titanium allergy

7/24/2019 titanium allergy

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Authors: Stuart Campbell,*MSc student;

Professor St John Crean, Dean of School

of Medicine and Dentsitry; and Professor

Waqar Ahmed, Head of Institute of

Nanotechnology and Bioengineering;

University of Central Lancashire.

*Corresponding author

E: [email protected]

Keywords:titanium, implants, allergy,

sensitivity

Titanium allergy: fact or fiction?by Stuart Campbell, St John Crean and Waqar Ahmed

Titanium is well suited to implantology: it is naturallyabundant, readily machined, shows up well on dentalradiographs and, perhaps most importantly, it is

biocompatable with human tissue. However, the dentalliterature suggests that metal sensitivity may occur afterexposure to titanium dental implants. The prevalenceof such cases is likely to increase and, although allergiesrepresent the most frequent chronic diseases in Europetoday, affecting the daily lives of more than 60 millionpeople, the role of titanium as a potential allergen isunder-investigated. With this in mind, this paper seeks toreview the literature to investigate if titanium in dentalimplants can induce clinically relevant hypersensitivityreactions.

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Stuart Campbell, St John Crean and Waqar AhmedDOI 10.1308/204268514X13859766312593

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FACULTY DENTAL JOURNALJanuary 2014 Volume 5 Issue 1


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Commercially available pure titanium(CPTi) and titanium alloy (Ti-4Al-6V)have been widely used to manufac-ture dental implants with subsequentsuccess rates.1,2 These metals areclassified according to their level ofpurity by the American Society forTesting Metals (ASTM). In implan-tology, ASTM grade 15 titanium isused. CPTi grade 1 has the highestpurity because of its low oxygen andiron content, while CPTi grade 4 hasthe highest maximum oxygen andiron percentage. ASTM grade 5 is a ti-tanium alloy with 4% aluminium and6% vanadium (Ti-4Al-6V) and is usedfor its high tensile strength values.

Titanium is well suited to implantol-ogy since it is naturally abundant,readily machined and shows up wellon dental radiographs. However, theprimary advantage of titanium is itsbiocompatability with vital humantissue. This is based on the fact thattitanium materials spontaneouslyform a thin (25nm) protective oxidelayer when exposed to air. Since puretitanium is inert and cannot binddirectly to the bone, osseointegrationis mediated by the attachment andproliferation of cellular adhesionmolecules to this oxide layer (Figure1 and 2).3

It is well known that physical or chem-ical changes to the titanium surfacecan influence bone cell attachment.There are three major ways in whichthe titanium implant surface can bemodified (Figure 3) and these are:1. Morphological changes: achieved

by using methods such as plasmaspraying, particle blasting, mi-cromachining, grinding andpolishing.

2. Chemical methods such as acidetching, alkali etching and anodi-sation.

3. Biochemical modificationmethods including micro andnanoscale coating with hydroxy-apatite/calcium phosphate/alu-mina incorporating biomolecules,antibacterial drugs and oestinduc-tive growth factors that can bedelivered directly to the titaniumsurface.

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Figure 1Formation of the oxide layer at the titanium surface. Reproduced from Wiskott HWA. Fixed Prosthodontics: PrinciClinics. 2011. With permission from Quintessence publishing, Berlin.

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Figure 2Molecular interface in direct contact with oxide layer. Reproduced from Wiskott HWA. Fixed Prosthodontics: PrinClinics. 2011. With permission from Quintessence publishing, Berlin.

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Figure 3Implant surface that has been modified using SLA (sandblasted, large grit, acid etched coating). ReproducedWiskott HWA. Fixed Prosthodontics: Principles and Clinics. 2011. With permission from Quintessence Publishing, Berlin.

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These technologies have enhancedtitanium biocompatibility and wid-ened the biomedical applications ofthis unique metal.4The medical anddental applications of titanium aresummarised in Table 1and Figure 4.No material, however, can be consid-ered universally biocompatible.5,6Allmetals in contact with a biological en-

vironment undergo corrosion.7,8Thisprocess is more likely with implantsmanufactured using grade 4 CPTi,owing to their higher iron content.9

Corrosion is detrimental because therelease of metal ions may alter thestructural integrity of the implant.6Released metal ions may remain inthe peri-implant tissue or disseminatesystemically10,11with the potential toinvoke immune responses.12

In orthopaedics, such events havebeen associated with the develop-ment of hypersensitivity reactionsand the failure of titanium alloy hipand knee implants.12Research in the

field of dermatology has implicatednickel, cobalt and chromium as themost common sensitising metals.13,14However, one finding from the den-tal literature is that metal sensitivitymay occur after exposure to titaniumdental implants.1517The prevalenceof these cases is likely to increase. Al-lergies represent the most frequentchronic diseases in Europe today,affecting the daily lives of more than60 million people.18

It has been stated that the relevanceof allergic reactions to dentalmaterials is poorly understood, andthe role of titanium as a potentialallergen is under-investigated.1921Consequently, this paper aims toreview the literature to investigate

whether titanium in dental implantscan induce clinically relevant hyper-sensitivity reactions.

HypersensitivityRepeated exposures to an allergen in-crease the likelihood of a hypersensi-tivity reaction.22For example, health-care workers repeatedly exposed tolatex gloves are at a higher risk oflatex sensitisation when compared

with the general public.23In addition,dental patients with palladium alloy

crowns are more likely to develophypersensitivity to this material com-pared with a control group.24

Titanium, like palladium, is a com-mon constituent in many house-hold items such as jewellery, sportsequipment, furniture and cars. Itis also present, as titanium diox-ide, in sunscreen, toothpaste andbeauty products, where it is used toproduce the white colour of theseproducts. Consequently, the generalpopulation is frequently exposed totitanium materials or compounds

from external sources, with the resultthat the human body typically has atitanium level of 50ppm.25

When a dental implant is inserted,the body receives an additional inter-nal exposure to titanium. Parr andco-workers25reported a titanium tis-sue level of 100300 ppm in patients

with dental implants. The cause ofthis is unclear. However, a number ofauthors believe that low-level corro-sion and wear of the implant releases

titanium ions, which may combinwith biomolecules such as nativeproteins and concentrate in the pimplant tissues.11,26In some patiethese protein-metal complexes mbecome immunogenic, triggeringhypersensitivity reaction.27

Hypersensitivity represents an immune reaction that produces injuto the tissues of the host. Accord-ing to the classification of Gell anCoombes,28four distinct types arepossible (Table 2). Hypersensitivitypes IIII are antibody-mediatedimmediate reactions that can occ

within minutes of exposure to thantigen. Type IV, or delayed hy-persensitivity (DH), involves tissuinjury from a cellular immune response. It is well established that reactions are initiated by sensitiselymphocytes that release proteolyenzymes in response to antigen. Tresultant inflammatory responsedevelops slowly and reaches a pea

within 2472 hours.

Contact dermatitis (CD) is a lo-calised form of DH, which can beinduced by a variety of chemicalsincluding metals. It is known thatindividuals become sensitised whprotein-metal complexes, or neo-

antigens, are taken by Langerhanantigen-presenting cells (APCs) tthe lymph nodes, where they are sented to T-helper cells. If a seconexposure to the neo-antigen occuT-helper cells mediate the releaseof lysosomal enzymes from macrophages that cause damage and lyto epidermal cells.29

Despite being described as a biocpatible material, several publishereports have raised the possibilitythat CPTi and Ti-alloys may causecalised and systemic DH.6,10,16,20,21,

Evidence for a hypersensitivity totitaniumSince the cessation of the AdversReaction Reporting project in 20it has become difficult to estimatthe prevalence of adverse reactioto dental materials in the UnitedKingdom.32,33Although recent stuies have demonstrated a steady riin the prevalence of metal allergy

within the general population, th

Dental implantsOrthopaedic implantsMaxillofacial mini-platesOrthodontic bracketsSpectacle framesCardiac pacemakersOsseointegrated hearing aidsOsseointegrated ocular prostheses

Table 1Applications of titanium in medicineand dentistry.

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Figure 4Medical and dental applications of titanium.Reproduced from Tan et al.4

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is a lack of large-scale epidemiologi-cal studies that show the prevalencerate of titanium sensitivity.34,35

Much of the evidence for titaniumsensitivity comes from orthopaedicresearch but its relevance to den-tistry must be inferred with caution.20The oral mucosa has different immu-nological properties than the skin.For example, it is less permeable,contains fewer Langerhan's APCsand is coated by salivary glycopro-teins. It has been proposed that oralmucosa must be exposed to allergenconcentrations 512 times greaterthan the skin in order to invoke thesame stimulus level.20

Evidence for hypersensitivity to tita-nium from dental sources is basedon cohort studies, case series andisolated clinical cases.

Du Preez and co-workers36were thefirst to describe a clinically relevanthypersensitivity reaction to titaniumdental implants. In their case, a49-year-old female experienced achronic inflammatory response,as well as foreign body giant cellreaction, to the insertion of sixTi-4Al-6V mandibular implants. Asimilar picture was presented in

the case reported by Egusa et al.15

Their 50-year-old Japanese femalepatient presented with a persistent,painful facial eczema following theplacement of two CPTi mandibu-lar implants (Figures 5 and 6). Inboth cases, complete resolutionof the inflammatory lesions wasobserved upon surgical removalof the implants. Interestingly, inthe latter case, the patients eczema

worsened immediately after implantremoval before eventually remitting.The authors suggested that this wastriggered by titanium debris created

during the implant removal surgery.

More recently, workers from Koreadescribed an allergy to a titanium-ni-tride implant abutment in a 70-year-old woman. The absence of radio-graphic pathology and subsequentpatch testing revealed that painfulsymptoms of peri-implant mucositis

were attributed to this abutmentmaterial. Resolution of symptoms

was observed when the patient wasrestored using CPTi abutments.31

Table 2 Hypersensitivity reactions (adapted from Gell and Coombes28).

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Type Description Onset Diagnostictest

Associatedfactors

I An immediatereaction thatcan result inan anaphylacticreaction

1530 minutesafter exposure

to antigen

ProvocationtestSkin testIgE RAST

Asthma Anaphylaxis

II Cytotoxicreactionmediated by IgMand IgG antibodyresponses tohost tissue

Minutes to hours IgG serumtest

Grave's diseaseThrombocytopeniaMyasthenia gravis

III IgG and IgMantibodiesform immunecomplexes withantigens in theblood

310 hours afterantigen exposure

IgG serumtest

Systemic lupusErythematosusSerum sickness

IV Delayed reactionthat is mediatedby memory Tcells

2472 hours Patch testMELISA

Mantoux testContact dermatitisProsthetic Implants

Figure 5Facial eczema lasted for two years following dental implant placement. One week afterremoval of dental implants, symptoms of eczema temporarily worsened. Ten months after removalof dental implants. Reproduced with permission from Professor Egusa and Elsevier Publishing.

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Figure 6Initial intra-oral presentation of patient in Figure 5.Reproduced with permission from ProfessorEgusa and Elsevier Publishing.

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Common to all these cases was theabsence of a past history of systemicdisease or history of contact-hyper-sensitivity reactions to metals.

A further point of interest is that theobserved sensitivities occurred inresponse to both CPTi and titaniumalloy.

More recent research was carriedout by Sicilia et alin 2008.20Theyscreened 1,500 consecutive implantpatients for titanium allergy using atwo-staged assessment. The first stageconsisted of exploring the patienthistory for evidence of titanium al-lergy. A total of 35 (2.3%) patients

were positive for allergy symptoms af-ter implant placement, unexplainedimplant failure and/or the presenceof hyperplastic peri-implant tissuelesions.

The second stage of assessmentinvolved patch testing for titaniumand titanium dioxide, which showedthat nine patients (representing0.6%of the original number) twomale, seven female demonstratedhypersensitivity to titanium. Inter-estingly, the authors assessmentprotocol meant that titanium al-lergy was diagnosed in five of thesepatients after implants were placed,

meaning that some limited dataon implant outcome in hypersensi-tive patients is available. Two of thepatients in this group suffered rapidimplant exfoliation. This led to seri-ous complications in one patient,

who suffered glottitis oedema andairway embarrassment that requiredemergency hospitalisation. Of theremaining three patients, one latefailure and two successful therapies

were reported.

The results from this study seem toindicate that the prevalence of tita-

nium allergy in the general popula-tion is low and that not all patientssensitised to titanium display com-plications following implant surgery.However, the authors failed to report

whether CPTi or Ti alloy implantswere used in their study. In doing so,it is possible that the investigatorsunderestimated the true prevalenceof clinically significant titanium al-lergy since the five ASTM grades ofdental titanium behave very differ-ently in terms of antigenicity.21

Several studies have attempted todetermine whether a relationshipexists between the titanium implatypology and the level of hypersetivity reaction. These have been cprehensively reviewed by Javed et

who reported that trace elementsof nickel, chromium and palladiuare present within many titaniumimplant systems. They hypothesisthat these elements, rather than tnium, may be responsible for triging hypersensitivity reactions. Thmay explain the increasing numbof reactions to titanium materialsreported by Pigatto and co-worke

A much higher incidence of sensity to titanium was described in astudy using the memory lymphocimmunostimulation assay (MELI-SA). Research has shown this in

vitro test is a clinically reliable tofor identifying and monitoring sesitisation to titanium in symptomexposed individuals.38

In evaluating 56 patients betweenthe ages of 14.384.1 years who hdeveloped symptoms of hypersensitivity following the placement otitanium-based dental implants, tauthors found: 21 patients (37.5%) tested posi

for sensitivity to titanium 32 patients (57.9%) who did noshow hypersensitivity (MELISAreactivity) to titanium, were likto have suffered an immune retion to contaminating metals suas nickel.

As a result of their symptoms, 5patients (96.4%) agreed to havtheir implants removed.

Removal led to recovery in allwithin six to nine months.

A further observation, consistentwith the results of other studies, w

the wide spectrum of allergic disepresentation that occurs in respoto titanium hypersensitivity.30

Clinical presentationThe clinical manifestations of contact allergy to dental material arenot uniform.26Patients may prese

with subjective complaints affectithe oral mucosa, including burnipain, and more objective conditiosuch as mucositis (Figures 79).19

Figure 7Exfoliative chielitis following placement of an implant adjacentto an amalgam root end filling. Reproduced with permission from GianpaoloGuzzi.

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Figure 8Painful mucositis of the mandibular molar regions abutments,adjacent to TiN-coated abutments. Reproduced from Lim et al31withpermission from Elsevier Publishing.

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Figure 9Resolution of symptoms of patient in Figure 8, 1 month afterremoval of TiN coated abutments. Reproduced from Lim et al31withpermission from Elsevier Publishing.

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Although the available dental litera-ture describing the clinical featuresof titanium hypersensitivity is sparse,the following associations have beenconsistently described: dermatitis facial eczema exfoliative chielitis gingival hyperplasia redness, pruritis and urticaria painful mucositis of peri-implant

tissue swellings in submental and labial

sulcus burning mouth.

Interestingly, oral lichen planus(OLP), which has a strong associa-tion with corroded dental amalgamsand other metals,42,43is not a widelyreported feature of titanium sensitiv-ity. In a Japanese study investigat-ing the outcome of the then-newhydroxyapatite-coated titaniumimplant in 78 patients, a single caseof OLP was reported as an incidentalfinding. The authors concluded thatthe presence of a direct cause-effectrelation between titanium and OLPremained unclear.44

ScreeningMany clinicians, including Papado-

poulos, lead author of the EuropeanAcademy of Allergy and ClinicalImmunology (EEACI)s positionpaper on research needs in allergy,18support the idea of patch testing pa-tients at high risk for metal sensitisa-tion before implants are placed.

Risk can be established by evalua-tion of the history and examinationof the face, lips, oral cavity andteeth.33,45

Patch testing is performed by thedermatologist, whereby an allergen

is applied to the skin for 34 daysand the development of an erythem-atous reaction is considered positive(Figures 10 and 11). All patientspresenting with symptoms possiblyrelated to dental allergens shouldbe tested to the British Contact Der-matitis Society (BCDS)s standardseries (details can be obtained viathe BCDS website, www.bad.org.uk/groups/bcds/). Additional series de-pend on the clinical situation but fordental patients may include a metal

Figure 11Positive patch test reaction totitanium nitride. Reproduced with permission fromProfessor Baeck and John Wiley and Sons Publishing.

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Figure 10Patch testing for metal sensitivity.

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37.5% of

patients testedpositive forsensitivity totitanium

57.9% had areaction tocontaminatingmetals

96.4% agreedto have theirimplantsremoved

Removal ledto recoveryin all patients

within 69months



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series such as mercury, palladiumand titanium.

A reported criticism of patch testingis that it has been validated only forepidermal rather than oral muco-sal antigen contact.30,46As reportedabove, in vitro testing with MELISAhas been used successfully to detecttitanium hypersensitivity. However,other workers have noted the needfor additional studies to support thisclaim.47Until proven otherwise, theguidelines of the British Associa-tion of Dermatologists48should befollowed, in that patch testing shouldbe considered the mainstay of diag-nostic testing.

Clinical relevanceLoss of osseointegration is an un-desirable and often multifactorialevent. Currently, there is insufficientresearch available to clarify all of thereasons for implant failure. Fromthe existing data, it appears thatimplant failure may be classifiedaccording to biological, mechani-cal, iatrogenic and patient-relatedfactors.49,50However, not all failurescan be explained and it is conceiv-able that titanium hypersensitivitymay play a role in such cases.51,52

This possibility has been highlightedby the above case reports and oneclinical study that presented implantfailures in patients who were allergicto titanium.15,20,31,36

Data is limited and several inves-tigators have suggested that theprevalence of titanium sensitivity-associated implant failure is grosslyunderestimated. They cite anunder-reporting of dental implant-related titanium-hypersensitivityby the profession as the reason forthis.1921,47To reverse this trend, the

authors recommended that theinitial assessment of implant patientsshould include patch testing for im-plant patients with a history of metalallergy. Furthermore, they advisepatch testing for all patients withunexplained implant failures.

From the limited data available, it ap-pears that corrosion of the titaniumimplant has an important role toplay in the hypersensitivity reaction.It has not yet been proven whether

an inflammatory process mediatedby hypersensitivity is responsiblefor corrosion, or whether corrosiontriggers an inflammatory process.6It is well known that biochemicaland mechanical stresses in the peri-implant micro-environment can leadto corrosion of the implant. Loweredtissue pH as a result of periapical pa-thology also strongly contributes tothe former.53The infiltration of salivabetween multi-metallic structures onor adjacent to titanium implants canbring different types of alloys intotemporary or permanent contact.This dynamic helps to establish a gal-

vanic cell. It has been reported thatimplants placed adjacent to amalgamroot end fillings and those fixturesrestored with nickel-chromiumsuperstructures are at risk of galvaniccorrosion.16,17,54

Taking steps to reduce these risksseem appropriate.

ConclusionsThere can be no doubt that thetitanium dental implant has a longrecord of reliability in dental prac-tice.55Providing there is no adversehistory, fixtures manufactured fromtitanium should be the first-choice

for implant dentistry.56,57

Currently, it seems that cases of sensi-tivity to titanium dental implants arerare. The case reports and studiespublished so far reflect the diagnos-tic uncertainties in evaluating sus-pected titanium hypersensitivity. As aresult, the true prevalence of sensitiv-ity to titanium dental implants maybe underestimated.21,47

In studying the aetiology, diagnosisand treatment of hypersensitivity, itcan be concluded that cases of tita-

nium allergy are likely to increase.18

One explanation for this may be thepresence of known sensitising agents(nickel, chromium and cobalt) inthe metal as a result of the produc-tion process. These trace metals maybe insignificant from a metallurgicalperspective, but may be sufficient totrigger allergic reactions in sensitisedpatients.45

Accordingly, it would seem sensibleto refer for patch testing those

patients who have a positive histoof metal allergy, and those patien

who have previously suffered failimplants. It should be rememberthat a positive patch test for titandoes not always accompany symptoms of hypersensitivity. Howeverthe risk of significant complicatioin particularly sensitive patients cnot be disregarded.20

There is a need for ongoing cliniand radiographic data monitorinall patients who have had an impand who are diagnosed with metasensitivity. We do not yet have a cplete understanding of the biologinteraction of titanium and, as a sequence, hypersensitivity reactiocannot be excluded as a reason fimplant failure.

Further research, together with animprovement in the reporting ofadverse reactions, is needed to cledefine the role of dental titaniumthe development of allergic reacti

References1. Jo HY, Hobo PK, Hobo S. Freestanding

and multiunit immediate loading of thexpandable implant: an up-to-40-montprospective survival study.J Prosthet Den2001;85: 148155.

2. Lekholm U, Grndahl K, Jemt T. Outcof oral implant treatment in partiallyedentulous jaws followed 20 years in clfunction. Clin Implant Dent Relat Res 20178186.

3. Sennerby L, Ericson LE, Thomsen P etStructure of the bone-titanium interfacretrieved clinical oral implants. Clin OrImplants Res 1991;2: 103111.

4. Tan AW, Pingguan-Murphy B, Ahmad Akbar SA. Review of titania nanotubesFabrication and cellular response. CeraInternational 2012;38: 4,4214,435.

5. Williams DF. Titanium: epitome ofbiocompatibility or cause for concern.Bone Joint Surg Br 1994;76: 348349.

6. Olmedo DG, Tasat DR, Duff G et al. Tissue of corrosion in dental implants: areview. Acta Odontol Latinoam 2009;22:

7. Guindy JS, Schiel H, Schmidli F, Wirz JCorrosion at the marginal gap of implasupported suprastructures and implanfailure. Int J Oral Maxillofac Implants 2019: 826831.

8. Nikolopoulou, F. Saliva and dental impImplant Dent 2006;15: 372376.

9. Jokstad A, Braegger U, Brunski JB et alQuality of dental implants. Int Dent J 2053: 409443.

10. Urban R, Jacobs J, Tomlinson M et al.Dissemination of wear particles to the lspleen, and abdominal lymph nodes opatients with hip or knee replacement.Bone Joint Surg Am 2000;82: 457476.

RESEARCH




8/8

11. Olmedo DG, Cabrini RL, Duffo G,Guglielmotti MB. Local effect of titaniumcorrosion: an experimental study in rats. Int

J Oral Maxillofac Surg 2008;37: 1,0321,038.12. Frigerio E, Pigatto PD, Guzzi G, Altomare

G. Metal sensitivity in patients with

orthopaedic implants: a prospective study.Contact Dermatitis 2011;64: 273279.

13. Pigatto PD, Guzzi G. Systemic contactdermatitis from nickel associated withorthodontic appliances. Contact Dermatitis2004;50: 100101.

14. Noble J, Ahing SI, Karaiskos NE, WiltshireWA. Nickel allergy and orthodontics, areview and report of two cases. Br Dent J2008;204: 297300.

15. Egusa H, Ko N, Shimazu T, Yatani H.Suspected association of an allergic reaction

with titanium dental implants: a clinicalreport.J Prosthet Dent 2008;100: 344347.

16. Evrard L, Waroquier D, Parent D. Allergiesto dental metals. Titanium: a new allergen.Rev Med Brux 2010;31: 4449.

17. Pigatto PD, Berti E, Spadari F et al.

Photoletter to the editor: Exfoliativecheilitis associated with titanium dentalimplants and mercury amalgam.J DermatolCase Rep 2011;5: 8990.

18. Papadopoulos NG, Agache I, Bavbek S etal. Research needs in allergy: an EAACIposition paper, in collaboration with EFA.Clin Transl Allergy 2012;2: 21.

19. Raap U, Stiesch M, Reh H et al.Investigation of contact allergy to dentalmetals in 206 patients. Contact Dermatitis2009;60: 339343.

20. Sicilia A, Cuesta S, Coma G et al. Titaniumallergy in dental implant patients: a clinicalstudy on 1500 consecutive patients. ClinOral Implants Res 2008;19: 823835.

21. Pigatto PD, Guzzi G, Brambilla L, SforzaC. Titanium allergy associated with dentalimplant failure. Clin Oral Implants Res 2009;

20: 857.22. Msges R. The increasing prevalence of

allergy: a challenge for the physician.Clinical & Experimental Allergy Reviews 2002;2: 1317.

23. Tarlo SM, Sussman GL, Holness DL. Latexsensitivity in dental students and staff: across-sectional study.J Allergy Clin Immunol1997;99: 396401.

24. Faurschou A, Menn T, JohansenJD, Thyssen JP. Metal allergen of the21st century a review on exposure,epidemiology and clinical manifestations ofpalladium allergy. Contact Dermatitis 2011;64: 185195.

25. Parr GR, Gardner LK, Toth RW. Titanium:the mystery metal of implant dentistry.

Dental materials aspects. J Prosthet Dent 1985;54: 410414.

26. Torgersen S, Gjerdet NR, Erichsen ES,Bang G. Metal particles and tissue changesadjacent to miniplates: A retrieval study.Acta Odontologica Scandinavica 1995:53:6571.

27. Hallab N, Merritt K, Jacobs JJ. Metalsensitivity in patients with orthopaedicimplants.J Bone Joint Surg Am 2001;83:428436.

28. Gell PGH, Coombs RRA, eds. Clinical Aspectsof Immunology. 1st ed. Oxford, England:Blackwell; 1963.

29. Kaplan DH, Igyrt BZ, Gaspari AA. Earlyimmune events in the induction of allergiccontact dermatitis. Nat Rev Immunol 2012;12: 114124.

30. Mller K, Valentine-Thon E.Hypersensitivity to titanium: clinical and

laboratory evidence. Neuro EndocrinolLett 2006;27: 3135. Erratum in: Neuro

Endocrinol Lett 2007; 28: iii.31. Lim HP, Lee KM, Koh YI, Park SW. Allergic

contact stomatitis caused by a titaniumnitride-coated implant abutment: a clinicalreport.J Prosthet Dent 2012;108: 209213.

32. Scott A, Egner W, Gawkrodger DJ et al.The national survey of adverse reactions todental materials in the UK: a preliminarystudy by the UK Adverse ReactionsReporting Project. Br Dent J 2004;196:471477.

33. Gawkrodger DJ. Investigation of reactionsto dental materials. Br J Dermatol 2005;153:479485.

34. Thyssen J P, Linneberg A, Menn T,Johansen J D. The epidemiology of

contact allergy in the general population prevalence and main finding. ContactDermatitis 2007;57: 287299.

35. Thyssen J P, Linneberg A, Menn T etal. Contact allergy to allergens of theTRUE-test (panels 1 and 2) has decreasedmodestly in the general population. Br J

Dermatol 2009:161: 1,1241,129.36. du Preez LA, Btow KW, Swart TJ. Implant

failure due to titanium hypersensitivity/allergy: Report of a case. SADJ 2007;62: 22,2425.

37. Javed F, Al-Hezaimi K, Almas K, RomanosGE. Is titanium sensitivity associated withallergic reactions in patients with dentalimplants? A systematic review. Clin Implant

Dent Relat Res2013; 15:4752.38. Valentine-Thon E, Mller K, Guzzi G,

Kreisel S et al. LTT-MELISA is clinically

relevant for detecting and monitoring metalsensitivity. Neuro Endocrinol Lett 2006;27:1724.

39. Lang NP, Wilson TG, Corbet EF. Biologicalcomplications with dental implants: theirprevention, diagnosis and treatment. ClinOral Implants Res 2000;1: 146155.

40. Rubel DM, Watchorn RB. Allergic contactdermatitis in dentistry. Australas J Dermatol2000;41: 6369.

41. Schedle A, Ortengren U, Eidler et al. Doadverse effects of dental materials exist?

What are the consequences, and how canthey be diagnosed and treated? Clin OralImplants Res2007; 18:232256.

42. Koch P, Bahmer FA. Oral lesions andsymptoms related to metals used in dentalrestorations: a clinical, allergological, andhistologic study.J Am Acad Dermatol 1999;41: 422430.

43. Martin MD, Broughton S, Drangsholt M.Oral lichen planus and dental materials: acase-control study. Contact Dermatitis 2003;48: 331336.

44. Takarada H, Kinebuchi T. Clinicalevaluation of hydroxyapatite-coatedtitanium artificial tooth root. Kokubyo GakkaiZasshi 1993;60: 532564.

45. Bernard S, Baeck M, Tennstedt D et al.Chromate or titanium allergy the roleof impurities? Contact Dermatitis 2013;68:191192.

RESEARCH

46. Oliva X, Oliva J, Oliva JD. Full-mouth oralrehabilitation in a titanium allergy patientusing zirconium oxide dental implantsand zirconium oxide restorations A casereport from an ongoing clinical study.Eur J

Esthet Dent 2010;5: 190203.

47. Siddiqi A, Payne AG, De Silva RK, DuncanWJ. Titanium allergy: could it affect dentalimplant integration? Clin Oral Implants Res2011;22: 673678.

48. Bourke J, Coulson I, English J. Guidelinesfor the management of contact dermatitis:an update. British Association of DermatologistsTherapy Guidelines and Audit Subcommittee. Br

J Dermatol 2009;160: 946954.49. Duyck J, Naert I. Failure of oral implants:

Aetiology, symptoms and influencingfactors. Clin Oral Investig 1998;2: 102114.

50. Esposito M, Thomsen P, Ericson LE,Lekholm U. Histopathologic observationson early oral implant failures. Int J OralMaxillofac Implants 1999;14: 798810.

51. Kwon SY, Takei H, Pioletti DP et al.Titanium particles inhibit osteoblast

adhesion to fibronectin-coated substrates.JOrthop Res 2000;18: 203211.52. Deas DE, Mikotowicz JJ, Mackey SA, Moritz

AJ. Implant failure with spontaneous rapidexfoliation: case reports. Implant Dent 2002;11: 235242.

53. Gil FJ, Rodriguez A, Espinar E et al. Effectof oral bacteria on the mechanical behaviorof titanium dental implants. Int J OralMaxillofac Implants 2012;27: 6468.

54. Ozkomur A, Erbil M, Akova T. Diamond-like carbon coating as a galvanic corrosionbarrier between dental implant abutmentsand nickel-chromium superstructures.Int J Oral Maxillofac Implants 2013;28:1,0371,047.

55. Lemmerman KJ, Lemmerman NE.Osseointegrated dental implants in privatepractice: a long-term case series study.J

Periodontol 2005;76: 310319.56. Newman MG. The single-tooth implant as

a standard of care (editorial). Int J Oral &Maxillofacial Implants 1999;14: 621622.

57. Wenz HJ, Bartsch J, Wolfart S, Kern M.Osseointegration and clinical success ofzirconia dental implants: a systematicreview. Int J Prosthodont 2008;21: 2736.

Figures 13 reproduced from Wiskott HWA.Fixed Prosthodontics: Principles and Clinics.London: Quintessence Publishing; 2011.


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