Metal allergy is a late-type allergic reaction of the immune system to chemical substances such as metal. In the 20th century, industrialization and modern life led to an extreme skin sensitivity to metals and thus an increase in metal allergy. There is a general focus on nickel, cobalt and chromium as these metals are the most common. Metals such as nickel, cobalt and chromium are ubiquitous in our environment.
In the first half of the 20th century, nickel allergy and contact dermatitis became more common among people working in the metal and coating industry. Nickel allergy, which is the most frequently encountered metal allergy today, is mostly explained by exposure to nickel-containing consumer products.
Metal allergy is high in the general population and it is estimated that 17% of women and 3% of men have nickel allergy. In addition, 1-3% of cobalt and chromium allergies can be seen. Allergies to new metals such as titanium have also been shown in the near term. This rate is higher in patients with dermatitis.
HOW METAL ALLERGY DEVELOPS
Genetic predisposition in the development of metal allergy has been investigated.
Although metal allergy is mainly an environmental disorder, mutations in some genetic complexes show an association between nickel allergy and impaired skin response.
Recently, mutations in the filagrin gene complex have been demonstrated in patients with nickel allergy or metal allergy dermatitis.
Metal allergy develops following repeated or prolonged skin contact with metal ions. Before metal ions can elicit an immune response in the skin, they must reach the living skin layer, the epidermis. Therefore, they must pass through the stratum corneum above the skin, which normally provides an effective barrier to many chemicals. Among the external causes of damage to the skin, such as sunlight, UV rays, skin pH, as well as the aging of the skin and the penetration of nickel into the tissue may change according to the skin areas in the body. As a result of all these, when the skin is damaged, metal ions can reach the lower layers of the skin and stimulate the immune system in the skin.
WHAT ARE THE MOST COMMON METAL ALLERGIES?
Today, with industrialization, metal goods and chemical substances, which are increasing day by day in modern life, lead to the development of new allergic reactions.
Nickel, cobalt and chromium are the metals that are most emphasized because they are the most widely used metals.
Allergic complaints about titanium, which has been used more and more in recent years, have begun to be published. It is seen that titanium allergies will increase, especially with the use of titanium in implants.
Nickel
Nickel began to be used a lot in modern life in the 1960s. Due to its use in dental fillings, it attracted attention with the occurrence of cases of tooth-related dermatitis in the mouth, then there was an explosion in the occurrence of dermatitis cases in the areas of stocking straps due to other uses. The increasing popularity of ear piercing and nickel-plated jewelry in the 1980s led to nickel allergy and dermatitis in a large number of women.
Many countries in Europe have made legal arrangements to restrict the use of nickel, so even if the use of nickel decreases, nickel is used in many places. Today, new sources of nickel allergies have been found to be in, for example, earplugs, mobile phones and fasteners in children’s clothing.
Occupational nickel exposure still remains a problem, despite the necessary precautions being taken in the workplace. Finally, an Australian study showed that nickel was the most common occupational allergen in female patients with dermatitis, while it was the 10th most common occupational allergen among men.
Chromium
The most important cause of chromium allergy is occupational exposure to cement. Chromium dermatitis, which was first seen in construction workers, later increased due to exposure to cement.
Mandatory addition of ferrous sulfate to cement in 1983 reduced the amount of water-soluble hexavalent chromium and the prevalence of chromium allergy among construction workers in Denmark. It has been observed that cement-related chromium dermatitis has decreased in the member countries of the Union.
Besides exposure to cement, occupational chromium exposure can result from contact with dyestuffs, metal alloys, pottery paints and rust inhibitors. It was found to be common on the hands of locksmiths, carpenters and cashiers. It showed that there is a danger for chromium allergy when contacting chromed metal products such as screws and fittings.
Recently, chromium exposure has become more of a problem for us consumers than an occupational problem. Today, about 90% of global leather production is made up of chromium sulfates. In the controls made in Germany, it was shown that more than half of 850 leather goods contain hexavalent chromium and one sixth contains more than 10 mg of chromium. Most chromium allergic patients appear to occur following exposure to chromium in finished leather products. Contact dermatitis is considered to occur due to chromium in leather products.
Cobalt
Cobalt is a metal used in the manufacture of alloys, magnets, prosthetics, paints, pigments and jewellery. The most common cause of dermatitis due to cobalt allergy in women is the use of cobalt mixed with nickel alloys in jewelry.
Simultaneous allergy to nickel and cobalt is explained by cosensitization rather than cross-reactivity.
The increased use of cobalt in dental alloys may be a source of sensitization that may have been overlooked before.
Isolated cobalt allergy has been observed in hard metal workers, the glass and ceramic industry, and among painters. Cobalt can be seen in isolation as a result of occupational exposure, or it can be seen together with nickel allergy.
Titanium
Although titanium allergy is not generally well known, it has been reported that approximately 4% of all patients will be allergic. Symptoms in people with a titanium allergy can be very different and variable. These can range from simple skin rashes to contact dermatitis or muscle pain and chronic fatigue.
Exposure to titanium (Ti) in implants and titanium used as nanoparticles (NP) from personal care products are the most common causes of titanium allergy.
Titanium dioxide (TiO 2 ) is widely used in consumer products because it is non-toxic, although it can trigger allergies in some people. It is known as the “pearl agent” because it makes paper and paint shiny and white. For titanium dioxide, it can be in the ingredients of foodstuffs, pills and cosmetics, especially products containing titanium
Orthopedic and surgical implants.
Dentistry: As a colored pigment in dental implants and composites.
Sunscreen ingredients: fine titanium dioxide blocks harmful ultraviolet rays from the sun.
Confectionery: Makes candy appear brighter and can be found, for example, in chewing gum.
Cosmetics: used to brighten and intensify make-up color. It is regularly found in eyeshadows, blushes, nail polishes, lotions, lipsticks, and powders.
Toothpaste: Used as a pigment agent to make Toothpaste whiter.
Paint: TiO 2 improves the durability of coatings and gives a white color.
Plastic carrier bags: increases durability and imparts a white colour.
Medical pills and vitamin supplements can also get the white coating from titanium dioxide.
Piercings and Jewellery: can be found in watches and all kinds of body piercing products.
Most people’s exposure to Titanium appears to come predominantly from dental and medical implants, personal care products, and food. Although Ti is considered to be highly biocompatible compared to other metals, titanium, especially in dental implants, could possibly be released into biological fluids and tissues under certain conditions.
In most studies, titanium does not penetrate the skin barrier in the form of pure Ti, alloys or nanoparticles such as Ti oxide. However, signs of Ti penetration were seen in the oral mucosa.
Patch testing with existing Ti preparations for detection of Type IV hypersensitivity is currently insufficient for Ti. Although several other methods for contact allergy detection, including lymphocyte stimulation tests, have been proposed, they have not yet gained general acceptance and diagnosis of Ti allergy is primarily based on clinical evaluation.
The diagnosis of Ti allergy is primarily based on clinical evaluation. Reports on clinical allergies and adverse events are rarely published. This is due to unawareness of possible reactions to this metal, difficulties in detection methods, or because the metal is actually considered to be relatively safe.
Gold, Palladium and Aluminum
Palladium and gold are often used in dental restorations and jewellery. Gold is also used for coronary stent and rheumatic treatment. Occupational palladium exposure can occur in the electronics and chemical industries.
Aluminum allergy is more associated with occupational exposure.
WHAT ARE THE DISEASES CAUSED BY METAL ALLERGY?
Metal allergies can be seen as contact dermatitis where the allergen comes into contact, or as diffuse systemic allergic contact dermatitis. The most important problem seen in metal allergies is the rejection of implants and stents used in orthopedic, dental or cardiovascular diseases, leading to implant failure.
1. Allergic contact dermatitis due to metal allergy
The mechanism required for the emergence of allergic contact dermatitis consists of two different phases. The first phase is the induction phase and the other phase is the emergence phase. The induction phase usually develops from a few days to a few weeks and includes events in the immune system following initial skin contact with metal. In this phase, antigen-specific T cells develop and the person becomes sensitized.
Activation of antigen-specific T cells results in dermatitis in the area of skin contacted by the allergen.
At the clinical level, the induction phase is called contact sensitivity or contact allergy, while the following phase is called allergic contact dermatitis. Contact allergy is considered a chronic and life-long condition.
Allergic contact dermatitis can occur anywhere on the whole body. Nickel- and cobalt-induced dermatitis typically occurs on the face (auricles), body (jewelry and piercing areas), and hands, while chromium dermatitis is found on the hands and feet. The clinical picture changes depending on the constant contact.
Acute dermatitis is characterized by erythema, edema, papules, vesicles, and pus-filled sores, while chronic dermatitis is characterized by scaly, rash, and dry and fissured clefts of the skin.
Studies have shown that chromium allergic patients have a particularly poor prognosis for dermatitis, whereas nickel dermatitis has a better prognosis in patients with limited or inhibited nickel contact.
2. Systemic allergic dermatitis due to metal allergy
Systemic allergic dermatitis is defined as a skin rash that occurs after systemic exposure to allergens, that is, orally or intravenously.
Considering the possible mechanisms of systemic allergic dermatitis, for example, in a study on systemic nickel allergy, it has been shown that there is a relationship between nickel intake from the digestive system and dermatitis exacerbation. It has been shown that there is a dose relationship between the amount of nickel and systemic allergic dermatitis. Low-nickel diets or nickel-binding drugs may cause improvement or amelioration of dermatitis in patients with nickel allergy.
Systemic exposure to chromium, cobalt and gold may cause systemic allergic dermatitis.
3. Allergic dermatitis and diseases caused by implants due to metal allergy
With regard to metal implants, which are widely used today, there is still a debate about the relationship between metal release, metal allergy and device failure in metal devices. very little is known.
When implants used in the body come into contact with body fluids, most of these metals corrode and the metal ions released into the environment can bind to proteins in the body and activate T cells, thus causing delayed-type allergic reactions on the immune system.
These late-type allergic reactions can sometimes present themselves as allergic contact dermatitis on the skin over the implants or cause the implant to fail.
The majority of Intracoronary stents used in heart disease are made of stainless steel containing nickel, chromium and molybdenum. In some studies, coronary stent restenosis has been shown to be associated with nickel allergy, especially in recurrent restenosis, it has been shown that nickel allergy may be a factor leading to vascular occlusion
Gold allergy has also been associated with restenosis in patients with gold-plated stents, and therefore gold use is of great concern. proportion abandoned.
Prostheses used by orthopedics are typically made using materials containing cobalt-chromium-molybdenum. Studies showing a possible relationship between metal allergy and implant failure, which have increased rapidly in recent years, raise concerns on this issue. Studies on metal allergy in hip arthroplasty patients indicate that the prevalence of metal allergy is around 60% among patients with failed or poorly functioning implants.
Allergic reactions have been observed mainly against cobalt, chromium, nickel and molybdenum. Apart from complications such as implant dysfunction due to allergic reaction, it has sometimes been shown to cause serious clinical reactions such as aseptic lymphocytic vasculitic lesions or pseudotumors, although they are few in number. In such cases, the implants can be replaced with titanium-based endoprostheses. However, hypersensitivity reactions have also been described after the placement of titanium implants, although titanium allergy is extremely rare.
In general, the allergic risk of titanium material is lower than that of other metal materials. However, pre-implant patients should be asked about their history of hypersensitivity reactions to metals, and patch testing should be recommended for patients who have experienced these reactions.
HOW IS METAL ALLERGY DIAGNOSED?
Is it possible to clinically determine metal sensitivity responses?
Approved methods used for diagnosis of metal allergy are in vitro blood tests including skin test (patch test) and lymphocyte transformation test (LTT).
Although commercial kits for patch testing exist for various common metals, there are questions about the applicability of skin testing for diagnosis, as orthopedic implants have problems in generating immune responses.
One of the most important tests for metal allergy is the blood lymphocyte transformation test. This test is based on measuring the change in lymphocytes after the chemical substances to which the patient is sensitive come into contact with the immune system cells in the blood. These blood tests can be used to confirm patch tests.
Other blood tests, lymphocyte migration inhibition test and lymphocyte immunostimulation assay (MELISA®), which is the newly developed form of LTT, can be used. Apart from all these, flow cytometric measurements can be used. However, there is no single test to diagnose allergic contact dermatitis.
It would be appropriate for these tests to be performed by allergy specialists and, if necessary, to be confirmed by blood tests in doubtful cases.
HOW TO TREAT METAL ALLERGY. ?
Metal allergies can be seen in many different clinics. It is important to investigate metal allergy, especially in patients with dermatitis complaints. Since metal allergies can lead to the failure of prostheses and implants, it is appropriate to diagnose patients with complaints before such procedures, and prosthesis and implants should be selected from non-allergic materials.
Since allergens and reactions leading to Metal Allergies can be very different from person to person, treatment of metal hypersensitivity should be individualized according to the allergens the patient comes into contact with.
The main treatment for metal allergies can be resolved by not using the substance that causes skin hypersensitivity. If dermatitis is prominent in the reaction in metal allergy, he may also recommend corticosteroid creams and ointments to reduce local inflammation. He or she may also prescribe oral antihistamines to reduce the allergic reaction.
Oral corticosteroids can also be used if the reactions are more in metal allergy, but prolonged use may cause side effects.
Systemic reactions may be more difficult to treat. Because it is usually caused by implants. It may be necessary to remove the implant, sometimes using a non-metallic head implant. However, if the allergy is caused by an artificial knee or hip prosthesis, it is rarely replaced with a non-metallic option, although it is difficult to replace. For these conditions, treatment can usually include topical and oral medications to reduce the allergic reaction. If the reactions cannot be stopped in patients with systemic complaints, removal is absolutely necessary.
If there is a systemic nickel allergy due to nickel, desensitization treatments are performed with nickel. Although successful results were obtained with this treatment, a complete procedure could not be established.
Because systemic metal allergies are difficult to treat, doctors sometimes recommend performing a hypersensitivity test before choosing an implant. It is extremely beneficial for the patient to decide on the implant or prosthesis to be selected after the tests.
CONCLUSION
Metal allergy is a late-type allergic reaction of the immune system to chemical substances such as metal. In the 20th century, industrialization and modern life led to an extreme skin sensitivity to metals and thus an increase in metal allergy.
Nickel allergy, which is the most frequently encountered metal allergy today, is mostly explained by exposure to nickel-containing consumer products.
Metal allergy is high in the general population and it is estimated that 17% of women and 3% of men have nickel allergy.
Titanium allergy is generally not well known, but it has been reported that approximately 4% of all patients will be allergic.
In general, the allergic risk of titanium material is lower than that of other metal materials. However, pre-implant patients should be asked about their history of hypersensitivity reactions to metals, and patch testing should be recommended for patients who have experienced these reactions.
Metal allergies can be seen as contact dermatitis where the allergen comes into contact, or as diffuse systemic allergic contact dermatitis. The most important problem seen in metal allergies is the rejection of implants and stents used in orthopedic, dental or cardiovascular diseases, leading to implant failure.
Approved methods used for diagnosis of metal allergy are in vitro blood tests including skin test (patch test) and lymphocyte transformation test (LTT).
After detecting the metal causing metal allergies, the patient must be removed from the metal causing the allergic reaction. For this reason, it will be beneficial for patients with metal allergies to be seen by allergy specialists before prosthesis and implant, and to choose the most suitable prosthesis or implant after the tests are done and the allergy is determined.
