Oral Medicine

Allergies to dental materials

William A. Wiltshire*/Mat7na R. FeiTeira**/At J. Ligthelm***

Abstract Allergies related to dentistry generally constitute delayed hypersensitive reactionsto specific dental tnaterials- Although true allergic hypersensitivity to dentalmaterials is rare, certain products have definite allergenic properties. Extensivereports in the literature substantiate that certain materials catise allergies inpatients, who exhibit ntueosal and skin symptoms. Currently, however, neithersubstantial data nor clinical experienee unequivocally contraindícate thediscontinuance of any ofthe tnaterials. which inchtde dental ainalgain and nickel-and chromium-containing metals. The dentist fortns a vital link in the teatnapproach to the differential diagnosis of allergenic biomaterials that elicitsymptoms in a patient, not only Intraorally. but also on unrelated parts ofthe body(Quintessence Int ¡996:27:513-520.)

Clinical relevance

Although the dentist should be aware of theallergenic materials used in practice, which includeacrylic resin, amalgam, impression materials, euge-nol products, and metal products, particularlynickel, currently neither substantial data nor clinicalexperience unequivocally contraindicates the dis-continuance of any ofthe materials.

Introduction

Allergic hypersensitivity related to dentistry is acquiredby exposure to specific dental material allergens atidthe altered capacity of the patient to react whenre-exposed to the allergen, Allei^ic reactions associ-ated with dental materials are generally delayed hyper-sensitive reactions that are usually not associated with

* Professor and Head, Departtnent of Orthodontics, University ofPretoria, Faeiilty of Dentistry, Pretoria, South Africa

*' Ftead Emeritus; Division of Dental Materiais, University ofPreturia,Faculty of Dentiïtrj', Pretoria, South Afriea,

*** Professor and Head, Department of Orai Pathology, University ofPretoria, Faculty of Dentistry, Pretoria, South Afriea,

Reprint requests: Prof W A. Wiitshire. Department of Orthodontics,University of Pretoria, c/o PO Box 73752, Lynnwood Ridge, Pretoria0040, South Africa,

circulating antibodies, because the causative agentsattain their allergenic properties by combining with themucosal tissues ofthe patient. The delayed hypersen-sitive reaction is not manifested clinically until severalhours after exposure.'

A contact allergy in dentistiy is the type of reactionin which a lesion of the skin or mucosa occurs at alocalized site after repeated contact with the allergenicmaterial.' The ability to cause contact sensitivityappears to be related to the ability of the simplechemical allergen to bind to proteins, especially thoseofthe epidermis,- and. in dentistry, specifically the oral

Contact dermatitis

Clinical features

As in all forms of eel I-mediated immunity, in contactdermatitis there is a minimum latent period of at least 5days between the first contact with the allergen and theability to react at a distant site to further contact with anonirritant concentration of the allergen. Reactionstake between 24 and 48 hours to develop and, if severe,may last for 7 to 10 days.-

Contact dermatitis is manifested by an itching orburning sensation at the site of contact, followed ashort while later by the appearance of erythema andthen vesicles. Once the vesicles have ruptured, theerosion may become more extensive, and secondaryinfection may develop,'

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Fig 1 A suspected allergic reaction lo a self-cunng acrylicresin provisional fixed partiai denture piaced in thG maxillaryanterior segment has developed at the corners of tine moutha few days toiiowing placement. The reaction is characte-rized by itching, vesicular formation, and crusting. Thecondition was alleviated when the permanent ceramometalfixed partial denture was placed 9 days later

The oral man ¡testa lions, known as contact stomatitisor stomatitis venenata, iticlude an inflamed andedematous mucosa, accompatiied by a severe burningsensation. Small, transiem vesicles may form; theserupture to fonn areas ol" erosion and ulcération.'Erythema, papules, and edema are characteristicailergic manifestations and, in severe reactions, largeweeping blisters may appear," Stomatitis venenataoccurs iess frequently than do allergic skin lesions.This can be ascribed to the diluting, digestive, andwashing effects of saliva,

Ahhough certain dental materials have been im-plicated as causes of contact stomatitis, the reportedincidence is low. However, wheti an ofFending dentalmaterial sensitizes an area ofthe mucosa, no matterhow small the area, the individual may becomesensitized,^

Treattnent and prognosis

Several tnethods of treating allergies have been re-ported, including íiymplomatic treatment, desensiti-zation, and elimination of the allergen. Because themechanism of the allergic reaction is not yet ftillyunderstood, the presently recommended method oftreatment may be elimination of the ailei^en."' Pres-ently, the only effective treatment for contact dermatitisor stomatitis is the discontinuance of all contact withthe allei^enic material, which usually results in promptremission of all the lesions.

This article will review allergic hypersensitivity tovarious modern dental materials.

Allergenic dental materials

Acrylic resin

Acrylic resin has been reported to occasionally inducean allergic hypersensitivity when used as a denturebase, restorative material, or provisional fixed partialdenture resin (Fig 1 ), Normally, the patient is exposedto the free monomer in acrylic resin, which may causeatoxic reaction, Hypersensitivily in denture wearersshould not be confused, however, with physicaiirritation of the oral mucosa caused by ill-fittingdentures. Acrylic resin hypersensitivity may developshortly after insertion of the denture or may notmanifest for an extended period of time, even manymonths' (Figs 2a and 2b), Clinical reactions mayoccur at secondary sites (Figs 3a and 3b),

Resit) composite

Lind^ reported that resin composite materials could bean etiologic factor in the development of lichenoidreactions in the oral mucosa. The pathogenic mech-anism may be related to contact allergy to formalde-hyde formed in resin composite restorations. Formal-dehyde causes more than one third of all allergicreactions caused by dental materials, A report by0ysaed et al indicated that formation of formaldehydewas found in light , ultraviolet light-, and chemicallyactivated resin composites,

Itnpression materials

Polyether impression materials have been reported tocause allergic problems in the past, but have sincechanged their compositions. Care should be taken tomix the material thoroughly and to avoid contact ofthearomatic sulfuric ester catalyst paste with the skin ormucosa because it may elicit adverse tissue reactions,

Ettgenol-containing products

Oil of cloves, or eugenol in its unrefined form, is mixedwith zinc oxide to form zinc oxide-eugenol (ZOE),which exhibits a combination of physical and thera-peutic properties making it useflil as a provisionalrestorative materiai, base material, and root canalfilling material. Zinc oxide-eugenol impression pastesand ZOE periodontal packs are also available. Euge-nol is highly soluble and is continuously released fromZOE, which can lead to short-term saturation oftheoral environrnent with eugenol in a concentration

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Fig 2a The upper lip and eyelidsare severely swollen 5 days a¡terinsertion of provisional acrylic resinfixed parfial denture.

Fig 2b One week after removal ofIhe provisional acrylic resin prosthe-sis and after replacement with apermanent ceramometal fixed par-tial denture, the swelling is gone.

Fig 3a (/eW An allergic reaction may occur at a secondarysite in acrylic resin allergy After placement of a newmaxiiiary complete denture, a secondary allergic reactionoccurred on the inside ol this patient's upper legs.

Fig 3b (below) The inside of the patienfs arm, and hisstomach and back, were also affected.

sufficient to cause cytotoxicity. This is why eugenolperiodontal packs, which are in contact with openmucosal wounds, are no longer popular.

Five ofthe periodontal dressing materials listed inAccepted Dental Therapeutic^ contain colophony(resin), and four of them contain eugenol. The onlyone that is eugenol free (Coe-pak, Coe Laboratories)contains, among other things, balsam of Peru.^ In this

context the cross reactivity between many allergenicsubstances, such as between eugenol and balsam ofPeru, should be borne in mind. Thus, when the causativeagent in an allergic reaction to periodontai dressingmaterials has not been positively identified, a choiceamong the materials, whether they are eugenol-frcc ornot, is impossible.^

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Fig 4 Suspected allergy to an amalgam alloy has causederythema and vesicle formation. The symptoms disappear-ed after a resin composite restorative material was placed.

Fig 5 Suspected allergic contact glossitis has developedadjacent to a gold crown The swelling and erythematouschanges disappeared after the restoration was replacedwith a porcelain orown.

The inilatumatory response caused in mucosaltissue by eugenol should not, however, be confusedwith allergic hypersensitivity. From a biologic point ofview. ZOE is in fact considered the least damagingrestorative material and possesses sedative or anodynepropetiies, which are very useful in dentistry."^"Despite the advantageous properties of eugenol, how-ever, sensitivity, tnanifested as positive inflammatoryresponses to eugenol in certain root canal sealers hasbeen described,'-

Metals

Amalgam

Althoughrare.allergyto mercury'-'as well as copper inamalgam'"* has been described. In addition, the releaseof mercury from amalgam restorations has been thecause of skin and mucosal disorders'^ (Fig 4). There isalso growing evidence that amalgam restorations maybe etiologic factors in some of the mucosal changesclassified as oral lichen pianus.'^ Some of thesedisorders may be considered a mucosal pattern ofresponse to several distinct pathogenic factors. Ailergyto amalgam compounds may be one such pathogenicmechanism." ln many cases, electrogalvanism mayenhance the allergic reaction as a transmitter ofreactive ions, justifying the term electrogalvanic whitelesion, used by Bánóczy et al.'^

Because erosive forms of oral lichen planus areknown to be susceptible to cancer deyelopment,patients should be given effective causal treatment.'^

Vernon et al "' reviewed 41 published cases of allergyto dental amalgam, which included 30 female and Umale patients. Twenty of the 41 patients recovered oaremoval of their amaigam restorations. The mostfrequent symptoms were of the remote cutaneous type(38 of 41 cases), while local symptoms, particularlygingivitis and stomatitis, occurred in 17 cases. Theauthors suggested that the figures probabiy under-estimate the true prevalence of the condition becauseof underreporting of cases. Mercury was found to bethe most common sensitizing agent, but other metals,particularly copper, zinc, and silver, could also beimplicated."

Gold

Gold is generally regarded as an inert and safematerial,-' but the belief that gold is nonsensitizing isnot substantiated by reported data. Comaish'^ re-ported allergic dermatitis to a gold wedding ring,Elgart and Higdan'** described stomatitis caused by agold dental restoration and concomitant dermatitis atsites in contact with gold jewelry worn by the patient.The number of confirmed cases of gold sensitivity isextremely low^ (Fig 5),

Nickel

In general, nickel, ranJted third among the five mostcommon causes of allergic contact dermatitis-" andfirst in most industrialized countries, is the mostcommon contact allergen in dentistry affecting femalesin Europe and the United States.'' Nickel hypersen-

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Fig 6a (left) Nickel dermatitis of the earlobe is common inniokef-sensilive individuals who v iear nickel-containingjewelry.

Fig 6b (below) Swelling and erythema of the earlobe areevident after removal of the earring.

sitivity is found more frequently among women thanamong men.-* Aboul 10% of females are sensitive tonickel, and the majority become sensitized throughjewelry,-- although one repot! indicates that up to 20%of females are sensitive to nickel.-- Nickel dermatitis ofthe earlobe is common in nickel-sensitive females-'(Figs 6a and 6b). Only 1% to 2% of males are found tobe nickel sensitive, indicating a striking sex differ-ence.-^-'' The signs and symptoms of nickel sensitivityoften are manifested when nickel-containing goldjewelry, suchas watches (Fig 7) and bracelets, is worn.With the increased popularity of metal-framed eye-wear, a new source of prolonged contact with nickelhas arisen.

Nickel accounts for between 64% and 78% ofthecomposition of some nickel-based base metal alloys.Nickel has been found to produce more contactdermatitis than all other metals combined, and evenpartial denture frameworks containing as little as 1.5%nickel have been reported to cause contact dermatitis,-^indicating that the allergic response is virtually doseindependent in a sensitized individual. Reactions tonickel at extraoral sites at areas of contact withchromium-plated jewelry, as well as at areas totallyunrelated to direct exposure to metal have also beenreported.-^

Clinical reactions to nickel include edema of theeyelids, swollen and fissured lips, and chronic eczemaof the cheeks and palms. ' Nickel dermatitis canspread symmetrically to secondary sites snch as thearm, eyelids, sides ofthe neck, and face. How nickeldennatitis spreads to distant areas is not known.

Fig 7 Contact dermatitis has developed after ej Dosure tonickel in a watchband.

However, such spreads to secondary sites may becaused by contaminated, perspiring fingers of thepatient during the initial eruptive stage.

In orthodontics, allergic reactions to nickel incervical headgear-' as well as allergic reactions toorthodontic wires-^ and nickel-titanium orthodonticwires, have been reported. However, a recent study didnot find that nickel-sensitive persons are at greater riskof developing discomfort in the oral cavity whenwearing an intraoral orthodontic appliance.-'

Despite the reported allergenicity of nickel, fewcases of adverse reactions to nickel-containing dentalprostheses have been reported. The evidence thatnickel absorption intraorally exacerbates existing der-matitis is also minimal. Furthermore, there is little

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evidence available to implicate nickel as playing anypart in the rejection of nickel-containing prostheses,dental or orthopedic,-^ and it must be concluded thatnickel materials are generally safe to use in dentistry.

Chromate

Chromium differs from nickel in that it is not antigenicin metal form, but usually only in the hexavaletit saltform as chromate. Minute quantities of chromium saltscan, however, sensitize. Chromium compounds, onthe other hand, can induce cotitact dermatitis and evencause severe corrosive irritation ofthe skin. Exposurenormally occurs due to industrial exposure or throughhandling or use of detetBents, bleaches, shavingcreams, lotions, matches, and chromated catgut,-*However, it has been found that neither chromium-containing alloys nor chromium-plated objects, suchas jewelry, produce allergic contact dertnatitis inchromium-sensitive individuals. Although allei^icreactions resulting from contact with chromium-typealloys do occur, such allergies are usually due to someother metal in the alloy, normally nickel.-'

Although base tnetal alloys contain between 11 %and 35% chromium,-* chromium allergy is rarely seen.It is a less common problem than is nickel allergy. Thechances of an adverse reaction to chromium found indental materials, therefore, appears to be remote,--'-^but clinicians should nevertheless always be on thealert.

Platinum

Documented cases of platinum hypersensitivity areeven more rare than is chromium allergy, Platinosis isnot caused by metallic platinum but by contact withcomplex platinum salts and mainly affects platinumrefiners. Manifestations include pruritis, erythema,eczema, and urticaria, usually limited to the exposedparts ^^"

Cobalt

Cobalt-chromium alloys, forming the framework ofmetal partial dentures, and base metal alloys containabout 60% to 65% cobalt. They are regarded asbiocompatible because of the absence of nickel andberyllium in their composition. Cobalt is neverthelesslisted as a sensitizing metal. Allergic reactions tocobalt used in dentistry are very rare, however. Inpatients with no known allergy, preventive screening isunnecessary, • '

RestorationsRecently, Suzuki ^ ^¡^^¿ ^^^ ^-ray fluorescence spec-troscope to detect the allergenic metals in intraoralmetal restorations and personal and household itetnsof metal-allergic patients, Ofthe 275 subjects who hadpositive reactions to M-9 series patch tests, the 10most common elements detected for restorations weresilver, copper, zinc, gold, palladium, tin, mercury,indium, nickel, and chronnium. Allergens were de-tected in 161 patients, and the five elements wilhhigher allergetiicity were mercury, nickel, tin, chro-mium, and cobalt. In personal and household items,the top five elements with higher allergenicity werecopper, nickel, chromium, zinc, and molybdenutn,

Suzuki'- concluded that metal allet^y should betaken into consideration whenever dental treatmentswith alloys are planned. For patients with metalallergies, as well as for those without, it is prudent toavoid the use of mercury, nickel, and other elemetitswith a high sensitization rate, if possible, Evetiprecious metals, such as gold or platinum, may causeallergies, especially for individuals with a history ofdirect contact with intradermal tissues. It is recom-mended that similar types of alloys be used in a singleoral environment, where possible, to prevent corro-sion and dissolution by intraoral electric current.'^

Hildebrand et al ^ reported on 139 published casesof allergy to dental restorations. The most frequentsymptoms were local gingivitis and stomatitis (99 of139} while general and remote symptoms occurred in33 patients. Ninety-two female and 47 male patientswere involved. In another review, the same authors ''reported that allergic reactions to nickel, cobalt, andchrotnium in dental prostheses and restorations tnayappear either locally as stomatitis or distantly in theform of general or local contact dermatitis.

Allergy testing

Allergy testing of dental materials consists of epicuta-neous patch testing, in which readings of skin reac-tions are made on removal of patches after 48. 72, or96 hours. The presence of erythema, combined withedematous infiltration with or without papules orvesicles, is used as the criterion for a positive result, ^There is no need to perfonn an epimucous test todetect contact allergy in the oral mucosa, because theepicutaneous test gives the applicable information.'^

Axell et a l" designed a hst for patch test screeningof dental materials in cooperation with The Nordic

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Institute of Dental Materials (NIOM), This patch testseries (dental screening) consists of 21 chemicals. Thesubstances used in the list were chosen from reports inthe literature on contact allergic reactions to dentalmaterials. The dental screening test series was devisedfor use mainly in the investigation of patients withstomatitis, to ritle out a possible allergic reactionto a component in the dental materials used. In thedental screening test series, the main group of com-pounds is the methacrylate monomers, which arefundamental in dental resin materials, such as resincotnposite restorations, pit and fissure sealants, resinbonding materials, resin veneering materials, anddenture base materials. Triethylene/glycol dimethacry-latc (TEGDMA); urethane dimethacrylate (UDMA);ethyleneglycol dimethacrylate (EGDMA); bisphenolA-glycidyl methacrylate (bis-GMA) as well as accel-erators (N,N-dimethyl-p-to]uidine and 2-hydroxy-4-metttoxybenzophenone); aromatic sulfuric esters (meth-yldichloroberrzene sulfonate); eugenol; colophony;nickel sulfate; copper sulfate; and formaldehyde,among others, are included in the test series.^^

More recently, Axell et al-' described a new methodfor intraoral patch testing in which maxillary acrylicresin plates carrying test pieces contaitting 66% nickelwere applied for 48 hours. Readings were performed24 hours after removal. Although few, if any, clinicalsigns were elicited in three test suhjects, two of whomwere contact sensitive to nickel, biopsy specimensfrom the mucosal contact sites revealed lichenoidreactiorrs. Biopsy specimens from control sites showedno or slight nonspecific inflammatory reactions.^^ Theuse of biopsy testing for allergy may raise ethicalproblems, however.

Although not allergy testing per se, the Fleigl test, asimple, inexpensive, and reliable test, has also beenused^ to determine which metal objects produce con-tact dertnatitis irr nickel-sensitive individuals. Place-ment of two or three drops of a 1% alcoholic solutionof dimethylglyoxime and a few drops of ammonia wateron a metallic object, on skin, or in a solution, producesa strawberry-red insoluble salt in the presence ofavailable nickel. Most rrickel-containing alloys, exceptstainless steel, yield a positive test.

Recomme nd atio ns

Extensive reports In the literature indicate that certainmaterials in dentistry cause allergic hypersensitivity inpatients; nevertheless, currently, neither substantialdata nor clinical experience unequivocally contra-

indicates the discontinuance of any ofthe materials,including mercury-, nickel-, chromium-, or eugenol-containing dental materials, ' ^ Nevertheless, it isadvisable to ask patients questions concerning pasthypersensitivity to dental materials or following dentalprocedures. As pari of the medical history, eachpatient should also be specifically asked whether a rashor eczema had ever developed following the wearing ofearrings or jewelry.

In most patients, there is no indication for patchtesting. Routine use of such a test for all patientsshould be avoided, because the test procedure tnay insome cases provoke sensitization ofthe patient.-' Themain indication for an ep i cutaneous test is thepresence of local symptoms in the mouth close to adental restoration or prosthetic or orthodontic ap-pliance.

When skin symptoms are present, the patient shouldbe referred to a dermatologist for consultation. Theepicutaneous test should be undertaken by a dermatol-ogist. ^ Once a positive test has been confirmed by thedermatologist, the offending material should be with-drav/n. Rapid remission ofthe symptoms will confirmthe positive allergy test, and the patient should bemade aware of his or her aüergie status and be advisedto report it to future dental practitioners, A repeat testmay be necessary for true confirmation of allergy, butbecause of ethical considerations, may not be clinicaUypossible.

The dentist forms an important link In the differen-tial diagnosis of allergy. Ail possible allergenic dentalmaterials should be considered when allergic patientswith symptoms, whether intraoral or on unrelatedparts ofthe body, are tested.

AcknowledgmentsThe authors are grateful to Mrs Yvonne Skinner, Deparlment ofOrthodontics, for typjni; Lht manuscript, an welt as Kobtis van derMerwe.Henriette Rothmann, and Lydia Faber for llie photographic work.

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