Allergic contact dermatitis caused by titanium screws and dental implants

Case

Report

Allergic

contact

dermatitis

caused

by

titanium

screws

and

dental

implants

Maki

Hosoki

DDS,

PhD

,

Keisuke

Nishigawa

DDS,

PhD

,

Youji

Miyamoto

DDS,

PhD

,

Go

Ohe

DDS,

PhD

,

Yoshizo

Matsuka

DDS,

PhD

*

a_{DepartmentofStomatognathicFunctionandOcclusalReconstruction,InstituteofBiomedicalSciences,Tokushima}

UniversityGraduateSchool,Tokushima,Japan

b_{DepartmentofOralSurgery,InstituteofHealthBiosciences,TokushimaUniversityGraduateSchool,Tokushima,}

Japan

1.

Introduction

AnincreaseintheprevalenceofallergicdiseasesinJapanhas

beenreportedrecently[1–3].Thatis,3–4%ofthepopulation

hasthesymptomsofasthma,30%sufferfromallergicrhinitis,

and20%juniorhighschoolstudentshaveatopicdermatitis.In

general,allergicdiseaseisbenign,butthequalityoflifecan

decrease remarkably.Itisnotanoverstatementtosaythat

preventionofallergicdiseaseisapublic-healthissue.

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Articlehistory:

Received12August2015

Receivedinrevisedform

28November2015

Accepted10December2015

Availableonline8January2016

Keywords: Titanium Dentalimplants Metalallergy Patchtesting Orthopedicsurgery

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Patients: Titaniumhasbeenconsideredtobeanon-allergenicmaterial.However,several

studieshavereportedcasesofmetalallergycausedbytitanium-containingmaterials.We

describe a 69-year-old male for whom significant pathologic findings around dental

implantshadneverbeenobserved.Heexhibitedallergicsymptoms(eczema)after

ortho-pedicsurgery.Thetitaniumscrewsusedintheorthopedicsurgerythatheunderwentwere

removed 1yearlater, buttheeczemaremained.Afterremoval ofdentalimplants,the

eczemadisappearedcompletely.

Discussion: Titaniumisusednotonlyformedicalapplicationssuchasplasticsurgeryand/or

dentalimplants,butalsoforpaints,whitepigments,photocatalysts,andvarioustypesof

everydaygoods.Mostoftheusageoftitaniumisintheformoftitaniumdioxide.Thisrapid

expansionoftitanium-containingproductshasincreasedpercutaneousandpermucosal

exposureoftitaniumtothepopulation.

Conclusions: Ingeneral,allergicriskoftitaniummaterialissmallerthanthatofothermetal

materials.However,wesuggestthatpre-implantpatientsshouldbeaskedaboutahistoryof

hypersensitivityreactionstometals,andpatchtestingshouldberecommendedtopatients

whohaveexperiencedsuchreactions.

#_{2016JapanProsthodonticSociety.PublishedbyElsevierLtd.Thisisanopenaccessarticle}

undertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

*Corresponding author at:Department of StomatognathicFunctionandOcclusal Reconstruction,Institute ofBiomedicalSciences,

TokushimaUniversityGraduateSchool,3-18-15Kuramoto-cho,Tokushima770-8504,Japan.Tel.:+81886337350;fax:+81886337391.

E-mailaddress:matsuka@tokushima-u.ac.jp(Y.Matsuka).

Available

online

at

www.sciencedirect.com

ScienceDirect

journalhomepage:www.elsevier.com/locate/jpor

http://dx.doi.org/10.1016/j.jpor.2015.12.004

1883-1958/#2016JapanProsthodonticSociety.PublishedbyElsevierLtd.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense

Varioustypesofmetallicandorganicmaterialshavebeen

usedfordentalprostheses.Someofthesematerialshavebeen

reportedtohavepro-allergenicproperties.Ourresearchteam

has been engaged in the treatment of patients allergic to

dentalmaterials.Wehavereportedontheclinicalsurveillance

ofdental allergic hypersensitivity at Tokushima University

DentalHospital(Tokushima,Japan)andevaluatedtheextent

andseverityofadversereactionstodentalmaterialsamong

thesepatients[4].Allergicsymptomsfromthesematerialsare

notrestrictedtothemouth;theyarealsofoundonthehands,

legs and all the skin on the body [4–7]. Mercury, nickel,

chromium,palladiumandcobaltareclassicallergens[8–12].

Titaniumisknowntopossessgoodbiocompatibility[13,14],

soseveralproductscontainingtitanium havebeen usedin

plasticsurgeryanddentalimplants.However,recentstudies

havereportedcasesofallergicsymptomscausedby

titanium-based materials. The amount of titanium in products has

increased with advances in smelting technology, thereby

providingmoreopportunitiesforhumanstobesensitizedto

thismetal.Thomasetal.reportedapatientwhodeveloped

eczemaupontitanium-basedosteosynthesis[15].Egusaetal.

reportedfacialeczemainassociationwithatitaniumdental

implant [16]. In their review, Siddiqi et al. suggested that

titaniumcaninducehypersensitivityinsusceptiblepatients,

andcouldplayacriticalpartinimplantfailure[17].Whether

dental materials comprising titanium are associated with

allergicsymptomsiscontroversial.

Here,wedescribeapatientwhohaddentalimplantsand

exhibited allergic symptoms after undergoing orthopedic

surgery. Thedental implant was functioning satisfactorily,

butallergicsymptoms(eczema)wereshown.Moreover,patch

testsrevealedpositivereactionstomanyreagents(including

titanium).

2.

Outline

of

the

case

A 69-year-old male who had never experienced allergic

symptoms apart from rhinitis and a reaction to leather

productsisdescribed.Hehadnohistoryof

contact-hypersen-sitivity reactions to metals. In 2008, he had two dental

implants using Fixture MicroThreadTM _{(Astra Tech Dental,}

Mo¨lndal,Sweden)andhaddisplayedgoodprogress.

In2010,hehadafractureofalowerlimbandunderwent

open reduction with titanium screws. Six months later,

nummulareczemadevelopedovertheskinsurface.Hewas

prescribedhistamine H1 antagonists,sodiumcromoglycate,

ascorbicacid,andcalciumpantothenate,buttheeczemadid

notimprove.Apatchtestat adermatologyclinicinOsaka

UniversityHospital(Osaka,Japan)revealedanallergy-positive

reactiontocobalt,tin,palladium,indium,andiridium,butalso

demonstratedafalse-positivereactiontocopperand

titani-um.Titaniumscrewswereplannedtoberemoved1-yearlater,

so medication and follow-up of allergic symptoms were

appliedatthattime.

In 2011, the titanium screws were removed from the

patient’slimbbytheplasticsurgeon.Aftertheneczemawas

recovered,butwasstillremained50%levelofthecondition

beforeremovingscrew.Sothedermatologistsuspecteddental

metal allergy and the patient for the previous dentist to

remove all metal prosthesis. After removing all metal

prosthesis exceptfordental implant andits abutment,the

patient’seczemawasrecovered30%levelbeforeremovingit,

butstillnotexhibitedcompleterecovery.

In2013,thepatientwasreferredtoourdentalmetalallergy

clinic. Fig. 1 shows a panoramic dental radiograph of the

patientathisfirstvisit.Thetwodentalimplantswereinthe

right mandibular molar area. No metallic restoration was

foundinthemouthapartfromtheabutmentsofthedental

implants.Significantpathologicfindingsaroundtheimplants

werenotobserved(Fig.2).Theseimplantsdidnotexhibitany

signofperi-implantitisand/ormechanicalproblemssuchas

loose screwandsuperstructurefracture.Radiograph

exami-nationdidnotfindanyimagesofboneresorptionaroundthe

implantfixture.Theimplantsandabutmentsweremadewith

pure titanium (ASTM F-67, grade 4 (N20.05, C20.08,

H20.013,Fe20.5)).Atemporaryacryliccrownwasattached

ontothemaxillaryandmandibularrightmolars.Atemporary

acryliccrownwasplacedontheabutments.

We altered temporary cement from poly carboxylate

cement that contains allergy positivezinc componentsfor

zincfreeglassionomercement.After4-monthfollow-upwith

anti-allergic medicationsby the dermatologist, the eczema

remained. Patch testing with 17 patch-test metal reagents

(Patch Test Reagents; Torii Pharmaceutical Corporation,

Tokyo,Japan)and11custom-madereagentswasundertaken

atourclinic.Thesereagentswereattachedtotheskinonthe

back with an adhesive plaster (Patch Tester Torii; Torii

PharmaceuticalCorporation).Reactionstothetestwereread

accordingtocriteriasetbytheInternationalContact

Derma-titisResearchGroupatD2,D3andD7afterapplication.

Atthattime,hedemonstratedanallergy-positivereaction

againstcobalt,tin,palladium,indiumandiridium(thesameas

inthe previouspatchtest).Moreover, titanium,gold,

plati-num,zincandironalsoelicitedanallergy-positivereaction

(Table1)(Fig.3).

From these results in April 2014, the abutments were

removed.Onemonthafterremovingimplantabutment,the

patient didnotexhibited remarkableprogress. Thepatient

keptmedicationfromthedermatologistduringthisperiod.In

May2014,the dentalimplantfixtureswereremovedat the

Department of Oral Surgery within Tokushima University

Hospital.Animplant-retrievaltool(NobelBiocareUSA,Yorba

Fig.1–Panoramicdentalradiographofthepatientathis

initialvisit.

journalofprosthodonticresearch 60(2016) 213–219

214

Linda, CA, USA) that enabled a less invasive effect in

peripheral bone during removal of the osseointegrated

implantwasused(Figs.4and5).Implant-retrievaltoolwas

connectedinsidethreadgroovesoftheimplantfixture.Then

oral surgeon applied implant reverse torque with hand

wrench. This instrument did not give implant fixture any

destructiveaffectduringremoving.Afterremovingintraoral

metallicrestorations,allergicsymptomssometimesdevelop

Fig.2–(a)–(c)Intraoralphotographsattheinitialvisit.

Fig.3–Resultsofpatchtests.(a)Upperbackbeforepatchtesting.(b)Resultofpatchtestingat48h.(c)Resultofpatchtesting

moreseverebeforeremoving.Thiscounterallergicreaction

seemstobecausedbycutting dustofmetallic restoration.

Since chance of additional titanium contamination was

minimumduringthisremovingprocedure,allergicsymptoms

ofthispatientdidnotexhibitsuchimmediatereaction.The

extentofthe eczema reducedrapidly.One month later,he

stopped taking medication and the eczema disappeared

completely. Figs.6and7showahypogastric skincondition

before and 2 months after removal of the dental implant

fixtures. After 2-months follow-up, the patients underwent

finalprosthetictreatmentwithzirconiafullveneercrownand

metalfreeremovabledenture.Fig.8showsintraoral

photo-graphsofthepatientafterprosthetictreatment.Fig.9showsthe

Table1–Patchtesting.

Metal-based allergen % Vehicle D2 D3 D7 1 CuSO4 1 aq ?+ + 2 PdCl2 1 aq ?+ + 3 K2Cr2O7 0.5 aq + + 4 NiSO4 5 aq 5a _NiSO 4 2 aq 6 CoCl2 2 aq + + ++ 7a _HgCl 2 0.1 aq + + 8 HgCl2 0.05 aq 9 SnCl4 1 aq + + + 10a _CdSO 4 1 aq ?+ ?+ ?+ 11 HAuCl4 0.2 aq + + 12 H2PtCl6 0.5 aq 13 FeCl3 2 aq ?+ 14 InCl3 1 aq ?+ 15 IrCl4 1 aq + + 16a _MoCl 5 1 aq ?+ + + 17 AgBr 2 pet 18a _SbCl 3 1 pet 19 ZnCl2 2 pet ?+ + + 20 MnCl2 2 pet 21a _BaCl 2 0.5 aq 22a _BaCl 2 0.1 aq 23 CrSO4 2 aq 24 Al2O3 2 aq 25a _TiO 2 30 pet 26a _TiO 2 10 pet 27a _TiCl 4 0.1 aq ?+ + 28a _TiCl 4 0.05 aq ?+ +

aq,aqueous;pet,petroleum.

Patch-test reagents (Torii Pharmaceutical Corporation, Tokyo, Japan).

a _{Custom-madereagents.}

Fig.4–Animplant-retrievaltoolwiththeimplantbodyis

shown.

Fig.6–Symptomaticprogress.Beforeremovalofimplants.

Fig.5–Intraoralphotograph2monthsafterremovalof

implants.

Fig.7–Symptomaticprogress.Twomonthsafterremoval

ofimplants(nomedication).

journalofprosthodonticresearch 60(2016) 213–219

216

hypogastricskincondition1yearafterremovaloftheimplants.

Severerecurrenceofeczemahasnotbeenobserved.

3.

Discussion

Wereportapatientwithallergiccontactdermatitiswhohad

dentalimplantprosthesesandwhoexhibitedallergic

symp-tomsafterorthopedicsurgery.Dentalimplantprosthesesand

screwfixationdidnotresultinspecificproblemsinalocalarea

ofthebody.Allergicsymptomsappearedonthegeneralskin

surface,andremovaloftitaniumscrewsdidnotreducethe

extent of skin eruptions. He clearly exhibited an

allergy-positivereactionforatitaniumreagent,andthesesymptoms

disappearedafterremovalofdentalimplantfixtures.

Our patient may have become sensitized to titanium

becauseofthetitaniumscrewsusedinorthopedicsurgery,

and presented symptoms simultaneously.Alternatively, he

might have presented allergic symptoms for the dental

implantsthathehadreceivedpreviously.Anotheroptionis

thathebecamesensitizedtotitaniumupondental

implanta-tionandsubsequentlydevelopedallergicsymptomsbecause

ofthetitaniumscrewsusedinorthopedicsurgery.

Hissymptomsremainedwhilehehaddentalimplantsand

aftertheremovaloftitaniumscrews.Thispatientdeveloped

eczema1yearafterorthopedicsurgery,sotheprimarycauseof

allergicsymptomsseemedtobetitaniumscrewsinthelower

limb. Nevertheless, the titanium component in the dental

implantwasthemostsuspiciouscauseofallergicsymptoms.

Some medicalstudies and dentalstudies have reported

casesoftitaniumallergy,and ourresearchteam, indental

metal allergy clinics, has documented suspicious cases of

titaniumallergy.Studieshaveshownthatmostinstancesof

titaniumallergyappearascontactdermatitisaroundtitanium

products[15,16,18].However,ourpatientdeveloped

dermati-tissymptomsonthegeneralskinsurface.

Osseointegrateddentalimplantsworkwell,butremovalof

such implants is notconsidered easy or free ofrisk. If an

osseointegratedimplantmustberemoved,thenan

implant-retrievaltoolisveryusefulbecauseitenablesalessinvasive

effectinperipheralbone.

Fig.8–(a)–(c)Intraoralphotographsofthepatientafterprosthetictreatment.

Fig.9–Symptomaticprogress.Oneyearafterremovalof

In the 1980s, dental implants became one of the major

choicesforthetreatmentofmissingteeth.Titaniumwasused

asamaterialfordentalimplantsataveryearlystageofthe

developmentofdentalimplants[19,20].Thehigh

biocompati-bilityofthismetalsuggestedthattitaniumwasanallergy-free

material,andseveralreportssupportedthesafetyoftitanium

[21–24].Today,titaniumisusedformedicalapplicationssuchas

plastic surgery,but also for paints, white pigments,

photo-catalysts,andvarioustypesofeverydaygoods[25].Mostofthe

usageoftitaniumisastitaniumdioxide.Thisrapidexpansionof

titanium-containingproductshasincreasedthepercutaneous

andpermucosalexposureoftitaniumtothepopulation.

However,thepatch-testreagentfortitaniumhasnotbeen

standardized worldwide.Nakajima examined theformand

densityofpatch-testreagentsfortitanium[26].Hereported

that reagents composed of pure titanium powder and the

petroleum jelly Vaseline (Unilever, Rotterdam, the

Netherlands)wasnotpreferablebecauseitwasastimulant

inthisform.Hesuggestedthattitaniumtetrachloride(0.1%)is

preferable as a patch-test reagent for titanium, and we

followedhisadvice.

Prevalence ofallergy-positive reactionsagainst titanium

reagentsisfarlowerthanthatfor‘‘risky’’materialssuchas

chromium, mercury, palladium and nickel. Nopatient has

exhibited an allergy-positive reaction only for a titanium

reagent. Hence, one could conclude that titanium is a

relativelysafematerialthatcausesallergicsymptomsrarely.

Thedetailedmechanismofactionofallergyand

hypersensi-tivitywithmetalmaterialsisnotknown,butwespeculatethat

thetotalamountofexposuretospecificmetallicionsisan

important parameter. Theextent ofexposure to

titanium-basedmaterialsineverydaylifeandmedicalapplicationsis

increasing,sothenumberofthetitanium-allergicpatientswill

probablyincreaseinthenearfuture.

4.

Conclusions

Wereportapatientwithallergiccontactdermatitiswhohad

dentalimplantprosthesesandwhoexhibitedallergic

symp-tomsafterorthopedicsurgery.Theallergicriskfortitaniumwas

lowerthanthatforothermetalmaterials.However,wesuggest

thatpre-implantpatientsshouldbeaskedaboutahistoryof

hypersensitivityreactionstometals,andpatchtestingshould

be recommended to patients who have experienced such

reactions.

Ethical

approval

This experimental protocol was approved by the Ethics

CommitteeofTokushima ClinicalTrialCenter for

Develop-mentalTherapeutics(number1036).

Source

of

funding

Thisresearch wassupportedbyaGrant-In-Aid((C)number

25463003)forScientificResearchfromtheMinistryof

Educa-tion,ScienceandCultureofJapan.

Conflicts

of

interest

Theauthorsdeclarethattheyhavenoconflictsofinterest.

Acknowledgements

The authors express their gratitude to Professor Emeritus

EiichiBando.Moreover,manythanksgotoMr.OsamuIshida

(dentaltechnicianinTokushimaUniversityHospital)forhis

assistanceincreatingprostheticappliances.

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