POLICY STATEMENT Organizational Principles to Guide and Define the Child Health Care System and/or Improve the Health of all Children

Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention Nanette B. Silverberg, MD, FAAP, FAAD,a Janice L. Pelletier, MD, FAAP,b,c Sharon E. Jacob, MD, FAAP, FAAD,d,e Lynda C. Schneider, MD, FAAP,f SECTION ON DERMATOLOGY, SECTION ON ALLERGY AND IMMUNOLOGY

Nickel is a ubiquitous metal added to jewelry and metallic substances for its abstract hardening properties and because it is inexpensive. Estimates suggest that at least aDepartments of Dermatology and Pediatrics, Mt Sinai Hospital and 1.1 million children in the United States are sensitized to nickel. Nickel allergic Icahn School of Medicine at Mt Sinai, New York, New York; bNorthern contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type Light Health, Bangor, Maine; cCollege of Medicine, University of New d hypersensitivity reaction worldwide. The incidence among children tested has England, Biddeford, Maine; Department of Dermatology, Loma Linda University, Loma Linda, California; eDepartments of Medicine and almost quadrupled over the past 3 decades. The associated morbidities include itch, Pediatrics, University of California, Riverside, California; and discomfort, school absence, and reduced quality of life. In adulthood, individuals fDepartment of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts with Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACD in children has been postulated to result from early and frequent exposure to Policy statements from the American Academy of Pediatrics benefit from expertise and resources of liaisons and internal (AAP) and metals with high amounts of nickel release (eg, as occurs with ear piercing or with external reviewers. However, policy statements from the American Academy of Pediatrics may not reflect the views of the liaisons or the products used daily in childhood such as toys, belt buckles, and electronics). organizations or government agencies that they represent. To reduce exposure to metal sources with high nickel release by prolonged Drs Silverberg, Pelletier, Jacob, and Schneider fully participated in the and direct contact with human skin, Denmark and the European Union conceptualization, drafting, and revision of this manuscript, and all legislated a directive several decades ago with the goal of reducing high nickel authors approved the final manuscript as submitted. release and the incidence of Ni-ACD. Since then, there has been a global The guidance in this statement does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking reduction in incidence of Ni-ACD in population-based studies of adults and into account individual circumstances, may be appropriate. studies of children and young adults being tested for allergic contact All policy statements from the American Academy of Pediatrics dermatitis. These data point to nickel exposure as a trigger for elicitation of automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. Ni-ACD and, further, provide evidence that legislation can have a favorable This document is copyrighted and is property of the American effect on the economic and medical health of a population. Academy of Pediatrics and its Board of Directors. All authors have filed This policy statement reviews the epidemiology, history, and appearances of conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process Ni-ACD. Examples of sources of high nickel release are discussed to highlight approved by the Board of Directors. The American Academy of fi Pediatrics has neither solicited nor accepted any commercial how dif cult it is to avoid this metal in modern daily lives. Treatments are involvement in the development of the content of this publication. outlined, and avoidance strategies are presented. Long-term epidemiological DOI: https://doi.org/10.1542/peds.2020-0628 interventions are addressed. Advocacy for smarter nickel use is reviewed. The American Academy of Pediatrics supports US legislation that advances safety To cite: Silverberg NB, Pelletier JL, Jacob SE, et al. AAP standards (as modeled by the European Union) that protect children from SECTION ON DERMATOLOGY, SECTION ON ALLERGY AND early and prolonged skin exposure to high–nickel-releasing items. Our final IMMUNOLOGY. Nickel Allergic Contact Dermatitis: aim for this article is to aid the pediatric community in developing nickel- Identification, Treatment, and Prevention. Pediatrics. 2020;145(5):e20200628 avoidance strategies on both individual and global levels.

Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 145, number 5, May 2020:e20200628 FROM THE AMERICAN ACADEMY OF PEDIATRICS INTRODUCTION and personal goods. Over time, Ni- were alloyed with copper. In the late ACD evolved from an occupational 1800s, steel production accelerated Nickel Is a Common Cutaneous eczema of electroplaters to a common because of the strength of steel Allergen form of allergic contact dermatitis products. During the 20th century, Recent estimates suggest that 1.1 (ACD) among both adults and nickel gained a solid place in industry million children in the United States children, currently affecting as many as part of manufactured stainless are potentially sensitized to nickel1; as 20% of Americans. Historically, Ni- steel alloy (along with chromate and however, this may be a gross ACD has been linked to a wide range iron). Today, two-thirds of nickel underestimate given that nickel of exposures, including suspenders in production in the world is devoted to allergic contact dermatitis (Ni-ACD) is the 1950s–1960s; zippers, buttons, the manufacture of stainless steel, found in approximately one-quarter and rivets in the 1970s; and ear 20% is for other specialized steel of children who undergo patch piercing in the 1980s.4 Environmental alloys (for military and aerospace), testing. Nickel is present in metallic nickel present in oxides and sulfides 9% is for plating, and the remainder items that are common in children’s is not as allergenic as the free nickel is for various uses, including environments, including earrings, present in metal fittings found in batteries, coins, and electronics.9,10 watches, toys, and fasteners on industry.4,6 clothing and belts. Chronic exposure Early Reporting of Nickel Allergy fi to nickel increases risk for Ni-ACD. Nickel Allergy Has Signi cant Weston et al11 first reported Ni-ACD Nickel has become the most common Symptomatology in young pediatric patients in 1984. metallic cause of allergic dermatitis Virtually any site of the body can be Until that point, it was unclear and was named the “Contact Allergen affected by Ni-ACD, but some of the whether cutaneous immune function of the Year” in 2008 by the American more commonly affected areas are in infants was mature enough to Contact Dermatitis Society. the eyelids (transfer from hands), mount such responses. After the Determining the presence of Ni-ACD face, neck, wrists, fingers and hands, report of this phenomenon by Weston in those with allergic dermatitis can periumbilical area, and thighs.7 et al,11 more attention to allergic be difficult and elusive, with patch Symptoms and signs of Ni-ACD range reactions in infants and young testing being a crucial tool used to from mild dermatitis with pruritus, to children made it clear that contact help differentiate Ni-ACD from other deep erythema with oozing and allergy to nickel can begin in infancy, forms of dermatitis.2 The risk of Ni- papulation, to a systemic reaction with some authors indicating ACD increases when ears are with generalized idiopathic 3 6,7 increasing incidence after the age of pierced. hypersensitivity. Although Ni-ACD – 5 years.12 16 Nickel’s place as a cause is a delayed-type hypersensitivity, of contact dermatitis in pediatrics Nickel Exposures Are Common symptoms can occur within the first was solidified by these early reports. Nickel is a ubiquitous metal, being the 30 minutes of exposure through fifth most common element in the a complex cascade of inflammatory Ni-ACD can cause systemic world. Worldwide use of nickel in the mediators generated after hypersensitivity in children, and this production of hardened metal items sensitization.8 was elucidated in 2 articles in 2002. has been increasing since World War Silverberg et al16 reported a group of 4 II. The process by which nickel use KEY POINTS IN THE EVOLUTION OF 30 children with clinical features of shifted from coins and military NICKEL ALLERGY AS A SERIOUS Ni-ACD manifested by persistent purposes to daily use products, such ALLERGEN umbilical or wrist dermatitis. In that as clothes and electronics, was cohort, all children had positive strongly influenced by metal use in Introduction of Nickel Into the results on patch testing for nickel; the post–World War II era. Among Manufacturing of Metals furthermore, 50% had an idiopathic adults who were screened in Nickel was first identified as an hypersensitivity reaction, Massachusetts General Hospital from element in 1751 by a Swiss chemist a hypersensitivity response 1996 to 2006, Ni-ACD was found in named Axel Cronstedt. In the 1800s, characterized by the presence of 22.1% of those 20 to 40 years of age nickel was introduced into the inflammatory papules on the extensor but in only 10.1% of those older than manufacturing of metal alloys with surfaces of the extremities in sites not 60 years, suggesting that Ni-ACD is copper and zinc. As an alloy, its high exposed to nickel.17 A similar article a problem of younger individuals value is related to many inherent from Sharma et al17 reviewed 38 (those raised or those who had their qualities: high strength, lengthy life, children with periumbilical papules ears pierced after World War II).5 anticorrosion, heat resistance, low consistent with Ni-ACD, all of whom Today, nickel has continued to be cost, and minimal maintenance. In the demonstrated an idiopathic a leading production metal in home mid-1800s, coins in the United States reaction.18 Systemic contact

Downloaded from www.aappublications.org/news by guest on September 24, 2021 2 FROM THE AMERICAN ACADEMY OF PEDIATRICS dermatitis has been defined as “a that is higher than that in the general detected in as many as 36.8% of generalized ACD rash from systemic population. children and adolescents tested and administration of a drug, chemical, or having an 80.4% relevance (ie, being food to which the patient previously Product Properties That Contribute identified as contributing to to Allergenicity experienced ACD.” There is no known dermatitis activity).28 general population-based prevalence The amount of nickel released to the of systemic nickel hypersensitivity, skin from contact with a metal object Population-based screening on neither for kids nor for adults. (not the presence of nickel) individuals (including adults) Strongly positive ($3 papular) nickel determines the potential for causing referred for patch testing have patch test results in these patients Ni-ACD. The development of Ni-ACD highlighted the pervasive issue of Ni- suggest that severe reactions from contact with a nickel-containing ACD in the United States. In 1978, correlate with systemic disease.17 object is promoted in a 3-step a population-based study of 1158 fi process: “1) the nickel in the material people identi ed 9% of individuals 1 Pathophysiology and Genetics of must be corroded, 2) the resulting with Ni-ACD, and approximately Nickel Allergic Sensitization nickel compounds must be 50% of those who were nickel allergic had never sought medical care.26 In Nickel-contact allergy is a delayed- solubilized, and 3) the nickel ions a recent meta-analysis of 5 ACD type (type IV) cutaneous must be absorbed by the skin to 23,24 studies representing 1507 pediatric hypersensitivity reaction that cause a reaction.” Other subjects, 22.9% had Ni-ACD.29 The develops through a biphasic process: contributory factors include the use current estimate of Ni-ACD in an induction phase is followed by an of products under occlusion (eg, children with suspected ACD who are elicitation phase. In the induction piercing holes) or prolonged contact patch tested is 28.3% according to phase, there are repeat exposures to with the skin such that sweat may the NACDG.27 free nickel that are beyond a minimal erode or release nickel (eg, underside threshold. During this initial phase, an of the thighs against a chair). Data from Denmark are the most antigen is presented by the skin’s Rising Prevalence of Nickel Allergy revealing when evaluating European dendritic cells to T cells (T helper 1 Union (EU) nickel directives because and T helper 17 cells), which causes The prevalence of nickel allergy in Denmark introduced the directives in the skin to develop a set of memory North America has increased 1990, 14 years before widespread EU fi fi T cells that speci cally recognize signi cantly since the 1980s in both adoption. The Nickel Directive states nickel. During the elicitation phase, adults and children. Data on that “consumer items intended to be fi there is ampli cation of the allergy prevalence in the United States are in direct and prolonged contact with through subsequent repetitive derived from patch testing, that is, the skin were not allowed to release exposures that result in the epicutaneous allergy testing, which more than 0.5 mcg nickel/cm2/week.” 4,6,18 manifestations of ACD. reveals contact sensitization but not This legislation was intended to relevance of the allergy, outcomes, Ni-ACD is influenced by reduce Ni-ACD but not eliminate and/or associated disabilities. The a combination of genetic and disease. The venture has been North American Contact Dermatitis environmental factors, the latter successful in reducing Ni-ACD in Group (NACDG) reported that nickel being more important, according to young women with ear piercings who sensitization rates increased steadily leading experts.4 Filaggrin mutations are patch tested. One particular between 1970 and 2002 in a mixed are associated with increased Ni-ACD outcome has been reduced severity of group of adults and children from risk. Another genetic determinant reaction on epicutaneous patch 11% to 16.9%.25 Pediatric-specific that may increase risk for Ni-ACD is testing to nickel, which suggests less data from Peltonen26 revealed HLA antigen expression.19,20 severity of disease. On the other hand, a prevalence of Ni-ACD of 2.5% in Staphylococcal biofilms may promote because the sale of nickel-laden 1981, and the NACDG series from the development of Ni-ACD in the agents is not criminalized, sales of 2001 to 2004 demonstrated 28.3% of setting of atopic dermatitis.21 items with nickel release persist in children with positive patch test fl 22 Europe, especially in outdoor ea Menné and Holm showed a twin results were nickel allergic, showing markets.3,30 concordance rate of 29% in patients an increase even more substantial in with Ni-ACD, confirmed from childhood than in adulthood.27 One Before EU legislation, the percentage a population-based survey. Half of the series revealed that although not all of female first-year college students pediatric patients with severe Ni-ACD children with Ni-ACD have disabling in Finland in 1995 with Ni-ACD was with additional idiopathic reactions symptoms, for those who undergo 39%, suggesting that the rate may had a parent with Ni-ACD in the a patch test series, Ni-ACD represents continue to increase further in the Silverberg et al16 cohort, a statistic a common relevant allergen, being United States if no population-based

Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 145, number 5, May 2020 3 restrictions are enacted.29,31,32 compared with 16.3% in children accessories, and shoes; nail clippers; Population-based data on true nickel without piercings.35,36 Nickel allergy razor blades; and cosmetics.1 Newer allergy in adolescents derived from in girls with pierced ears has nickel sources reported to cause survey data in Sweden reported in dramatically decreased in Denmark dermatitis include devices such as 2008, 7 years after EU legislation was over the last 3 decades since strict metallic cell phone cases (a persistent put into action, revealed that 14.8% nickel-release legislation was plaque on the hollow of the cheek), of 6095 adolescents polled believed enacted.14 Although piercings have laptop cases and handheld device they had Ni-ACD, with confirmation in been linked to nickel sensitization, cases (fingertip, hand, lap, and 9.9%, revealing how EU nickel occurrence of Ni-ACD is also common periocular dermatitis), makeup directives may be benefiting in children without piercings; applicators and ferrules (site of adolescents.33 Data from a Danish therefore, reduction of nickel release application), eye makeup, dog tag pediatric contact dermatology is needed across all costume jewelry necklaces, and lip balm containers – database reveal ongoing reduction in types.6 A recent review of NACDG (lip and perioral).42 48 Table 1 nickel sensitization, with ACD rates of data revealed that of 1894 pediatric contains a brief compendium of items 9.7% in those tested (252 of 2587) patients who were patch tested, of daily use linked to nickel exposure from 2003 to 2011 and 7% (107 of 23.7% had nickel contact dermatitis and allergy.4,6 Many of these newer 1540) from 2012 to 2016 (adjusted and 36.4% had a pattern of skin nickel sources are more difficult to odds ratio, 0.69; 95% confidence disease consistent with all types of diagnose because the site of allergy interval, 0.55–0.88). Predominance of jewelry as the source of the nickel.37 can be areas not in direct contact, for girls in the Ni-ACD group persisted in example, the eyes.43 The timing and this study, as with previous The High Cost of Nickel Allergy in the type of nickel exposures throughout studies.33,34 United States life are important. Ni-ACD was shown The 2004 estimates in the United to be much less common when ear Piercings and Jewelry Are Leading States suggest that contact dermatitis, piercing occurred after placement of Sources of Nickel Sensitization which includes nickel sensitization, metal dental braces, compared with Piercings, costume jewelry, watches, accounted for $1.918 billion in health when piercing occurred before belt buckles, and clothing fasteners care costs (including direct medical exposure to braces. So, less nickel (grommets, buttons, studs, and costs and lost productivity costs) and sensitization may occur if placement toggles) are leading sources of affected 72.29 million people. Given of braces occurs first and piercing epicutaneous nickel sensitization in that nickel-contact sensitization is later.44 This phenomenon may be countries without legislation noted in approximately one-quarter analogous to the enteral tolerance controlling nickel release.6 The same of patients, it is likely that nickel that develops to lessen peanut allergy 1995 Finnish study of first-year allergy contributes heavily to this and may be akin to reasoning college students revealed that burden.24 Recent data from the forwarded by the Learning Early piercings in female students were American Academy of Dermatology About Peanut Allergy study.49 associated with a rate of 42% nickel reveal that contact allergy costs more allergy, compared withs 14% for than $1.5 billion in 2013.38 Given that female students without piercings.31 nickel allergy is the number one THE CLINICAL APPEARANCE OF NICKEL A study of 960 girls 8 to 15 years of allergen nationwide in all age groups, CONTACT DERMATITIS IS PROTEAN age in Sweden (published in 1985) nickel allergy is costly. Ni-ACD commonly is diagnosed on with piercings revealed that 13% the basis of the appearance of itchy, were nickel allergic, compared with Other Sources of Nickel-Contact persistent, erythematous, and/or 1% of girls without piercings.23 In Sensitization lichenified papules and plaques that patch testing of school-aged girls for Contact with commonplace nickel appear to conform to the area Ni-ACD from 1999 to 2000, older girls alloy metallic products, such as toys, matching the exposure pattern of the who had piercings before Danish can lead to nickel release that metal object with the skin, for regulations were implemented were 4 deposits on a child’s skin.39,40 In example, a circular erythematous to 5 times as likely as those who had a recent radiograph fluorescence plaque on the extensor wrist at the piercings after regulations to be spectroscopy study of US jewelry, 79 site of exposure to the backside of the allergic to nickel (17.1% vs 3.9%, of 96 samples released nickel.41 In wristwatch. Ni-ACD can also be respectively). A Norwegian pediatric a case series of children and caused by a child playing with contact allergy study of 7- to 12-year- adolescents from Brazil, the source of a nickel-releasing object and then old schoolchildren, published in 1994, nickel exposure in the setting of Ni- transferring the nickel to other identified a rate of 30.8% nickel ACD included jewelry piercings; metal sites.1,45,46 Ni-ACD has also been allergy in children with piercings, clothing appliques on garments, described with nail polish from

Downloaded from www.aappublications.org/news by guest on September 24, 2021 4 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 1 Sources of Nickel Exposure in TABLE 1 Continued Idiopathic reactions, or diffuse Children Sources hypersensitivity reactions, to nickel Sources Overalls can occur. These may be associated Artwork Rivets with dietary or complementary White metal statues Snaps supplements as the source of nickel Cleaners and detergents Zippers ingestion,55 creating generalized Steel wool Scissors pruritus and exacerbating pruritus at Coins Tools the site of cutaneous nickel exposure, Cooking Toys or they may come from a generalized Pans Adapted from Jacob SE, Goldenberg A, Pelletier JL, Pots Fonacier LS, Usatine R, Silverberg N. Nickel allergy and idiopathic hypersensitivity reaction Stainless steel cookware used to cook acidic our children’s health: a review of indexed cases and triggered by ongoing cutaneous foods a view of future prevention. Pediatr Dermatol. 2015;32(6): exposures (a type of systemic contact Utensils (eg, silverware, spatula, and tongs) 779–78 and Tuchman M, Silverberg JI, Jacob SE, Silver- dermatitis), the latter of which is Electronics berg N. Nickel contact dermatitis in children. Clin Der- – Batteries matol. 2015;33(3):320 326. manifested by extensor papules and a The most commonly identified nickel-allergy sources in Cell phone cases and electric shaversa lichenoid (flat-topped) papules and clinical practice. Mobile phonesa plaques over extensor surfaces. a Laptops Idiopathic reactions (also called Tabletsa dermatophytid) are similar to those Foods (Mislankar and Zirwas50 and Sharma51) a bottle with nickel metal balls 47 Especially canned food included. This itchy rash is often seen in some patients with tinea Seafood diffuse and can occur on other less capitis when starting oral griseofulvin Beans common areas, such as the scalp and therapy.4,6 Chocolate eyelids. Furniture Dental amalgams, caps, and braces Brushed-metal furniture that contain or release nickel in Other jewelry-related patterns of Metal fittings and studs higher concentration are associated Grooming appearance include a plaque over the with perioral Ni-ACD as well as Ni- Nail clippers upper back at the site of a necklace ACD in eccentric sites such as ears, Razors clasp pressed against the skin, Hair clips the waist, and wrists. Ni-ACD may periumbilical plaques at the site of Bobby pins precede or be caused by dental belt buckle or button fly skin contact, Metal brushes devices containing nickel. Curling irons midback plaques where bra hooks Furthermore, such Ni-ACD can be Implants press against the skin, and earring Cardiac associated with lip swelling and plaques and/or nodules at the site of 52,56–58 Dental a burning oral sensation. piercing because of exposure to Orthopedic – Keys high nickel-releasing earring Although most allergic reactions to 16,17,48 Makeup posts. Dental amalgams are nickel are of a type IV delayed-type Eyelash curlers rarely high nickel releasing, but they hypersensitivity, rare reports have Ferrules still can cause oral lesions such as appeared in the literature of Lip balm containers persistent oral lichenoid reactions individuals with systemic nickel Musical instruments Horns near the amalgam, anesthetic hypersensitivity of a type I or 52 Wind instrument mouthpieces sensation, and/or systemic lesions. immediate-type hypersensitivity. Occupational Other types of allergic reactions to Metal workers When the source of nickel shifts nickel may occur after oral nickel Miners against the skin, (eg, chair nail heads, exposure, causing symptoms as minor Hospital cleaning staff fl Ornamentation belt buckles, and coins in the pocket), as ares of earlier nickel-allergic Accessories the contact dermatitis may be more eczema sites, to a generalized Ball and chain necklacesa papular and/or diffuse, making the maculopapular or vasculitislike rash, a Belt buckles and/or belts source less obvious. Furthermore, to more severe symptoms, including Button fliesa patients with atopic dermatitis may urticaria, headache malaise, diarrhea, Glasses 59,60 Grommets have background disease activity that fever, and arthralgia. Skin prick Jewelry (costume, white gold, and low-karat prevents the margins of the Ni-ACD testing has been performed in rare gold)a from being clearly cases but remains a 4,16,17,53 Earrings distinguished. In adults, controversial.52,59,60 It is still most Necklacesa nickel has been identified as a contact likely, even in such settings, that the Ringsa a allergen that can worsen reaction to nickel is a delayed-type Watches 54 palmoplantar or scalp psoriasis. hypersensitivity because rapid

Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 145, number 5, May 2020 5 reactions as fast as 10 to 30 minutes TABLE 2 Handout for Patients can be described in Ni-ACD delayed Nickel is a metal that is added to many metal objects to harden them. Nickel can be found in almost all type.61 The data on these cases are costume jewelry (including earrings, necklaces, watch backs, rings, and bracelets), some belt extremely limited, and no buckles, and such jewelry as ball and chain necklaces, dog tags, metal tabs, grommets, and button fl recommendation can be made until ies. When you sweat, the nickel is released from the metal, even if it is only a small amount or percentage of additional broad-based population the metal. Stainless steel is a stronger white metal and does not release nickel as easily. data become available for testing. If you are allergic to nickel, your rash will keep returning until you avoid nickel completely. There are many steps required to avoid nickel completely. It is not easy, but it is necessary to make you feel better. OVERLAP WITH ATOPIC DERMATITIS 1. Remove all nonessential metal from your clothing; replace button flies with plastic buttons and wear a belt that ties or has a plastic buckle. The NACDG demonstrated that 34% 2. For metal that you cannot remove, such as grommets on the side pockets of your jeans or the back of children with a positive contact of your watch, coat with 2 coats of clear nail polish every week or after washings. allergy result on testing had 3. Avoid sitting in shorts on metal chairs or plastic chairs with metal tabs. concurrent atopic dermatitis.62 In 4. Do not cook acidic foods in stainless steel cookware. Avoid stainless steel cookware if you can. children with atopic dermatitis, Ni- 5. Tucking in your shirt does not prevent you from reacting to the nickel in your belt buckle or button fly. ACD can trigger severe exacerbations 6 6. Avoid ear piercing, especially if dental work, such as braces, is expected. of pruritus. In the setting of atopic 7. Sources of nickel in jewelry include costume jewelry, including earring posts that are not stainless dermatitis, Ni-ACD overlap is steel, white gold, and all low-karat gold jewelry. Sterling silver and high-karat yellow gold jewelry associated with more extensive atopic are expected to have a low content of nickel but are not generally nickel free. dermatitis and greater difficulty in 8. Tests to look for nickel released from household metals can be found at the following Web sites: https://nonickel.com/collections/nickel-test-kit-for-jewelry-and-meteorites and https://www. diagnosing Ni-ACD.7 Because the delasco.com/spot-test-for-nickel/. More information can be found at https://athenaallergy.com/ background population data on nickel pages/how-to-test-for-nickel-using-nickel-alert-dimethylglyoxime-test. allergy does not differ in prevalence, Ni-ACD can only be viewed as an aggravating or obscuring factor and nickel sources hidden in daily Treatment of Skin Inflammation not necessarily as a cause of disease. activities. Inflammatory symptoms, including eczematous changes and pruritus, are One of the hallmarks of good clinical MANAGEMENT OF NI-ACD the main symptoms of Ni-ACD–induced care in ACD is education on how to inflammation. There is no US Food The broad goals of medical therapy in avoid allergen-laden goods. Such is and Drug Administration–approved Ni-ACD are as follows: the case in Ni-ACD. Patients with Ni- therapy for Ni-ACD; however, Ni-ACD 1. identification and avoidance of ACD can be counseled to recognize is a steroid-responsive dermatosis, nickel; objects that may be high-release nickel, to test such objects, and to and therefore topical corticosteroids 2. treatment of skin inflammation; protect the skin from prolonged and may be helpful in conjunction with and direct contact with the objects. prevention of retriggering of 3. restoration of the skin barrier and Table 2 is a handout that can be used dermatitis through avoidance of skin protection. to help educate parents and children suspected sources of nickel exposure and adolescents about nickel and with therapeutics to aid in Identification and Avoidance of avoidance. In general, piercing with pruritus or itch reduction. Although no Nickel nickel-free earrings can minimize risk specific regimen of topical Identifying sources of nickel requires of Ni-ACD, as can use of low-release corticosteroids has been endorsed by investigation of personal adornments, nickel, but the latter still results in any organization for Ni-ACD, the hobbies (eg, instruments played), and some release of nickel. Sterling silver American Academy of Pediatrics jobs (eg, leisure-time activities and (which is 92.5% pure silver), 18-karat recommends choosing the review of everyday device usage). yellow gold (which is 75% gold) or corticosteroid class on the basis of the Patients should be asked about more-pure gold, platinum, titanium, site of application and severity. Like in garments or uniforms worn at work and plastic earrings are alternatives atopic dermatitis, off-label use of or school. Avoidance of nickel can be that have low or no nickel content. topical calcineurin inhibitors (eg, enhanced through testing objects for Silver that is not sterling, such as pimecrolimus and tacrolimus) can be nickel content (see Avoidance of nickel silver, 800 silver (80% silver), effective in steroid-resistant Ni-ACD Nickel Exposure in Childhood and German silver (which contains no cases.63,64 These topical therapies are section). Using Table 1 as a guide, silver at all; an alloy of nickel and used in combination with nickel pediatricians can ask patients zinc), are not ideal for the patient avoidance, which is the cornerstone of targeted questions to determine with Ni-ACD. treatment of Ni-ACD. Prevention is

Downloaded from www.aappublications.org/news by guest on September 24, 2021 6 FROM THE AMERICAN ACADEMY OF PEDIATRICS paramount because there is no cure is negative but clinical history screen for metal allergy and Ni-ACD for Ni-ACD and because the disease supports Ni-ACD, a late reading in this setting; it is more prudent to is lifelong.65 In recalcitrant cases or should be considered 7 to 10 days proceed with patch testing by using in the setting of severe Ni-ACD and after the patch test application. There the extended metal series.73 Titanium severe pruritus or for those with is a US Food and Drug bars can be used safely in patients widespread lesions, oral steroids Administration–approved series of 36 with Ni-ACD if they are identified for several days and then tapered, patches (T.R.U.E. Test; SmartPractice, before surgery as having no together with antihistamines for Phoenix, AZ) that contains nickel at previously reported allergic events.70 pruritus, can aid in symptomatic 200 mg/cm2 nickel sulfate, which resolution.66 corresponds to 160 mg of nickel per patch. In pediatrics, standardized PREVENTION OF NI-ACD Restoration of the Skin Barrier and comprehensive patch testing is often Skin Protection custom tailored by history, and Avoidance of Nickel Exposure in Emollients can be used to enhance testing is performed with nickel Childhood the skin barrier in children with sulfate hexahydrate 2.5% in Ni-ACD is a threat to pediatric public atopic dermatitis and may benefit petrolatum, as would be found in the health that persists as a problematic children with Ni-ACD and concurrent American Contact Dermatitis Society skin disease into adulthood. Ni-ACD is dermatitis symptoms. Skin protection Core series.4,53 Broad-metal contact the most common cutaneous allergy can be achieved through thick allergy screening should be and involves lifelong hazards that can physical blockage of nickel-containing performed when multiple metals are affect people’s lives both personally metal objects, for example, cell phone suspected as the potential source of and professionally.74 Common cases, backing button flies in denim, contact dermatitis. This screening can cutaneous nickel-containing items or replacing metal buttons with be accomplished by using an include earring posts, belt buckles, plastic buttons. Thin fabrics and epicutaneous metal contact allergy jewelry, zippers, snaps, clasps, strategies such as tucking in one’s panel containing nickel, gold, grommets, electronics, coins, keys, shirt may not be fully protective.4,53 titanium, copper, cobalt, zinc, and paper clips, chairs, braces, and more than a dozen other metals. implants.2,24,45,75–77 To reduce the fi Con rmation of Suspected Ni-ACD risk and severity of Ni-ACD, When a typical pattern of Ni-ACD Although children with obvious nickel avoidance of skin contact with nickel appears on the wrist or periumbilical allergy usually do not need is critical. According to European region, no confirmatory testing is confirmatory patch testing for nickel, reports, earrings appear to be the needed.16,17,67 In some cases in which they may need testing for other metal most common source of elicitation of suspicion is harder to confirm, patch allergens when metal appliances for Ni-ACD, providing credence to take testing, otherwise known as dental work or implants are preventive and economic measures. 68,69 epicutaneous skin testing, is a form of needed. In particular, the Nuss The United States should heed the testing in which a dilute version of procedure, which is a placement of European lead to reduce nickel the allergen is placed in metal rods for the repair of pectus release from common contacts in a hypoallergenic well (sometimes excavatum, has been associated with children to serve and protect called a Finn chamber) and applied to complications in patients with metal population health. Using the handout the back. Contact time with the skin allergy, especially to nickel. in Table 2, parents can identify of the upper back or inner upper Consequences include extensive sources of high-release nickel in their arms is up to 48 hours. After this granulation tissue formation, children’s lives. The purchase of items period, the patches are removed, and localized edema, dermatitis, with no nickel or with a low release of the test results are read. The patches lymphadenopathy, pleural effusion, nickel can be guided by the use of the are read again at a delayed point and inflammation and/or infection, dimethylglyoxime test, which between 72 and 120 hours after which may require removal of indicates a pink or red color on 70,71 placement. Interpretation of results is stainless steel rods in some cases. exposure to a nickel-releasing based on the appearance of redness Because of the potential metallic item. Currently, because of and/or papules and/or a plaque in consequences of undiagnosed Ni-ACD the lack of labeling of low–nickel- the shape of the chamber. Papular in such patients, surgeons performing release or nickel-free metal items, ($3 severity) reactions at the site of the procedure often refer patients for parents can screen metal objects for testing are common in nickel allergy patch testing to nickel and other nickel release using such test kits, 72 in children, and they can be metals before the procedure. which can be purchased on medical associated with idiopathic systemic Stainless steel discs provided by the Web sites (eg, https://www.delasco. hypersensitivity. If the testing result manufacturer are suboptimal to com/spot-test-for-nickel/ and

Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 145, number 5, May 2020 7 https://athenaallergy.com/pages/ watches, buttons, zippers, and now “approved materials for adult body- how-to-test-for-nickel-using-nickel- mobile phone cases.83 The EU piercing jewelry.”4,84,85 alert-dimethylglyoxime-test).78 directive was born from the original The effect of the Danish decree was However, it would be more ideal if work in Denmark, where the Nickel a drastic decrease in pediatric nickel labeling of low–nickel-release or Directive was designed to limit the sensitization from 24.8% to 9.2%.85 nickel-free items was available for maximum release of nickel in contact Reduction in Ni-ACD after Denmark’s parents. with human skin to an amount less Nickel Directive resulted in cost than 0.2 µg/cm2 per week for posts savings that grew to more than $2 Reduction in Dietary Nickel Exposure inserted into pierced skin and not µ 2 billion (US dollars) over the 2 Withdrawal diets in children cannot more than 0.5 g/cm per week for 4 decades after implementation. The be recommended because of products with prolonged and direct EU followed the commanding lead of inadequate pediatric data and risk of skin contact.83,84 The European the Danish dermatologists who malnutrition with a limited standard EN 1811:20111A1:2015 is worked with the Danish ministry to diet.50,79,80 Data on the use of low- a standardized testing system that is advance this innovative health nickel diets in children are approved by the EU to measure the directive. In 2006, the Nickel lacking.51,81,82 potential amount of nickel release Directive was incorporated into the under the conditions of direct and EU regulation of toxins, which is Advocacy prolonged contact with the skin. called Registration, Evaluation, fi Articles, such as those used for Ni-ACD represents a signi cant and Authorization, and Restriction of earrings in children, should not preventable pediatric public health Chemicals (REACH).84 After this release nickel more than 0.2 mg/cm2 burden. Regulation of nickel release regulation, there was a significant per week (by EN 1811 testing) to in materials that comes in contact reduction of Ni-ACD in patients prevent children from becoming with skin can decrease both the high younger than 30 years studied in allergic to nickel or having pediatric prevalence and treatment European countries.83 National a dermatitis reaction if they are costs of the disease. There is a call in databases involving 180 390 patients 2 already allergic to nickel. This nickel- the United States for such regulation with suspected ACD reveal an release rate is for the parts of given the high number of children approximately 10% reduction in Ni- earrings that are in contact with the affected by this disease. The ACD in young women, specifically skin and within the pierced part of American Academy of Dermatology from the following 4 countries, in the the ear.4,83 Germany and Sweden has recently accepted a proposal in years 1985–2010: Denmark, joined in the legislation and support of reduced nickel release in Germany, Italy, and the United manufacturing.82 Adoption of eventually Korea and China did as 83 Kingdom (2004–2010 only). legislation similar to that in the EU by well. the US Congress would represent REACH is a complex bill that outlines a promise for prevention by starting Because the rate of release of nickel industry obligations regarding 30 000 to reduce the nickel-related health (and not nickel content itself) is chemicals. REACH is far more burden. important and relevant in “reaching” than is the US counterpart, determining whether there is a risk the Toxic Substances Control Act for Ni-ACD, articles may contain (TSCA) of 1975,86 which regulates A REVIEW OF EU POLICY nickel but not cause a dermatitis chemicals but does not differentiate Nickel is ubiquitous, and people are reaction. For example, surgical toxic from nontoxic chemicals. The exposed to it primarily via metal stainless steel (grade 316L), which TSCA was supplanted by the Chemical objects throughout their lifetimes. contains 10% to 15% nickel and does Safety for the 21st Century Act, Preventive models of safer exposures, not release nickel more than 0.2 mg/ introduced in the Senate in 2015 and 2 or those less likely to trigger Ni-ACD, cm per week (by using EN 1811 passed in the House of have been demonstrated by other testing), is therefore regarded as Representatives in May 2016. countries to be medically and appropriate for use in articles in Although the TSCA required the economically beneficial. The EU direct and prolonged contact with the Environmental Protection Agency Nickel Directive of 1994 (approved skin. The American Section of the (EPA) to consider least burdensome June 30, 1994, and in full effect June International Association for Testing chemical regulations for industry, the 2001) regulated the method for Materials Standard Consumer Safety Chemical Safety for the 21st Century measuring nickel release onto human Specification for Adult Jewelry Act tasks the EPA to focus on skin and established regulations for (designation: F2999-13) lists surgical unreasonable risk to human health nickel allowed to be released onto stainless steel (typically containing and the environment; however, exposed skin over time, including for 10%–15% nickel) as one of the unfortunately, this may not apply to

Downloaded from www.aappublications.org/news by guest on September 24, 2021 8 FROM THE AMERICAN ACADEMY OF PEDIATRICS jewelry and cosmetics.86–88 Although understand the complex 7. If orthodontic metal braces are the EPA acknowledges the hazards of relationship between nickel anticipated, families should nickel as a cause of ACD, no current exposure and population health. consider delaying ear piercing ruling restricts nickel exposures in 3. Companies and industries using until after dental work is childhood; however, this regulatory metal in products should completed. foundation has room to act to reduce voluntarily create labeling for 8. Until such legislation can be 86–89 risk for Ni-ACD in children. The low–nickel-release products and passed, voluntary manufacturer United States stands to improve Web-based resources to identify reduction of nickel-releasing metal collective health status and lower those items in the United States in children’s clothing and close related medical costs if it were to that follow EU legislation contacts, including grommets, ’ follow Denmark s lead and the EU guidelines, allowing individuals button flies, belt buckles, school model in protecting the public from who are nickel allergic to shop chairs, and tables, aimed for use by the hazards of high nickel exposure. more wisely. Ideally, the children would reduce Ni-ACD Stakeholders may note that the development of trustable disease burden. Reporting of nonprofit organization Nickel resources for those with Ni-ACD voluntary reduction on labels and Producers Environmental Research can be met through physician and on public Web sites would help Association does support the industry partnership to develop parents of children and elimination of high-release nickel educational resources about nickel adolescents with Ni-ACD identify alloys and plating used in products allergy that can be easily hypoallergenic metal objects, with dermal contact such as jewelry understood and accessed by further enhancing reduction of and electronics.7,90 US legislators children, parents, and teachers. disease symptomatology and should advance evidenced-based 4. Physicians and other health care burden. policies to adopt a twofold guideline: providers can support the (1) adoption of the EU guidelines on reduction of Ni-ACD by CONCLUSIONS nickel release in manufacturing and encouraging parents to request Ni-ACD is a common chronic (2) adoption of a policy to avoid that posts for piercings in their dermatitis with detrimental effects on usage of nickel in plating in children’s ears be made of children now and as they progress household electronic devices. If the surgical-grade steel with low into adulthood. The burden of United States can incorporate safety nickel release, per EU standards. It symptoms and cost is high. The directives and sound is recommended that all United States can act on EU data recommendations regarding nickel individuals who perform piercing revealing that legislation to limit production and usage, as has been services mention Ni-ACD as exposures in childhood, especially done in the EU, then the population a potential complication of with earrings, can impact the can achieve significant reductions in piercing. prevalence and potentially the Ni-ACD in the next 2 to 3 decades. 5. Nickel allergy can be genetic; severity of disease. Until and even if therefore, physicians and other legislation is available, pediatricians RECOMMENDATIONS providers should consider can help patients by identifying the educating at-risk groups to avoid allergy early and intervening with The following are recommended to nickel-based body piercings. There reduce the US pediatric burden of Ni- a plan of prevention and care of is further genetic reason to believe disease. ACD: that children from families with 1. To minimize nickel-induced ACD a history of Ni-ACD would benefit in children, use of nickel in the from reduced exposure in LEAD AUTHORS manufacture of items that have childhood through the universal Nanette B. Silverberg, MD, FAAP, FAAD direct or prolonged contact with use of low–nickel-releasing Janice L. Pelletier, MD, FAAP Sharon E. Jacob, MD, FAAP, FAAD the skin (eg, jewelry, electronic jewelry. Lynda C. Schneider, MD, FAAP devices, toys, etc) should be 6. It is likely that most children limited. Regulations similar to the would benefit from lower SECTION ON DERMATOLOGY EXECUTIVE EU Nickel Directive that limit the exposure to such contact, even in COMMITTEE, 2018–2019 weekly allowable release of nickel the absence of family history of Ni- µ 2 to less than 0.5 g/cm /week ACD, because such family history Bernard Cohen, MD, FAAP should be adopted. Kimberly A. Horii, MD, FAAP, Chairperson is only present in approximately Leonard Kristal, MD, FAAP 2. Additional safety and toxicity half of cases of documented Sheilagh M. Maguiness, MD, FAAP studies are needed to better disease. Megha Mathakia Tollefson, MD, FAAP

Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 145, number 5, May 2020 9 Miriam G. Weinstein, MD, FRCPC, FAAP John A. Bird, MD, FAAP Teresa S. Wright, MD, FAAP Carla McGuire Davis, MD, FAAP ABBREVIATIONS Albert C. Yan, MD, FAAD, FAAP, Immediate Vivian Pilar Hernandez-Trujillo, MD, FAAP ACD: allergic contact dermatitis Past Chairperson Jordan S. Orange, MD, PhD, FAAP Michael Pistiner, MD, MMSc, FAAP EPA: Environmental Protection Julie Wang, MD, FAAP Agency LIAISON EU: European Union Nicholas V. Nguyen, MD – Section on Early NACDG: North American Contact Career Physicians LIAISONS Dermatitis Group Todd A. Mahr, MD, FAAP – American College Ni-ACD: nickel allergic contact STAFF of Allergy, Asthma, and Immunology dermatitis Paul V. Williams, MD, FAAP – American REACH: Registration, Evaluation, Jennifer Gorlewski, MHA Academy of Allergy, Asthma, and Immunology Authorization, and Re- striction of Chemicals SECTION ON ALLERGY AND IMMUNOLOGY TSCA: Toxic Substances – EXECUTIVE COMMITTEE, 2018 2019 STAFF Control Act Elizabeth C. Matsui, MD, FAAP, Chairperson Debra L. Burrowes, MHA

Address correspondence to Nanette B. Silverberg, MD. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2020 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: Dr Jacob has indicated she is the Past President and is serving her last year on the Executive Director Board of the American Contact Dermatitis Society.

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