Metal Allergy pp 373-386 | Cite as

Metal Allergy: Copper

  • Simon W. Fage


Worldwide production of copper is increasing. Among other sources, human skin is exposed to copper from jewellery, coins, door fittings, knobs and taps. Mucosal exposure occurs through dental materials and copper-containing intrauterine contraceptive devices. Despite the fact that several studies show release of copper ions from different materials in a biological-like milieu, and although copper has many chemical similarities with nickel, a strong sensitizer, only few cases of copper allergy have been reported. Hence, copper seems to be a weak sensitizer that should be considered in select cases. Here we review the sources of exposure, chemistry, biology and cumulative data including case reports to clarify the implications of copper allergy.


  1. 1.
    London Metal Exchange. Accessed 11 May 2016.
  2. 2.
    Emsley J. Nature’s building blocks: an A-Z guide to the elements. Oxford: Oxford University Press; 2003. p. 121–5.Google Scholar
  3. 3.
    Suárez CP, Fernández-Redondo V, Toribio J. Bingo-hall worker’s occupational copper contact dermatitis from coins. Contact Dermatitis. 2002;47:182.CrossRefGoogle Scholar
  4. 4.
    Wöhrl S, Hemmer W, Focke M, Götz M, Jarisch R. Copper allergy revisited. J Am Acad Dermatol. 2001;45:863–70.CrossRefGoogle Scholar
  5. 5.
    Hamann CR, Hamann D, Hamann C, Thyssen JP, Lidén C. The cost of nickel allergy: a global investigation of coin composition and nickel and cobalt release. Contact Dermatitis. 2013;68:15–22.CrossRefGoogle Scholar
  6. 6.
    Thyssen JP, Gawkrodger DJ, White IR, Julander A, Menné T, Lidén C. Coin exposure may cause allergic nickel dermatitis: a review. Contact Dermatitis. 2013;68:3–14.CrossRefGoogle Scholar
  7. 7.
    Flint GN. A metallurgical approach to metal contact dermatitis. Contact Dermatitis. 1998;39:213–21.CrossRefGoogle Scholar
  8. 8.
    Hamann D, Thyssen JP, Hamann CR, Hamann C, Menné T, Johansen JD, Spiewak R, Maibach H, Lundgren L, Lidén C. Jewellery: alloy composition and release of nickel, cobalt and lead assessed with the EU synthetic sweat method. Contact Dermatitis. 2015;73(4):231–8.CrossRefGoogle Scholar
  9. 9.
    Stoffolani N, Damiani F, Lilli C, et al. Ion release from orthodontic appliances. J Dent. 1999;27:449–54.CrossRefGoogle Scholar
  10. 10.
    Vilaplana J, Romaguera C. New developments in jewellery and dental materials. Contact Dermatitis. 1998;39:55–7.CrossRefGoogle Scholar
  11. 11.
    Hostynek JJ, Maibach HI. Copper hypersensitivity: dermatologic aspects – an overview. Rev Environ Health. 2003;18:153–83.CrossRefGoogle Scholar
  12. 12.
    Vilaplana J, Romaguera C. Contact dermatitis and adverse oral mucous membrane reactions related to the use of dental prostheses. Contact Dermatitis. 2000;43:183–5.PubMedGoogle Scholar
  13. 13.
    Sonfield A. Popularity disparity: attitudes about the IUD in Europe and the United States, The Guttmacher Institute. 2012. Accessed 11 May 2016.
  14. 14.
    Frentz G, Teilum D. Cutaneous eruptions and intrauterine contraceptive copper device. Acta Derm Venereol. 1980;60:69–71.Google Scholar
  15. 15.
    Sven OS, Kresten RP. Danish Society of Obstetrics and Gynecology, authors translation. 2013. Accessed 11 May 2016.
  16. 16.
    Rademaker M. Occupational contact dermatitis among New Zealand farmers. Australas J Dermatol. 1998;39:164–7.CrossRefGoogle Scholar
  17. 17.
    Warnes SL, Keevil CW. Death and genome destruction of methicillin-resistant and methicillin-sensitive strains of Staphylococcus aureus on wet or dry copper alloy surfaces does not involve Fenton chemistry. Appl Environ Microbiol. 2016. pii: AEM.03861-15 [Epub ahead of print].Google Scholar
  18. 18.
    Warnes SL, Summersgill EN, Keevil CW. Inactivation of murine norovirus on a range of copper alloy surfaces is accompanied by loss of capsid integrity. Appl Environ Microbiol. 2015;81(3):1085–91.CrossRefGoogle Scholar
  19. 19.
    Warnes SL, Highmore CJ, Keevil CW. Horizontal transfer of antibiotic resistance genes on abiotic touch surfaces: implications for public health. MBio. 2012;3(6). pii: e00489-12.CrossRefGoogle Scholar
  20. 20.
    Salgado CD, Sepkowitz KA, John JF, Cantey JR, Attaway HH, Freeman KD, Sharpe PA, Michels HT, Schmidt MG. Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol. 2013;34(5):479–86.CrossRefGoogle Scholar
  21. 21.
    Michels HT, Noyce JO, Keevil CW. Effects of temperature and humidity on the efficacy of methicillin-resistant staphylococcus aureus challenged antimicrobial materials containing silver and copper. Lett Appl Microbiol. 2009;49:191–5.CrossRefGoogle Scholar
  22. 22.
    Mehtar S, Wiid I, Todorov SD. The antimicrobial activity of copper and copper alloys against nosocomial pathogens and mycobacterium tuberculosis isolated from healthcare facilities in the Western Cape: an in-vitro study. J Hosp Infect. 2008;68:45–51.CrossRefGoogle Scholar
  23. 23.
    Noyce JO, Michels H, Keevil CW. Inactivation of influenza A virus on copper versus stainless steel surfaces. Appl Environ Microbiol. 2007;73:2748–50.CrossRefGoogle Scholar
  24. 24.
    Sun LH. The bacteria-fighting super element that’s making a comeback in hospitals: copper. The Washington Post. 20 Sept 2015.Google Scholar
  25. 25.
    Global Rail News. Chilean subway protected with antimicrobial copper. 2011. Accessed 11 May 2016.
  26. 26.
    Bryony S. Copper Development Association. Chilean subway protected with antimicrobial copper. 2011. Accessed 11 May 2016.
  27. 27.
    Boman A, Karlberg AT, Einarsson O, Wahlberg JE. Dissolving of copper by synthetic sweat. Contact Dermatitis. 1983;9:159–60.CrossRefGoogle Scholar
  28. 28.
    Lidén C, Nordenadler M, Skare L. Metal release from gold-containing jewelry materials: no gold release detected. Contact Dermatitis. 1998;39:281–5.CrossRefGoogle Scholar
  29. 29.
    Fournier PG, Govers TR. Contamination by nickel, copper and zinc during the handling of euro coins. Contact Dermatitis. 2003;48:181–8.CrossRefGoogle Scholar
  30. 30.
    Fukuyama T, Ueda H, Hayashi K, et al. Sensitizing potential of chromated copper arsenate in local lymph node assays differs with the solvent used. J Immunotoxicol. 2008;5:99–106.CrossRefGoogle Scholar
  31. 31.
    Basketter DA, Gerberick GF, Kimber I, Loveless SE. The local lymph node assay: a viable alternative to currently accepted skin sensitization tests. Food Chem Toxicol. 1996;34:985–97.CrossRefGoogle Scholar
  32. 32.
    Haneke KE, Tice RR, Carson BL, Margolin BH, Stokes WS. ICCVAM evaluation of the murine local lymph node assay. Data analyses completed by the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods. Regul Toxicol Pharmacol. 2001;34:274–86.CrossRefGoogle Scholar
  33. 33.
    Boman A, Wahlberg JE, Hagelthorn G. Sensitizing potential of beryllium, copper and molybdenum compounds studied by the guinea pig maximization method. Contact Dermatitis. 1979;5:332–3.CrossRefGoogle Scholar
  34. 34.
    Karlberg AT, Boman A, Wahlberg JE. Copper – a rare sensitizer. Contact Dermatitis. 1983;9:134–9.CrossRefGoogle Scholar
  35. 35.
    Basketter DA, Scholes EW. Comparison of the local lymph node assay with the guinea-pig maximization test for the detection of a range of contact allergens. Food Chem Toxicol. 1992;30:65–9.CrossRefGoogle Scholar
  36. 36.
    Ikarashi Y, Tsuchiya T, Nakamura A. Detection of contact sensitivity of metal salts using the murine local lymph node assay. Toxicol Lett. 1992;62:53–61.CrossRefGoogle Scholar
  37. 37.
    Yamano T, Shimizu M, Noda T. Allergenicity and cross-reactivity of naphthenic acid and its metallic salts in experimental animals. Contact Dermatitis. 2006;54:25–8.CrossRefGoogle Scholar
  38. 38.
    Nonaka H, Nakada T, Iijima M, Maibach HI. Metal patch test results from 1990–2009. J Dermatol. 2011;38:267–71.CrossRefGoogle Scholar
  39. 39.
    Lee JY, Yoo JM, Cho BK, Kim HO. Contact dermatitis in Korean dental technicians. Contact Dermatitis. 2001;45:13–6.CrossRefGoogle Scholar
  40. 40.
    Wöhrl S, Kriechbaumer N, Hemmer W, et al. A cream containing the chelator DTPA (diethylenetriaminepenta-acetic acid) can prevent contact allergic reactions to metals. Contact Dermatitis. 2001;44:224–8.CrossRefGoogle Scholar
  41. 41.
    Epstein S. Cross-sensitivity between nickel and copper; with remarks on cross-sensitivity between nickel, cobalt and chromates. J Invest Dermatol. 1955;25:269–74.CrossRefGoogle Scholar
  42. 42.
    Dhir GG, Rao DS, Mehrotra MP. Contact dermatitis caused by copper sulfate used as coloring material in commercial alcohol. Ann Allergy. 1977;39:204.PubMedGoogle Scholar
  43. 43.
    Walton S. Investigation into patch testing with copper sulphate. Contact Dermatitis. 1983;9:89–90.CrossRefGoogle Scholar
  44. 44.
    Lisi P, Caraffini S, Assalve D. Irritation and sensitization potential of pesticides. Contact Dermatitis. 1987;17:212–8.CrossRefGoogle Scholar
  45. 45.
    Romaguera C, Grimalt F, Vilaplana J. Contact dermatitis from nickel: an investigation of its sources. Contact Dermatitis. 1988;19:52–7.CrossRefGoogle Scholar
  46. 46.
    van Joost T, Habets JM, Stolz E, Naafs B. The meaning of positive patch tests to copper sulphate in nickel allergy. Contact Dermatitis. 1988;18:101–2.CrossRefGoogle Scholar
  47. 47.
    Santucci B, Cannistraci C, Cristaudo A, Picardo M. Interaction of metals in nickel-sensitive patients. Contact Dermatitis. 1993;29:251–3.CrossRefGoogle Scholar
  48. 48.
    Lisi P, Brunelli L, Stingeni L. Co-sensitivity between cobalt and other transition metals. Contact Dermatitis. 2003;48:172–3.CrossRefGoogle Scholar
  49. 49.
    Stenman E, Bergman M. Hypersensitivity reactions to dental materials in a referred group of patients. Scand J Dent Res. 1989;97:76–83.PubMedGoogle Scholar
  50. 50.
    Vilaplana J, Romaguera C, Cornellana F. Contact dermatitis and adverse oral mucous membrane reactions related to the use of dental prostheses. Contact Dermatitis. 1994;30:80–4.CrossRefGoogle Scholar
  51. 51.
    Marcusson JA. Contact allergies to nickel sulfate, gold sodium thiosulfate and palladium chloride in patients claiming side-effects from dental alloy components. Contact Dermatitis. 1996;34:320–3.CrossRefGoogle Scholar
  52. 52.
    Laine J, Happonen RP, Vainio O, Kalimo K. In vitro lymphocyte proliferation test in the diagnosis of oral mucosal hypersensitivity reactions to dental amalgam. J Oral Pathol Med. 1997;26:362–6.CrossRefGoogle Scholar
  53. 53.
    Koch P, Bahmer FA. Oral lesions and symptoms related to metals used in dental restorations: a clinical, allergological, and histologic study. J Am Acad Dermatol. 1999;41(Pt 1):422–30.CrossRefGoogle Scholar
  54. 54.
    Kanerva L, Rantanen T, Aalto-Korte K, et al. A multicenter study of patch test reactions with dental screening series. Am J Contact Dermat. 2001;12:83–7.PubMedGoogle Scholar
  55. 55.
    Ditrichova D, Kapralova S, Tichy M, et al. Oral lichenoid lesions and allergy to dental materials. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007;151:333–9.CrossRefGoogle Scholar
  56. 56.
    Oshima H, Kawahara D, Kosugi H, Nakamura M, Sugai T, Tamaki T. Epidemiologic study on occupational allergy in the dental clinic. Contact Dermatitis. 1991;24:138–9.CrossRefGoogle Scholar
  57. 57.
    Kawahara D, Oshima H, Kosugi H, Nakamura M, Sugai T, Tamaki T. Further epidemiologic study of occupational contact dermatitis in the dental clinic. Contact Dermatitis. 1993;28:114–5.CrossRefGoogle Scholar
  58. 58.
    Kanerva L, Estlander T, Jolanki R, Tarvainen K. Occupational allergic contact dermatitis caused by exposure to acrylates during work with dental prostheses. Contact Dermatitis. 1993;28:268–75.CrossRefGoogle Scholar
  59. 59.
    Uveges RE, Grimwood RE, Slawsky LD, Marks JG Jr. Epidemiology of hand dermatitis in dental personnel. Mil Med. 1995;160:335–8.CrossRefGoogle Scholar
  60. 60.
    Dry J, Leynadier F, Bennani A, Piquet P, Salat J. Intrauterine copper contraceptive devices and allergy to copper and nickel. Ann Allergy. 1978;41:194.Google Scholar
  61. 61.
    Jouppila P, Niinimäki A, Mikkonen M. Copper allergy and copper IUD. Contraception. 1979;19:631–7.CrossRefGoogle Scholar
  62. 62.
    Romaguera C, Grimalt F. Contact dermatitis from a copper-containing intrauterine contraceptive device. Contact Dermatitis. 1981;7:163–4.CrossRefGoogle Scholar
  63. 63.
    Motolese A, Truzzi M, Giannini A, Seidenari S. Contact dermatitis and contact sensitization among enamellers and decorators in the ceramics industry. Contact Dermatitis. 1993;28:59–62.CrossRefGoogle Scholar
  64. 64.
    Santucci B, Cannistraci C, Cristaudo A, Picardo M. Multiple sensitivities to transition metals: the nickel palladium reactions. Contact Dermatitis. 1996;35:283–6.CrossRefGoogle Scholar
  65. 65.
    Nakada T, Iijima M, Nakayama H, Maibach HI. Role of ear piercing in metal allergic contact dermatitis. Contact Dermatitis. 1997;36:233–6.CrossRefGoogle Scholar
  66. 66.
    Walton S. Patch testing with copper sulphate. Contact Dermatitis. 1983;9:337.CrossRefGoogle Scholar
  67. 67.
    Pistoor FH, Kapsenberg ML, Bos JD, Meinardi MM, von Blomberg ME, Scheper RJ. Cross-reactivity of human nickel-reactive T-lymphocyte clones with copper and palladium. J Invest Dermatol. 1995;105:92–5.CrossRefGoogle Scholar
  68. 68.
    Barranco VP. Eczematous dermatitis caused by internal exposure to copper. Arch Dermatol. 1972;106:386–7.CrossRefGoogle Scholar
  69. 69.
    Barkoff JR. Urticaria secondary to a copper intrauterine device. Int J Dermatol. 1976;15:594–5.CrossRefGoogle Scholar
  70. 70.
    Förström L, Kiistala R, Tarvainen K. Hypersensitivity to copper verified by test with 0.1% CuSO4. Contact Dermatitis. 1977;3:280–1.CrossRefGoogle Scholar
  71. 71.
    Shelley WB, Shelley ED, Ho AK. Cholinergic urticaria: acetylcholine-receptor-dependent immediate-type hypersensitivity reaction to copper. Lancet. 1983;1:843–6.CrossRefGoogle Scholar
  72. 72.
    Bezzon OL. Allergic sensitivity to several base metals: a clinical report. J Prosthet Dent. 1993;69:243–4.CrossRefGoogle Scholar
  73. 73.
    Saltzer EI, Wilson JW. Allergic contact dermatitis due to copper. Arch Dermatol. 1968;98:375–6.CrossRefGoogle Scholar
  74. 74.
    van Joost TH, van Ulsen J, van Loon LA. Contact allergy to denture materials in the burning mouth syndrome. Contact Dermatitis. 1988;18:97–9.CrossRefGoogle Scholar
  75. 75.
    Sterry W, Schmoll M. Contact urticaria and dermatitis from self-adhesive pads. Contact Dermatitis. 1985;13:284–5.CrossRefGoogle Scholar
  76. 76.
    Laubstein B. Copper allergy – a rare form of sensitization. Dermatol Monatsschr. 1990;176:421–5.PubMedGoogle Scholar
  77. 77.
    Romagnoli P, Labhardt AM, Sinigaglia F. Selective interaction of Ni with an MHC-bound peptide. EMBO J. 1991;10:1303–6.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Romagnoli P, Spinas GA, Sinigaglia F. Gold-specific T cells in rheumatoid arthritis patients treated with gold. J Clin Invest. 1992;89:254–8.CrossRefGoogle Scholar
  79. 79.
    Sinigaglia F. The molecular basis of metal recognition by T cells. J Invest Dermatol. 1994;102:398–401.CrossRefGoogle Scholar
  80. 80.
    Moulon C, Vollmer J, Weltzien HU. Characterization of processing requirements and metal cross-reactivities in T cell clones from patients with allergic contact dermatitis to nickel. Eur J Immunol. 1995;25:3308–15.CrossRefGoogle Scholar
  81. 81.
    Ross-Hansen K, Østergaard O, Tanassi JT, Thyssen JP, Johansen JD, Menné T, Heegaard NH. Filaggrin is a predominant member of the denaturation-resistant nickel-binding proteome of human epidermis. J Invest Dermatol. 2014;134(4):1164–6.CrossRefGoogle Scholar
  82. 82.
    Martin SF, Esser PR, Weber FC, et al. Mechanisms of chemical-induced innate immunity in allergic contact dermatitis. Allergy. 2011;66:1152–63.CrossRefGoogle Scholar
  83. 83.
    Rachmawati D, Bontkes HJ, Verstege MI, et al. Transition metal sensing by Toll-like receptor-4: next to nickel, cobalt and palladium are potent human dendritic cell stimulators. Contact Dermatitis. 2013;68:331–8.CrossRefGoogle Scholar
  84. 84.
    Schmidt M, Raghavan B, Müller V, et al. Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat Immunol. 2010;11:814–9.CrossRefGoogle Scholar
  85. 85.
    Downey D. Porphyria induced by palladium–copper dental prostheses: a clinical report. J Prosthet Dent. 1992;67:5–6.CrossRefGoogle Scholar
  86. 86.
    Black H. Dermatitis from nickel and copper in coins. Contact Dermatitis Newslett. 1972;12:326–7.Google Scholar
  87. 87.
    Walker-Smith PK, Keith DJ, Kennedy CT, Sansom JE. Allergic contact dermatitis caused by copper. Contact Dermatitis. 2016;75(3):186–7.CrossRefGoogle Scholar
  88. 88.
    Vergara G, Silvestre JF, Botella R, Albares MP, Pascual JC. Oral lichen planus and sensitization to copper sulfate. Contact Dermatitis. 2004;50:374.CrossRefGoogle Scholar
  89. 89.
    Reid DJ. Allergic reaction to copper cement. Br Dent J. 1968;125:92.PubMedGoogle Scholar
  90. 90.
    Frykholm KO, Frithiof L, Fernström AI, Moberger G, Blohm SG, Björn E. Allergy to copper derived from dental alloys as a possible cause of oral lesions of lichen planus. Acta Derm Venereol. 1969;49:268–81.PubMedGoogle Scholar
  91. 91.
    Rongioletti F, Rivara G, Rebora A. Contact dermatitis to a copper-containing intra-uterine device. Contact Dermatitis. 1985;13:343.CrossRefGoogle Scholar
  92. 92.
    Pujol RM, Randazzo L, Miralles J, Alomar A. Perimenstrual dermatitis secondary to a copper-containing intrauterine contraceptive device. Contact Dermatitis. 1998;38:288.CrossRefGoogle Scholar
  93. 93.
    Purello D’Ambrosio F, Ricciardi L, Isola S, et al. Systemic contact dermatitis to copper-containing IUD. Allergy. 1996;51:658–9.Google Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Dermato-VenereologyAarhus University HospitalAarhusDenmark

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