Contact Dermatitis, Nickel (Nickel allergic contact dermatitis, allergic contact dermatitis to nickel, nickel allergy)

Are You Confident of the Diagnosis?

Contact dermatitis is a common eczematous skin dermatitis characterized by inflammation, resulting in erythematous and pruritic skin lesions after contact with a foreign substance. Contact dermatitis can be divided into two groups, irritant and allergic. Irritant contact dermatitisis caused by exposure to a foreign substance that causes a nonimmunologic reaction in the skin, whereas allergic contact dermatitis is caused by a hypersensitivity reaction.

Nickel is one of the most common substances to cause allergic contact dermatitis. When reviewing all metals that cause allergic contact dermatitis, nickel causes more allergic contact dermatitis than all other metals added together. Nickel, anatomic number 28, is a silvery-white lustrous metal with a slight golden tinge that is found in the Earth’s core, soil, water and air. It belongs to the transition metal (iron) group and its most important ore minerals include laterites, specifically limonite and garnierite, and pentlandite. It is found in the environment in very low levels and its most common use is for the production of steel. It is widely used in metallurgy because of its ease of use with other metals.

Nickel is found in many different composite metals, including white gold, German silver, gold-plating, solder and some forms of stainless steel. The diagnosis of contact dermatitis to nickel can be made clinically with confirmation by patch testing. One should look for common substances that are a source of nickel in the history, such as jewelry (earrings, other piercings), belt buckle, watchband, jean snaps, etc.

Characteristic findings on physical examination

The characteristic finding on physical examination of allergic contact dermatitis to nickel is the shape and location of the rash. The pattern of inflammation usually correlates to the shape of the offending agent. It can occur anywhere on the body that the skin is exposed to the allergen, but the common locations include periumbilical (from belt buckles, buttons/snaps), earlobes (from earrings; Figure 1), neck (from necklaces), wrist (from watches), dorsum of the foot (from snaps on shoes), chest (zippers), and mid-back (bra snaps/clasps). It presents as an erythematous, well-demarcated, geographic bordered papular eczematous patch or plaque with +/- scaling and pruritus at the site of nickel contact. Weeping and crusting can be seen acutely. Chronic allergic contact dermatitis can present as localized lichenification.

Table I.

Contact nickel sensitivity threshold
µg nickel/cm²/week	% sensitive
.02	0
.05	1
.8	10
10	50
150	90

A Cobalt Allergy Spot Test Kit has been developed. It is similar in nature to the DMG kit for nickel. An individual swabs an item with the supplied cotton tip applicators. If cobalt is present a color change will be observed in the swab.

Who is at Risk for Developing this Disease?

Those that are genetically predisposed are the patients that are at risk for developing allergic contact dermatitis. There has been some postulation to an association with null mutations in the filaggrin gene complex. However, environmental factors also play a major role. There must be at least one to several exposures to cause sensitization.

Other factors include female sex and younger age. It has been observed in 10-30% of women and up to 10% in men. Ear piercing is also a risk factor for nickel sensitization. Additionally, workers in some occupations, such as metal workers, retail clerks, hairdressers, domestic cleaners, and caterers, are particularly at risk secondary to repeated exposures to the offending agent.

Because of the increasing prevalence of nickel sensitivity (Table II), several countries have implemented regulations to limit the amount the nickel that is released from objects that come in contact with skin. For example, the European Union Nickel Directive, whichwas formed in the 1990s, mandates that no more than 0.05% nickel can be used for objects that contact the skin and that no more than 0.5 µg nickel/cm²/week can be released from the objects that are in contact with the skin (jewelry, snaps, buttons, zippers). The EU also goes further and limits posts to release no more than 0.2 µg nickel/cm²/week.

Table II.

Rates of contact dermatitis to nickel based on the North American Contact Dermatitis Group data
Study period	Rate of nickel positivity
1994-1996	14.3%
1996-1998	14.2%
1998-2000	16.2%
2001-2002	16.7%
2003-2004	18.7%
2005-2006	19.0%

These regulations have significantly decreased the rates of nickel sensitization in these countries. In Germany, the frequency of nickel sensitization decreased from 36.7% to 25.8% in women after the legislation was implicated. In Denmark, nickel sensitivity in children significantly declined from 24.8% to 9.2%. The EU regulations do not apply to other common items such as cell phones.

Table I shows why the EU Nickel directive chose 0.02 µg nickel/cm ²/week for posts, as this is a level which does not induce sensitivity.

What is the Cause of the Disease?

Etiology

Allergic contact dermatitis develops within 12-48 hours of exposure to the offending allergen, once sensitization has occurred, and persists for 3-4 weeks. It is caused by a type IV T cell-mediated, delayed hypersensitivity reaction.

Pathophysiology

Its pathophysiology involves a reaction that occurs when the foreign substance, i.e., nickel, comes in contact with the skin. It involves two phases, the initial sensitization phase and the elicitation phase. The sensitization phase takes place once the allergen is exposed to the skin. The allergen is internalized by the Langerhan cells in the epidermal basal layer, linked to a protein forming an antigen complex, and then expressed on the surface of the Langerhan cell. This cell migrates to the regional lymph nodes and is recognized by the T lymphocytes, which initiate a sensitization reaction.

When the skin is re-exposed to the substance, the previously sensitized T cells become activated and an inflammatory cascade is activated, resulting in the skin changes seen in allergic contact dermatitis. This is termed as the elicitation phase. Some allergens are strong, such as poison ivy, that only require two exposures for sensitization; however, most allergens are weak and require multiple repeated small dose exposures before sensitization occurs.

Systemic Implications and Complications

Complications of contact dermatitis can involve bacterial superinfection, such as impetigo or less likely a dermatophyte or fungal infection. A bacterial culture should be done when there is presence of exudate, weeping and crusting of the lesions. If tinea or Candida is suspected, a potassium hydroxide (KOH) preparation can be done.

Systemic allergic contact dermatitis may occur secondary to ingestion of nickel. Small amounts of nickel are found in various food sources (Table III), and those patients that are particularly sensitive to nickel may develop a systemic contact dermatitis. In these cases, a Nickle-reduced diet may be helpful in treating the dermatitis. The diet should be followed strictly for 6-8 weeks before one makes a clinical decision to continue or discontinue the diet based on response.

Table III.

chocolate/cocoa	licorice	oysters	tomatoes
legumes	potatoes	asparagus	peas
shellfish/fish	oats	beans	pears
nuts	soybeans	mushrooms	rhubarb
canned foods	whole grain flour	onions	tea
dried fruits	spinach	corn	baking powder
broccoli	oatmeal	chick peas	kale
raspberries	parsley	parsnip	garlic

Depending on the conditions (content of nickel in soil, amount of pesticides with nickel applied, etc.,) affecting cultivation of various foods, the nickel content will vary.

There is no current FDA-recommended daily allowance for nickel. Most adults in the United States are estimated to normally intake 0.3-0.5 mg daily. It has been estimated that at most 10% of nickel is absorbed in the gastrointestinal tract; the rest is passed unabsorbed.

The role nickel plays in contact sensitization to implanted materials (joint prosthesis, stents, pacemakers, etc.,) is still to be completely defined. I recommend the chapter on Contact Dermatitis-Devices/Implants as a resource. Metal core activity is also common; in one study, 23% of nickel-allergic patients also reacted to cobalt and chromium. This is critical to know. When one clinically diagnoses a nickel allergy without patch testing, you may be wrong. If the patient does not respond to nickel avoidance, patch testing is warranted to determine whether another agent is causing the reaction.

Treatment Options

Treatment options are summarized in Table IV.

Table IV.

Treatment options for contact dermatitis, nickel
Medical Treatment	Barrier creams/Prevention	Surgical
Avoidance and education	Tape/fabric sewn over metal snaps	None
Topical steroids	Clear nail polish applied to metal snaps,etc
Topical Immunomodulators	Nickel Guard® applied to metal snaps, etc
Systemic antihistamines	Replace nickel snaps with aluminum snaps
Systemic steroids	Legislation – Through congress or local officials (copying the EU directive would be a good first start) – unlikely in the near future to occur
Topial PUVA (chronic hand dermatitis)
Oral Chelators ( Disulfiram)

Most barrier creams are made with silicone (Barrier cream 222®, LaRoche Posey Biomedic Barrier cream 33% silicone®) or dimethicone, which reduce or in some cases prevent the nickel from reaching the skin in high enough concentrations to cause a reaction. They may be helpful if avoidance is impossible.

Typically, jewelry made of 14K gold or higher, silver, and platinum are safe to use in the nickel-allergic patient. Only the most sensitive individuals will react to nickel in those types of stainless steel that contain nickel. Patients must avoid all costume jewelry and jewelry that is not clearly labeled. Metal snaps should be covered with a minimum of two coats of nail polish or Nickel Guard®, and reapplied after 4-5 cycles of cloth washing.

Oral hyposensitization may be attempted. It has had variable results. In my limited experience (unsuccessful), as it should be considered if all other attempts at avoidance and therapy have not helped.

The use of oral chelators has shown some efficacy in those with chronic allergic contact dermatitis to nickel. This should be reserved for patients who cannot avoid the metal and have tried all other therapies. Disulfiram has been the most studied agent. The dose is 250 mg orally daily. Strict alcohol avoidance is a must, and routine monitoring for serious side effects (elevated liver function tests causing a chemical hepatitis) needs to be followed. There is no known length of time that someone can stay on this medication for this purpose.

Optimal Therapeutic Approach for this Disease

The first approach to management of allergic contact dermatitis to nickel is to avoid products containing nickel. Specific educational handouts should be given to patients that list common products that contain nickel. Patients that work with nickel should use vinyl gloves, as nickel is much less likely to penetrate vinyl than rubber gloves.

One can use cool compresses to soothe the symptoms. If the offending agent cannot be totally avoided, then steps to minimize exposure, such as covering the metal tab of jeans with an iron-on patch or a few coats of clear nail polish (2-3 coats) or nickel guard, or even duct tape should be recommended. After 4-5 clothes washings, the nail polish or nickel guard should be reapplied.

Nickel chelator creams, such as disodium ethylenediamine tetra-acetate or diethylenetriaminepentaacetic, can be applied to help chelate the positive ions released by the nickel. Lesions can be treated with mid- to high-potency topical steroids, such as triamcinolone 0.5% or clobetasol 0.05% cream, twice daily for 2-4 weeks. Lower-potency steroids are advised on the face, such as desonide ointment, or topical calcineurin inhibitors, such as tacrolimus ointment twice daily, can be used.

If the dermatitis involves greater than 20% body surface area, eyelid swelling, significant hand and foot involvement, or if it is severe, systemic steroid therapy can be required. The recommended treatment in this case is prednisone 0.5-1 mg/kg/day tapered over 14 days. Antihistamines can be used to relieve pruritus (Benadryl 25 mg orally every 4-8 hours as needed, or hydroxyzine 25 mg orally every 6-12 hours as needed, or cetirizine 5-10 mg orally daily or Doxepin 10-25 mg once orally in the evening). Sedating antihistamines should not be used in those patients who operate machinery, etc., for safety reasons.

Topical PUVA may be used with varying results in patients with chronic allergic contact dermatitis to nickel of the hands. It is not used for other areas of the body as the response is unpredictable.

Patient Management

Patients should be educated to avoid the nickel allergen. They can be educated to use the dimethylglyoxime spot test. If avoidance is not possible, then barriers mentioned above can be used in order to decrease the exposure.

Those that are extremely sensitive to nickel and have repeated reactions should be educated in avoiding foods that contain nickel (see Table III). They should be educated in avoiding canned foods and foods cooked in nickel-plated pans and avoid using nickel plated utensils, along with avoiding oysters, asparagus, beans, mushrooms, onions, corn, spinach, tomatoes, peas, whole grain flour, pears, rhubarb, tea, cocoa, chocolate and baking powder. Nickel-reduced diets are available (http://www.dermnetnz.org/dermatitis/nickel-allergy.html) but these diets are restrictive and difficult to follow.

There has been a decrease in nickel allergy prevalence in Denmark and Germany following regulatory interventions to restrict the release of nickel from consumer items. However, in United States and Canada there are no regulations on nickel exposure.

Unusual Clinical Scenarios to Consider in Patient Management

Systemic contact dermatitis from oral ingestion of nickel is a rare entity. A nickel-reduced diet and strict avoidance of topical nickel is a must.

Most stainless steel products contain nickel, but only the most sensitive of individuals have a problem. It is not routinely recommended to avoid stainless steel products in all nickel-allergic patients. This is especially true in children with braces for their teeth. Some stainless steel products do not even contain nickel.

Occupationally induced nickel-allergic contact dermatitis almost always takes the form of hand dermatitis. An occupational history is critical, and in some cases a site visit may be the only way to determine the exposure source.

Patients with localized allergic contact dermatitis to nickel may form an Id reaction. This appears as a widespread monomorphic pruritic papular eruption. Avoidance of nickel and use of triamcinolone 0.1% cream twice daily for 2 weeks or the use of oral prednisone 1 mg/kg/day tapered over 2 weeks is curative.

Dyshidrotic eczema has been recognized as a possible cutaneous manifestation to nickel allergy (both external and internal exposure). This has yet to be proven.

It is possible that jewelers will replace nickel with cobalt, due to the EU nickel directive, and that we will potentially see an increase in the incidence of allergic contact dermatitis to cobalt, or another metal. Time will tell.

Patients with a history of atopic dermatitis may show a false positive reaction to nickel. In these patients, patch testing may show an irritant morphology (follicular based tiny papules/pustules). Repeating the patch test with a lower concentration of nickel sulfate will help determine the significance of these reactions.

Contact urticaria has only rarely been reported in association with nickel exposure; in a suspected case prick testing by an allergist is warranted.

For some patients who have a piece of jewelry that is an heirloom and must be worn, an option would be to have the areas that come in contact with the skin plated with platinum.

Those using clear nail polish to cover snaps may become allergic over time to a component of the nail polish. The most common agent would be tosylamide formaldehyde resin and or formaldehyde.

There is a least one case report showing nickel as the cause of both cutaneous vasculitis and erythema multiforme.

There is no point in taking a fecal or hair sample and analyzing for nickel content in assessing patients with systemic allergic contact dermatitis.

What is the Evidence?

Usatine, RP, Riojas, M. “Diagnosis and management of contact dermatitis”. Am Fam Physician. vol. 82. 2010. pp. 249-55. (This article highlights the diagnosis and management of contact dermatitis, with specific management for nickel dermatitis.)

Schram, SE, Warshaw, EM, Laumann, A. “Nickel hypersensitivity: a clinical review and call to action”. Int J Dermatol. vol. 49. 2010. pp. 115-25. (A thorough review on nickel sensitivity and its association with body piercing and environmental factors, including implantable metal medical devices. It also highlights the current European legislation that limits nickel release from objects.)

Lu, LK, Warshaw, EM, Dunnick, CA. “Prevention of nickel allergy: the case for regulation?”. Dermatol Clin. 2009. pp. 155-61. (This article discusses the specific tools for prevention of nickel dermatitis, including chemical and nonchemical barriers.)

Thyssen, JP, Menne, T. “Metal allergy – a review on exposures, penetration, genetics, prevalence, and clinical implications Chem Res Toxicol”. vol. 23. 2010. pp. 309-18. (Great review of nickel dermatitis and its clinical implications. It details the biochemical process involved in sensitization after nickel exposure with the skin.)

Thyssen, JP. “Nickel allergy in Danish women before and after nickel regulation”. N Engl J Med. vol. 360. 2009. pp. 2259-60. (This article highlights the impact of the European directive on limiting the amount of nickel released in objects.)

Habif, TP. ” Allergic Contact Dermatitis”. Clinical Dermatology. 2009.

Sprigle, AM, Marks, JG, Anderson, BE. ” Prevention of nickel release with barrier coatings”. Dermatitis. vol. 19. 2008. pp. 28-31. (Discusses the use of various barrier coatings to prevent the release of nickel from metal jean snaps. The coatings were directly applied to the metal and subsequently tested with the DMG test to determine if nickel was released.)

Torres, F, Gracas, M, Melo, M, Tosti, A. “Management of contact dermatitis due to nickel allergy: an update”. Clin Cosmet Investig Dermatol. vol. 2. 2009. pp. 39-48. (The most recent and best overview of nickel allergy. Discusses the epidemiology, pathophysiology, therapies, and unusual clinical situations that can arise from nickel allergy. For those who are looking for an excellent all-around resource, this is it.)

Veien, NK, Hattel, T, Laurberg, G. “Low nickel diet: an open, prospective, trial”. J Am Acad Dermatol. vol. 29. 1993. pp. 1002-7. (This study looks at how reduction of nickel in the diet can benefit nickel-sensitive patients.)

Fowler, JF. “Disulfiram is effective for nickel allergic hand eczema”. Am J Contact Dermatitis. vol. 3. 1992. pp. 175-8. (The study looked at nine patients with chronic hand eczema who were allergic to nickel by patch testing. One patient dropped out of the study due to pregnancy. A 2-month crossover study was done using 250 mg orally per day of disulfiram. Almost all patients treated noted improvement.)

Rietschel, RL, Fowler, JF. “Fisher's Contact Dermatitis”. 2001. pp. 605-62. (An excellent resource, one of the best.)

McLean, L, Yewchuck, L, Israel, D. “Acute onset of generalized pruritic rash in a toddler”. Pediatric Dermatol . vol. 28. 2011. pp. 53-4. (Case report of a 2-year-old with a generalized rash and fever. He had previously known allergy to metal snaps. He was found to have ingested multiple coins that contained nickel. The rash was felt to be caused by nickel ingestion and a systemic allergic contact dermatitis. After removal and 3 days of prednisone the rash resolved. It recurred a year later after he ingested another coin.)

Yoshihisa, Y, Shimizu, T. “Metal Allergy and Systemic Contact Dermatitis: An Overview”. Dermatology Research and Practice. 2012. (Contact dermatitis to metals is frequently encountered. This review discusses systemic contact dermatitis to various metals. It discusses new techniques, such as the analysis of cytokine production by mononuclear cell cultures on exposure to various metals, and compares these methods to lymphocyte stimulation testing.)

Sharma, AD. “Low Nickel Diet in Dermatology”. Indian Journal of Dermatology. vol. 58. 2013. pp. 3- 240. (Systemic contact allergy is difficult to diagnose. When treating someone with a presumed systemic allergy to nickel, avoidance, or at the very least, minimizing intake of nickel is a must. This article is a nice resource to individuals that are trying to have a nickel free or nickel reduced diet. It does a nice job of listing foods high in nickel content and some alternative options.)

Warshaw, EM, Maibach, HI, Taylor, JS, Sasseville, D, DeKoven, JG, Zirwas, MJ, Fransway, AF, Mathias, CG, Zug, KA, DeLeo, VA, Fowler, JF, Marks, JG, Pratt, MD, Storrs, FJ, Belsito, DV. Dermatitis. vol. 26. 2011-2012. pp. 49-59. (Gives prevalence of contact allergy to various allergens from pooled data obtained by US and Canadian expert patch testers.)

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