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Orofacial reaction to methacrylates in dental materials: A clinical report
Orofacial reaction to methacrylates in dental materials: A clinical report Nicolas Martin, BDS, PhD, PgCert Ed, MFDS RCS,a Hazel K. Bell, MRCP, MRCGP, MD,b Lesley P. Longman, BSc, BDS, PhD,c and Clodagh M. King, MDd Liverpool University Dental Hospital and Royal Liverpool University Hospital, Liverpool, United Kingdom This clinical report presents an unusual response of acute gingivostomatitis caused by contact sensitivity to the methacrylate compounds present in a dental restorative material. (J Prosthet Dent 2003;90: 225-7.)
M
ethacrylate resins are found in a variety of dental materials including denture base polymers, synthetic teeth, provisional and definitive fixed prostheses, sealants, dentin adhesives, luting agents for crowns and fixed partial dentures, and tooth-colored restorative materials. In spite of the proven efficiency and safety of these materials, they contain several contact allergens.1,2 Dental personnel and patients may become sensitized to these constituents. Hydroxy-ethyl-methacrylate (HEMA) is a hydrophilic acrylate monomer commonly found in dentin bonding systems in solution in either water or a volatile solvent such as acetone or alcohol.3,4 It is also found in many medical devices and materials, such as electrosurgical grounding plates, soft contact lenses, and drug delivery systems.5 Most resin-based medical devices containing dimethacrylate monomers are polymerized at high pressure and temperature forming highly crosslinked 3-dimensional network systems with the HEMA component in a bound state.6,7 However, in dentistry, resin-based adhesives and luting agents require polymerization intraorally, which precludes the use of elevated pressure and temperature to achieve a high degree of conversion. As a result, under optimal conditions, there may be at least 30% unpolymerized residual monomer that may leach out to the surrounding tooth or oral environment. Direct measurement of acrylate release from a range of resin-based materials has shown that triethylene glycol dimethacrylate, HEMA, and benzyl peroxide can elute into an aqueous medium such as saliva and facilitate sensitization.8 In addition, HEMA has been shown to diffuse through dentin in teeth restored with resin-based glass ionomers and compomers.9 This diffusion is in a sustained movement into the pulp space during the first day of restoring the tooth, with exponential decline thereafter. To date, most of the research examining the degree of polymerization of resin-based dental restorative systems has been concerned with the effects on the mechanical
properties of the system. Residual methacrylate groups, resulting from a reduced degree of polymerization, have been implicated in causing a reduction in the hardness, wear resistance, strength, and color stability of Bis-phenol glycidyl-dimethacrylate– based dental restorative systems.10,11 However, there is little mention in the literature of the effect of these residual methacrylate monomers in causing allergic reactions. Fisher12 first described allergic sensitization of the skin and oral mucosa to acrylic resin denture materials in 1956, and methacrylates are now well recognized as contact allergens. Two reviews of patch testing with methacrylates13,14 have identified the most common allergens to be 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, 2-HEMA, and triethylene glycol dimethacrylate. This cannot be interpreted as an accurate ranking because many methacrylate compounds contain undeclared “other” components.13 The patient presented in this report reacted to many methacrylate compounds, and cross-reactions between acrylates are known to occur.15 In spite of the widespread use of methacrylates in dental materials, in a study of Swedish dentists with hand eczema, only 5% showed positive patch test reactions to methacrylates, all of them reacting to HEMA and most, also, to ethyleneglycol dimethacrylate (EGDMA).16 Intraoral reactions in patients are less common. In a 15year study of patch testing to methacrylates, 67 patients with positive reactions were identified, 47 of whom had been sensitized at work and no oral reactions in dental patients were reported.14 Methacrylates rarely have been implicated in oral lichenoid reactions.17 Two patients with severe gingivostomatitis have been described, 1 caused by sensitivity to an epoxy diacrylate18 and the other to methyl methacrylate in a provisional crown.19 This clinical report describes a patient whose medical history and patch test results indicated a type IV delayed hypersensitivity reaction to methacrylate constituents of the dental materials to which she was exposed.
a
CLINICAL REPORT
Lecturer and Hon. Specialist Registrar in Restorative Dentistry. Consultant in Dermatology. c Consultant in Restorative Dentistry. d Consultant in Dermatology. b
SEPTEMBER 2003
A 47-year-old woman attended the Accident and Emergency Department of the Liverpool University THE JOURNAL OF PROSTHETIC DENTISTRY 225
THE JOURNAL OF PROSTHETIC DENTISTRY
Table I. Patch tests results at 96 hrs 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Epoxy Resin ⫹⫹ Nickel Sulphate ⫹⫹ Methyl Methacrylate ⫹⫹ Triethylene glycol dimethacrylate ⫹⫹ Ethyleneglycol dimethacrylate ⫹⫹ Bis-GMA ⫹⫹ Butanediol dimethacrylate ⫹⫹ Hydroxyethylmethacrylate ⫹⫹⫹⫹ Dimethylaminoethyl methacrylate ⫹⫹ Tetrahydrofurfuryl methacrylate ⫹⫹
⫹ ⫹⫹ ⫹⫹⫹ ⫹⫹⫹⫹
Erythema Erythema and edema Erythema, edema and vesicles Bullous or ulcerative reaction
Dental Hospital with swelling and discomfort of the lips, tongue and gingival tissues of the maxillary anterior teeth. A resin bonded fixed partial denture replacing a maxillary central incisor had been reluted with a composite luting agent (Nexus lute; Kerr, Orange, Calif) by her dentist the previous day, and symptoms began several hours post dental treatment. On examination, the chin, lips, tongue, and anterior hard palate were swollen, with blister formation. She had previously commenced therapy with chlorpheniramine (4 mg/every 4 to 6 hours), and a combination-preparation of ampicillin (250 mg) and flucloxacillin (250 mg, every 6 hours) prescribed by her physician. In addition, on presentation, the patient was given intramuscular hydrocortisone (100 mg) and oral aciclovir (400 mg, 5 times daily, 5 days), because herpes simplex stomatitis20 could not be excluded. Bacterial and viral swabs were subsequently reported to be negative. At the 24-hour recall appointment, resolution of the inflammation and reduction in the number and size of blisters could be seen, and full resolution occurred within 10 days. The fixed partial denture had originally been luted 2 years earlier with the same materials with no adverse effects. However, the patient experienced a similar, but less severe, reaction 6 months after placement of the fixed partial denture during refitting, when no local anesthetic was used. There was no history of atopy. The patient wore latex gloves regularly without problems and was not taking any medication at the time. The materials used at the original episode included nonpowdered latex gloves; local anaesthetic, 4% prilocaine; a metal-ceramic fixed-partial denture of semiprecious alloy (unspecified) and resin-based adhesive and composite luting agent (Nexus lute) containing ethyl alcohol and un-polymerized methacrylate ester monomers, HEMA, and Bis-phenol glycidyl-dimethacrylate, as purported by the manufacturer (Kerr, Orange, Calif). A provisional diagnosis of contact allergy was reached and the patient was referred to the dermatology clinic for further investigation. Skin prick tests to natural rub226
MARTIN ET AL
ber latex, procaine and prilocaine (with and without octapressin), and lignocaine with adrenaline were negative. Patch testing with the European Standard Battery,21 a steroid battery, natural rubber latex, a local anaesthetic series, and a dental battery were also performed. The results at 96 hours are shown in Table I. The clinical presentation and time course of the reaction are consistent with a type IV delayed hypersensitivity reaction to the methacrylate constituents of dental materials to which the patient was exposed. In addition to the acrylates, she also demonstrated positive patch test reactions to nickel and epoxy resin. Although nickel may have been present in the metal-ceramic fixed partial denture, the severity and time course of the reaction and the strongly positive patch test results to multiple methacrylate compounds suggest that the latter allergens were responsible. The sensitivity to epoxy resin may have been due to historical use of a popular household glue based on epoxy resin (Araldite; Vantico AG, Basel, Switzerland) or alternatively may have been the result of contamination of the methacrylate compounds with epoxy resin. This has previously been believed to be the mechanism behind concomitant sensitivities in dental personnel.1
SUMMARY Delayed hypersensitivity reactions in and around the mouth of patients exposed to methacrylate compounds in dental materials are rare. This clinical report describes a patient whose medical history and patch test results indicated a type IV delayed hypersensitivity reaction to methacrylate constituents of the dental materials to which she was exposed. It explains why resin-based dental materials are more likely to trigger this type of reaction. It is important that contact allergy is recognized by dental and medical staff, because repeated exposure may lead to increasingly severe reactions. The authors greatly appreciate the support of Dr Anne Field, Senior Lecturer and Honorary Consultant in Oral Medicine at Liverpool University Dental Hospital.
REFERENCES 1. Kanerva L, Estlander T, Jolanki R. Allergic contact dermatitis from dental composite resins due to aromatic epoxy acrylates and aliphatic acrylates. Contact Dermatitis 1989;20:201-11. 2. Jolanki R, Kanerva L, Estlander T. Occupational allergic contact dermatitis caused by epoxy diacrylate in ultraviolet-light-cured paint and bisphenol A in dental composite resin. Contact Dermatitis 1995;33:94-9. 3. Rosales-Leal JI, Osorio R, Holgado-Terriza JA, Cabrerizo-Vilchez MA, Toledano M. Dentin wetting by four adhesive systems. Dent Mater 2001; 17:526-32. 4. Abate PF, Rodriguez VI, Macchi RL. Evaporation of solvent in one-bottle adhesives. J Dent 2000;28:437-40. 5. Kanerva L, Alanko K. Allergic contact dermatitis from 2-hydroxyethyl methacrylate in an adhesive on an electrosurgical earthing plate. Eur J Dermatol 1998;8:521-4. 6. Court JL, Redman RP, Wang JH, Leppard SW, OByrne VJ, Small SA, et al. A novel phosphorylcholine-coated contact lens for extended wear use. Biomaterials 2001;22:3261-72.
VOLUME 90 NUMBER 3
MARTIN ET AL
7. Kantarci Z, Aksoy S, Hasirci N. Estimation of monomer content in polymethyl methacrylate contact lens materials by Raman spectroscopy. Int J Artif Organs 1997;20:407-11. 8. Hume WR, Gerzia TM. Bioavailability of components of resin-based materials which are applied to the teeth. Crit Rev Oral Biol Med 1996;7: 172-9. 9. Hamid A, Okamoto A, Iwaku M, Hume WR. Component release from light-activated glass ionomer and compomer cements. J Oral Rehabil 1998;25:94-9. 10. Eliades GC, Vougiouklakis GJ, Caputo AA. Degree of double bond conversion in light-cured composites. Dent Mater 1987;3:19-25. 11. Ferracane JL, Greener EH. Fourier transform infrared analysis of degree of polymerization in unfilled resins—methods comparison. J Dent Res 1984; 63:1093-5. 12. Fisher AA. Allergic sensitization of the skin and oral mucosa to acrylic resin denture materials. J Prosthet Dent 1956;593– 602. 13. Kanerva L, Jolanki R, Estlander T. 10 years of patch testing with the (meth) acrylate series. Contact Dermatitis 1997;37:255-8. 14. Tucker SC, Beck MH. A 15-year study of patch testing to (meth) acrylates. Contact Dermatitis 1999;40:278-9. 15. Jordan WP Jr. Cross-sensitization patterns in acrylate allergies. Contact Dermatitis 1975;1:13-5. 16. Wallenhammar LM, Ortengren U, Andreasson H, Barregard L, Bjorkner B, Karlsson S, et al. Contact allergy and hand eczema in Swedish dentists. Contact Dermatitis 2000;43:192-9. 17. Auzerie V, Mahe E, Marck Y, Auffret N, Descamps V, Crickx B. Oral lichenoid eruption due to methacrylate allergy. Contact Dermatitis 2001; 45:241.
SEPTEMBER 2003
THE JOURNAL OF PROSTHETIC DENTISTRY
18. Kanerva L, Zwanenburg R. Allergic contact reactions to poly(oxy-1,2ethanediyl) alpha, alpha'-[(1-methylethylidene)di-4,1-phenylene]bis[omega-[(2-methyl-1-oxo-2-propenyl)oxy](BIS-EMA). Contact Dermatitis 2000;43:115-7. 19. Hochman N, Zalkind M. Hypersensitivity to methyl methacrylate: mode of treatment. J Prosthet Dent 1997;77:93-6. 20. Field A, Longman L. Tyldesley’s oral medicine. 5th ed. Oxford: Oxford University Press; 2003. p. 41-2. 21. Bruynzeel DP, Anderson KE, Camaras JG, Lachapelle JM, Menne T, White IR. The European standard series. European Environmental and Contact Dermatitis Research Group (EECDRG). Contact Dermatitis 1995;33: 145-8. Reprint requests to: DR N. MARTIN LIVERPOOL UNIVERSITY DENTAL HOSPITAL PEMBROKE PLACE LIVERPOOL L3 5PS UK FAX: ⫹44 7065803 E-MAIL: [email protected] Copyright © 2003 by The Editorial Council of The Journal of Prosthetic Dentistry. 0022-3913/2003/$30.00 ⫹ 0
doi:10.1016/S0022-3913(03)00331-7
227
M
ethacrylate resins are found in a variety of dental materials including denture base polymers, synthetic teeth, provisional and definitive fixed prostheses, sealants, dentin adhesives, luting agents for crowns and fixed partial dentures, and tooth-colored restorative materials. In spite of the proven efficiency and safety of these materials, they contain several contact allergens.1,2 Dental personnel and patients may become sensitized to these constituents. Hydroxy-ethyl-methacrylate (HEMA) is a hydrophilic acrylate monomer commonly found in dentin bonding systems in solution in either water or a volatile solvent such as acetone or alcohol.3,4 It is also found in many medical devices and materials, such as electrosurgical grounding plates, soft contact lenses, and drug delivery systems.5 Most resin-based medical devices containing dimethacrylate monomers are polymerized at high pressure and temperature forming highly crosslinked 3-dimensional network systems with the HEMA component in a bound state.6,7 However, in dentistry, resin-based adhesives and luting agents require polymerization intraorally, which precludes the use of elevated pressure and temperature to achieve a high degree of conversion. As a result, under optimal conditions, there may be at least 30% unpolymerized residual monomer that may leach out to the surrounding tooth or oral environment. Direct measurement of acrylate release from a range of resin-based materials has shown that triethylene glycol dimethacrylate, HEMA, and benzyl peroxide can elute into an aqueous medium such as saliva and facilitate sensitization.8 In addition, HEMA has been shown to diffuse through dentin in teeth restored with resin-based glass ionomers and compomers.9 This diffusion is in a sustained movement into the pulp space during the first day of restoring the tooth, with exponential decline thereafter. To date, most of the research examining the degree of polymerization of resin-based dental restorative systems has been concerned with the effects on the mechanical
properties of the system. Residual methacrylate groups, resulting from a reduced degree of polymerization, have been implicated in causing a reduction in the hardness, wear resistance, strength, and color stability of Bis-phenol glycidyl-dimethacrylate– based dental restorative systems.10,11 However, there is little mention in the literature of the effect of these residual methacrylate monomers in causing allergic reactions. Fisher12 first described allergic sensitization of the skin and oral mucosa to acrylic resin denture materials in 1956, and methacrylates are now well recognized as contact allergens. Two reviews of patch testing with methacrylates13,14 have identified the most common allergens to be 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, 2-HEMA, and triethylene glycol dimethacrylate. This cannot be interpreted as an accurate ranking because many methacrylate compounds contain undeclared “other” components.13 The patient presented in this report reacted to many methacrylate compounds, and cross-reactions between acrylates are known to occur.15 In spite of the widespread use of methacrylates in dental materials, in a study of Swedish dentists with hand eczema, only 5% showed positive patch test reactions to methacrylates, all of them reacting to HEMA and most, also, to ethyleneglycol dimethacrylate (EGDMA).16 Intraoral reactions in patients are less common. In a 15year study of patch testing to methacrylates, 67 patients with positive reactions were identified, 47 of whom had been sensitized at work and no oral reactions in dental patients were reported.14 Methacrylates rarely have been implicated in oral lichenoid reactions.17 Two patients with severe gingivostomatitis have been described, 1 caused by sensitivity to an epoxy diacrylate18 and the other to methyl methacrylate in a provisional crown.19 This clinical report describes a patient whose medical history and patch test results indicated a type IV delayed hypersensitivity reaction to methacrylate constituents of the dental materials to which she was exposed.
a
CLINICAL REPORT
Lecturer and Hon. Specialist Registrar in Restorative Dentistry. Consultant in Dermatology. c Consultant in Restorative Dentistry. d Consultant in Dermatology. b
SEPTEMBER 2003
A 47-year-old woman attended the Accident and Emergency Department of the Liverpool University THE JOURNAL OF PROSTHETIC DENTISTRY 225
THE JOURNAL OF PROSTHETIC DENTISTRY
Table I. Patch tests results at 96 hrs 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Epoxy Resin ⫹⫹ Nickel Sulphate ⫹⫹ Methyl Methacrylate ⫹⫹ Triethylene glycol dimethacrylate ⫹⫹ Ethyleneglycol dimethacrylate ⫹⫹ Bis-GMA ⫹⫹ Butanediol dimethacrylate ⫹⫹ Hydroxyethylmethacrylate ⫹⫹⫹⫹ Dimethylaminoethyl methacrylate ⫹⫹ Tetrahydrofurfuryl methacrylate ⫹⫹
⫹ ⫹⫹ ⫹⫹⫹ ⫹⫹⫹⫹
Erythema Erythema and edema Erythema, edema and vesicles Bullous or ulcerative reaction
Dental Hospital with swelling and discomfort of the lips, tongue and gingival tissues of the maxillary anterior teeth. A resin bonded fixed partial denture replacing a maxillary central incisor had been reluted with a composite luting agent (Nexus lute; Kerr, Orange, Calif) by her dentist the previous day, and symptoms began several hours post dental treatment. On examination, the chin, lips, tongue, and anterior hard palate were swollen, with blister formation. She had previously commenced therapy with chlorpheniramine (4 mg/every 4 to 6 hours), and a combination-preparation of ampicillin (250 mg) and flucloxacillin (250 mg, every 6 hours) prescribed by her physician. In addition, on presentation, the patient was given intramuscular hydrocortisone (100 mg) and oral aciclovir (400 mg, 5 times daily, 5 days), because herpes simplex stomatitis20 could not be excluded. Bacterial and viral swabs were subsequently reported to be negative. At the 24-hour recall appointment, resolution of the inflammation and reduction in the number and size of blisters could be seen, and full resolution occurred within 10 days. The fixed partial denture had originally been luted 2 years earlier with the same materials with no adverse effects. However, the patient experienced a similar, but less severe, reaction 6 months after placement of the fixed partial denture during refitting, when no local anesthetic was used. There was no history of atopy. The patient wore latex gloves regularly without problems and was not taking any medication at the time. The materials used at the original episode included nonpowdered latex gloves; local anaesthetic, 4% prilocaine; a metal-ceramic fixed-partial denture of semiprecious alloy (unspecified) and resin-based adhesive and composite luting agent (Nexus lute) containing ethyl alcohol and un-polymerized methacrylate ester monomers, HEMA, and Bis-phenol glycidyl-dimethacrylate, as purported by the manufacturer (Kerr, Orange, Calif). A provisional diagnosis of contact allergy was reached and the patient was referred to the dermatology clinic for further investigation. Skin prick tests to natural rub226
MARTIN ET AL
ber latex, procaine and prilocaine (with and without octapressin), and lignocaine with adrenaline were negative. Patch testing with the European Standard Battery,21 a steroid battery, natural rubber latex, a local anaesthetic series, and a dental battery were also performed. The results at 96 hours are shown in Table I. The clinical presentation and time course of the reaction are consistent with a type IV delayed hypersensitivity reaction to the methacrylate constituents of dental materials to which the patient was exposed. In addition to the acrylates, she also demonstrated positive patch test reactions to nickel and epoxy resin. Although nickel may have been present in the metal-ceramic fixed partial denture, the severity and time course of the reaction and the strongly positive patch test results to multiple methacrylate compounds suggest that the latter allergens were responsible. The sensitivity to epoxy resin may have been due to historical use of a popular household glue based on epoxy resin (Araldite; Vantico AG, Basel, Switzerland) or alternatively may have been the result of contamination of the methacrylate compounds with epoxy resin. This has previously been believed to be the mechanism behind concomitant sensitivities in dental personnel.1
SUMMARY Delayed hypersensitivity reactions in and around the mouth of patients exposed to methacrylate compounds in dental materials are rare. This clinical report describes a patient whose medical history and patch test results indicated a type IV delayed hypersensitivity reaction to methacrylate constituents of the dental materials to which she was exposed. It explains why resin-based dental materials are more likely to trigger this type of reaction. It is important that contact allergy is recognized by dental and medical staff, because repeated exposure may lead to increasingly severe reactions. The authors greatly appreciate the support of Dr Anne Field, Senior Lecturer and Honorary Consultant in Oral Medicine at Liverpool University Dental Hospital.
REFERENCES 1. Kanerva L, Estlander T, Jolanki R. Allergic contact dermatitis from dental composite resins due to aromatic epoxy acrylates and aliphatic acrylates. Contact Dermatitis 1989;20:201-11. 2. Jolanki R, Kanerva L, Estlander T. Occupational allergic contact dermatitis caused by epoxy diacrylate in ultraviolet-light-cured paint and bisphenol A in dental composite resin. Contact Dermatitis 1995;33:94-9. 3. Rosales-Leal JI, Osorio R, Holgado-Terriza JA, Cabrerizo-Vilchez MA, Toledano M. Dentin wetting by four adhesive systems. Dent Mater 2001; 17:526-32. 4. Abate PF, Rodriguez VI, Macchi RL. Evaporation of solvent in one-bottle adhesives. J Dent 2000;28:437-40. 5. Kanerva L, Alanko K. Allergic contact dermatitis from 2-hydroxyethyl methacrylate in an adhesive on an electrosurgical earthing plate. Eur J Dermatol 1998;8:521-4. 6. Court JL, Redman RP, Wang JH, Leppard SW, OByrne VJ, Small SA, et al. A novel phosphorylcholine-coated contact lens for extended wear use. Biomaterials 2001;22:3261-72.
VOLUME 90 NUMBER 3
MARTIN ET AL
7. Kantarci Z, Aksoy S, Hasirci N. Estimation of monomer content in polymethyl methacrylate contact lens materials by Raman spectroscopy. Int J Artif Organs 1997;20:407-11. 8. Hume WR, Gerzia TM. Bioavailability of components of resin-based materials which are applied to the teeth. Crit Rev Oral Biol Med 1996;7: 172-9. 9. Hamid A, Okamoto A, Iwaku M, Hume WR. Component release from light-activated glass ionomer and compomer cements. J Oral Rehabil 1998;25:94-9. 10. Eliades GC, Vougiouklakis GJ, Caputo AA. Degree of double bond conversion in light-cured composites. Dent Mater 1987;3:19-25. 11. Ferracane JL, Greener EH. Fourier transform infrared analysis of degree of polymerization in unfilled resins—methods comparison. J Dent Res 1984; 63:1093-5. 12. Fisher AA. Allergic sensitization of the skin and oral mucosa to acrylic resin denture materials. J Prosthet Dent 1956;593– 602. 13. Kanerva L, Jolanki R, Estlander T. 10 years of patch testing with the (meth) acrylate series. Contact Dermatitis 1997;37:255-8. 14. Tucker SC, Beck MH. A 15-year study of patch testing to (meth) acrylates. Contact Dermatitis 1999;40:278-9. 15. Jordan WP Jr. Cross-sensitization patterns in acrylate allergies. Contact Dermatitis 1975;1:13-5. 16. Wallenhammar LM, Ortengren U, Andreasson H, Barregard L, Bjorkner B, Karlsson S, et al. Contact allergy and hand eczema in Swedish dentists. Contact Dermatitis 2000;43:192-9. 17. Auzerie V, Mahe E, Marck Y, Auffret N, Descamps V, Crickx B. Oral lichenoid eruption due to methacrylate allergy. Contact Dermatitis 2001; 45:241.
SEPTEMBER 2003
THE JOURNAL OF PROSTHETIC DENTISTRY
18. Kanerva L, Zwanenburg R. Allergic contact reactions to poly(oxy-1,2ethanediyl) alpha, alpha'-[(1-methylethylidene)di-4,1-phenylene]bis[omega-[(2-methyl-1-oxo-2-propenyl)oxy](BIS-EMA). Contact Dermatitis 2000;43:115-7. 19. Hochman N, Zalkind M. Hypersensitivity to methyl methacrylate: mode of treatment. J Prosthet Dent 1997;77:93-6. 20. Field A, Longman L. Tyldesley’s oral medicine. 5th ed. Oxford: Oxford University Press; 2003. p. 41-2. 21. Bruynzeel DP, Anderson KE, Camaras JG, Lachapelle JM, Menne T, White IR. The European standard series. European Environmental and Contact Dermatitis Research Group (EECDRG). Contact Dermatitis 1995;33: 145-8. Reprint requests to: DR N. MARTIN LIVERPOOL UNIVERSITY DENTAL HOSPITAL PEMBROKE PLACE LIVERPOOL L3 5PS UK FAX: ⫹44 7065803 E-MAIL: [email protected] Copyright © 2003 by The Editorial Council of The Journal of Prosthetic Dentistry. 0022-3913/2003/$30.00 ⫹ 0
doi:10.1016/S0022-3913(03)00331-7
227