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

Nickel Allergic Contact Dermatitis:Identification, Treatment,and PreventionNanette 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

abstractNickel is a ubiquitous metal added to jewelry and metallic substances for itshardening properties and because it is inexpensive. Estimates suggest that at least1.1 million children in the United States are sensitized to nickel. Nickel allergiccontact dermatitis (Ni-ACD) is the most common cutaneous delayed-typehypersensitivity reaction worldwide. The incidence among children tested hasalmost quadrupled over the past 3 decades. The associated morbidities include itch,discomfort, school absence, and reduced quality of life. In adulthood, individualswith Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACDin children has been postulated to result from early and frequent exposure tometals with high amounts of nickel release (eg, as occurs with ear piercing or withproducts used daily in childhood such as toys, belt buckles, and electronics).To reduce exposure to metal sources with high nickel release by prolongedand direct contact with human skin, Denmark and the European Unionlegislated a directive several decades ago with the goal of reducing high nickelrelease and the incidence of Ni-ACD. Since then, there has been a globalreduction in incidence of Ni-ACD in population-based studies of adults andstudies of children and young adults being tested for allergic contactdermatitis. These data point to nickel exposure as a trigger for elicitation ofNi-ACD and, further, provide evidence that legislation can have a favorableeffect on the economic and medical health of a population.This policy statement reviews the epidemiology, history, and appearances ofNi-ACD. Examples of sources of high nickel release are discussed to highlighthow difficult it is to avoid this metal in modern daily lives. Treatments areoutlined, and avoidance strategies are presented. Long-term epidemiologicalinterventions are addressed. Advocacy for smarter nickel use is reviewed. TheAmerican Academy of Pediatrics supports US legislation that advances safetystandards (as modeled by the European Union) that protect children fromearly and prolonged skin exposure to high–nickel-releasing items. Our finalaim for this article is to aid the pediatric community in developing nickel-avoidance strategies on both individual and global levels.

aDepartments of Dermatology and Pediatrics, Mt Sinai Hospital andIcahn School of Medicine at Mt Sinai, New York, New York; bNorthernLight Health, Bangor, Maine; cCollege of Medicine, University of NewEngland, Biddeford, Maine; dDepartment of Dermatology, Loma LindaUniversity, Loma Linda, California; eDepartments of Medicine andPediatrics, University of California, Riverside, California; andfDepartment of Pediatrics, Boston Children’s Hospital and HarvardMedical School, Boston, Massachusetts

Policy statements from the American Academy of Pediatrics benefitfrom expertise and resources of liaisons and internal (AAP) andexternal reviewers. However, policy statements from the AmericanAcademy of Pediatrics may not reflect the views of the liaisons or theorganizations or government agencies that they represent.

Drs Silverberg, Pelletier, Jacob, and Schneider fully participated in theconceptualization, drafting, and revision of this manuscript, and allauthors approved the final manuscript as submitted.

The guidance in this statement does not indicate an exclusive courseof treatment or serve as a standard of medical care. Variations, takinginto account individual circumstances, may be appropriate.

All policy statements from the American Academy of Pediatricsautomatically expire 5 years after publication unless reaffirmed,revised, or retired at or before that time.

This document is copyrighted and is property of the AmericanAcademy of Pediatrics and its Board of Directors. All authors have filedconflict of interest statements with the American Academy ofPediatrics. Any conflicts have been resolved through a processapproved by the Board of Directors. The American Academy ofPediatrics has neither solicited nor accepted any commercialinvolvement in the development of the content of this publication.

DOI: https://doi.org/10.1542/peds.2020-0628

To cite: Silverberg NB, Pelletier JL, Jacob SE, et al. AAPSECTION ON DERMATOLOGY, SECTION ON ALLERGY ANDIMMUNOLOGY. Nickel Allergic Contact Dermatitis:Identification, Treatment, and Prevention. Pediatrics.2020;145(5):e20200628

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INTRODUCTION

Nickel Is a Common CutaneousAllergen

Recent estimates suggest that 1.1million children in the United Statesare potentially sensitized to nickel1;however, this may be a grossunderestimate given that nickelallergic contact dermatitis (Ni-ACD) isfound in approximately one-quarterof children who undergo patchtesting. Nickel is present in metallicitems that are common in children’senvironments, including earrings,watches, toys, and fasteners onclothing and belts. Chronic exposureto nickel increases risk for Ni-ACD.Nickel has become the most commonmetallic cause of allergic dermatitisand was named the “Contact Allergenof the Year” in 2008 by the AmericanContact Dermatitis Society.Determining the presence of Ni-ACDin those with allergic dermatitis canbe difficult and elusive, with patchtesting being a crucial tool used tohelp differentiate Ni-ACD from otherforms of dermatitis.2 The risk of Ni-ACD increases when ears arepierced.3

Nickel Exposures Are Common

Nickel is a ubiquitous metal, being thefifth most common element in theworld. Worldwide use of nickel in theproduction of hardened metal itemshas been increasing since World WarII.4 The process by which nickel useshifted from coins and militarypurposes to daily use products, suchas clothes and electronics, wasstrongly influenced by metal use inthe post–World War II era. Amongadults who were screened inMassachusetts General Hospital from1996 to 2006, Ni-ACD was found in22.1% of those 20 to 40 years of agebut in only 10.1% of those older than60 years, suggesting that Ni-ACD isa problem of younger individuals(those raised or those who had theirears pierced after World War II).5

Today, nickel has continued to bea leading production metal in home

and personal goods. Over time, Ni-ACD evolved from an occupationaleczema of electroplaters to a commonform of allergic contact dermatitis(ACD) among both adults andchildren, currently affecting as manyas 20% of Americans. Historically, Ni-ACD has been linked to a wide rangeof exposures, including suspenders inthe 1950s–1960s; zippers, buttons,and rivets in the 1970s; and earpiercing in the 1980s.4 Environmentalnickel present in oxides and sulfidesis not as allergenic as the free nickelpresent in metal fittings found inindustry.4,6

Nickel Allergy Has SignificantSymptomatology

Virtually any site of the body can beaffected by Ni-ACD, but some of themore commonly affected areas arethe eyelids (transfer from hands),face, neck, wrists, fingers and hands,periumbilical area, and thighs.7

Symptoms and signs of Ni-ACD rangefrom mild dermatitis with pruritus, todeep erythema with oozing andpapulation, to a systemic reactionwith generalized idiopathichypersensitivity.6,7 Although Ni-ACDis a delayed-type hypersensitivity,symptoms can occur within the first30 minutes of exposure througha complex cascade of inflammatorymediators generated aftersensitization.8

KEY POINTS IN THE EVOLUTION OFNICKEL ALLERGY AS A SERIOUSALLERGEN

Introduction of Nickel Into theManufacturing of Metals

Nickel was first identified as anelement in 1751 by a Swiss chemistnamed Axel Cronstedt. In the 1800s,nickel was introduced into themanufacturing of metal alloys withcopper and zinc. As an alloy, its highvalue is related to many inherentqualities: high strength, lengthy life,anticorrosion, heat resistance, lowcost, and minimal maintenance. In themid-1800s, coins in the United States

were alloyed with copper. In the late1800s, steel production acceleratedbecause of the strength of steelproducts. During the 20th century,nickel gained a solid place in industryas part of manufactured stainlesssteel alloy (along with chromate andiron). Today, two-thirds of nickelproduction in the world is devoted tothe manufacture of stainless steel,20% is for other specialized steelalloys (for military and aerospace),9% is for plating, and the remainderis for various uses, includingbatteries, coins, and electronics.9,10

Early Reporting of Nickel Allergy

Weston et al11 first reported Ni-ACDin young pediatric patients in 1984.Until that point, it was unclearwhether cutaneous immune functionin infants was mature enough tomount such responses. After thereport of this phenomenon by Westonet al,11 more attention to allergicreactions in infants and youngchildren made it clear that contactallergy to nickel can begin in infancy,with some authors indicatingincreasing incidence after the age of5 years.12–16 Nickel’s place as a causeof contact dermatitis in pediatricswas solidified by these early reports.

Ni-ACD can cause systemichypersensitivity in children, and thiswas elucidated in 2 articles in 2002.Silverberg et al16 reported a group of30 children with clinical features ofNi-ACD manifested by persistentumbilical or wrist dermatitis. In thatcohort, all children had positiveresults on patch testing for nickel;furthermore, 50% had an idiopathichypersensitivity reaction,a hypersensitivity responsecharacterized by the presence ofinflammatory papules on the extensorsurfaces of the extremities in sites notexposed to nickel.17 A similar articlefrom Sharma et al17 reviewed 38children with periumbilical papulesconsistent with Ni-ACD, all of whomdemonstrated an idiopathicreaction.18 Systemic contact

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dermatitis has been defined as “ageneralized ACD rash from systemicadministration of a drug, chemical, orfood to which the patient previouslyexperienced ACD.” There is no knowngeneral population-based prevalenceof systemic nickel hypersensitivity,neither for kids nor for adults.Strongly positive ($3 papular) nickelpatch test results in these patientssuggest that severe reactionscorrelate with systemic disease.17

Pathophysiology and Genetics ofNickel Allergic Sensitization

Nickel-contact allergy is a delayed-type (type IV) cutaneoushypersensitivity reaction thatdevelops through a biphasic process:an induction phase is followed by anelicitation phase. In the inductionphase, there are repeat exposures tofree nickel that are beyond a minimalthreshold. During this initial phase, anantigen is presented by the skin’sdendritic cells to T cells (T helper 1and T helper 17 cells), which causesthe skin to develop a set of memoryT cells that specifically recognizenickel. During the elicitation phase,there is amplification of the allergythrough subsequent repetitiveexposures that result in themanifestations of ACD.4,6,18

Ni-ACD is influenced bya combination of genetic andenvironmental factors, the latterbeing more important, according toleading experts.4 Filaggrin mutationsare associated with increased Ni-ACDrisk. Another genetic determinantthat may increase risk for Ni-ACD isHLA antigen expression.19,20

Staphylococcal biofilms may promotethe development of Ni-ACD in thesetting of atopic dermatitis.21

Menné and Holm22 showed a twinconcordance rate of 29% in patientswith Ni-ACD, confirmed froma population-based survey. Half of thepediatric patients with severe Ni-ACDwith additional idiopathic reactionshad a parent with Ni-ACD in theSilverberg et al16 cohort, a statistic

that is higher than that in the generalpopulation.

Product Properties That Contributeto Allergenicity

The amount of nickel released to theskin from contact with a metal object(not the presence of nickel)determines the potential for causingNi-ACD. The development of Ni-ACDfrom contact with a nickel-containingobject is promoted in a 3-stepprocess: “1) the nickel in the materialmust be corroded, 2) the resultingnickel compounds must besolubilized, and 3) the nickel ionsmust be absorbed by the skin tocause a reaction.”23,24 Othercontributory factors include the useof products under occlusion (eg,piercing holes) or prolonged contactwith the skin such that sweat mayerode or release nickel (eg, undersideof the thighs against a chair).

Rising Prevalence of Nickel Allergy

The prevalence of nickel allergy inNorth America has increasedsignificantly since the 1980s in bothadults and children. Data onprevalence in the United States arederived from patch testing, that is,epicutaneous allergy testing, whichreveals contact sensitization but notrelevance of the allergy, outcomes,and/or associated disabilities. TheNorth American Contact DermatitisGroup (NACDG) reported that nickelsensitization rates increased steadilybetween 1970 and 2002 in a mixedgroup of adults and children from11% to 16.9%.25 Pediatric-specificdata from Peltonen26 revealeda prevalence of Ni-ACD of 2.5% in1981, and the NACDG series from2001 to 2004 demonstrated 28.3% ofchildren with positive patch testresults were nickel allergic, showingan increase even more substantial inchildhood than in adulthood.27 Oneseries revealed that although not allchildren with Ni-ACD have disablingsymptoms, for those who undergoa patch test series, Ni-ACD representsa common relevant allergen, being

detected in as many as 36.8% ofchildren and adolescents tested andhaving an 80.4% relevance (ie, beingidentified as contributing todermatitis activity).28

Population-based screening onindividuals (including adults)referred for patch testing havehighlighted the pervasive issue of Ni-ACD in the United States. In 1978,a population-based study of 1158people identified 9% of individualswith Ni-ACD,1 and approximately50% of those who were nickel allergichad never sought medical care.26 Ina recent meta-analysis of 5 ACDstudies representing 1507 pediatricsubjects, 22.9% had Ni-ACD.29 Thecurrent estimate of Ni-ACD inchildren with suspected ACD who arepatch tested is 28.3% according tothe NACDG.27

Data from Denmark are the mostrevealing when evaluating EuropeanUnion (EU) nickel directives becauseDenmark introduced the directives in1990, 14 years before widespread EUadoption. The Nickel Directive statesthat “consumer items intended to bein direct and prolonged contact withthe skin were not allowed to releasemore than 0.5 mcg nickel/cm2/week.”This legislation was intended toreduce Ni-ACD but not eliminatedisease. The venture has beensuccessful in reducing Ni-ACD inyoung women with ear piercings whoare patch tested. One particularoutcome has been reduced severity ofreaction on epicutaneous patchtesting to nickel, which suggests lessseverity of disease. On the other hand,because the sale of nickel-ladenagents is not criminalized, sales ofitems with nickel release persist inEurope, especially in outdoor fleamarkets.3,30

Before EU legislation, the percentageof female first-year college studentsin Finland in 1995 with Ni-ACD was39%, suggesting that the rate maycontinue to increase further in theUnited States if no population-based

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restrictions are enacted.29,31,32

Population-based data on true nickelallergy in adolescents derived fromsurvey data in Sweden reported in2008, 7 years after EU legislation wasput into action, revealed that 14.8%of 6095 adolescents polled believedthey had Ni-ACD, with confirmation in9.9%, revealing how EU nickeldirectives may be benefitingadolescents.33 Data from a Danishpediatric contact dermatologydatabase reveal ongoing reduction innickel sensitization, with ACD rates of9.7% in those tested (252 of 2587)from 2003 to 2011 and 7% (107 of1540) from 2012 to 2016 (adjustedodds ratio, 0.69; 95% confidenceinterval, 0.55–0.88). Predominance ofgirls in the Ni-ACD group persisted inthis study, as with previousstudies.33,34

Piercings and Jewelry Are LeadingSources of Nickel Sensitization

Piercings, costume jewelry, watches,belt buckles, and clothing fasteners(grommets, buttons, studs, andtoggles) are leading sources ofepicutaneous nickel sensitization incountries without legislationcontrolling nickel release.6 The same1995 Finnish study of first-yearcollege students revealed thatpiercings in female students wereassociated with a rate of 42% nickelallergy, compared withs 14% forfemale students without piercings.31

A study of 960 girls 8 to 15 years ofage in Sweden (published in 1985)with piercings revealed that 13%were nickel allergic, compared with1% of girls without piercings.23 Inpatch testing of school-aged girls forNi-ACD from 1999 to 2000, older girlswho had piercings before Danishregulations were implemented were 4to 5 times as likely as those who hadpiercings after regulations to beallergic to nickel (17.1% vs 3.9%,respectively). A Norwegian pediatriccontact allergy study of 7- to 12-year-old schoolchildren, published in 1994,identified a rate of 30.8% nickelallergy in children with piercings,

compared with 16.3% in childrenwithout piercings.35,36 Nickel allergyin girls with pierced ears hasdramatically decreased in Denmarkover the last 3 decades since strictnickel-release legislation wasenacted.14 Although piercings havebeen linked to nickel sensitization,occurrence of Ni-ACD is also commonin children without piercings;therefore, reduction of nickel releaseis needed across all costume jewelrytypes.6 A recent review of NACDGdata revealed that of 1894 pediatricpatients who were patch tested,23.7% had nickel contact dermatitisand 36.4% had a pattern of skindisease consistent with all types ofjewelry as the source of the nickel.37

The High Cost of Nickel Allergy in theUnited States

The 2004 estimates in the UnitedStates suggest that contact dermatitis,which includes nickel sensitization,accounted for $1.918 billion in healthcare costs (including direct medicalcosts and lost productivity costs) andaffected 72.29 million people. Giventhat nickel-contact sensitization isnoted in approximately one-quarterof patients, it is likely that nickelallergy contributes heavily to thisburden.24 Recent data from theAmerican Academy of Dermatologyreveal that contact allergy costs morethan $1.5 billion in 2013.38 Given thatnickel allergy is the number oneallergen nationwide in all age groups,nickel allergy is costly.

Other Sources of Nickel-ContactSensitization

Contact with commonplace nickelalloy metallic products, such as toys,can lead to nickel release thatdeposits on a child’s skin.39,40 Ina recent radiograph fluorescencespectroscopy study of US jewelry, 79of 96 samples released nickel.41 Ina case series of children andadolescents from Brazil, the source ofnickel exposure in the setting of Ni-ACD included jewelry piercings; metalclothing appliques on garments,

accessories, and shoes; nail clippers;razor blades; and cosmetics.1 Newernickel sources reported to causedermatitis include devices such asmetallic cell phone cases (a persistentplaque on the hollow of the cheek),laptop cases and handheld devicecases (fingertip, hand, lap, andperiocular dermatitis), makeupapplicators and ferrules (site ofapplication), eye makeup, dog tagnecklaces, and lip balm containers(lip and perioral).42–48 Table 1contains a brief compendium of itemsof daily use linked to nickel exposureand allergy.4,6 Many of these newernickel sources are more difficult todiagnose because the site of allergycan be areas not in direct contact, forexample, the eyes.43 The timing andtype of nickel exposures throughoutlife are important. Ni-ACD was shownto be much less common when earpiercing occurred after placement ofmetal dental braces, compared withwhen piercing occurred beforeexposure to braces. So, less nickelsensitization may occur if placementof braces occurs first and piercinglater.44 This phenomenon may beanalogous to the enteral tolerancethat develops to lessen peanut allergyand may be akin to reasoningforwarded by the Learning EarlyAbout Peanut Allergy study.49

THE CLINICAL APPEARANCE OF NICKELCONTACT DERMATITIS IS PROTEAN

Ni-ACD commonly is diagnosed onthe basis of the appearance of itchy,persistent, erythematous, and/orlichenified papules and plaques thatappear to conform to the areamatching the exposure pattern of themetal object with the skin, forexample, a circular erythematousplaque on the extensor wrist at thesite of exposure to the backside of thewristwatch. Ni-ACD can also becaused by a child playing witha nickel-releasing object and thentransferring the nickel to othersites.1,45,46 Ni-ACD has also beendescribed with nail polish from

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a bottle with nickel metal ballsincluded.47 This itchy rash is oftendiffuse and can occur on other lesscommon areas, such as the scalp andeyelids.

Other jewelry-related patterns ofappearance include a plaque over theupper back at the site of a necklaceclasp pressed against the skin,periumbilical plaques at the site ofbelt buckle or button fly skin contact,midback plaques where bra hookspress against the skin, and earringplaques and/or nodules at the site ofpiercing because of exposure tohigh–nickel-releasing earringposts.16,17,48 Dental amalgams arerarely high nickel releasing, but theystill can cause oral lesions such aspersistent oral lichenoid reactionsnear the amalgam, anestheticsensation, and/or systemic lesions.52

When the source of nickel shiftsagainst the skin, (eg, chair nail heads,belt buckles, and coins in the pocket),the contact dermatitis may be morepapular and/or diffuse, making thesource less obvious. Furthermore,patients with atopic dermatitis mayhave background disease activity thatprevents the margins of the Ni-ACDfrom being clearlydistinguished.4,16,17,53 In adults,nickel has been identified as a contactallergen that can worsenpalmoplantar or scalp psoriasis.54

Idiopathic reactions, or diffusehypersensitivity reactions, to nickelcan occur. These may be associatedwith dietary or complementarysupplements as the source of nickelingestion,55 creating generalizedpruritus and exacerbating pruritus atthe site of cutaneous nickel exposure,or they may come from a generalizedidiopathic hypersensitivity reactiontriggered by ongoing cutaneousexposures (a type of systemic contactdermatitis), the latter of which ismanifested by extensor papules andlichenoid (flat-topped) papules andplaques over extensor surfaces.Idiopathic reactions (also calleddermatophytid) are similar to thoseseen in some patients with tineacapitis when starting oral griseofulvintherapy.4,6

Dental amalgams, caps, and bracesthat contain or release nickel inhigher concentration are associatedwith perioral Ni-ACD as well as Ni-ACD in eccentric sites such as ears,the waist, and wrists. Ni-ACD mayprecede or be caused by dentaldevices containing nickel.Furthermore, such Ni-ACD can beassociated with lip swelling anda burning oral sensation.52,56–58

Although most allergic reactions tonickel are of a type IV delayed-typehypersensitivity, rare reports haveappeared in the literature ofindividuals with systemic nickelhypersensitivity of a type I orimmediate-type hypersensitivity.Other types of allergic reactions tonickel may occur after oral nickelexposure, causing symptoms as minoras flares of earlier nickel-allergiceczema sites, to a generalizedmaculopapular or vasculitislike rash,to more severe symptoms, includingurticaria, headache malaise, diarrhea,fever, and arthralgia.59,60 Skin pricktesting has been performed in rarecases but remainscontroversial.52,59,60 It is still mostlikely, even in such settings, that thereaction to nickel is a delayed-typehypersensitivity because rapid

TABLE 1 Sources of Nickel Exposure inChildren

Sources

ArtworkWhite metal statues

Cleaners and detergentsSteel wool

CoinsCookingPansPotsStainless steel cookware used to cook acidic

foodsUtensils (eg, silverware, spatula, and tongs)

ElectronicsBatteriesCell phone cases and electric shaversa

Mobile phonesa

Laptopsa

Tabletsa

Foods (Mislankar and Zirwas50 and Sharma51)Especially canned foodSeafoodBeansChocolate

FurnitureBrushed-metal furnitureMetal fittings and studs

GroomingNail clippersRazors

Hair clipsBobby pinsMetal brushesCurling irons

ImplantsCardiacDentalOrthopedic

KeysMakeupEyelash curlersFerrulesLip balm containers

Musical instrumentsHornsWind instrument mouthpieces

OccupationalMetal workersMinersHospital cleaning staff

OrnamentationAccessoriesBall and chain necklacesa

Belt buckles and/or beltsa

Button fliesa

GlassesGrommetsJewelry (costume, white gold, and low-karat

gold)a

Earringsa

Necklacesa

Ringsa

Watchesa

TABLE 1 Continued

Sources

OverallsRivetsSnapsZippers

ScissorsToolsToys

Adapted from Jacob SE, Goldenberg A, Pelletier JL,Fonacier LS, Usatine R, Silverberg N. Nickel allergy andour children’s health: a review of indexed cases anda view of future prevention. Pediatr Dermatol. 2015;32(6):779–78 and Tuchman M, Silverberg JI, Jacob SE, Silver-berg N. Nickel contact dermatitis in children. Clin Der-matol. 2015;33(3):320–326.a The most commonly identified nickel-allergy sources inclinical practice.

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reactions as fast as 10 to 30 minutescan be described in Ni-ACD delayedtype.61 The data on these cases areextremely limited, and norecommendation can be made untiladditional broad-based populationdata become available for testing.

OVERLAP WITH ATOPIC DERMATITIS

The NACDG demonstrated that 34%of children with a positive contactallergy result on testing hadconcurrent atopic dermatitis.62 Inchildren with atopic dermatitis, Ni-ACD can trigger severe exacerbationsof pruritus.6 In the setting of atopicdermatitis, Ni-ACD overlap isassociated with more extensive atopicdermatitis and greater difficulty indiagnosing Ni-ACD.7 Because thebackground population data on nickelallergy does not differ in prevalence,Ni-ACD can only be viewed as anaggravating or obscuring factor andnot necessarily as a cause of disease.

MANAGEMENT OF NI-ACD

The broad goals of medical therapy inNi-ACD are as follows:

1. identification and avoidance ofnickel;

2. treatment of skin inflammation;and

3. restoration of the skin barrier andskin protection.

Identification and Avoidance ofNickel

Identifying sources of nickel requiresinvestigation of personal adornments,hobbies (eg, instruments played), andjobs (eg, leisure-time activities andreview of everyday device usage).Patients should be asked aboutgarments or uniforms worn at workor school. Avoidance of nickel can beenhanced through testing objects fornickel content (see Avoidance ofNickel Exposure in Childhoodsection). Using Table 1 as a guide,pediatricians can ask patientstargeted questions to determine

nickel sources hidden in dailyactivities.

One of the hallmarks of good clinicalcare in ACD is education on how toavoid allergen-laden goods. Such isthe case in Ni-ACD. Patients with Ni-ACD can be counseled to recognizeobjects that may be high-releasenickel, to test such objects, and toprotect the skin from prolonged anddirect contact with the objects.Table 2 is a handout that can be usedto help educate parents and childrenand adolescents about nickelavoidance. In general, piercing withnickel-free earrings can minimize riskof Ni-ACD, as can use of low-releasenickel, but the latter still results insome release of nickel. Sterling silver(which is 92.5% pure silver), 18-karatyellow gold (which is 75% gold) ormore-pure gold, platinum, titanium,and plastic earrings are alternativesthat have low or no nickel content.Silver that is not sterling, such asnickel silver, 800 silver (80% silver),and German silver (which contains nosilver at all; an alloy of nickel andzinc), are not ideal for the patientwith Ni-ACD.

Treatment of Skin Inflammation

Inflammatory symptoms, includingeczematous changes and pruritus, arethe main symptoms of Ni-ACD–inducedinflammation. There is no US Foodand Drug Administration–approvedtherapy for Ni-ACD; however, Ni-ACDis a steroid-responsive dermatosis,and therefore topical corticosteroidsmay be helpful in conjunction withprevention of retriggering ofdermatitis through avoidance ofsuspected sources of nickel exposureand with therapeutics to aid inpruritus or itch reduction. Although nospecific regimen of topicalcorticosteroids has been endorsed byany organization for Ni-ACD, theAmerican Academy of Pediatricsrecommends choosing thecorticosteroid class on the basis of thesite of application and severity. Like inatopic dermatitis, off-label use oftopical calcineurin inhibitors (eg,pimecrolimus and tacrolimus) can beeffective in steroid-resistant Ni-ACDcases.63,64 These topical therapies areused in combination with nickelavoidance, which is the cornerstone oftreatment of Ni-ACD. Prevention is

TABLE 2 Handout for Patients

Nickel is a metal that is added to many metal objects to harden them. Nickel can be found in almost allcostume jewelry (including earrings, necklaces, watch backs, rings, and bracelets), some beltbuckles, and such jewelry as ball and chain necklaces, dog tags, metal tabs, grommets, and buttonflies.

When you sweat, the nickel is released from the metal, even if it is only a small amount or percentage ofthe metal. Stainless steel is a stronger white metal and does not release nickel as easily.

If you are allergic to nickel, your rash will keep returning until you avoid nickel completely. There aremany steps required to avoid nickel completely. It is not easy, but it is necessary to make you feelbetter.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.2. For metal that you cannot remove, such as grommets on the side pockets of your jeans or the back

of your watch, coat with 2 coats of clear nail polish every week or after washings.3. Avoid sitting in shorts on metal chairs or plastic chairs with metal tabs.4. Do not cook acidic foods in stainless steel cookware. Avoid stainless steel cookware if you can.5. Tucking in your shirt does not prevent you from reacting to the nickel in your belt buckle or button

fly.6. Avoid ear piercing, especially if dental work, such as braces, is expected.7. Sources of nickel in jewelry include costume jewelry, including earring posts that are not stainless

steel, white gold, and all low-karat gold jewelry. Sterling silver and high-karat yellow gold jewelryare expected to have a low content of nickel but are not generally nickel free.

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.delasco.com/spot-test-for-nickel/. More information can be found at https://athenaallergy.com/pages/how-to-test-for-nickel-using-nickel-alert-dimethylglyoxime-test.

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paramount because there is no curefor Ni-ACD and because the diseaseis lifelong.65 In recalcitrant cases orin the setting of severe Ni-ACD andsevere pruritus or for those withwidespread lesions, oral steroidsfor several days and then tapered,together with antihistamines forpruritus, can aid in symptomaticresolution.66

Restoration of the Skin Barrier andSkin Protection

Emollients can be used to enhancethe skin barrier in children withatopic dermatitis and may benefitchildren with Ni-ACD and concurrentdermatitis symptoms. Skin protectioncan be achieved through thickphysical blockage of nickel-containingmetal objects, for example, cell phonecases, backing button flies in denim,or replacing metal buttons withplastic buttons. Thin fabrics andstrategies such as tucking in one’sshirt may not be fully protective.4,53

Confirmation of Suspected Ni-ACD

When a typical pattern of Ni-ACDappears on the wrist or periumbilicalregion, no confirmatory testing isneeded.16,17,67 In some cases in whichsuspicion is harder to confirm, patchtesting, otherwise known asepicutaneous skin testing, is a form oftesting in which a dilute version ofthe allergen is placed ina hypoallergenic well (sometimescalled a Finn chamber) and applied tothe back. Contact time with the skinof the upper back or inner upperarms is up to 48 hours. After thisperiod, the patches are removed, andthe test results are read. The patchesare read again at a delayed pointbetween 72 and 120 hours afterplacement. Interpretation of results isbased on the appearance of rednessand/or papules and/or a plaque inthe shape of the chamber. Papular($3 severity) reactions at the site oftesting are common in nickel allergyin children, and they can beassociated with idiopathic systemichypersensitivity. If the testing result

is negative but clinical historysupports Ni-ACD, a late readingshould be considered 7 to 10 daysafter the patch test application. Thereis a US Food and DrugAdministration–approved series of 36patches (T.R.U.E. Test; SmartPractice,Phoenix, AZ) that contains nickel at200 mg/cm2 nickel sulfate, whichcorresponds to 160 mg of nickel perpatch. In pediatrics, standardizedcomprehensive patch testing is oftencustom tailored by history, andtesting is performed with nickelsulfate hexahydrate 2.5% inpetrolatum, as would be found in theAmerican Contact Dermatitis SocietyCore series.4,53 Broad-metal contactallergy screening should beperformed when multiple metals aresuspected as the potential source ofcontact dermatitis. This screening canbe accomplished by using anepicutaneous metal contact allergypanel containing nickel, gold,titanium, copper, cobalt, zinc, andmore than a dozen other metals.

Although children with obvious nickelallergy usually do not needconfirmatory patch testing for nickel,they may need testing for other metalallergens when metal appliances fordental work or implants areneeded.68,69 In particular, the Nussprocedure, which is a placement ofmetal rods for the repair of pectusexcavatum, has been associated withcomplications in patients with metalallergy, especially to nickel.Consequences include extensivegranulation tissue formation,localized edema, dermatitis,lymphadenopathy, pleural effusion,and inflammation and/or infection,which may require removal ofstainless steel rods in some cases.70,71

Because of the potentialconsequences of undiagnosed Ni-ACDin such patients, surgeons performingthe procedure often refer patients forpatch testing to nickel and othermetals before the procedure.72

Stainless steel discs provided by themanufacturer are suboptimal to

screen for metal allergy and Ni-ACDin this setting; it is more prudent toproceed with patch testing by usingthe extended metal series.73 Titaniumbars can be used safely in patientswith Ni-ACD if they are identifiedbefore surgery as having nopreviously reported allergic events.70

PREVENTION OF NI-ACD

Avoidance of Nickel Exposure inChildhood

Ni-ACD is a threat to pediatric publichealth that persists as a problematicskin disease into adulthood. Ni-ACD isthe most common cutaneous allergyand involves lifelong hazards that canaffect people’s lives both personallyand professionally.74 Commoncutaneous nickel-containing itemsinclude earring posts, belt buckles,jewelry, zippers, snaps, clasps,grommets, electronics, coins, keys,paper clips, chairs, braces, andimplants.2,24,45,75–77 To reduce therisk and severity of Ni-ACD,avoidance of skin contact with nickelis critical. According to Europeanreports, earrings appear to be themost common source of elicitation ofNi-ACD, providing credence to takepreventive and economic measures.The United States should heed theEuropean lead to reduce nickelrelease from common contacts inchildren to serve and protectpopulation health. Using the handoutin Table 2, parents can identifysources of high-release nickel in theirchildren’s lives. The purchase of itemswith no nickel or with a low release ofnickel can be guided by the use of thedimethylglyoxime test, whichindicates a pink or red color onexposure to a nickel-releasingmetallic item. Currently, because ofthe lack of labeling of low–nickel-release or nickel-free metal items,parents can screen metal objects fornickel release using such test kits,which can be purchased on medicalWeb sites (eg, https://www.delasco.com/spot-test-for-nickel/ and

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https://athenaallergy.com/pages/how-to-test-for-nickel-using-nickel-alert-dimethylglyoxime-test).78

However, it would be more ideal iflabeling of low–nickel-release ornickel-free items was available forparents.

Reduction in Dietary Nickel Exposure

Withdrawal diets in children cannotbe recommended because ofinadequate pediatric data and risk ofmalnutrition with a limiteddiet.50,79,80 Data on the use of low-nickel diets in children arelacking.51,81,82

Advocacy

Ni-ACD represents a significant andpreventable pediatric public healthburden. Regulation of nickel releasein materials that comes in contactwith skin can decrease both the highpediatric prevalence and treatmentcosts of the disease. There is a call inthe United States for such regulation2

given the high number of childrenaffected by this disease. TheAmerican Academy of Dermatologyhas recently accepted a proposal insupport of reduced nickel release inmanufacturing.82 Adoption oflegislation similar to that in the EU bythe US Congress would representa promise for prevention by startingto reduce the nickel-related healthburden.

A REVIEW OF EU POLICY

Nickel is ubiquitous, and people areexposed to it primarily via metalobjects throughout their lifetimes.Preventive models of safer exposures,or those less likely to trigger Ni-ACD,have been demonstrated by othercountries to be medically andeconomically beneficial. The EUNickel Directive of 1994 (approvedJune 30, 1994, and in full effect June2001) regulated the method formeasuring nickel release onto humanskin and established regulations fornickel allowed to be released ontoexposed skin over time, including for

watches, buttons, zippers, and nowmobile phone cases.83 The EUdirective was born from the originalwork in Denmark, where the NickelDirective was designed to limit themaximum release of nickel in contactwith human skin to an amount lessthan 0.2 µg/cm2 per week for postsinserted into pierced skin and notmore than 0.5 µg/cm2 per week forproducts with prolonged and directskin contact.83,84 The Europeanstandard EN 1811:20111A1:2015 isa standardized testing system that isapproved by the EU to measure thepotential amount of nickel releaseunder the conditions of direct andprolonged contact with the skin.Articles, such as those used forearrings in children, should notrelease nickel more than 0.2 mg/cm2

per week (by EN 1811 testing) toprevent children from becomingallergic to nickel or havinga dermatitis reaction if they arealready allergic to nickel. This nickel-release rate is for the parts ofearrings that are in contact with theskin and within the pierced part ofthe ear.4,83 Germany and Swedenjoined in the legislation andeventually Korea and China did aswell.83

Because the rate of release of nickel(and not nickel content itself) isimportant and relevant indetermining whether there is a riskfor Ni-ACD, articles may containnickel but not cause a dermatitisreaction. For example, surgicalstainless steel (grade 316L), whichcontains 10% to 15% nickel and doesnot release nickel more than 0.2 mg/cm2 per week (by using EN 1811testing), is therefore regarded asappropriate for use in articles indirect and prolonged contact with theskin. The American Section of theInternational Association for TestingMaterials Standard Consumer SafetySpecification for Adult Jewelry(designation: F2999-13) lists surgicalstainless steel (typically containing10%–15% nickel) as one of the

“approved materials for adult body-piercing jewelry.”4,84,85

The effect of the Danish decree wasa drastic decrease in pediatric nickelsensitization from 24.8% to 9.2%.85

Reduction in Ni-ACD after Denmark’sNickel Directive resulted in costsavings that grew to more than $2billion (US dollars) over the 2decades after implementation.4 TheEU followed the commanding lead ofthe Danish dermatologists whoworked with the Danish ministry toadvance this innovative healthdirective. In 2006, the NickelDirective was incorporated into theEU regulation of toxins, which iscalled Registration, Evaluation,Authorization, and Restriction ofChemicals (REACH).84 After thisregulation, there was a significantreduction of Ni-ACD in patientsyounger than 30 years studied inEuropean countries.83 Nationaldatabases involving 180 390 patientswith suspected ACD reveal anapproximately 10% reduction in Ni-ACD in young women, specificallyfrom the following 4 countries, in theyears 1985–2010: Denmark,Germany, Italy, and the UnitedKingdom (2004–2010 only).

REACH is a complex bill that outlinesindustry obligations regarding 30 000chemicals. REACH is far more“reaching” than is the US counterpart,the Toxic Substances Control Act(TSCA) of 1975,86 which regulateschemicals but does not differentiatetoxic from nontoxic chemicals. TheTSCA was supplanted by the ChemicalSafety for the 21st Century Act,introduced in the Senate in 2015 andpassed in the House ofRepresentatives in May 2016.Although the TSCA required theEnvironmental Protection Agency(EPA) to consider least burdensomechemical regulations for industry, theChemical Safety for the 21st CenturyAct tasks the EPA to focus onunreasonable risk to human healthand the environment; however,unfortunately, this may not apply to

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jewelry and cosmetics.86–88 Althoughthe EPA acknowledges the hazards ofnickel as a cause of ACD, no currentruling restricts nickel exposures inchildhood; however, this regulatoryfoundation has room to act to reducerisk for Ni-ACD in children.86–89 TheUnited States stands to improvecollective health status and lowerrelated medical costs if it were tofollow Denmark’s lead and the EUmodel in protecting the public fromthe hazards of high nickel exposure.

Stakeholders may note that thenonprofit organization NickelProducers Environmental ResearchAssociation does support theelimination of high-release nickelalloys and plating used in productswith dermal contact such as jewelryand electronics.7,90 US legislatorsshould advance evidenced-basedpolicies to adopt a twofold guideline:(1) adoption of the EU guidelines onnickel release in manufacturing and(2) adoption of a policy to avoidusage of nickel in plating inhousehold electronic devices. If theUnited States can incorporate safetydirectives and soundrecommendations regarding nickelproduction and usage, as has beendone in the EU, then the populationcan achieve significant reductions inNi-ACD in the next 2 to 3 decades.

RECOMMENDATIONS

The following are recommended toreduce the US pediatric burden of Ni-ACD:

1. To minimize nickel-induced ACDin children, use of nickel in themanufacture of items that havedirect or prolonged contact withthe skin (eg, jewelry, electronicdevices, toys, etc) should belimited. Regulations similar to theEU Nickel Directive that limit theweekly allowable release of nickelto less than 0.5 µg/cm2/weekshould be adopted.

2. Additional safety and toxicitystudies are needed to better

understand the complexrelationship between nickelexposure and population health.

3. Companies and industries usingmetal in products shouldvoluntarily create labeling forlow–nickel-release products andWeb-based resources to identifythose items in the United Statesthat follow EU legislationguidelines, allowing individualswho are nickel allergic to shopmore wisely. Ideally, thedevelopment of trustableresources for those with Ni-ACDcan be met through physician andindustry partnership to developeducational resources about nickelallergy that can be easilyunderstood and accessed bychildren, parents, and teachers.

4. Physicians and other health careproviders can support thereduction of Ni-ACD byencouraging parents to requestthat posts for piercings in theirchildren’s ears be made ofsurgical-grade steel with lownickel release, per EU standards. Itis recommended that allindividuals who perform piercingservices mention Ni-ACD asa potential complication ofpiercing.

5. Nickel allergy can be genetic;therefore, physicians and otherproviders should considereducating at-risk groups to avoidnickel-based body piercings. Thereis further genetic reason to believethat children from families witha history of Ni-ACD would benefitfrom reduced exposure inchildhood through the universaluse of low–nickel-releasingjewelry.

6. It is likely that most childrenwould benefit from lowerexposure to such contact, even inthe absence of family history of Ni-ACD, because such family historyis only present in approximatelyhalf of cases of documenteddisease.

7. If orthodontic metal braces areanticipated, families shouldconsider delaying ear piercinguntil after dental work iscompleted.

8. Until such legislation can bepassed, voluntary manufacturerreduction of nickel-releasing metalin children’s clothing and closecontacts, including grommets,button flies, belt buckles, schoolchairs, and tables, aimed for use bychildren would reduce Ni-ACDdisease burden. Reporting ofvoluntary reduction on labels andon public Web sites would helpparents of children andadolescents with Ni-ACD identifyhypoallergenic metal objects,further enhancing reduction ofdisease symptomatology andburden.

CONCLUSIONS

Ni-ACD is a common chronicdermatitis with detrimental effects onchildren now and as they progressinto adulthood. The burden ofsymptoms and cost is high. TheUnited States can act on EU datarevealing that legislation to limitexposures in childhood, especiallywith earrings, can impact theprevalence and potentially theseverity of disease. Until and even iflegislation is available, pediatricianscan help patients by identifying theallergy early and intervening witha plan of prevention and care ofdisease.

LEAD AUTHORS

Nanette B. Silverberg, MD, FAAP, FAADJanice L. Pelletier, MD, FAAPSharon E. Jacob, MD, FAAP, FAADLynda C. Schneider, MD, FAAP

SECTION ON DERMATOLOGY EXECUTIVECOMMITTEE, 2018–2019

Bernard Cohen, MD, FAAPKimberly A. Horii, MD, FAAP, ChairpersonLeonard Kristal, MD, FAAPSheilagh M. Maguiness, MD, FAAPMegha Mathakia Tollefson, MD, FAAP

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Miriam G. Weinstein, MD, FRCPC, FAAPTeresa S. Wright, MD, FAAPAlbert C. Yan, MD, FAAD, FAAP, ImmediatePast Chairperson

LIAISON

Nicholas V. Nguyen, MD – Section on EarlyCareer Physicians

STAFF

Jennifer Gorlewski, MHA

SECTION ON ALLERGY AND IMMUNOLOGYEXECUTIVE COMMITTEE, 2018–2019

Elizabeth C. Matsui, MD, FAAP, Chairperson

John A. Bird, MD, FAAPCarla McGuire Davis, MD, FAAPVivian Pilar Hernandez-Trujillo, MD, FAAPJordan S. Orange, MD, PhD, FAAPMichael Pistiner, MD, MMSc, FAAPJulie Wang, MD, FAAP

LIAISONS

Todd A. Mahr, MD, FAAP – American Collegeof Allergy, Asthma, and ImmunologyPaul V. Williams, MD, FAAP – AmericanAcademy of Allergy, Asthma, and Immunology

STAFF

Debra L. Burrowes, MHA

ABBREVIATIONS

ACD: allergic contact dermatitisEPA: Environmental Protection

AgencyEU: European UnionNACDG: North American Contact

Dermatitis GroupNi-ACD: nickel allergic contact

dermatitisREACH: Registration, Evaluation,

Authorization, and Re-striction of Chemicals

TSCA: Toxic SubstancesControl Act

Address correspondence to Nanette B. Silverberg, MD. E-mail: nanette.silverberg@mountsinai.org

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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