Is it possible to be allergic to a metal?

Yes, however by themselves, metals do not cause allergies. They are essentially too small and are invisible to the immune system. However, they can elicit immune responses and allergic reactions when they assume the role of a hapten. A hapten is a small molecule that elicits an immune response only when it is bound to binds to a carrier protein. This newly formed complex is what initiates the immune response.

Metal allergies are Type IV hypersensitivity reactions, which are cell mediated. These involve the cellular immune system. Specialized cells in the immune system orchestrate the cascade of reactions that ultimately cause the allergic response.

The cascade of reactions begins when an allergen activates specialized cells called T-cells. These activated T-cells then release substances known as cytokines which influence other cells. Two of these cell types are cytotoxic CD8-positive T-cells and macrophages.

These macrophages and CD8+ T-cells release inflammatory mediators, which enhance vascular permeability and cause damage to local tissue. Evidence for this includes erythema, cellular infiltration, induration, and formation of vesicles.

Unlike the first three types of allergic reactions which occur rapidly, the Type IV reaction is delayed, which means that there is a lag time from the initial exposure to the allergen to the time when the immune system manifests a response. Typically, it takes 1 to 3 days for a response to occur. Infectious contact dermatitis, transplant rejection, and graft-versus-host disease are all Type IV reactions.

Common antigens that cause Type IV reactions include poison ivy, topical medications, detergents, perfumes, rubber products, and other chemicals. Many individuals also develop contact dermatitis to metal jewelry or piercings.

Many metals can elicit an allergic response however, chromium, cobalt, copper, and nickel are the most common culprits. These 4 metals along with others are also found in many medical and dental devices which are permanently implanted in the human body.

Allergic reactions to these implanted metals can lead to adverse sequelae and subsequent impairment. Of these, nickel has been studied most extensively.

Nickel is the fifth most abundant element on Earth. It is often combined with other metals to form alloys and in addition to medical devices, it is found in jewelry, clothing items, watches, cellphones, household utensils, and in foods.

Hypersensitivity to nickel and other metals can start at an early age. Many children at a young age are exposed to nickel found in jewelry, toys, clothing, and electronic devices, and this exposure to nickel and other metals can lead to an allergic reaction. Three pathways have been described by which nickel and likely other metals can activate T-cells and cause a cell-mediated allergic reaction. In his article in Expert Review Clinical Immunology, Radoslaw Spiewak provides an excellent understanding of these mechanisms.1

Nickel allergic contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type hypersensitivity reaction worldwide, and in the United States, estimates suggest that at least 1.1 million children are sensitized to nickel, and the incidence of hypersensitivity to nickel appears to be increasing.The incidence among children has almost quadrupled over the past 3 decades.²

There are morbidities associated with allergies to nickel in children and these include itch, discomfort, school absence, and reduced quality of life. In adulthood, individuals with Ni-ACD may have severe disabling hand eczema.²

There is ongoing exposure to nickel and to other metals during a person’s lifetime, and each year, an increasing number of individuals undergo invasive procedures where metallic medical and dental devices are being implanted. More than 600,000 coronary artery stents are implanted yearly. Approximately 1.5 million individuals in the United States per year undergo total hip and knee replacement, and according to an iData Research 2018 report, approximately 1.62 million instrumented spinal procedures are performed annually. Three million individuals in the U.S. alone have dental implants, and this number is growing by 500,000 every year.

As many as 13% of people are sensitive to nickel, cobalt, or chromium. 17% of women and 3% of men are allergic to nickel, and 1-2% of people are allergic to cobalt, chromium, or both. It is not surprising that immune response to medical implants is commonly reported in the literature, including hypersensitivity to pacemakers or other cardiovascular devices, dental implants, and orthopedic hardware, including joint replacement prostheses, fracture fixation devices, and pain-relief stimulators.¹⁴

In another study, the majority of overweight people, especially women of menopausal age, had a nickel allergy. 59.7% of women of menopausal age who were overweight were found to be allergic to nickel.¹⁰

A small percentage of the individuals who undergo implantation of metallic medical and dental devices develop allergies to one or more of the implanted metals. This could lead to adverse sequelae. In fact, in one study on patients with orthopedic implants, contact allergy to metals was found in 25.0% of the patients: nickel 20.8%, palladium 10.4%, cobalt 16.7%, chromium 8.3%, vanadium 2.1%. The authors concluded that metal orthopedic implants may be the primary cause of allergies that may lead to implant failure, and people with confirmed allergies to metals should be provided with implants free from allergenic metals.⁶

Other complications in patients with metallic medical implants have been reported and range from dermatitis and skin reactions to notable joint pain, joint effusions, implant loosening, and impaired wound healing.¹¹ These are not insignificant, and as a result, increasing attention is being directed to the diagnosis and treatment of metal allergies.

Dermatitis and Skin Reactions