Reakcije tipa IV, ili reakcije kasne preosjetljivosti, jedna su od manifestacija stanične imunosti. Te su reakcije uzrokovane specifično senzibiliziranim T-limfocitima. U stomatologiji posebice zanimljiva kontaktna preosjetljivost. Nadomjestci su u dugotrajnom izravnom doticaju s oralnim tkivima i slinom, a ujedno se u funkciji troše i savijaju. Ta zbivanja dovode do korozivnih procesa koji rezultiraju oslobađanjem iona, njihovom akumulacijom u tkivima i mogućom senzibilizacijom, to jest alergijskom reakcijom. Stomatolozi bi u svojemu radu trebali birati slitine s manjom tendencijom otpuštanja iona, odnosno dobre biosnošljivosti. Preporuča se izbjegavati uporabu slitina s visokim udjelom nikla.
Epikutani (patch) test indiciran je u svakoga pacijenta koji u svojoj povijesti bolesti navodi preosjetljivost na kovine ili druge materijale koji će se upotrijebiti za izradbu protetskoga nadomjestka.Type IV reactions, reactions of delayed hypersensitivity, are manifestations of cellular immunity. Such reactions are caused by sensitised T-lymphocytes. In dental medicine contact sensitivity is of particular interest, as restorations are in long-term direct contact with oral tissues and saliva and during function they wear and bend, leading to corrosive processes which result in the release of ions, their accumulation in the tissues and possible sensitivity, i.e. allergic reaction. Dentists need to chose alloys with less tendency to the release of ions, in other words good biotolerance. It is recommended that the use of alloy with a high share of nickel should be avoided. Patch test is indicated for all patients with a history of hypersensitivity to metal or other materials used in the construction of a prosthetic restoration

Ketij Mehulić

Muharem Mehulić

Patricija Kos

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A S CActa Stomatol Croat, Vol. 39, br. 2, 2005. 189Contact Sensitivity to DentalProsthetic Materials - AlloysSummaryType IV reactions, reactions of delayed hypersensitivity, are mani-festations of cellular immunity. Such reactions are caused by sensitisedT-lymphocytes. In dental medicine contact sensitivity is of particularinterest, as restorations are in long-term direct contact with oral tis-sues and saliva and during function they wear and bend, leading to cor-rosive processes which result in the release of ions, their accumula-tion in the tissues and possible sensitivity, i.e. allergic reaction. Den-tists need to chose alloys with less tendency to the release of ions, inother words good biotolerance. It is recommended that the use of alloywith a high share of nickel should be avoided. Patch test is indicatedfor all patients with a history of hypersensitivity to metal or other mate-rials used in the construction of a prosthetic restoration.Key words: contact hypersensitivity, dental prosthetic materials -alloys, patch test.Ketij MehuliÊ1Muharem MehuliÊ2Patricija Kos31Department of DentalProsthetics School of DentalMedicineUniversity of Zagreb2University Hospital for LungDiseases “Jordanovac”,Zagreb3Private Dental Practice, BujeActa Stomat Croat2005; 189-193REVIEWReceived: October 15, 2003Address for correspondence: Ketij MehuliÊDepartment of DentalProstheticsSchool of Dental MedicineGunduliÊeva 5, 10000 Zagrebe-mail mehulic@sfzg.hrIntroductionReactions of hypersensitivity to prosthetic mate-rials used in dentistry have still not been entirelyexplained. The dramatic increase in the incidence ofallergic diseases in the general population (1), andthe large number of new prosthetic fabrication and aux-iliary materials on the market, constitute an intrigu-ing combination. The aetiology of a lesion in the oralcavity, developing after insertion of a restoration isfrequently unclear, the opinion of clinicians variedand diagnosis challenging and costly (2). This article will attempt to answer the questionof whether prosthetic patients, because of direct,long-term contact with a restoration are a risk groupor exempt from the problem of allergy.Thanks to Spector (1951) allergological testingto dental prosthetic alloys gained importance, becameacknowledged and was gradually introduced intopractice (3). The introduction of fluorescent X-rayspectroscope, electronic microscope and Energy Dis-persion X-ray Microanalysis System (EDX), thedetection and quantification of metal ions releasedfrom fixed prosthetic restorations in saliva and gin-gival fluid (4) and analysis of specimens (5-7)became simpler and greatly contributed to illumi-nating the problem of allergies in industry. Ten ofthe most frequently released metal ions are ions ofA S C Acta Stomatol Croat, Vol. 39, br. 2, 2005.190Ketij MehuliÊ et al. Contact Sensitivity to Dental Prosthetic Materials - Alloyssilver, copper, zinc, nickel, gold, palladium, kositer,indium and chromium (4).The basic criterion in the choice of the materialfor a restoration is its biological tolerance. Howev-er, the occurrence of undesired reactions, chemi-cal, toxic, allergic or even cancerogenic, raises scep-ticism with regard to the lack of clinical researchor even incomplete description of the material com-position (8-12).With their insertion into the oral cavity restora-tions are simultaneously exposed to different process-es: bending, wear and corrosion (13), during whichthe disintegration of the passive layer on the surfaceof the restoration occurs, uniform corrosion and dis-solution of the material and release of ions (14).Wear of the restoration increases the surface fromwhich increased amounts of ions are released. Cor-rosion and wear, with the release of ions, close thevicious circle. Fractures and grooves are the mostfrequent sites affected by corrosion (15). The exis-tence of different types of metal in the mouth (indirect contact with saliva as an electrolyte and with-out an isolator) can easily induce galvanic corrosion,resultant passivity and the release (16) and accu-mulation of metal remains in the tissue (17-20).In 1963 Coombs and Gell proposed classifica-tion of allergic reactions according to immune mech-anisms which cause tissue damage. According totheir classification (supplemented in 1975) allergicreactions are classified as humoral: type 1, type 2and type 3, and cellular: type 4, which is the mostimportant type for the dentist. Type 4 reaction iscaused by specifically sensitised T-lymphocytes, andis determined by patch test. The reaction developsslowly at the site of contact with the antigen, simi-larly to inflammation. It takes 48-72 hours for thereaction to become positive, and in the cellular infil-trate lymphocytes and Langerhan cells are charac-teristic. After contact with the antigen recruited cells(monocytes, basophils and neutrophils) and residentcells (mononuclear phagocytes, mastocytes) becomeactive. With the release of metal ions from the restora-tion so-called sensitising agents form, which are notantigens but which acquire such characteristics bybinding to tissue (directly or after intermediary chem-ical reactions) creating a conjugate hapten-protein.These complexes cause sensitisation and delayedhypersensitivity whenever the skin or mucosa comesinto contact with the same or a chemically similarsubstance (21, 22).Several cases have been described of stomatitis,stomatopyrosis, lichen, lichenoid reactions and otherdiseases of the oral cavity, developing after inser-tion of a restoration (23-25). Marcusson (26) asso-ciated the insertion of a prosthetic restoration andhypersensitivity to nickel with the occurrence ofchronic tiredness syndrome, impaired concentration,disturbed sleep, headaches, pain in the joints andmuscles and sensitive teeth. He also reported burn-ing mouth and tongue, dry mouth, a feeling of elec-tricity in the mouth and pain and TMZ fatigue (27).Merritt (19) described the occurrence of metal tastein the mouth after prosthetic treatment with a restora-tion of cobalt-chromium alloy. The occurrence of contact dermatitis has alsobecome more frequent in therapists and dental tech-nicians, particularly after long-term exposure toprosthetic materials (28-31), and occurs in otherfields of dentistry (32-33).Diagnosis of delayed hypersensitivityCareful case history is the first link in the chainfor diagnosis of allergy, during which it is necessaryto determine earlier allergic diseases and the exis-tence of atopic diathesis. Information on current ther-apy is also important, and the environment in whichthe patient lives, profession and workplace, types ofpreparations used for personal hygiene, etc. (34).Van Arsdel (35) proposes allergological analysis foreach patient with a positive history, prior to pros-thetic therapy.The allergological test in the diagnosis of delayedhypersensitivity, which is performed on patients (invivo), is the patch test, and if necessary in vitro testsare also performed (36). Patch test is a biologicaltest by which the presence or absence of delayedallergic reaction to a specific antigen is determined(37). Testing is performed in accordance with therecommendations of the International Contact Der-matitis Research Group (ICDRG) (34). Allergens ina non-toxic concentration are used, usually 2% vase-line, paraffin, water (38), petrolatum (39) or someother solvent (methanol, ethanol, acetone) (40),placed in a disk of cellulose, covered with imper-A S CActa Stomatol Croat, Vol. 39, br. 2, 2005. 191Ketij MehuliÊ et al. Contact Sensitivity to Dental Prosthetic Materials - Alloysmeable aluminium paper and covered with poly-ethylene. Allergens are placed on clean, intact skin,usually of the upper part of the back or upper outerpart of the upper arm, where they remain coveredfor 48 hours, until the first results are read and after72 and 96 hours. Reactions may be negative (indi-viduals not sensitised to a particular antigen) or pos-itive, depending on the intensity of the reaction, andclassified as follows:+ Insignificant erythema and oedema with red-ness, possible papules without vesicles.++ Insignificant erythema, oedema, sporadic papulesand one or two vesicles.+++ Numerous papules and vesicles, sporadic bul-lae, eroded surface and extreme moistness (36,37, 41).There is a possibility of false positive and falsenegative results. Namely, a false positive result iscaused by an extremely high concentration of hap-ten, cross-reaction with undefined substances,inflammation near the tested site, irritation afterocclusion, etc. The reasons for false negative resultsare errors in the technique of performing the test andanergy (temporary or permanent). Temporary aner-gy may be caused by acute infections, vaccination,radiation, acute alcoholism, and immunosuppressivedrugs. Permanent anergy may be caused by diseasesof the lymph system (lymphoma, chronic anaemia),malignant tumours and other serious chronic dis-eases, age, spontaneous loss of delayed hypersen-sitivity in otherwise healthy individuals, and numer-ous other unknown genetically conditioned reasons(35, 42).The test can be performed epimucously, andAxell (43) described intraoral testing. In diagnosisof delayed hypersensitivity in clinical immunology,in vitro, migration inhibition test and lymphocytetransformation tests are used (36, 44). Some stud-ies have been engaged in the identification of metal-specific lymphocytes, which are used as biomark-ers during diagnosis of hypersensitivity (45).Allergenic potential of metalsSchaffran (46) reported some interesting corre-lations. Namely, patients positive to gold were alsopositive to nickel, and those positive to palladiumwere also positive to nickel. The risk of the use ofpalladium in dental prosthetic alloys is extremelylow due to the low values of released palladium ions(46). Kansu and Aydin (47) put platinum and its saltin seventh place with regard to allergenic potential.Allergy to chromium can only occur throughtransformation into six-valency salt-chromium. Sen-sitisation is facilitated by exposure to detergents,bleaches and cosmetic preparations (48). In hisinvestigations Merritt (49) and Sunderman (50)showed that all cobalt ions administered orally wereexcreted in the urine within 48 hours.Allergies to nickel are more frequent in indus-trially developed countries and more frequent inwomen (10%) than men (1-2%), probably becauseof their sensitivity via jewellery (48,51). Nickel caus-es more contact allergic reactions than all other met-als together, and even in those alloys which con-tain a very small concentration of nickel (1.5%) (47).Allergenic effects of nickel and beryllium in dentalpatients and the toxic effects in dental techniciansrepresent a potential problem in dentistry (52, 53).Corrosion of alloy containing nickel results in therelease of ions and their accumulation both in adja-cent tissue (54-58) and in distant organs (59, 60).However, Goh (53) states that systemic responseto elementary nickel and nickel compounds over alonger period has still not been sufficiently investi-gated. It is known that some alloys, based on nick-el, particularly those which contain beryllium, areprone to intense corrosion, particularly at lower pHvalues (52, 57). In sensitised individuals the con-centration in alloys is not decisive for provokingallergic reactions (62, 62). The concentration ofnickel of 2.5 μg/mL proved to be toxic for gingivalcells in tissue culture (63). Ions of nickel, cobalt andchromium bind to proteins (most frequently albu-min) and are thus transported through the body.Binding has a tendency to reversibility and metalcan be transported to a specific site (e.g. the kidney)freed of proteins and eliminated via the urine. Nick-el administered orally to experimental animals wasexcreted in the urine within 24 hours (64, 65).Although research on the role of metal ions is lim-ited, it is known that nickel is chemo-attractive andtherefore increases acute inflammatory reaction,which is usually of short duration, although casesA S C Acta Stomatol Croat, Vol. 39, br. 2, 2005.192Ketij MehuliÊ et al. Contact Sensitivity to Dental Prosthetic Materials - Alloyshave been reported of longer duration (66). In somecompounds, particularly subsulphide or nickel-car-bonyl, nickel has proved carcinogenic in the case ofconstant exposure at the workplace (67-69). Thepresence of allergy to nickel has proved decisive fordetermination of sensitivity to palladium, becausethe majority of people (93-100%) who are hyper-sensitive to palladium ions are also hypersensitiveto nickel (20). According to Geurtsen, this percent-age is much lower and amounts to 34-65.5% (11).The aforementioned clinical cases could lead tothe wrong conclusion that alloy with nickel will fre-quently induce an allergic reaction, which in clini-cal practice is not the case. Such cases are few andthe majority of recent studies on the clinical use ofalloy with a specific share of nickel, for orthopedicand dental purposes, have demonstrated its wideapplication without the occurrence of allergy (70).Namely, if the high percentage of the populationwho are allergic to nickel (15% according to Gohu)(53), rejected restorations containing this metal, therewould be cause for great concern, as it is present inthe composition of many dental prosthetic alloys.Although the frequency of hypersensitivity andallergic response cannot be disregarded, it should bekept in mind that there are many more people withhypersensitivity to metal than those who actuallyreact to a prosthetic restoration (71).Allergies to gold are contradictory. Anhlide (72)states that allergies to prosthetic restorations fabri-cated from gold alloys do not exist, and this asser-tion is corroborated by Alanko (40), while Ahlgren(73) and Björkner (74) point out the occurrence ofcontact allergies and positive skin test to gold salt.Indium-sulphate, indium-chloride and iridiumchloride are inert compounds (75). Zinc, rubidium,reni, silica, manganese, tungsten and other elementsare included in dental prosthetic alloys in a lowerpercentage, and no allergy to them has been foundin available literature. Cadmium, once in use, hasbeen rejected because of its carcinogenicity (76).More recently titan has become a particularlyinteresting material in prosthetics, because of its lowcost and biocompatibility. The resistance of titanto the environment primarily depends on the thin,resilient membrane of the surface oxide. This pas-sive oxide membrane is stable in a wide range of pHpotentials and temperatures. Consequently, titan isgenerally resistant to mildly reductive, neutral andhighly oxidative environments. This oxide film onlydisintegrates under highly reductive conditions,when there is a possibility of corrosion, althoughsuch conditions are not usually found in the mouth.Paradoxically to the above, overuse of the most fre-quent preventive means in dental medicine and sur-face application of fluorides, can have a harmfuleffect on the self-formed protective film (77).ConclusionThe frequent occurrence of allergic reactions todifferent substances includes the possibility of thedevelopment of hypersensitivity to dental prosthet-ic restorations and auxiliary materials. Prostheticalloys, their composition and technological treat-ment, i.e. quality of the cast, contribute to the achieve-ment of better structures and characteristics in clin-ical application. A restoration in the mouth is sub-ject to corrosive processes, the release of ions andformation of corrosive complexes which can lead tosensitisation of the organism. Nickel induces morecontact allergic reactions than all other metalstogether. In their elementary state chromium and plat-inum are not allergenic, although their salts mayshow such an effect.Palladium and platinum show exceptionally lowvalues of ion release from alloys and thus the riskof the use of dental prosthetic alloys containing theseelements is low. In the case of gold contradictorydata can be found in relevant databases, althoughclinicians agree that highly precious gold alloys arevery reliable in the oral cavity.In the case of doubt, based on patient informa-tion, clinical finding or clinical tests on allergy toany dental prosthetic material, prior to constructionof the restoration, tests must be carried out on the tar-geted allergens and relevant blood tests performed,after which the material can be selected for con-struction of the restoration. An exceptionally thor-ough case history, which in everyday dental practiceis often absent, will once again be useful and unavoid-able. It is a mistake to solve problems when symp-toms occur, both from the ethical and the materialviewpoint. Thus, the dentist should be encouragedA S CActa Stomatol Croat, Vol. 39, br. 2, 2005. 193Ketij MehuliÊ i sur. Kontaktna preosjetljivost na stomatoloπke protetske materijale - slitinetesting for all prosthetic patients, because of theextremely small number of those in whom allergicreaction develops after insertion of a restoration.to respect all the above steps, particularly in the caseof patients with atopic history. On the other hand itis unnecessary and costly to carry out allergological

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