dependent mechanism regulated by TLR4 and Jak-STAT pathways. J. Invest. Dermatol. 137, 2140–2148 (2017).

    Article  CAS  PubMed  Google Scholar 

  133. Connor, L. M. et al. Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles. J. Exp. Med. 214, 125–142 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Larson, R. P. et al. Dibutyl phthalate-induced thymic stromal lymphopoietin is required for Th2 contact hypersensitivity responses. J. Immunol. 184, 2974–2984 (2010).

    Article  CAS  PubMed  Google Scholar 

  135. Dhingra, N. et al. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J. Allergy Clin. Immunol. 134, 362–372 (2014). This study identified differential up-regulation of specific T cell axes in response to varied contact allergens, with important implications for both understanding disease mechanisms and treatment approaches.

    Article  CAS  PubMed  Google Scholar 

  136. Nicolai, S. et al. Human T cell response to CD1a and contact dermatitis allergens in botanical extracts and commercial skin care products. Sci. Immunol. 5, eaax5430 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Betts, R. J. et al. Contact sensitizers trigger human CD1-autoreactive T-cell responses. Eur. J. Immunol. 47, 1171–1180 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Nieuwenhuis, E. E. et al. CD1d and CD1d-restricted iNKT-cells play a pivotal role in contact hypersensitivity. Exp. Dermatol. 14, 250–258 (2005).

    Article  PubMed  Google Scholar 

  139. Goubier, A. et al. Invariant NKT cells suppress CD8+ T-cell-mediated allergic contact dermatitis independently of regulatory CD4+ T cells. J. Invest. Dermatol. 133, 980–987 (2013).

    Article  CAS  PubMed  Google Scholar 

  140. Shimizuhira, C. et al. Natural killer T cells are essential for the development of contact hypersensitivity in BALB/c mice. J. Invest. Dermatol. 134, 2709–2718 (2014).

    Article  CAS  PubMed  Google Scholar 

  141. Kim, J. H. et al. CD1a on Langerhans cells controls inflammatory skin disease. Nat. Immunol. 17, 1159–1166 (2016). These investigators used both mouse models and human tissues to study the CD1a recognition of urushiol, the subsequent inflammatory responses and the effects of CD1a blocking antibodies, with evidence supporting CD1a as a potential therapeutic target in cCD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Wang, K. et al. TLR4 supports the expansion of FasL+CD5+CD1dhi regulatory B cells, which decreases in contact hypersensitivity. Mol. Immunol. 87, 188–199 (2017).

    Article  CAS  PubMed  Google Scholar 

  143. Vocanson, M. et al. Inducible costimulator (ICOS) is a marker for highly suppressive antigen-specific T cells sharing features of TH17/TH1 and regulatory T cells. J. Allergy Clin. Immunol. 126, 280–289, 289.e1-7 (2010).

    Article  CAS  PubMed  Google Scholar 

  144. Ring, S., Enk, A. H. & Mahnke, K. Regulatory T cells from IL-10-deficient mice fail to suppress contact hypersensitivity reactions due to lack of adenosine production. J. Invest. Dermatol. 131, 1494–1502 (2011).

    Article  CAS  PubMed  Google Scholar 

  145. Mahnke, K. et al. Down-regulation of CD62L shedding in T cells by CD39+ regulatory T cells leads to defective sensitization in contact hypersensitivity reactions. J. Invest. Dermatol. 137, 106–114 (2017).

    Article  CAS  PubMed  Google Scholar 

  146. El Beidaq, A. et al. In vivo expansion of endogenous regulatory T cell populations induces long-term suppression of contact hypersensitivity. J. Immunol. 197, 1567–1576 (2016).

    Article  CAS  PubMed  Google Scholar 

  147. Gorbachev, A. V. & Fairchild, R. L. CD4+CD25+ regulatory T cells utilize FasL as a mechanism to restrict DC priming functions in cutaneous immune responses. Eur. J. Immunol. 40, 2006–2015 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Ring, S., Karakhanova, S., Johnson, T., Enk, A. H. & Mahnke, K. Gap junctions between regulatory T cells and dendritic cells prevent sensitization of CD8+ T cells. J. Allergy Clin. Immunol. 125, 237–246.e1-7 (2010).

    Article  CAS  PubMed  Google Scholar 

  149. Kish, D. D., Gorbachev, A. V. & Fairchild, R. L. CD8+ T cells produce IL-2, which is required for CD4+CD25+ T cell regulation of effector CD8+T cell development for contact hypersensitivity responses. J. Leukoc. Biol. 78, 725–735 (2005).

    Article  CAS  PubMed  Google Scholar 

  150. Silva-Vilches, C. et al. Production of extracellular adenosine by CD73+ dendritic cells is crucial for induction of tolerance in contact hypersensitivity reactions. J. Invest. Dermatol. 139, 541–551 (2019).

    Article  CAS  PubMed  Google Scholar 

  151. Luckey, U. et al. T cell killing by tolerogenic dendritic cells protects mice from allergy. J. Clin. Invest. 121, 3860–3871 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Nish, S. A. et al. T cell-intrinsic role of IL-6 signaling in primary and memory responses. eLife 3, e01949 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Gamradt, P. et al. Inhibitory checkpoint receptors control CD8+ resident memory T cells to prevent skin allergy. J. Allergy Clin. Immunol. 143, 2147–2157 (2019).

    Article  CAS  PubMed  Google Scholar 

  154. Dyring-Andersen, B. et al. CD4+ T cells producing interleukin (IL)-17, IL-22 and interferon-gamma are major effector T cells in nickel allergy. Contact Dermatitis 68, 339–347 (2013).

    Article  CAS  PubMed  Google Scholar 

  155. Gober, M. D., Fishelevich, R., Zhao, Y., Unutmaz, D. & Gaspari, A. A. Human natural killer T cells infiltrate into the skin at elicitation sites of allergic contact dermatitis. J. Invest. Dermatol. 128, 1460–1469 (2008).

    Article  CAS  PubMed  Google Scholar 

  156. Carbone, T. et al. CD56highCD16-CD62L- NK cells accumulate in allergic contact dermatitis and contribute to the expression of allergic responses. J. Immunol. 184, 1102–1110 (2010).

    Article  CAS  PubMed  Google Scholar 

  157. Rafei-Shamsabadi, D. A. et al. Lack of type 2 innate lymphoid cells promotes a type I-driven enhanced immune response in contact hypersensitivity. J. Invest. Dermatol. 138, 1962–1972 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Simon, D., Aeberhard, C., Erdemoglu, Y. & Simon, H. U. Th17 cells and tissue remodeling in atopic and contact dermatitis. Allergy 69, 125–131 (2014).

    Article  CAS  PubMed  Google Scholar 

  159. Kawano, M. et al. NKG2D+ IFN-γ+ CD8+ T cells are responsible for palladium allergy. PLoS One 9, e86810 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  160. Kish, D. D. et al. Neutrophil cathepsin G regulates dendritic cell production of IL-12 during development of CD4 T cell responses to antigens in the skin. J. Immunol. 202, 1045–1056 (2019).

    Article  CAS  PubMed  Google Scholar 

  161. Takeshita, K., Yamasaki, T., Akira, S., Gantner, F. & Bacon, K. B. Essential role of MHC II-independent CD4+ T cells, IL-4 and STAT6 in contact hypersensitivity induced by fluorescein isothiocyanate in the mouse. Int. Immunol. 16, 685–695 (2004).

    Article  CAS  PubMed  Google Scholar 

  162. Gautam, S. C., Matriano, J. A., Chikkala, N. F., Edinger, M. G. & Tubbs, R. R. L3T4 (CD4+) cells that mediate contact sensitivity to trinitrochlorobenzene express I-A determinants. Cell Immunol. 135, 27–41 (1991).

    Article  CAS  PubMed  Google Scholar 

  163. Kish, D. D., Volokh, N., Baldwin, W. M. 3rd & Fairchild, R. L. Hapten application to the skin induces an inflammatory program directing hapten-primed effector CD8 T cell interaction with hapten-presenting endothelial cells. J. Immunol. 186, 2117–2126 (2011).

    Article  CAS  PubMed  Google Scholar 

  164. Trautmann, A. et al. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J. Clin. Invest. 106, 25–35 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Akiba, H. et al. Skin inflammation during contact hypersensitivity is mediated by early recruitment of CD8+T cytotoxic 1 cells inducing keratinocyte apoptosis. J. Immunol. 168, 3079–3087 (2002).

    Article  CAS  PubMed  Google Scholar 

  166. He, D. et al. and IFN-gamma mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses. J. Immunol. 183, 1463–1470 (2009).

    Article  CAS  PubMed  Google Scholar 

  167. Chong, S. Z. et al. CD8 T cells regulate allergic contact dermatitis by modulating CCR2-dependent TNF/iNOS-expressing Ly6C+CD11b+monocytic cells. J. Invest. Dermatol. 134, 666–676 (2014).

    Article  CAS  PubMed  Google Scholar 

  168. Kish, D. D., Gorbachev, A. V., Parameswaran, N., Gupta, N. & Fairchild, R. L. Neutrophil expression of Fas ligand and perforin directs effector CD8 T cell infiltration into antigen-challenged skin. J. Immunol. 189, 2191–2202 (2012).

    Article  CAS  PubMed  Google Scholar 

  169. Engeman, T., Gorbachev, A. V., Kish, D. D. & Fairchild, R. L. The intensity of neutrophil infiltration controls the number of antigen-primed CD8 T cells recruited into cutaneous antigen challenge sites. J. Leukoc. Biol. 76, 941–949 (2004).

    Article  CAS  PubMed  Google Scholar 

  170. Jiang, X. et al. Dermal gammadelta T cells do not freely re-circulate out of skin and produce IL-17 to promote neutrophil infiltration during primary contact hypersensitivity. PLoS One 12, e0169397 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  171. Nakae, S. et al. Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity 17, 375–387 (2002).

    Article  CAS  PubMed  Google Scholar 

  172. Dey, N., Szczepanik, M., Lau, K., Majewska-Szczepanik, M. & Askenase, P. W. Stimulatory lipids accumulate in the mouse liver within 30 min of contact sensitization to facilitate the activation of Naive iNKT cells in a CD1d-dependent fashion. Scand. J. Immunol. 74, 52–61 (2011).

    Article  CAS  PubMed  Google Scholar 

  173. Campos, R. A. et al. Cutaneous immunization rapidly activates liver invariant Valpha14 NKT cells stimulating B-1 B cells to initiate T cell recruitment for elicitation of contact sensitivity. J. Exp. Med. 198, 1785–1796 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Natsuaki, Y. et al. Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin. Nat. Immunol. 15, 1064–1069 (2014).

    Article  CAS  PubMed  Google Scholar 

  175. Liu, Z. et al. Visualization of T cell-regulated monocyte clusters mediating keratinocyte death in acquired cutaneous immunity. J. Invest. Dermatol. 138, 1328–1337 (2018).

    Article  CAS  PubMed  Google Scholar 

  176. Kehren, J. et al. Cytotoxicity is mandatory for CD8+ T cell-mediated contact hypersensitivity. J. Exp. Med. 189, 779–786 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Pennino, D. et al. IL-17 amplifies human contact hypersensitivity by licensing hapten nonspecific Th1 cells to kill autologous keratinocytes. J. Immunol. 184, 4880–4888 (2010).

    Article  CAS  PubMed  Google Scholar 

  178. Balato, A. et al. CD1d-dependent, iNKT-cell cytotoxicity against keratinocytes in allergic contact dermatitis. Exp. Dermatol. 21, 915–920 (2012).

    Article  CAS  PubMed  Google Scholar 

  179. Suzuki, K., Meguro, K., Nakagomi, D. & Nakajima, H. Roles of alternatively activated M2 macrophages in allergic contact dermatitis. Allergol. Int. 66, 392–397 (2017).

    Article  CAS  PubMed  Google Scholar 

  180. O’Leary, J. G., Goodarzi, M., Drayton, D. L. & von Andrian, U. H. T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nat. Immunol. 7, 507–516 (2006).

    Article  CAS  PubMed  Google Scholar 

  181. Zhang, L. H., Shin, J. H., Haggadone, M. D. & Sunwoo, J. B. The aryl hydrocarbon receptor is required for the maintenance of liver-resident natural killer cells. J. Exp. Med. 213, 2249–2257 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Stary, V. et al. A discrete subset of epigenetically primed human NK cells mediates antigen-specific immune responses. Sci. Immunol. 5, eaba6232 (2020).

    Article  CAS  PubMed  Google Scholar 

  183. Rouzaire, P. et al. Natural killer cells and T cells induce different types of skin reactions during recall responses to haptens. Eur. J. Immunol. 42, 80–88 (2012).

    Article  CAS  PubMed  Google Scholar 

  184. Paust, S. et al. Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses. Nat. Immunol. 11, 1127–1135 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. van den Boorn, J. G. et al. Inflammasome-dependent induction of adaptive NK cell memory. Immunity 44, 1406–1421 (2016).

    Article  CAS  PubMed  Google Scholar 

  186. Tomura, M. et al. Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice. J. Clin. Invest. 120, 883–893 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Nakashima, H. et al. CD22 expression mediates the regulatory functions of peritoneal B-1a cells during the remission phase of contact hypersensitivity reactions. J. Immunol. 184, 4637–4645 (2010).

    Article  CAS  PubMed  Google Scholar 

  188. Hitzler, M. et al. Human Langerhans cells control Th cells via programmed death-ligand 1 in response to bacterial stimuli and nickel-induced contact allergy. PLoS One 7, e46776 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Ritprajak, P., Hashiguchi, M., Tsushima, F., Chalermsarp, N. & Azuma, M. Keratinocyte-associated B7-H1 directly regulates cutaneous effector CD8+T cell responses. J. Immunol. 184, 4918–4925 (2010).

    Article  CAS  PubMed  Google Scholar 

  190. Hirano, T. PD-L1 on mast cells suppresses effector CD8+ T-cell activation in the skin in murine contact hypersensitivity. J. Allergy Clin. Immunol., https://doi.org/10.1016/j.jaci.2020.12.654 (2021).

  191. Ikebuchi, R. et al. Functional phenotypic diversity of regulatory T cells remaining in inflamed skin. Front. Immunol. 10, 1098 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Braun, A. et al. Integrin αE(CD103) Is Involved in Regulatory T-Cell Function in Allergic Contact Hypersensitivity. J. Invest. Dermatol. 135, 2982–2991 (2015).

    Article  CAS  PubMed  Google Scholar 

  193. Lehtimäki, S. et al. The temporal and spatial dynamics of Foxp3+Treg cell-mediated suppression during contact hypersensitivity responses in a murine model. J. Invest. Dermatol. 132, 2744–2751 (2012).

    Article  CAS  PubMed  Google Scholar 

  194. Christensen, A. D., Skov, S., Kvist, P. H. & Haase, C. Depletion of regulatory T cells in a hapten-induced inflammation model results in prolonged and increased inflammation driven by T cells. Clin. Exp. Immunol. 179, 485–499 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Ikebuchi, R. et al. A rare subset of skin-tropic regulatory T cells expressing Il10/Gzmb inhibits the cutaneous immune response. Sci. Rep. 6, 35002 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Ring, S., Oliver, S. J., Cronstein, B. N., Enk, A. H. & Mahnke, K. CD4+CD25+ regulatory T cells suppress contact hypersensitivity reactions through a CD39, adenosine-dependent mechanism. J. Allergy Clin. Immunol. 123, 1287–1296.e2 (2009).

    Article  CAS  PubMed  Google Scholar 

  197. Ring, S. et al. Regulatory T cells prevent neutrophilic infiltration of skin during contact hypersensitivity reactions by strengthening the endothelial barrier. J. Invest. Dermatol., https://doi.org/10.1016/j.jid.2021.01.027 (2021).

  198. Campbell, C. & Rudensky, A. Roles of regulatory T cells in tissue pathophysiology and metabolism. Cell Metab. 31, 18–25 (2020).

    Article  CAS  PubMed  Google Scholar 

  199. Gaide, O. et al. Common clonal origin of central and resident memory T cells following skin immunization. Nat. Med. 21, 647–653 (2015). Using studies of both mouse models and human tissue, this group identified the generation of both central memory T cells in the lymph nodes and resident memory T cells in the skin in response to cutaneous immunization.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Mbitikon-Kobo, F. M. et al. Characterization of a CD44/CD122int memory CD8 T cell subset generated under sterile inflammatory conditions. J. Immunol. 182, 3846–3854 (2009).

    Article  CAS  PubMed  Google Scholar 

  201. Schmidt, J. D. et al. Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8+ T cells. Contact Dermatitis 76, 218–227 (2017).

    Article  CAS  PubMed  Google Scholar 

  202. Adachi, T. et al. Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma. Nat. Med. 21, 1272–1279 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Hirai, T. et al. Competition for active TGFβ cytokine allows for selective retention of antigen-specific tissue- resident memory T cells in the epidermal niche. Immunity 54, 84–98 (2021).

    Article  CAS  PubMed  Google Scholar 

  204. Jensen, C. D., Johansen, J. D., Menné, T. & Andersen, K. E. Increased retest reactivity by both patch and use test with methyldibromoglutaronitrile in sensitized individuals. Acta Derm. Venereol. 86, 8–12 (2006).

    CAS  PubMed  Google Scholar 

  205. Nahhas, A. F., Oberlin, D. M., Braunberger, T. L. & Lim, H. W. Recent developments in the diagnosis and management of photosensitive disorders. Am. J. Clin. Dermatol. 19, 707–731 (2018).

    Article  PubMed  Google Scholar 

  206. Greenspoon, J., Ahluwalia, R., Juma, N. & Rosen, C. F. Allergic and photoallergic contact dermatitis: a 10-year experience. Dermatitis 24, 29–32 (2013).

    Article  CAS  PubMed  Google Scholar 

  207. Maverakis, E. et al. Light, including ultraviolet. J. Autoimmun. 34, J247–257 (2010).

    Article  CAS  PubMed  Google Scholar 

  208. Zaheer, M. R. et al. Molecular mechanisms of drug photodegradation and photosensitization. Curr. Pharm. Des. 22, 768–782 (2016).

    Article  CAS  PubMed  Google Scholar 

  209. Nathan, C. & Ding, A. SnapShot: reactive oxygen intermediates (ROI). Cell 140, 951–951.e2 (2010).

    Article  PubMed  Google Scholar 

  210. de Jager, T. L., Cockrell, A. E., Du & Plessis, S. S. Ultraviolet light induced generation of reactive oxygen species. Adv. Exp. Med. Biol. 996, 15–23 (2017).

    Article  CAS  PubMed  Google Scholar 

  211. Schieber, M. & Chandel, N. S. ROS function in redox signaling and oxidative stress. Curr. Biol. 24, R453–462 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Nathan, C. & Cunningham-Bussel, A. Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat. Rev. Immunol. 13, 349–361 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Pathak, M. A. & Fitzpatrick, T. B. The evolution of photochemotherapy with psoralens and UVA (PUVA): 2000 BC to 1992 AD. J. Photochem. Photobiol. B. 14, 3–22 (1992).

    Article  CAS  PubMed  Google Scholar 

  214. Devleeschouwer, V., Roelandts, R., Garmyn, M. & Goossens, A. Allergic and photoallergic contact dermatitis from ketoprofen: results of (photo) patch testing and follow-up of 42 patients. Contact Dermatitis 58, 159–166 (2008).

    Article  CAS  PubMed  Google Scholar 

  215. Asensio, T., Sanchís, M. E., Sánchez, P., Vega, J. M. & García, J. C. Photocontact dermatitis because of oral dexketoprofen. Contact Dermatitis 58, 59–60 (2008).

    Article  CAS  PubMed  Google Scholar 

  216. Tokura, Y. Drug photoallergy. J. Cutan. Immunol. Allergy 1, 48–57 (2018).

    Article  Google Scholar 

  217. Abeyama, K. et al. A role for NF-kappaB-dependent gene transactivation in sunburn. J. Clin. Invest. 105, 1751–1759 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Hasegawa, T., Nakashima, M. & Suzuki, Y. Nuclear DNA damage-triggered NLRP3 inflammasome activation promotes UVB-induced inflammatory responses in human keratinocytes. Biochem. Biophys. Res. Commun. 477, 329–335 (2016).

    Article  CAS  PubMed  Google Scholar 

  219. Hotamisligil, G. S. & Davis, R. J. Cell signaling and stress responses. Cold Spring Harb. Perspect. Biol. 8, a006072 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  220. Leighton, S., Kok, L. F., Halliday, G. M. & Byrne, S. N. Inhibition of UV-induced uric acid production using allopurinol prevents suppression of the contact hypersensitivity response. Exp. Dermatol. 22, 189–194 (2013).

    Article  CAS  PubMed  Google Scholar 

  221. Garg, A. D. et al. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J. 31, 1062–1079 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Kurita, M. et al. Induction of keratinocyte apoptosis by photosensitizing chemicals plus UVA. J. Dermatol. Sci. 45, 105–112 (2007).

    Article  CAS  PubMed  Google Scholar 

  223. Dos Santos, A. F. et al. Distinct photo-oxidation-induced cell death pathways lead to selective killing of human breast cancer cells. Cell Death Dis. 11, 1070 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  224. Vassileva, S. G., Mateev, G. & Parish, L. C. Antimicrobial photosensitive reactions. Arch. Intern. Med. 158, 1993–2000 (1998).

    Article  CAS  PubMed  Google Scholar 

  225. Calnan, C. D. & Wells, G. C. Suspender dermatitis and nickel sensitivity. Br. Med. J. 1, 1265–1268 (1956).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Williams, J., Cahill, J. & Nixon, R. Occupational autoeczematization or atopic eczema precipitated by occupational contact dermatitis? Contact Dermatitis 56, 21–26 (2007).

    Article  PubMed  Google Scholar 

  227. Häusermann, P., Harr, T. & Bircher, A. J. Baboon syndrome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome? Contact Dermatitis 51, 297–310 (2004).

    Article  PubMed  Google Scholar 

  228. Veien, N. K. Systemic contact dermatitis. Int. J. Dermatol. 50, 1445–1456 (2011).

    Article  CAS  PubMed  Google Scholar 

  229. Cressey, B. D. & Scheinman, P. L. Periocular dermatitis from systemic exposure to nickel in a palatal expander and dental braces. Dermatitis 23, 179 (2012).

    Article  PubMed  Google Scholar 

  230. Ham, J. E., Siegel, P. D. & Maibach, H. Undeclared formaldehyde levels in patient consumer products: formaldehyde test kit utility. Cutan. Ocul. Toxicol. 38, 112–117 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Nikle, A., Ericson, M. & Warshaw, E. Formaldehyde release from personal care products: chromotropic acid method analysis. Dermatitis 30, 67–73 (2019).

    Article  CAS  PubMed  Google Scholar 

  232. Herman, A. et al. Allergic contact dermatitis caused by isobornyl acrylate in Freestyle® Libre, a newly introduced glucose sensor. Contact Dermatitis 77, 367–373 (2017).

    Article  CAS  PubMed  Google Scholar 

  233. Friis, U. F., Menné, T., Flyvholm, M. A., Bonde, J. P. & Johansen, J. D. Difficulties in using Material Safety Data Sheets to analyse occupational exposures to contact allergens. Contact Dermatitis 72, 147–153 (2015).

    Article  PubMed  Google Scholar 

  234. Bruze, M., Frick, M. & Persson, L. Patch testing with thin-layer chromatograms. Contact Dermatitis 48, 278–279 (2003).

    Article  CAS  PubMed  Google Scholar 

  235. Lammintausta, K. et al. An epidemic of furniture-related dermatitis: searching for a cause. Br. J. Dermatol. 162, 108–116 (2010).

    Article  CAS  PubMed  Google Scholar 

  236. Erfani, B., Midander, K., Lidén, C. & Julander, A. Development, validation and testing of a skin sampling method for assessment of metal exposure. Contact Dermatitis 77, 17–24 (2017).

    Article  CAS  PubMed  Google Scholar 

  237. Johansen, J. D. et al. European Society of Contact Dermatitis guideline for diagnostic patch testing - recommendations on best practice. Contact Dermatitis 73, 195–221 (2015). The European Society of Contact Dermatitis guidelines represent a comprehensive set of recommendations for patch testing in clinical practice.

    Article  PubMed  Google Scholar 

  238. Bruze, M., Isaksson, M., Gruvberger, B. & Frick-Engfeldt, M. Recommendation of appropriate amounts of petrolatum preparation to be applied at patch testing. Contact Dermatitis 56, 281–285 (2007).

    Article  CAS  PubMed  Google Scholar 

  239. van Amerongen, C. C. A., Ofenloch, R., Dittmar, D. & Schuttelaar, M. L. A. New positive patch test reactions on day 7 — the additional value of the day 7 patch test reading. Contact Dermatitis 81, 280–287 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  240. Davis, M. D. et al. Delayed patch test reading after 5 days: the Mayo Clinic experience. J. Am. Acad. Dermatol. 59, 225–233 (2008).

    Article  PubMed  Google Scholar 

  241. Santiago, F., Gonçalo, M., Vieira, R., Coelho, S. & Figueiredo, A. Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS). Contact Dermatitis 62, 47–53 (2010).

    Article  CAS  PubMed  Google Scholar 

  242. Gonçalo, M. et al. Photopatch testing: recommendations for a European photopatch test baseline series. Contact Dermatitis.68, 239–243 (2013).

    Article  PubMed  Google Scholar 

  243. DeGroot A. C. Patch testing: test concentrations and vehicles for 4900 chemicals (Elsevier, 2018).

  244. Friis, U. F., Menné, T., Flyvholm, M. A., Bonde, J. P. & Johansen, J. D. Occupational allergic contact dermatitis diagnosed by a systematic stepwise exposure assessment of allergens in the work environment. Contact Dermatitis 69, 153–163 (2013).

    Article  CAS  PubMed  Google Scholar 

  245. Hjorth, N. & Roed-Petersen, J. Occupational protein contact dermatitis in food handlers. Contact Dermatitis 2, 28–42 (1976).

    Article  CAS  PubMed  Google Scholar 

  246. Vester, L., Thyssen, J. P., Menné, T. & Johansen, J. D. Consequences of occupational food-related hand dermatoses with a focus on protein contact dermatitis. Contact Dermatitis 67, 328–333 (2012).

    Article  PubMed  Google Scholar 

  247. Friis, U. F. et al. Occupational irritant contact dermatitis diagnosed by analysis of contact irritants and allergens in the work environment. Contact Dermatitis 71, 364–370 (2014).

    Article  PubMed  Google Scholar 

  248. Agner, T. et al. Classification of hand eczema. J. Eur. Acad. Dermatol. Venereol. 29, 2417–2422 (2015).

    Article  CAS  PubMed  Google Scholar 

  249. Diepgen, T. L. et al. Hand eczema classification: a cross-sectional, multicentre study of the aetiology and morphology of hand eczema. Br. J. Dermatol. 160, 353–358 (2009).

    Article  CAS  PubMed  Google Scholar 

  250. Mathias, C. G. Contact dermatitis and workers’ compensation: criteria for establishing occupational causation and aggravation. J. Am. Acad. Dermatol. 20, 842–848 (1989). The ‘Mathias Critera’ continue to serve as the basis for the evaluation of occupational CD.

    Article  CAS  PubMed  Google Scholar 

  251. Johansen, J. D. et al. The repeated open application test: suggestions for a scale of evaluation. Contact Dermatitis 39, 95–96 (1998).

    Article  CAS  PubMed  Google Scholar 

  252. Fischer, L. A., Voelund, A., Andersen, K. E., Menné, T. & Johansen, J. D. The dose-response relationship between the patch test and ROAT and the potential use for regulatory purposes. Contact Dermatitis 61, 201–208 (2009).

    Article  CAS  PubMed  Google Scholar 

  253. Goldminz, A. M., Wald, M. S. & Scheinman, P. L. Positive occluded patch test in the face of negative repeat open application test. Dermatitis 29, 162–163 (2018).

    Article  PubMed  Google Scholar 

  254. Hindsén, M., Bruze, M. & Christensen, O. B. Flare-up reactions after oral challenge with nickel in relation to challenge dose and intensity and time of previous patch test reactions. J. Am. Acad. Dermatol. 44, 616–623 (2001).

    Article  PubMed  Google Scholar 

  255. Bregnhøj, A., Menné, T., Johansen, J. D. & Søsted, H. Prevention of hand eczema among Danish hairdressing apprentices: an intervention study. Occup. Env. Med. 69, 310–316 (2012).

    Article  Google Scholar 

  256. Held, E., Mygind, K., Wolff, C., Gyntelberg, F. & Agner, T. Prevention of work related skin problems: an intervention study in wet work employees. Occup. Env. Med. 59, 556–561 (2002).

    Article  CAS  Google Scholar 

  257. Schwensen, J. F., Bregnbak, D. & Johansen, J. D. Recent trends in epidemiology, sensitization and legal requirements of selected relevant contact allergens. Expert Rev. Clin. Immunol. 12, 289–300 (2016).

    Article  CAS  PubMed  Google Scholar 

  258. Hald, M., Agner, T., Blands, J. & Johansen, J. D. Delay in medical attention to hand eczema: a follow-up study. Brit. J. Dermatol. 161, 1294–1300 (2009).

    Article  CAS  Google Scholar 

  259. Silvestri, D. L. & Barmettler, S. Pruritus ani as a manifestation of systemic contact dermatitis: resolution with dietary nickel restriction. Dermatitis 22, 50–55 (2011).

    Article  CAS  PubMed  Google Scholar 

  260. Thyssen, J. P. & Menné, T. Metal allergy–a review on exposures, penetration, genetics, prevalence, and clinical implications. Chem. Res. Toxicol. 23, 309–318 (2010).

    Article  CAS  PubMed  Google Scholar 

  261. Jacob, S. E. & Castanedo-Tardan, M. P. Pharmacotherapy for allergic contact dermatitis. Expert Opin. Pharmacother. 8, 2757–2774 (2007).

    Article  CAS  PubMed  Google Scholar 

  262. Wollenberg, A. et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J. Eur. Acad. Dermatol. Venereol. 32, 657–682 (2018).

    Article  CAS  PubMed  Google Scholar 

  263. Saripalli, Y. V., Gadzia, J. E. & Belsito, D. V. Tacrolimus ointment 0.1% in the treatment of nickel-induced allergic contact dermatitis. J. Am. Acad. Dermatol. 49, 477–482 (2003).

    Article  PubMed  Google Scholar 

  264. Mose, K. F. et al. Anti-inflammatory potency testing of topical corticosteroids and calcineurin inhibitors in human volunteers sensitized to diphenylcyclopropenone. Br. J. Clin. Pharmacol. 84, 1719–1728 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  265. Lejding, T. et al. Skin application of glutathione and iron sulfate can inhibit elicitation of allergic contact dermatitis from hexavalent chromium. Contact Dermatitis 82, 45–53 (2020).

    Article  CAS  PubMed  Google Scholar 

  266. Kemény, L., Varga, E. & Novak, Z. Advances in phototherapy for psoriasis and atopic dermatitis. Expert Rev. Clin. Immunol. 15, 1205–1214 (2019).

    Article  PubMed  Google Scholar 

  267. Schempp, C. M., Müller, H., Czech, W., Schöpf, E. & Simon, J. C. Treatment of chronic palmoplantar eczema with local bath-PUVA therapy. J. Am. Acad. Dermatol. 36, 733–737 (1997).

    Article  CAS  PubMed  Google Scholar 

  268. Sezer, E. & Etikan, I. Local narrowband UVB phototherapy vs. local PUVA in the treatment of chronic hand eczema. Photodermatol. Photoimmunol. Photomed. 23, 10–14 (2007).

    Article  PubMed  Google Scholar 

  269. Sung, C. T., McGowan, M. A., Machler, B. C. & Jacob, S. E. Systemic treatments for allergic contact dermatitis. Dermatitis 30, 46–53 (2019).

    Article  CAS  PubMed  Google Scholar 

  270. Cinats, A., Heck, E. & Robertson, L. Janus kinase inhibitors: a review of their emerging applications in dermatology. Skin. Ther. Lett. 23, 5–9 (2018).

    CAS  Google Scholar 

  271. Mowad, C. M. et al. Allergic contact dermatitis: patient management and education. J. Am. Acad. Dermatol. 74, 1043–1054 (2016).

    Article  PubMed  Google Scholar 

  272. Scheinman, P. L. The foul side of fragrance-free products: what every clinician should know about managing patients with fragrance allergy. J. Am. Acad. Dermatol. 41, 1020–1024 (1999).

    Article  CAS  PubMed  Google Scholar 

  273. Rubin, C. B. & Brod, B. Natural does not mean safe — the dirt on clean beauty products. 155, 1344–1345 (2019).

  274. Lönnroth, E. C., Wellendorf, H. & Ruyter, E. Permeability of different types of medical protective gloves to acrylic monomers. Eur. J. Oral. Sci. 111, 440–446 (2003).

    Article  PubMed  Google Scholar 

  275. Scheman, A. et al. Alternatives for Allergens in the 2018 American Contact dermatitis society core series: report by the American Contact Alternatives Group. Dermatitis 30, 87–105 (2019).

    Article  PubMed  Google Scholar 

  276. Dizdarevic, A. et al. Intervention study to evaluate the importance of information given to patients with contact allergy: a randomized, investigator-blinded clinical trial. Br. J. Dermatol. 184, 43–49 (2020).

    Article  PubMed  Google Scholar 

  277. Dou, X., Liu, L. L. & Zhu, X. J. Nickel-elicited systemic contact dermatitis. Contact Dermatitis 48, 126–129 (2003).

    Article  CAS  PubMed  Google Scholar 

  278. Stuckert, J. & Nedorost, S. Low-cobalt diet for dyshidrotic eczema patients. Contact Dermatitis 59, 361–365 (2008).

    Article  CAS  PubMed  Google Scholar 

  279. Mislankar, M. & Zirwas, M. J. Low-nickel diet scoring system for systemic nickel allergy. Dermatitis 24, 190–195 (2013).

    Article  CAS  PubMed  Google Scholar 

  280. Jensen, C. S., Menné, T. & Johansen, J. D. Systemic contact dermatitis after oral exposure to nickel: a review with a modified meta-analysis. Contact Dermatitis 54, 79–86 (2006).

    Article  CAS  PubMed  Google Scholar 

  281. Salam, T. N. & Fowler, J. F. Jr. Balsam-related systemic contact dermatitis. J. Am. Acad. Dermatol. 45, 377–381 (2001).

    Article  CAS  PubMed  Google Scholar 

  282. Scheman, A., Cha, C., Jacob, S. E. & Nedorost, S. Food avoidance diets for systemic, lip, and oral contact allergy: an american contact alternatives group article. Dermatitis 23, 248–257 (2012).

    Article  CAS  PubMed  Google Scholar 

  283. Tammaro, A., De Marco, G., Persechino, S., Narcisi, A. & Camplone, G. Allergy to nickel: first results on patients administered with an oral hyposensitization therapy. Int. J. Immunopathol. Pharmacol. 22, 837–840 (2009).

    Article  CAS  PubMed  Google Scholar 

  284. Christensen, J. D. Disulfiram treatment of three patients with nickel dermatitis. Contact Dermatitis 8, 105–108 (1982).

    Article  CAS  PubMed  Google Scholar 

  285. Kaaber, K., Menné, T., Veien, N. & Hougaard, P. Treatment of nickel dermatitis with Antabuse; a double blind study. Contact Dermatitis 9, 297–299 (1983).

    Article  CAS  PubMed  Google Scholar 

  286. Peddawad, D., Nagendra, S., Chatterjee, R., Faldu, H. & Chheda, A. Fulminant encephalopathy with unusual brain imaging in disulfiram toxicity. Neurology 90, 518–519 (2018).

    Article  PubMed  Google Scholar 

  287. Davis, M. D., Mowad, C. M. & Scheinman, P. Orthopedic prostheses: is there any point in patch testing? Dermatitis 15, 210–212 (2004).

    PubMed  Google Scholar 

  288. Schalock, P. C. & Thyssen, J. P. Metal hypersensitivity reactions to implants: opinions and practices of patch testing dermatologists. Dermatitis 24, 313–320 (2013).

    Article  CAS  PubMed  Google Scholar 

  289. Resor, C. D. & et al. Systemic allergic contact dermatitis due to a GORE CARDIOFORM septal occluder device. A case report and literature review. J. Am. Coll. Cardiol. Case Rep. 2, 1867–1871 (2020).

    Google Scholar 

  290. Aquino, M. & Mucci, T. Systemic contact dermatitis and allergy to biomedical devices. Curr. Allergy Asthma Rep. 13, 518–527 (2013).

    Article  CAS  PubMed  Google Scholar 

  291. Bibas, N., Lassere, J., Paul, C., Aquilina, C. & Giordano-Labadie, F. Nickel-induced systemic contact dermatitis and intratubal implants: the baboon syndrome revisited. Dermatitis 24, 35–36 (2013).

    Article  CAS  PubMed  Google Scholar 

  292. Lindsey, R. W. & Harper, A. Unusual complications related to spinal implants. JBJS Case Connect. 8, e10 (2018).

    Article  PubMed  Google Scholar 

  293. Jia, Z., Tu, J., Wang, K., Jiang, G. & Wang, W. Allergic reaction following implantation of a nitinol alloy inferior vena cava filter. J. Vasc. Interv. Radiol. 26, 1375–1377 (2015).

    Article  PubMed  Google Scholar 

  294. Pigatto, P. D. et al. Systemic allergic contact dermatitis associated with allergy to intraoral metals.Dermatol. Online J. 20, 13030/qt74632201 (2014).

    Article  PubMed  Google Scholar 

  295. Andrews, I. D. & Scheinman, P. Systemic hypersensitivity reaction (without cutaneous manifestations) to an implantable cardioverter-defibrillator. Dermatitis 22, 161–164 (2011).

    Article  PubMed  Google Scholar 

  296. Sharma, V. et al. Surgical explantation of atrial septal closure devices for refractory nickel allergy symptoms. J. Thorac. Cardiovasc. Surg. 160, 502–509.e1 (2020).

    Article  CAS  PubMed  Google Scholar 

  297. Schalock, P. C. et al. Hypersensitivity reactions to metallic implants - diagnostic algorithm and suggested patch test series for clinical use. Contact Dermatitis 66, 4–19 (2012).

    Article  CAS  PubMed  Google Scholar 

  298. Schalock, P. C. et al. Patch testing for evaluation of hypersensitivity to implanted metal devices: a perspective from the American Contact Dermatitis Society. Dermatitis 27, 241–247 (2016).

    Article  CAS  PubMed  Google Scholar 

  299. Lai, D. W., Saver, J. L., Araujo, J. A., Reidl, M. & Tobis, J. Pericarditis associated with nickel hypersensitivity to the Amplatzer occluder device: a case report. Catheter. Cardiovasc. Interv. 66, 424–426 (2005).

    Article  PubMed  Google Scholar 

  300. Kimyon, R. S. & Warshaw, E. M. Airborne allergic contact dermatitis: management and responsible allergens on the American Contact Dermatitis Society core series. Dermatitis 30, 106–115 (2019).

    Article  PubMed  Google Scholar 

  301. Gruye, L. E., Yanovsky, R. L. & Goldminz, A. M. Preventing relapses of airborne allergic contact dermatitis to isothiazolinones in wall paint by painting over with an isothiazolinone-free paint. Contact Dermatitis 82, 130–131 (2020).

    Article  PubMed  Google Scholar 

  302. Walls, A. C. & Silvestri, D. L. Prevention of airborne propolis-induced allergic contact dermatitis with barrier cream. Dermatitis 23, 128–129 (2012).

    Article  PubMed  Google Scholar 

  303. Dogra, S., Parsad, D. & Handa, S. Narrowband ultraviolet B in airborne contact dermatitis: a ray of hope! Br. J. Dermatol. 150, 373–374 (2004).

    Article  CAS  PubMed  Google Scholar 

  304. Verma, K. K., Sethuraman, G. & Kalavani, M. Weekly azathioprine pulse versus daily azathioprine in the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study. Indian J. Dermatol. Venereol. Leprol. 81, 251–256 (2015).

    Article  PubMed  Google Scholar 

  305. De, D., Sarangal, R. & Handa, S. The comparative efficacy and safety of azathioprine vs methotrexate as steroid-sparing agent in the treatment of airborne-contact dermatitis due to Parthenium. Indian J. Dermatol. Venereol. Leprol. 79, 240–241 (2013).

    Article  PubMed  Google Scholar 

  306. Lakshmi, C., Srinivas, C. R. & Jayaraman, A. Ciclosporin in parthenium dermatitis–a report of 2 cases. Contact Dermatitis 59, 245–248 (2008).

    Article  PubMed  Google Scholar 

  307. Snyder, M., Turrentine, J. E. & Cruz, P. D. Jr. Photocontact dermatitis and its clinical mimics: an overview for the allergist. Clin. Rev. Allergy Immunol. 56, 32–40 (2019).

    Article  PubMed  Google Scholar 

  308. Yu, J. et al. Occupational dermatitis to facial personal protective equipment in healthcare workers: a systematic review. J. Am. Acad. Dermatol. 84, 486–494 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  309. Weisshaar, E. et al. Multicentre study ‘rehabilitation of occupational skin diseases -optimization and quality assurance of inpatient management (ROQ)’-results from 12-month follow-up. Contact Dermatitis 68, 169–174 (2013).

    Article  PubMed  Google Scholar 

  310. van Gils, R. F. et al. Process evaluation of an integrated, multidisciplinary intervention programme for hand eczema. Contact Dermatitis 66, 254–263 (2012).

    Article  PubMed  Google Scholar 

  311. van Gils, R. F. et al. The effectiveness of integrated care for patients with hand eczema: results of a randomized, controlled trial. Contact Dermatitis 66, 197–204 (2012).

    Article  PubMed  Google Scholar 

  312. Gomez, P., Kudla, I. & Wozniak, G. The impact of a multidisciplinary team and a dedicated return-to-work coordinator for workers with work-related skin disease. Dermatitis 22, 308–309 (2011).

    Google Scholar 

  313. Kurt, O. K. & Basaran, N. Occupational exposure to metals and solvents: allergy and airway diseases. Curr. Allergy Asthma Rep. 20, 38 (2020).

    Article  PubMed  Google Scholar 

  314. Lazarov, A., Rabin, B., Fraidlin, N. & Abraham, D. Medical and psychosocial outcome of patients with occupational contact dermatitis in Israel. J. Eur. Acad. Dermatol. Venereol. 20, 1061–1065 (2006).

    Article  CAS  PubMed  Google Scholar 

  315. Ng, W. T. & Koh, D. Occupational contact dermatitis in manual cloud seeding operations. Singap. Med. J. 52, e85–87 (2011).

    CAS  Google Scholar 

  316. Yan, Y. et al. Consensus of Chinese experts on protection of skin and mucous membrane barrier for health-care workers fighting against coronavirus disease 2019. Dermatol. Ther. 33, e13310 (2020).

    Article  CAS  PubMed  Google Scholar 

  317. Holness, D. L. Occupational skin allergies: testing and treatment (the case of occupational allergic contact dermatitis). Curr. Allergy Asthma Rep. 14, 410 (2014).

    Article  CAS  PubMed  Google Scholar 

  318. Holness, D. L. Occupational dermatosis. Curr. Allergy Asthma Rep. 19, 42 (2019).

    Article  PubMed  Google Scholar 

  319. Mercader, P., de la Cuadra-Oyanguren, J., Rodríguez-Serna, M., Pitarch-Bort, G. & Fortea-Baixauli, J. M. Treatment of protein contact dermatitis with topical tacrolimus. Acta Derm. Venereol. 85, 555–556 (2005).

    CAS  PubMed  Google Scholar 

  320. Karimkhani, C. et al. Global skin disease morbidity and mortality: an update from the global burden of disease study 2013. JAMA Dermatol. 153, 406–412 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  321. Lau, M. Y., Burgess, J. A., Nixon, R., Dharmage, S. C. & Matheson, M. C. A review of the impact of occupational contact dermatitis on quality of life. J. Allergy 2011, 964509 (2011).

    Article  Google Scholar 

  322. Holness, D. L. et al. Hand and upper extremity function in workers with hand dermatitis. Dermatitis 24, 131–136 (2013).

    Article  PubMed  Google Scholar 

  323. Anderson, R. T. & Rajagopalan, R. Development and validation of a quality of life instrument for cutaneous diseases. J. Am. Acad. Dermatol. 37, 41–50 (1997).

    Article  CAS  PubMed  Google Scholar 

  324. Boonchai, W., Charoenpipatsin, N., Winayanuwattikun, W., Phaitoonwattanakij, S. & Sukakul, T. Assessment of the quality of life (QoL) of patients with dermatitis and the impact of patch testing on QoL: A study of 519 patients diagnosed with dermatitis. Contact Dermatitis 83, 182–188 (2020).

    Article  CAS  PubMed  Google Scholar 

  325. Ramirez, F., Chren, M. M. & Botto, N. A review of the impact of patch testing on quality of life in allergic contact dermatitis. J. Am. Acad. Dermatol. 76, 1000–1004 (2017).

    Article  PubMed  Google Scholar 

  326. Bhatia, R., Sharma, V. K., Ramam, M., Sethuraman, G. & Yadav, C. P. Clinical profile and quality of life of patients with occupational contact dermatitis from New Delhi, India. Contact Dermatitis 73, 172–181 (2015).

    Article  CAS  PubMed  Google Scholar 

  327. Nagpal, N., Gordon-Elliott, J. & Lipner, S. Comparison of quality of life and illness perception among patients with acne, eczema, and psoriasis. Dermatol. Online J. 25, 13030/qt3fk3f989 (2019).

    Article  PubMed  Google Scholar 

  328. Kadyk, D. L., McCarter, K., Achen, F. & Belsito, D. V. Quality of life in patients with allergic contact dermatitis. J. Am. Acad. Dermatol. 49, 1037–1048 (2003).

    Article  PubMed  Google Scholar 

  329. Anderson, R. T. & Rajagopalan, R. Effects of allergic dermatosis on health-related quality of life. Curr. Allergy Asthma Rep. 1, 309–315 (2001).

    Article  CAS  PubMed  Google Scholar 

  330. Botto, N. et al. Validating a quality-of-life instrument for allergic contact dermatitis. Dermatitis 30, 300–305 (2019). This is the first quality of life instrument validated for use in allergic CD.

    Article  PubMed  Google Scholar 

  331. Raffi, J., Elaine Allen, I. & Botto, N. Validating responsiveness of a quality-of-life instrument for allergic contact dermatitis. Dermatitis 31, 209–214 (2020).

    Article  PubMed  Google Scholar 

  332. Boehm, D. et al. Anxiety, depression and impaired health-related quality of life in patients with occupational hand eczema. Contact Dermatitis 67, 184–192 (2012).

    Article  PubMed  Google Scholar 

  333. Rajagopalan, R. et al. An economic evaluation of patch testing in the diagnosis and management of allergic contact dermatitis. Am. J. Contact Dermatitis 9, 149–154 (1998).

    CAS  Google Scholar 

  334. Thomson, K. F., Wilkinson, S. M., Sommer, S. & Pollock, B. Eczema: quality of life by body site and the effect of patch testing. Br. J. Dermatol. 146, 627–630 (2002).

    Article  CAS  PubMed  Google Scholar 

  335. Woo, P. N., Hay, I. C. & Ormerod, A. D. An audit of the value of patch testing and its effect on quality of life. Contact Dermatitis.48, 244–247 (2003).

    Article  CAS  PubMed  Google Scholar 

  336. Korkmaz, P. & Boyvat, A. Effect of patch testing on the course of allergic contact dermatitis and prognostic factors that influence outcomes. Dermatitis 30, 135–141 (2019).

    Article  PubMed  Google Scholar 

  337. De Groot, A. C. New contact allergens: 2008 to 2015. Dermatitis 26, 199–215 (2015).

    Article  CAS  PubMed  Google Scholar 

  338. Wilkinson, M. et al. The European baseline series and recommended additions: 2019. Contact Dermatitis 80, 1–4 (2019).

    Article  PubMed  Google Scholar 

  339. Uter, W., Lessmann, H., Geier, J. & Schnuch, A. Is the irritant benzalkonium chloride a contact allergen? A contribution to the ongoing debate from a clinical perspective. Contact Dermatitis 58, 359–363 (2008).

    Article  PubMed  Google Scholar 

  340. Basketter, D. A., Marriott, M., Gilmour, N. J. & White, I. R. Strong irritants masquerading as skin allergens: The case of benzalkonium chloride. Contact Dermatitis 50, 213–217 (2004).

    Article  CAS  PubMed  Google Scholar 

  341. Schnuch, A., Lessmann, H., Geier, J. & Uter, W. Is cocamidopropyl betaine a contact allergen? Analysis of network data and short review of the literature. Contact Dermatitis 64, 203–211 (2011).

    Article  PubMed  Google Scholar 

  342. Rietschel R. L., Fowler J. F. & Fisher A. A. in Contact Dermatitis 7th edn Ch. “Rubber” (eds Fowler, J. F. & Zirwas, M. J.) (Contact Dermatitis Institute, 2019).

  343. Geier, J., Uter, W., Pirker, C. & Frosch, P. J. Patch testing with the irritant sodium lauryl sulfate (SLS) is useful in interpreting weak reactions to contact allergens as allergic or irritant. Contact Dermatitis 48, 99–107 (2003).

    Article  CAS  PubMed  Google Scholar 

  344. Löffler, H., Becker, D., Brasch, J. & Geier, J. Simultaneous sodium lauryl sulphate testing improves the diagnostic validity of allergic patch tests. Results from a prospective multicentre study of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG). Br. J. Dermatol. 152, 709–719 (2005).

    Article  PubMed  Google Scholar 

  345. Goh, C. L., Wong, W. K. & Ng, S. K. Comparison between 1-day and 2-day occlusion times in patch testing. Contact Dermatitis.31, 48–50 (1994).

    Article  CAS  PubMed  Google Scholar 

  346. Rudzki, E., Zakrzewski, Z., Prokopczyk, G. & Kozłowska, A. Patch tests with potassium dichromate removed after 24 and 48 hours. Contact Dermatitis 2, 309–310 (1976).

    Article  CAS  PubMed  Google Scholar 

  347. Brasch, J. et al. Reproducibility of patch tests. A multicenter study of synchronous left-versus right-sided patch tests by the German Contact Dermatitis Research Group. J. Am. Acad. Dermatol. 31, 584–591 (1994).

    Article  CAS  PubMed  Google Scholar 

  348. Machácková, J. & Seda, O. Reproducibility of patch tests. J. Am. Acad. Dermatol. 25, 732–733 (1991).

    Article  PubMed  Google Scholar 

  349. Ale, S. I. & Maibach, H. I. 24-Hour versus 48-hour occlusion in patch testing. Exog. Dermatol. 2, 270–276 (2003).

    Article  Google Scholar 

  350. Higgins, C. L., Palmer, A. M., Cahill, J. L. & Nixon, R. L. Occupational skin disease among Australian healthcare workers: a retrospective analysis from an occupational dermatology clinic, 1993-2014. Contact Dermatitis 75, 213–222 (2016).

    Article  CAS  PubMed  Google Scholar 

  351. Halbert, A. R., Gebauer, K. A. & Wall, L. M. Prognosis of occupational chromate dermatitis. Contact Dermatitis 27, 214–219 (1992).

    Article  CAS  PubMed  Google Scholar 

  352. Nichol, K., Copes, R., Kersey, K., Eriksson, J. & Holness, D. L. Screening for hand dermatitis in healthcare workers: comparing workplace screening with dermatologist photo screening. Contact Dermatitis 80, 374–381 (2019).

    Article  PubMed  Google Scholar 

  353. Fisker, M. H., Ebbehøj, N. E., Jungersted, J. M. & Agner, T. What do patients with occupational hand eczema know about skin care? Contact Dermatitis 69, 93–98 (2013).

    Article  PubMed  Google Scholar 

  354. Graversgaard, C., Agner, T., Jemec, G. B. E., Thomsen, S. F. & Ibler, K. S. A long-term follow-up study of the Hand Eczema Trial (HET): a randomized clinical trial of a secondary preventive programme introduced to Danish healthcare workers. Contact Dermatitis 78, 329–334 (2018).

    Article  PubMed  Google Scholar 

  355. Clemmensen, K. K. B., Randbøll, I., Ryborg, M. F., Ebbehøj, N. E. & Agner, T. Evidence-based training as primary prevention of hand eczema in a population of hospital cleaning workers. Contact Dermatitis 72, 47–54 (2015).

    Article  PubMed  Google Scholar 

  356. Olesen, C. M., Agner, T., Ebbehøj, N. E. & Carøe, T. K. Factors influencing prognosis for occupational hand eczema: new trends. Br. J. Dermatol. 181, 1280–1286 (2019).

    Article  CAS  PubMed  Google Scholar 

  357. Keegel, T. et al. Incidence and prevalence rates for occupational contact dermatitis in an Australian suburban area. Contact Dermatitis 52, 254–259 (2005).

    Article  PubMed  Google Scholar 

  358. Nurmohamed, S., Bodley, T., Thompson, A. & Holness, D. L. Health care utilization characteristics in patch test patients. Dermatitis 25, 268–272 (2014).

    Article  PubMed  Google Scholar 

  359. Koppes, S. A. et al. Current knowledge on biomarkers for contact sensitization and allergic contact dermatitis. Contact Dermatitis 77, 1–16 (2017).

    Article  PubMed  Google Scholar 

  360. Wei, Z. et al. Two-dimensional cellular and three-dimensional bio-printed skin models to screen topical-use compounds for irritation potential. Front. Bioeng. Biotechnol. 8, 109 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  361. Malmberg, P., Guttenberg, T., Ericson, M. & Hagvall, L. Imaging mass spectrometry for novel insights into contact allergy - a proof-of-concept study on nickel. Contact Dermatitis 78, 109–116 (2018).

    Article  CAS  PubMed  Google Scholar 

  362. Hamilton, J. D., Ungar, B. & Guttman-Yassky, E. Drug evaluation review: dupilumab in atopic dermatitis. Immunotherapy 7, 1043–1058 (2015).

    Article  CAS  PubMed  Google Scholar 

  363. Machler, B. C. et al. Dupilumab use in allergic contact dermatitis. J. Am. Acad. Dermatol. 80, 280–281.e281 (2019).

    Article  PubMed  Google Scholar 

  364. Maloney, N. J. et al. Dupilumab in dermatology: potential for uses beyond atopic dermatitis. J. Drugs Dermatol. 18, S1545961619P1053X (2019).

    PubMed  Google Scholar 

  365. Puza, C. J. & Atwater, A. R. Positive patch test reaction in a patient taking dupilumab. Dermatitis 29, 89–89 (2018).

    Article  PubMed  Google Scholar 

  366. Ruge, I. F., Skov, L., Zachariae, C. & Thyssen, J. P. Dupilumab treatment in two patients with severe allergic contact dermatitis caused by sesquiterpene lactones. Contact Dermatitis 83, 137–139 (2020).

    Article  PubMed  Google Scholar 

  367. Joshi, S. R. & Khan, D. A. Effective use of dupilumab in managing systemic allergic contact dermatitis. Dermatitis 29, 282–284 (2018).

    Article  CAS  PubMed  Google Scholar 

  368. Goldminz, A. M. & Scheinman, P. L. A case series of dupilumab-treated allergic contact dermatitis patients. Dermatol. Ther. 31, 8–10 (2018).

    Article  Google Scholar 

  369. Raffi, J. The impact of dupilumab on patch testing and the prevalence of comorbid allergic contact dermatitis in recalcitrant atopic dermatitis: a retrospective chart review. J. Am. Acad. Dermatol. 82, 132–138 (2020).

    Article  CAS  PubMed  Google Scholar 

  370. Tuckermann, J. P. et al. Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy. J. Clin. Invest. 117, 1381–1390 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  371. Suwanpradid, J. et al. Arginase1 deficiency in monocytes/macrophages upregulates inducible nitric oxide synthase to promote cutaneous contact hypersensitivity. J. Immunol. 199, 1827–1834 (2017).

    Article  CAS  PubMed  Google Scholar 

  372. Smith, J. S., Rajagopal, S. & Atwater, A. R. Chemokine signaling in allergic contact dermatitis: toward targeted therapies. Dermatitis 29, 179–186 (2018). For many years, allergen avoidance, topical corticosteroids, phototherapy and traditional, systemic immunosuppressants have been the mainstay for the treatment of CD; targeted therapies represent a new and exciting approach to benefit patients with recalcitrant disease.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  373. Alonso, M. D. et al. Occupational protein contact dermatitis from lettuce. Contact Dermatitis 29, 109–110 (1993).

    Article  CAS  PubMed  Google Scholar 

  374. Hafner, J., Riess, C. E. & Wüthrich, B. Protein contact dermatitis from paprika and curry in a cook. Contact Dermatitis 26, 51–52 (1992).

    Article  CAS  PubMed  Google Scholar 

  375. Iliev, D. & Wüthrich, B. Occupational protein contact dermatitis with type I allergy to different kinds of meat and vegetables. Int. Arch. Occup. Env. Health 71, 289–292 (1998).

    Article  CAS  Google Scholar 

  376. Kumar, A. & Freeman, S. Protein contact dermatitis in food workers. Case report of a meat sorter and summary of seven other cases. Australas. J. Dermatol. 40, 138–140 (1999).

    Article  CAS  PubMed  Google Scholar 

  377. Laurière, M. et al. Hydrolysed wheat proteins present in cosmetics can induce immediate hypersensitivities. Contact Dermatitis.54, 283–289 (2006).

    Article  PubMed  Google Scholar 

  378. Crippa, M., Sala, E. & Alessio, L. Occupational protein contact dermatitis from milk proteins. Contact Dermatitis 51, 42 (2004).

    Article  CAS  PubMed  Google Scholar 

  379. Doyen, V. et al. Protein contact dermatitis and food allergy to mare milk. Ann. Allergy Asthma Immunol. 110, 390–391 (2013).

    Article  PubMed  Google Scholar 

  380. Kanerva, L., Vanhanen, M. & Tupasela, O. Occupational contact urticaria from cellulase enzyme. Contact Dermatitis 38, 176–177 (1998).

    Article  CAS  PubMed  Google Scholar 

  381. Nettis, E., Colanardi, M. C. & Ferrannini, A. Type I latex allergy in health care workers with latex-induced contact urticaria syndrome: a follow-up study. Allergy 59, 718–723 (2004).

    Article  CAS  PubMed  Google Scholar 

  382. Crisi, G. & Belsito, D. V. Contact urticaria from latex in a patient with immediate hypersensitivity to banana, avocado and peach. Contact Dermatitis 28, 247–248 (1993).

    Article  CAS  PubMed  Google Scholar 

  383. Uter, W., Gefeller, O., Mahler, V. & Geier, J. Trends and current spectrum of contact allergy in Central Europe: results of the information network of departments of dermatology (IVDK) 2007-2018. Br. J. Dermatol. 183, 857–865 (2020).

    Article  CAS  PubMed  Google Scholar 

  384. Tagka, A. et al. Prevalence of contact dermatitis in the Greek population: a retrospective observational study. Contact Dermatitis 81, 460–462 (2019).

    Article  PubMed  Google Scholar 

  385. Ochi, H., Cheng, S. W., Leow, Y. H. & Goon, A. T. Contact allergy trends in Singapore - a retrospective study of patch test data from 2009 to 2013. Contact Dermatitis 76, 49–50 (2017).

    Article  PubMed  Google Scholar 

  386. Süß, H. et al. Contact urticaria: frequency, elicitors and cofactors in three cohorts (Information Network of Departments of Dermatology; Network of Anaphylaxis; and Department of Dermatology, University Hospital Erlangen, Germany). Contact Dermatitis 81, 341–353 (2019).

    Article  PubMed  CAS  Google Scholar 

  387. Amaro, C. & Goossens, A. Immunological occupational contact urticaria and contact dermatitis from proteins: a review. Contact Dermatitis 58, 67–75 (2008).

    Article  PubMed  Google Scholar 

  388. Saluja, S. S., Davis, C. L., Chong, T. A. & Powell, D. L. Contact urticaria to nickel: a series of 11 patients who were prick test positive and patch test negative to nickel sulfate 2.5% and 5.0. Dermatitis 27, 282–287 (2016).

    Article  CAS  PubMed  Google Scholar 

  389. Verhulst, L. & Goossens, A. Cosmetic components causing contact urticaria: a review and update. Contact Dermatitis 75, 333–344 (2016).

    Article  CAS  PubMed  Google Scholar 

  390. Bhatia, R., Alikhan, A. & Maibach, H. I. Contact urticaria: present scenario. Indian J. Dermatol. 54, 264–268 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, USA

    Pamela L. Scheinman & Ari M. Goldminz

  2. CIRI - Centre International de Recherche en Infectiologie, INSERM, U1111; Univ Lyon; Université Claude Bernard Lyon 1; Ecole Normale Supérieure de Lyon; CNRS, UMR, 5308, Lyon, France

    Marc Vocanson & Johanna Morot

  3. National Allergy Research Centre, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

    Jacob P. Thyssen & Jeanne Duus Johansen

  4. Skin Health Institute - Occupational Dermatology Research and Education Centre, Carlton, VIC, Australia

    Rosemary L. Nixon & Kate Dear

  5. Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA

    Nina C. Botto

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  1. Pamela L. Scheinman
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Contributions

Introduction (A.M.G.); Epidemiology (K.D. and R.L.N.); Mechanisms/pathophysiology (M.V. and J.M.); Diagnosis, screening and prevention (J.P.T. and J.D.J.); Management (P.L.S.); Quality of life (N.C.B.); Outlook (K.D. and R.L.N.); Overview of Primer (A.M.G.).

Corresponding author

Correspondence to Ari M. Goldminz.

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Competing interests

P.L.S. is a member of the American Academy of Dermatology and the American Contact Dermatitis Society and has held leadership and committee positions for both of these organizations. P.L.S. is a consultant for Ella-Ola brands. N.C.B. is a member of the American Academy of Dermatology and the American Contact Dermatitis Society and has held leadership and committee positions for both of these organizations. A.M.G. is a member of the American Academy of Dermatology and the American Contact Dermatitis Society and has held leadership and/or committee positions for both of these organizations. A.M.G. is an investigator with research grants from Regeneron and The Human Skin Disease Research Center. A.M.G.’s spouse owns stock in Johnson and Johnson. All other authors declare no competing interests.

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Nature Reviews Disease Primers thanks J. English, M. Gonçalo, S. Martin, M. Pallardy, and T. Rustemeyer for their contribution to the peer review of this work.

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Supplementary information

Glossary

Allergen

A substance, usually a protein, that can stimulate the immune system and induce sensitization.

Irritant

A substance that has irritant properties that does not rely on the process of sensitization or immunological memory.

Hapten

A chemical that reacts with skin self-proteins through a process termed haptenization; haptens bind to self-proteins and generate hapten–self-protein complexes (or haptenated proteins) that will be processed in hapten–self-peptide complexes (or neo-antigens). These neo-antigens will then be presented in MHC to T cells.

Sensitization

The initial phase of contact allergy where the immune system is primed to the allergen after exposure, with subsequent immune memory that can recognize the allergen with re-exposure.

Elicitation

In a previously sensitized individual, re-exposure to an allergen can cause mobilization of the immune system (immunological memory).

Prehaptens

Haptens that need to be activated by exogenous triggers (such as UV light, air or others) before they can react with self-proteins.

Prohaptens

Haptens that need to be activated by endogenous mechanisms (via enzymes or other biological processes) before they can react with self-proteins.

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Scheinman, P.L., Vocanson, M., Thyssen, J.P. et al. Contact dermatitis. Nat Rev Dis Primers 7, 38 (2021). https://doi.org/10.1038/s41572-021-00271-4

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