Nickel allergy


Nickel allergy is any of several allergic conditions provoked by exposure to the chemical element nickel. Nickel allergy often takes the form of nickel allergic contact dermatitis, a form of allergic contact dermatitis. Ni-ACD typically causes a rash that is red and itchy and that may be bumpy or scaly. The main treatment for it is avoiding contact with nickel-releasing metals, such as inexpensive jewelry. Another form of nickel allergy is a systemic form: systemic nickel allergy syndrome can mimic some of the symptoms of irritable bowel syndrome and also has a dermatologic component.

Signs and symptoms

The most common sign of nickel allergy is inflammation of the skin at an area that comes into regular contact with nickel. This often takes the form of a reddened patch of skin with raised bumps or small blisters, and edema. People with chronic dermatitis tend to have dry, scaly, and cracked skin at the site of contact. These sites of inflammation can occur anywhere on the skin that contacts nickel, but are most common on the hands, face, or anywhere that contacts metal objects such as jewelry or metal clothes buttons. Particularly high levels of nickel exposure can cause irritated patches of skin to appear at other sites on the body. These typically occur as blistering rashes on the hands, eyelids, and at the inside of flexing joints.
Ingestion of nickel may cause a systemic reaction, which can result in generalized inflammation of the skin across the body, small blisters in the hands, irritation inside the flexing joints, and redness and irritation of both buttocks.
Systemic contact dermatitis is defined as a dermatitis occurring in an epi-cutaneously contact-sensitized person when exposed to haptens systemically such as orally, per rectum, intravesically, transcutaneously, intrauterinely, intravenously, or by inhalation.
The pathophysiology of systemic nickel allergy syndrome is not well understood. The clinical course is determined by an immunological interplay between two types of T cells. SCD is often considered a subset of SNAS, but with only skin manifestations. SNAS presents with an array of symptoms ranging from respiratory to generalized skin rash to gastrointestinal symptoms. The gastrointestinal symptoms may mimic those of irritable bowel syndrome. A meta review evaluating SNAS found that 1% of patients sensitized to nickel reacted to the nickel content of a 'normal' diet, and with increasing doses of nickel more individuals reacted. SNAS is a multilayered immunological response demonstrating variance between individuals and doses of nickel exposure.

Causes

Nickel exposure

Nickel is both naturally abundant – it is the fifth most common element on earth – and widely used in industry and commercial goods. Workplace nickel exposure is common in many industries, and the performance of normal work tasks can result in nickel skin levels sufficient to elicit dermatitis. Within the workplace, individuals may be exposed to significant amounts of nickel, airborne from the combustion of fossil fuels or from contact with tools that are nickel plated. Historically, workplaces where prolonged contact with soluble nickel has been high have shown high risks for allergic contact nickel dermatitis. For example, nickel dermatitis was common in the past among nickel platers. Outbreaks of nickel allergy from consumer goods have been documented throughout the 20th century, with jewelry, stocking suspenders, and metallic buttons on blue jeans each resulting in dermatitis at the point of contact. Nickel can also be present in food and drinking water; ingestion of increased nickel is not associated with systemic allergic disease, but is associated with flare-ups of dermatitis or aggravation of vesicular hand eczema. Similarly, aggravation of dermatitis has been reported in response to nickel-containing surgical implants or dental gear.
The risk of an object eliciting nickel allergy is linked to the amount of nickel released by its surface. Suspected objects can be screened by wiping the surface with a 1% dimethylglyoxime solution that turns pink if more than 0.5 μg/cm2 per week is released by the surface. Various methods exist to test the skin or nails for nickel exposure, typically relying on wiping the skin, then quantifying the nickel on the wipe via mass spectrometry.
Dietary nickel exposure may come from high-nickel foods, possibly canned food, possibly stainless steel cookware, or plumbing.

Physiology

Nickel allergy results in a skin response after the skin comes in contact with an item that releases a large amount of nickel from its surface. It is commonly associated with nickel-containing belt buckles coming into prolonged contact with the skin. The skin reaction can occur at the site of contact, or sometimes spread beyond to the rest of the body. Free nickel that is able to penetrate the skin is taken up by scavenger cells and then presented to the immune system T-Cells. With each subsequent exposure to nickel these T cells become stimulated and duplicate themselves. With enough exposure to nickel, the amassing clones of T-cells reach "threshold" and the skin develops a rash. The rash can appear as acute, subacute, or chronic eczema-like skin patches, primarily at the site of contact with the nickel. From the time of exposure, the rash usually appears within 12–120 hours and can last for 3–4 weeks or for the continued duration of nickel contact/exposure.
Three simultaneous conditions must occur to trigger Ni-ACD:
  1. Direct skin contact with nickel-releasing item
  2. Prolonged skin contact with nickel-releasing item
  3. A sufficient amount of nickel is released and absorbed into the skin to cause a reaction
The pathophysiology is divided into induction elicitation phases. Induction is the critical phase when skin contact to nickel results in antigen presentation to the T cells, and T cell duplication occurs. The metal cation Ni++ is a low molecular weight hapten that easily penetrates the stratum corneum. Nickel then binds to skin protein carriers creating an antigenic epitope. The determining factor in sensitization is exposure of significant amounts of "free nickel". This is important because different metal alloys release different amounts of free nickel. The antigenic epitope is collected by dermal dendritic cells and Langerhans cells, the antigen-presenting cells of the skin, and undergo maturation and migration to regional lymph nodes. The complex is predominantly expressed on major histocompatibility complex II, which activates and clonally expands naive CD4+ T cells. Upon re-exposure these now primed T cells will be activated and massively recruited to the skin, resulting in the elicitation phase and the clinical presentation of Ni-ACD.
Although ACD has been considered a Th1 predominate process, recent studies highlight a more complex picture. In Ni-ACD other cells are involved including: Th17, Th22, Th1/IFN and the innate immune responses consistent with toll-like receptor 4.

Prevention

Nickel has a wide utility of application in manufactured metals because it is both strong and malleable, leading to ubiquitous presence and the potential for consumers to be in contact with it daily. However, for those who have the rash of allergic contact dermatitis due to a nickel allergy, it can be a challenge to avoid. Foods, common kitchen utensils, cell phones, jewelry, and many other items may contain nickel and be a source of irritation due to the allergic reaction caused by the absorption of free released nickel through direct and prolonged contact. The most appropriate measure for nickel-allergic persons is to prevent contact with the allergen.
In 2011, researchers showed that applying a thin layer of glycerine emollient containing nanoparticles of either calcium carbonate or calcium phosphate on an isolated piece of pig skin and on the skin of mice prevents the penetration of nickel ions into the skin. The nanoparticles capture nickel ions by cation exchange, and remain on the surface of the skin, allowing them to be removed by simple washing with water. Approximately 11-fold fewer nanoparticles by mass are required to achieve the same efficacy as the chelating agent ethylenediamine tetraacetic acid. Using nanoparticles with diameters smaller than 500 nm in topical creams may be an effective way to limit the exposure to metal ions that can cause skin irritation'.
Pre-emptive avoidance strategies might ultimately lower the sensitization rates of children who would develop ACD It is theorized that prevention of exposure to nickel early on could reduce the number of those that are sensitive to nickel by one-quarter to one-third. Identification of the many sources of nickel is vital to understanding the nickel sensitization story, food like chocolate and fish, zippers, buttons, cell phones and even orthodontic braces and eyeglass frames might contain nickel. Items that contain sentimental value could be treated with an enamel or rhodium plating.
The Dermatitis Academy has created an educational website to provide more information about nickel, including information about prevention, exposure, sources, and general information about nickel allergy. These resources provide guidance in a prevention initiative for children worldwide.
Prevention of SNAS includes modifying dietary choices to avoid certain foods that are higher in nickel than others.

Diagnosis

Nickel allergy is typically diagnosed by patch testing – applying a patch with 2.5% or 5% nickel sulfate to the upper back and looking for irritation on the skin. As with other causes of allergic contact dermatitis, patches containing several common allergens are typically applied to the back for 48 hours, removed, then the spots examined for allergic reactions 2 to 5 days later.
SNAS can often mimic IBS and may be more common than is widely appreciated. It therefore should be considered as a differential diagnosis item when a doctor is considering a diagnosis of IBS, and nickel allergy testing is advisable as a means to exclude or confirm SNAS. Even before such testing, some differentiating factors in the medical history are if certain foods prompt the symptoms, whereas IBS is not specific to those foods.