Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Contact Allergy

  • Chapter
  • First Online:
Environment and Skin

  • 651 Accesses

Abstract

The skin forms a protective barrier that fends off environmental threats such as infections, UV light, and chemicals. Some chemicals penetrate the skin and cause an inflammatory skin disease, allergic contact dermatitis. This skin disease is mediated by our immune system and requires reactive chemicals that are able to activate both the innate and adaptive immune system. In this chapter I discuss mechanisms underlying the activation of the innate immune system by contact sensitizers. Based on these mechanisms, I further discuss heterologous innate immune stimulation and mechanism-based strategies for causative therapies and development of in vitro alternatives to animal testing for contact allergen identification.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 99.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ACD:

Allergic contact dermatitis

CHS:

Contact hypersensitivity

DAMPs:

Damage-associated molecular patterns

DC:

Dendritic cell

DNFB:

2,4-Dinitrofluorobenzene

ICD:

Irritant contact dermatitis

NLR:

NOD-like receptor

PAMPs:

Pathogen-associated molecular patterns

PRR:

Pattern recognition receptor

ROS:

Reactive oxygen species

TLR:

Toll-like receptor

TNCB:

2,4,6-Trinitrochlorobenzene

References

  1. Peiser M, Tralau T, Heidler J, Api AM, Arts JH, Basketter DA, English J, Diepgen TL, Fuhlbrigge RC, Gaspari AA, Johansen JD, Karlberg AT, Kimber I, Lepoittevin JP, Liebsch M, Maibach HI, Martin SF, Merk HF, Platzek T, Rustemeyer T, Schnuch A, Vandebriel RJ, White IR, Luch A. Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. Current knowledge assembled at an international workshop at BfR, Germany. Cell Mol Life Sci. 2012;69(5):763–81. doi:10.1007/s00018-011-0846-8.

    Article  CAS  PubMed  Google Scholar 

  2. Brasch J, Becker D, Aberer W, Bircher A, Kranke B, Jung K, Przybilla B, Biedermann T, Werfel T, John SM, Elsner P, Diepgen T, Trautmann A, Merk HF, Fuchs T, Schnuch A. Guideline contact dermatitis: S1-Guidelines of the German Contact Allergy Group (DKG) of the German Dermatology Society (DDG), the Information Network of Dermatological Clinics (IVDK), the German Society for Allergology and Clinical Immunology (DGAKI), the Working Group for Occupational and Environmental Dermatology (ABD) of the DDG, the Medical Association of German Allergologists (AeDA), the Professional Association of German Dermatologists (BVDD) and the DDG. Allergo J Int. 2014;23(4):126–38. doi:10.1007/s40629-014-0013-5.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Holness DL. Occupational skin allergies: testing and treatment (the case of occupational allergic contact dermatitis). Curr Allergy Asthma Rep. 2014;14(2):410. doi:10.1007/s11882-013-0410-8.

    Article  PubMed  Google Scholar 

  4. Wiszniewska M, Walusiak-Skorupa J. Recent trends in occupational contact dermatitis. Curr Allergy Asthma Rep. 2015;15(7):43. doi:10.1007/s11882-015-0543-z.

    Article  PubMed  Google Scholar 

  5. Fyhrquist N, Lehto E, Lauerma A. New findings in allergic contact dermatitis. Curr Opin Allergy Clin Immunol. 2014;14(5):430–5. doi:10.1097/ACI.0000000000000092.

    Article  CAS  PubMed  Google Scholar 

  6. Martin SF. Immunological mechanisms in allergic contact dermatitis. Curr Opin Allergy Clin Immunol. 2015;15(2):124–30. doi:10.1097/ACI.0000000000000142.

    Article  CAS  PubMed  Google Scholar 

  7. Vocanson M, Hennino A, Rozieres A, Poyet G, Nicolas JF. Effector and regulatory mechanisms in allergic contact dermatitis. Allergy. 2009;64(12):1699–714. doi:10.1111/j.1398-9995.2009.02082.x.

    Article  CAS  PubMed  Google Scholar 

  8. Martin SF, Esser PR, Schmucker S, Dietz L, Naisbitt DJ, Park BK, Vocanson M, Nicolas JF, Keller M, Pichler WJ, Peiser M, Luch A, Wanner R, Maggi E, Cavani A, Rustemeyer T, Richter A, Thierse HJ, Sallusto F. T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays. Cell Mol Life Sci. 2010;67(24):4171–84. doi:10.1007/s00018-010-0495-3.

    Article  CAS  PubMed  Google Scholar 

  9. Goubier A, Vocanson M, Macari C, Poyet G, Herbelin A, Nicolas JF, Dubois B, Kaiserlian D. Invariant NKT cells suppress CD8(+) T-cell-mediated allergic contact dermatitis independently of regulatory CD4(+) T cells. J Invest Dermatol. 2013;133(4):980–7. doi:10.1038/jid.2012.404.

    Article  CAS  PubMed  Google Scholar 

  10. Dhingra N, Shemer A, Correa da Rosa J, Rozenblit M, Fuentes-Duculan J, Gittler JK, Finney R, Czarnowicki T, Zheng X, Xu H, Estrada YD, Cardinale I, Suarez-Farinas M, Krueger JG, Guttman-Yassky E. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J Allergy Clin Immunol. 2014;134(2):362–72. doi:10.1016/j.jaci.2014.03.009.

    Article  CAS  PubMed  Google Scholar 

  11. Quaranta M, Knapp B, Garzorz N, Mattii M, Pullabhatla V, Pennino D, Andres C, Traidl-Hoffmann C, Cavani A, Theis FJ, Ring J, Schmidt-Weber CB, Eyerich S, Eyerich K. Intraindividual genome expression analysis reveals a specific molecular signature of psoriasis and eczema. Sci Transl Med. 2014;6(244):244ra290. doi:10.1126/scitranslmed.3008946.

    Article  Google Scholar 

  12. Martin SF. Allergic contact dermatitis: xenoinflammation of the skin. Curr Opin Immunol. 2012;24(6):720–9. doi:10.1016/j.coi.2012.08.003.

    Article  CAS  PubMed  Google Scholar 

  13. Kaplan DH, Igyarto BZ, Gaspari AA. Early immune events in the induction of allergic contact dermatitis. Nat Rev Immunol. 2012;12(2):114–24. doi:10.1038/nri3150.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 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. 2013;133(2):303–15. doi:10.1038/jid.2012.284.

    Article  CAS  PubMed  Google Scholar 

  15. Schmidt M, Raghavan B, Muller V, Vogl T, Fejer G, Tchaptchet S, Keck S, Kalis C, Nielsen PJ, Galanos C, Roth J, Skerra A, Martin SF, Freudenberg MA, Goebeler M. Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat Immunol. 2010;11(9):814–9. doi:10.1038/ni.1919.

    Article  CAS  PubMed  Google Scholar 

  16. Raghavan B, Martin SF, Esser PR, Goebeler M, Schmidt M. Metal allergens nickel and cobalt facilitate TLR4 homodimerization independently of MD2. EMBO Rep. 2012;13(12):1109–15. doi:10.1038/embor.2012.155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Martin SF, Dudda JC, Bachtanian E, Lembo A, Liller S, Durr C, Heimesaat MM, Bereswill S, Fejer G, Vassileva R, Jakob T, Freudenberg N, Termeer CC, Johner C, Galanos C, Freudenberg MA. Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity. J Exp Med. 2008;205(9):2151–62. doi:10.1084/jem.20070509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Esser PR, Wolfle U, Durr C, von Loewenich FD, Schempp CM, Freudenberg MA, Jakob T, Martin SF. Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation. PLoS One. 2012;7(7):e41340. doi:10.1371/journal.pone.0041340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. El Ali Z, Gerbeix C, Hemon P, Esser PR, Martin SF, Pallardy M, Kerdine-Romer S. Allergic skin inflammation induced by chemical sensitizers is controlled by the transcription factor Nrf2. Toxicol Sci. 2013;134(1):39–48. doi:10.1093/toxsci/kft084.

    Article  PubMed  Google Scholar 

  20. Weber FC, Esser PR, Muller T, Ganesan J, Pellegatti P, Simon MM, Zeiser R, Idzko M, Jakob T, Martin SF. Lack of the purinergic receptor P2X(7) results in resistance to contact hypersensitivity. J Exp Med. 2010;207(12):2609–19. doi:10.1084/jem.20092489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yasukawa S, Miyazaki Y, Yoshii C, Nakaya M, Ozaki N, Toda S, Kuroda E, Ishibashi K, Yasuda T, Natsuaki Y, Mi-ichi F, Iizasa E, Nakahara T, Yamazaki M, Kabashima K, Iwakura Y, Takai T, Saito T, Kurosaki T, Malissen B, Ohno N, Furue M, Yoshida H, Hara H. An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells. Nature Commun. 2014;5:3755. doi:10.1038/ncomms4755.

    Article  CAS  Google Scholar 

  22. Dudeck A, Dudeck J, Scholten J, Petzold A, Surianarayanan S, Kohler A, Peschke K, Vohringer D, Waskow C, Krieg T, Muller W, Waisman A, Hartmann K, Gunzer M, Roers A. Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens. Immunity. 2011;34(6):973–84. doi:10.1016/j.immuni.2011.03.028.

    Article  CAS  PubMed  Google Scholar 

  23. Weber FC, Nemeth T, Csepregi JZ, Dudeck A, Roers A, Ozsvari B, Oswald E, Puskas LG, Jakob T, Mocsai A, Martin SF. Neutrophils are required for both the sensitization and elicitation phase of contact hypersensitivity. J Exp Med. 2015;212(1):15–22. doi:10.1084/jem.20130062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Schwab L, Goroncy L, Palaniyandi S, Gautam S, Triantafyllopoulou A, Mocsai A, Reichardt W, Karlsson FJ, Radhakrishnan SV, Hanke K, Schmitt-Graeff A, Freudenberg M, von Loewenich FD, Wolf P, Leonhardt F, Baxan N, Pfeifer D, Schmah O, Schonle A, Martin SF, Mertelsmann R, Duyster J, Finke J, Prinz M, Henneke P, Hacker H, Hildebrandt GC, Hacker G, Zeiser R. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med. 2014;20(6):648–54. doi:10.1038/nm.3517.

    Article  CAS  PubMed  Google Scholar 

  25. Lim K, Hyun YM, Lambert-Emo K, Capece T, Bae S, Miller R, Topham DJ, Kim M. Neutrophil trails guide influenza-specific CD8(+) T cells in the airways. Science. 2015;349(6252):aaa4352. doi:10.1126/science.aaa4352.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hampton HR, Bailey J, Tomura M, Brink R, Chtanova T. Microbe-dependent lymphatic migration of neutrophils modulates lymphocyte proliferation in lymph nodes. Nat Commun. 2015;6:7139. doi:10.1038/ncomms8139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. MacKay C, Davies M, Summerfield V, Maxwell G. From pathways to people: applying the adverse outcome pathway (AOP) for skin sensitization to risk assessment. ALTEX. 2013;30(4):473–86.

    Article  PubMed  Google Scholar 

  28. Leist M, Hasiwa N, Rovida C, Daneshian M, Basketter D, Kimber I, Clewell H, Gocht T, Goldberg A, Busquet F, Rossi AM, Schwarz M, Stephens M, Taalman R, Knudsen TB, McKim J, Harris G, Pamies D, Hartung T. Consensus report on the future of animal-free systemic toxicity testing. ALTEX. 2014;31(3):341–56. doi:10.14573/altex.1406091.

    PubMed  Google Scholar 

  29. Wong CL, Ghassabian S, Smith MT, Lam AL. In vitro methods for hazard assessment of industrial chemicals – opportunities and challenges. Front Pharmacol. 2015;6:94. doi:10.3389/fphar.2015.00094.

    PubMed  PubMed Central  Google Scholar 

  30. Reisinger K, Hoffmann S, Alepee N, Ashikaga T, Barroso J, Elcombe C, Gellatly N, Galbiati V, Gibbs S, Groux H, Hibatallah J, Keller D, Kern P, Klaric M, Kolle S, Kuehnl J, Lambrechts N, Lindstedt M, Millet M, Martinozzi-Teissier S, Natsch A, Petersohn D, Pike I, Sakaguchi H, Schepky A, Tailhardat M, Templier M, van Vliet E, Maxwell G. Systematic evaluation of non-animal test methods for skin sensitisation safety assessment. Toxicol In Vitro. 2015;29(1):259–70. doi:10.1016/j.tiv.2014.10.018.

    Article  CAS  PubMed  Google Scholar 

  31. Urbisch D, Mehling A, Guth K, Ramirez T, Honarvar N, Kolle S, Landsiedel R, Jaworska J, Kern PS, Gerberick F, Natsch A, Emter R, Ashikaga T, Miyazawa M, Sakaguchi H. Assessing skin sensitization hazard in mice and men using non-animal test methods. Regul Toxicol Pharmacol. 2015;71(2):337–51. doi:10.1016/j.yrtph.2014.12.008.

    Article  CAS  PubMed  Google Scholar 

  32. Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39(4):199–218. doi:10.1016/j.tibs.2014.02.002.

    Article  CAS  PubMed  Google Scholar 

  33. Tebay LE, Robertson H, Durant ST, Vitale SR, Penning TM, Dinkova-Kostova AT, Hayes JD. Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic Biol Med. 2015;88(Pt B):108–46. doi:10.1016/j.freeradbiomed.2015.06.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Agner T, Johansen JD, Overgaard L, Volund A, Basketter D, Menne T. Combined effects of irritants and allergens. Synergistic effects of nickel and sodium lauryl sulfate in nickel- sensitized individuals. Contact Dermatitis. 2002;47(1):21–6.

    Article  CAS  PubMed  Google Scholar 

  35. Pedersen LK, Johansen JD, Held E, Agner T. Augmentation of skin response by exposure to a combination of allergens and irritants – a review. Contact Dermatitis. 2004;50(5):265–73. doi:10.1111/j.0105-1873.2004.00342.x.

    Article  CAS  PubMed  Google Scholar 

  36. Bonefeld CM, Nielsen MM, Rubin IM, Vennegaard MT, Dabelsteen S, Gimenez-Arnau E, Lepoittevin JP, Geisler C, Johansen JD. Enhanced sensitization and elicitation responses caused by mixtures of common fragrance allergens. Contact Dermatitis. 2011;65(6):336–42. doi:10.1111/j.1600-0536.2011.01945.x.

    Article  CAS  PubMed  Google Scholar 

  37. Martin SF. Adaptation in the innate immune system and heterologous innate immunity. Cell Mol Life Sci. 2014;71(21):4115–30. doi:10.1007/s00018-014-1676-2.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Allergy Research Group, Department of Dermatology, Medical Center – University of Freiburg, Hauptstrasse 7, 79104, Freiburg, Germany

    Stefan F. Martin Ph.D.

  2. Faculty of Medicine, University of Freiburg, Hauptstrasse 7, 79104, Freiburg, Germany

    Stefan F. Martin Ph.D.

Authors
  1. Stefan F. Martin Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefan F. Martin Ph.D. .

Editor information

Editors and Affiliations

  1. IUF – Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany

    Jean Krutmann

  2. Universitätsklinikum Aachen Klinik für Dermatologie u. Allergologie, Aachen, Germany

    Hans F. Merk

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Martin, S.F. (2018). Contact Allergy. In: Krutmann, J., Merk, H. (eds) Environment and Skin. Springer, Cham. https://doi.org/10.1007/978-3-319-43102-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-43102-4_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-43100-0

  • Online ISBN: 978-3-319-43102-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation