Nickel is unrivaled as the most common cause of contact allergy worldwide.1 Nickel is commonly used as a hardening agent in metal products, and complete avoidance is challenging due to numerous potential exposures (eg, direct contact, airborne, dietary, medical implantation). Allergic contact dermatitis to nickel (Ni-ACD) can lead to decreased quality of life, inability to work, and considerable health care expenses.1 Here, we review the epidemiology of nickel allergy, regulation of nickel in the United States and Europe, common clinical presentations, and pearls on avoidance.
Epidemiology
Nickel continues to be the most common cause of contact allergy worldwide. Data from the 2015-2016 North American Contact Dermatitis Group patch test cycle (N=5597) showed nickel sulfate to be positive in 17.5% of patients patch tested to nickel.2 The prevalence of nickel allergy has been relatively stable in North America since 2005 (Figure 1). Although Ni-ACD historically was identified as an occupational disease of the hands in male nickel platers, the epidemiology of nickel allergy has shifted.1 Today, most cases are nonoccupational and affect women more often than men,3 in part due to improved industrial hygiene, pervasive incorporation of nickel in consumer items, and differences in cultural practices such as piercings.1,3 Piercings in particular have been implicated as important sources of nickel exposure, as this practice disrupts normal skin barrier function and is a potentially sensitizing event. Multiple studies including a large-scale epidemiologic analysis from 2017 have found piercings to be associated with an increased frequency of Ni-ACD (24.4% with piercing vs 9.6% without piercing). Interestingly, the degree of nickel sensitivity also was found to increase with the number of piercings (14.3% with 1 piercing vs 34.0% with ≥5 piercings).4
Figure 1. Positive patch tests to nickel from 2005 to 2016 from the North American Contact Dermatitis Group.2
Regulation
Nickel content has been regulated in parts of the European Union (EU) since the 1990s, but regulation in the United States is lacking. In an attempt to reduce the prevalence of nickel allergy, the EU limits the level of nickel release from consumer items intended to be in direct and prolonged contact with the skin. These limits were first introduced in Denmark in 1990, followed closely by the EU Nickel Directive in 1994, which has resulted in consistent patterns of decreasing prevalence of Ni-ACD in multiple European countries.5 Notably, a Danish study comparing the prevalence of sensitization between girls with ears pierced before vs after implementation of nickel regulation found a decrease in prevalence from 17.1% to 3.9%.6 Additionally, this initiative has greatly reduced the economic burden of nickel dermatitis. It is estimated that Denmark alone has saved US $2 billion over a 20-year period in both direct and indirect health care costs.7
However, a policy is only effective if it is enforced, and it has been reported in the EU that 8% to 32% of tested jewelry exceeds the limit placed on nickel release, with imported jewelry being especially problematic.5 Also of interest, the 1 and 2 euro coins are known to release more nickel than pure nickel itself, releasing 240 to 320 times more than is allowed under the EU Nickel Directive (Figure 2).8 Although coins are not explicitly mentioned as items having prolonged contact with the skin, they can and do exacerbate allergic contact dermatitis of the hands, especially in occupational groups such as cashiers.9 Unsurprisingly, during the discussions to determine the composition of coins prior to the mass adoption of the euro in the EU in 2002, dermatologists and nickel industry experts remained divided in their recommendations.10 However, the EU regulation is considered a public health success overall, and the trends of Ni-ACD and economic burden are opposite of the United States, where legislation has yet to be adopted.
Figure 2. A dimethylglyoxime test demonstrated release of nickel from 1 and 2 euro coins.
Patch Testing to Nickel
In North America, the 2 available patch test systems are the chamber method and the Thin-layer Rapid Use Epicutaneous (T.R.U.E.) test (SmartPractice). In the T.R.U.E. test, nickel sulfate is used to formulate the patch at 200 µg/cm2 using hydroxypropyl cellulose as the gel vehicle. In the chamber method, nickel sulfate is used on either an aluminum or plastic chamber, most commonly at concentrations of 2.5% or 5% in petrolatum. Nickel sulfate 2.5% is most frequently used in US-based patch test clinics. A 2018 study (N=205) comparing the sensitivities of the 2.5% and 5% concentrations of nickel found 5% to be more sensitive; 31% of the cohort tested positive at 5% but only 20% at 2.5%, suggesting the 5% formulation is superior at detecting nickel allergy.11
Similar to other metals, nickel may react later than other allergens. A 2019 analysis of the prevalence of new patch test reactions on day 7 showed that 17% of 607 patients were negative on day 3 but were positive on day 7, further emphasizing the importance of a properly timed delayed reading.12