Metal Allergy and Tolerance Development

  • Angela Rizzi
  • Eleonora Nucera
  • Domenico Schiavino


Metals are ubiquitous in our environment and often cause allergic contact dermatitis (ACD), an inflammatory disease categorized as a delayed-type hypersensitivity (DTH) reaction. In epidemiological studies, nickel (Ni) represents the hapten with the highest prevalence in the pathogenesis of ACD.

Nickel hypersensitivity can induce not only ACD but also a more complex disease known as systemic nickel allergy syndrome (SNAS), characterized by a combination of manifestations caused by the intake of Ni with the diet.

Despite similar exposure patterns, only a minority of exposed individuals develop ACD suggesting an active role of immunological tolerance, orchestrated by CD4+CD25+ T regulatory cells (Tregs). Animal model studies, conducted both in vivo and in vitro, have demonstrated that the development of contact hypersensitivity (CHS) can be prevented by preceding repeated oral doses of metal salts. Oral tolerance is a long-lasting and hapten-specific process. This prophylactic effect of oral Ni exposure was confirmed in humans by epidemiological observations that reported lower prevalence rates of contact allergy to nickel in individuals wearing orthodontic braces (oral nickel exposure) prior to ear piercing (cutaneous nickel exposure), as compared to those who underwent piercing first. Recent evidence that nickel allergy is a highly regulated process has been provided by trials of Ni oral hyposensitizing treatment (NiOHT) in patients suffering from ACD and SNAS.


Allergic contact dermatitis (ACD) Immunological tolerance Hyposensitization Tregs Systemic nickel allergy syndrome (SNAS) 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Angela Rizzi
    • 1
  • Eleonora Nucera
    • 1
  • Domenico Schiavino
    • 1
  1. 1.Department of Rheumatology, Immunology, Dermatology and Uro-Nefrological Sciences, Allergy UnitFondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro CuoreRomeItaly

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