Continuing Education Activity

Nickel allergy is a type of contact dermatitis caused by direct contact with nickel. It is the most common identifiable cause of metal-related contact dermatitis and may be encountered in a variety of healthcare settings, from primary care clinics to emergency departments. This activity reviews the evaluation and treatment of nickel allergy and highlights the role of the interprofessional team in managing patients with this condition.

Objectives:

• Outline the etiology and epidemiology of nickel allergy.
• Identify key factors in appropriately recognizing and evaluating patients with a nickel allergy.
• Summarize the treatment and management options available for patients with a nickel allergy.
• Explain the importance of improving coordination of care amongst the interprofessional team to ensure appropriate diagnosis and management in patients with a nickel allergy.

Introduction

Allergic contact dermatitis (ACD) occurs after repeated exposure to an irritant or allergen. ACD is the most frequent occupational skin disease. It is based on a delayed-hypersensitivity reaction and can result from contact with metals, most commonly nickel.[1] The metals that most frequently cause these reactions can be found in a variety of everyday items (e.g., kitchen tools, watches, earrings, bracelets), medical devices, and industrial applications.

Etiology

Nickel allergy is a type of allergic contact dermatitis. A nickel allergy is commonly encountered with jewelry, kitchen tools, and silverware. In individuals who are sensitive to nickel, ingestions of certain foods (e.g., chocolate, nuts, oats, green beans, peas) may cause systemic nickel allergy syndrome (SNAS) or lead to chronic dermatitis.[2] Implantable devices also lead to an increased risk of a systemic reaction.[3] It is believed certain underlying inflammatory conditions (e.g., ulcerative colitis) can increase the likelihood of developing a nickel allergy.[4]

Epidemiology

In a cross-sectional analysis of over 44,000 patients patch tested by the North American Contact Dermatitis Group from 1994 to 2014, the average frequency of nickel sensitivity was 17.5 percent, and 55.5 percent of those reactions were thought to be clinically relevant.[5] In a meta-analysis of 28 studies, including over 20,000 patch-tested individuals from the general population, the pooled prevalence of contact allergy was 20.1 percent, with nickel being the most common allergen.[6] There is a female predominance.[5] Sensitization to nickel may correlate directly with the number of body piercings, suggesting that increased frequency of exposure increases the risk for developing a nickel allergy.[7]

Pathophysiology

Allergic contact dermatitis represents the classic presentation of a T cell-mediated, delayed-type hypersensitivity response to exogenous agents. The initial step in the development of allergic contact dermatitis, as in nickel allergy, is hapten binding to a skin carrier protein. A hapten by itself is not immunogenic but becomes so after binding to a skin protein carrier. The hapten protein complex forms through covalent bonds between the hapten and amino acid side chains of target proteins within the skin.[8] The complex ultimately produces the sensitization of T cells. Sensitized T cells encountering the antigen at any time later will then lead to the release of cytokines, which in turn leads to macrophage activation and produces the immune response.[8] In summary, the sensitization process requires an initial exposure to allow the immune system to recognize the antigen later and lead to the immune response that causes ACD.

History and Physical

A patient's history plays a significant role in the diagnosis of allergic contact dermatitis. An extensive history, over multiple years, is helpful. An in-depth review of the patient's activities, including occupation and hobbies, is key in the identification of a source for dermatitis. Close attention should be given to the products and objects of personal use (e.g., cosmetics, hair dyes, fragrances, eyeglasses, clothing, jewelry). The incidence of allergic contact dermatitis increases with age but does not spare any age group. Nickel allergy dermatitis is often a diagnosis that will require multiple visits within the healthcare system. Physical examination findings can include lesions consisting of erythema, induration, scaling plaques, vesicles, bullae, and edema in the acute phase. The spectrum of physical findings can progress to include dryness, scaling, hyperkeratosis, hyperpigmentation, lichenification, and fissuring in the subacute or chronic phases.

Evaluation

Diagnosis of allergic contact dermatitis is clinical, based on obtaining a good history and physical examination. A positive nickel contact history with physical exam findings consistent with a nickel allergy dermatitis should allow for the formulation of the diagnosis. Laboratory and radiographic testing are not typically required and generally offer little to the workup. The need for additional workup should be determined on a case-by-case basis and is likely to occur in conjunction with an immunologist or dermatologist. Patch testing can help confirm suspected cases and identify additional allergens.

Treatment / Management

The key element of appropriate treatment and management of allergic contact dermatitis due to nickel allergy is the identification and removal of the source object. Identifying the source may require a log of all daily exposures, an intense review of these exposures, and is likely to require multiple visits within the healthcare system. Providing patients with a list of objects that may be high in nickel is helpful as they may not realize conventional household products contain the metal.  Nickel test kits are commercially available and may be useful in the identification of potential sources. If the patient is determined to have a nickel allergy, management begins with avoidance of repeat exposure, as this is the most effective treatment option. It is important for patients to avoid scratching as it can lead to excoriation and increases the risk of infection. Patients should also avoid foods that are routinely high in nickel content, such as cocoa, chocolate, oatmeal, various nuts, and legumes.[2] In cases where avoidance is ineffective or not entirely possible, consider adding barriers (e.g., creams, emollients, gloves) and perform frequent washing, remembering to moisturize to prevent breaks in the skin.  For cases not improved by the conservative measures listed above, the first-line pharmacologic therapy utilized is topical corticosteroids, beginning with low potency agents and advancing therapies as indicated. Topical calcineurin inhibitors (e.g., tacrolimus) are an alternative therapy available. Treatment is unlikely to require oral corticosteroids, but they can be considered in intractable cases. Several studies have suggested the improvement of scaling and frequency of flares in patients taking disulfiram for dermatitis. However, the extensive side effect profile of disulfiram limits this medication's ability to become mainstream therapy.[9][10][11] In cases of nickel allergies that are resistant to the above therapeutic modalities, referral to dermatology may be beneficial. There seems to be evidence suggesting a benefit from probiotics in patients with GI disturbances related to nickel allergy.[12]

Differential Diagnosis

Life-threatening allergic reactions and anaphylaxis should be ruled out in the beginning. Once the stability of the patient is confirmed, consideration for other causes of allergic contact dermatitis, e.g., plants, cosmetics, skin lotions, soaps, detergents, may begin. Assess for skin and soft tissue infections. Consider fungal infections - diagnosis by potassium hydroxide preparation of skin scrapings. There should also be a consideration for underlying inflammatory diseases, such as psoriasis, lupus, and ulcerative colitis - these can mimic and increase the risk for allergic contact dermatitis due to nickel allergy.[4]

Prognosis

The overall prognosis for nickel allergy is excellent.

Complications

A nickel allergy rarely causes significant complications unless the offending agent is left to irritate the patient continually or if the patient develops openings in the skin. The skin may become excoriated and broken, leading to an increased risk of infection. The skin breaks and infections can lead to the development of a superimposed infection (cellulitis). Cellulitis can complicate the treatment plan for the patient, and topical corticosteroids may limit the patient's local immune response to fight the cellulitis. Treatment of the skin infection must be completed along with the removal of the offending agent to allow the skin to heal properly.

Consultations

It is unlikely any consultations will be needed, but consider referral to dermatology in therapy-resistant cases. If there is a concern for any underlying inflammatory conditions (such as ulcerative colitis), referral to specialists may be deemed necessary.

Deterrence and Patient Education

Patient education will center around avoidance of nickel, including identifying potential exposure sources and lifestyle modifications. Avoidance is the single best way to deter nickel allergy dermatitis. Additional education should be provided on appropriate skin care and wound healing, including instructions regarding the treatment of existing lesions, and the importance of not scratching the lesions to avoid excoriations and an increased risk for infection.

Pearls and Other Issues

As with other allergic contact dermatitides, identification of nickel allergy can be challenging. It may be helpful for patients to create a list of daily exposures, including soaps, medications, lotions, etc., starting with the most recent additions. Unfortunately, often an underlying cause of symptoms is never identified. Nickel allergy is likely one of the more identifiable causes as it tends to be more localized to common areas of exposure - low midline abdomen due to belt buckles, wrists due to watches, and ears due to earrings.

Enhancing Healthcare Team Outcomes

The location of a rash and thorough history are the keys to makings a diagnosis of nickel allergy. Information such as a recently purchased piece of jewelry may lead to the discovery of an identifiable and treatable cause. Often, the patient will have multiple healthcare visits across specialties until a trigger for the contact dermatitis is identified. While it is unlikely there will be much direct communication between specialties for suspected allergic contact dermatitis, good documentation of patient visits, and lists of exposures may help improve timely identification. A team approach involving providers, nurses, and laboratory technicians to identify nickel allergy and make appropriate referrals will result in the best outcomes.

Review Questions

• Access free multiple choice questions on this topic.
• Click here for a simplified version.
• Comment on this article.

References

1.

Warshaw EM, Belsito DV, Taylor JS, Sasseville D, DeKoven JG, Zirwas MJ, Fransway AF, Mathias CG, Zug KA, DeLeo VA, Fowler JF, Marks JG, Pratt MD, Storrs FJ, Maibach HI. North American Contact Dermatitis Group patch test results: 2009 to 2010. Dermatitis. 2013 Mar-Apr;24(2):50-9. [PubMed: 23474444]

2.

Guerra L, Rogkakou A, Massacane P, Gamalero C, Compalati E, Zanella C, Scordamaglia A, Canonica WG, Passalacqua G. Role of contact sensitization in chronic urticaria. J Am Acad Dermatol. 2007 Jan;56(1):88-90. [PubMed: 17190624]

3.

Schalock PC, Thyssen JP. Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants. Dermatitis. 2013 Jul-Aug;24(4):183-5. [PubMed: 23857019]

4.

Kageyama Y, Shimokawa Y, Kawauchi K, Morimoto M, Aida K, Akiyama T, Nakamura T. Higher Prevalence of Nickel and Palladium Hypersensitivity in Patients with Ulcerative Colitis. Int Arch Allergy Immunol. 2020;181(6):456-461. [PubMed: 32316004]

5.

Warshaw EM, Zhang AJ, DeKoven JG, Maibach HI, Belsito DV, Sasseville D, Fowler JF, Fransway AF, Mathias T, Pratt MD, Marks JG, Zug KA, Zirwas MJ, Taylor JS, DeLeo VA. Epidemiology of nickel sensitivity: Retrospective cross-sectional analysis of North American Contact Dermatitis Group data 1994-2014. J Am Acad Dermatol. 2019 Mar;80(3):701-713. [PubMed: 30342160]

6.

Alinaghi F, Bennike NH, Egeberg A, Thyssen JP, Johansen JD. Prevalence of contact allergy in the general population: A systematic review and meta-analysis. Contact Dermatitis. 2019 Feb;80(2):77-85. [PubMed: 30370565]

7.

Warshaw EM, Aschenbeck KA, DeKoven JG, Maibach HI, Taylor JS, Sasseville D, Belsito DV, Fowler JF, Zug KA, Zirwas MJ, Fransway AF, DeLeo VA, Marks JG, Pratt MD, Mathias T. Piercing and Metal Sensitivity: Extended Analysis of the North American Contact Dermatitis Group Data, 2007-2014. Dermatitis. 2017 Nov/Dec;28(6):333-341. [PubMed: 29135681]

8.

Divkovic M, Pease CK, Gerberick GF, Basketter DA. Hapten-protein binding: from theory to practical application in the in vitro prediction of skin sensitization. Contact Dermatitis. 2005 Oct;53(4):189-200. [PubMed: 16191014]

9.

Kaaber K, Menné T, Veien N, Hougaard P. Treatment of nickel dermatitis with Antabuse; a double blind study. Contact Dermatitis. 1983 Jul;9(4):297-9. [PubMed: 6352169]

10.

Kaaber K, Menne T, Veien NK, Baadsgaard O. Some adverse effects of disulfiram in the treatment of nickel-allergic patients. Derm Beruf Umwelt. 1987 Nov-Dec;35(6):209-11. [PubMed: 3440439]

11.

Menne T, Kaaber K, Tjell JC. Treatment of nickel dermatitis. (The influence of tetraethylthiuramdisulfide (Antabuse) on nickel metabolism). Ann Clin Lab Sci. 1980 Mar-Apr;10(2):160-4. [PubMed: 7387122]

12.

Lombardi F, Fiasca F, Minelli M, Maio D, Mattei A, Vergallo I, Cifone MG, Cinque B, Minelli M. The Effects of Low-Nickel Diet Combined with Oral Administration of Selected Probiotics on Patients with Systemic Nickel Allergy Syndrome (SNAS) and Gut Dysbiosis. Nutrients. 2020 Apr 09;12(4) [PMC free article: PMC7230804] [PubMed: 32283870]

Disclosure: Colton Rishor-Olney declares no relevant financial relationships with ineligible companies.

Disclosure: David Gnugnoli declares no relevant financial relationships with ineligible companies.