9.biocompatibility of nickel containing dental alloys a review of literature

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31 JOURNAL OF DENTAL SCIENCES Volume 2 Issue 1 BIOCOMPATIBILITY OF NICKEL CONTAINING DENTAL ALLOYS : A REVIEW OF LITERATURE Address for Correspondence : Dr. Rakesh G. Makwana Department of Prosthodontics, Faculty of Dental Science, Dharmsinh Desai University, NADIAD-387001. GUJARAT Mobile : 9825395427 E-mail : [email protected] Dr. Rakesh G. Makwana Reader Department of Prosthodontics, Faculty of Dental Science, Dharmsinh Desai University, NADIAD-387001. GUJARAT Introduction “Nickel is with you and does things for you from the time you get up in the morning until you go to sleep at night.” This phrase from the brochure “The Romance of Nickel” clearly shows that this metal is present in a large variety of products, 1,2 and therefore is almost impossible to avoid. Nickel is an important cause of allergic contact dermatitis in the general population, both among children and adults, with 3 a worldwide prevalence of around 8.6%. The prevalence 4 among young females is even higher, around 17%. Sensitization to nickel can occur from skin contact with jewelry and consumer products, from occupational exposure and experimentally. It can occur either by exogenous (skin contact) or endogenous exposure (oral, inhalation). Nickel-containing dental alloys continue to be used successfully in the provision of various forms of dental care. Many of these alloys have applications in the construction of restorations designed to remain in clinical service for many years, including crowns, fixed bridgework, and removable partial dentures. Furthermore, nickel-containing alloys find extensive application in orthodontics, including metallic brackets, arch wires, bands, springs and ligature wires. Many instruments and devices, for example, endodontic instruments also contain nickel. An international workshop was held in Michigan, USA in 1985 on the biocompatibility, toxicity and hypersensitivity to alloy systems used in dentistry. The workshop summary concluded that despite the apparent lack of data on the biocompatibility of many cast and wrought dental alloys, their clinical efficacy is established. Given the importance of nickel in the development of optimal qualities of alloys used in dentistry, it is considered important to periodically provide a comprehensive, evidence based review of the existing knowledge and understanding of the biological reactions to and the biocompatibility of nickel containing dental alloys as the possible adverse effects have concerned both the people who have these alloys intraorally and the clinicians and dental technologists who work with them. Immune response to nickel a) Allergy to nickel-containing dental alloys Although many common allergens are found in dental materials, few allergic reactions are associated with the use of them. Mucosal allergy to metals may be rare for several reasons: saliva is constantly washing away potential allergens, which are swallowed; the vascularity of the oral mucosa allows for rapid dispersion of potential allergens; particulate metals may have a suppressive effect on chemotaxis, phagocytosis and immune response in 5 6 Abstract Nickel is very widely used in various applications in dentistry i.e. crown and bridge, cast partial dentures and orthodontic appliances to name a few. However, nickel is an important cause of allergic contact dermatitis in general population and as a result there have been a concern about the safety of both the people who have these alloys intraorally and the clinicians and dental technologists who work with them. The purpose of this article is to review the information regarding the biologic reactions to nickel in dentistry. Nickel is an allergen, but there is no evidence that individual patients are at a significant risk of developing sensitivity solely due to contact with nickel-containing dental appliances and restorations. Hypersensitivity reactions to nickel are only likely to occur with prior sensitization from non-dental contacts and even these are rare. Clinical evidence has been presented to show that small doses of nickel, e.g. from dental appliances,may induce tolerance to this allergen. The papers reviewed report low rates of release of nickel from dental alloys. Some nickel compounds, which are mildly cytotoxic, have been implicated as carcinogens by inhalation in industrial settings, but these compounds are not present in dentistry-related operations, including dental technology procedures. Nickel-containing alloys and compounds have not been associated with increased cancer risk by oral or dermal routes of exposure. It is concluded that, subject to use according to established techniques, nickel-containing dental alloys do not pose a risk to patients or members of the dental team. Key words - Nickel, Alloys, Dental appliances, Biomaterials, Toxicology, Allergy, Oral Lichen Planus, Hyposensitization

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Page 1: 9.Biocompatibility of Nickel Containing Dental Alloys a Review of Literature

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JOURNAL OF DENTAL SCIENCES Volume 2 Issue 1

BIOCOMPATIBILITY OF NICKEL CONTAININGDENTAL ALLOYS : A REVIEW OF LITERATURE

Address for Correspondence :Dr. Rakesh G. MakwanaDepartment of Prosthodontics, Faculty of Dental Science,Dharmsinh Desai University, NADIAD-387001. GUJARATMobile : 9825395427E-mail : [email protected]

Dr. Rakesh G. Makwana

Reader

Department of Prosthodontics, Faculty of Dental Science,Dharmsinh Desai University, NADIAD-387001. GUJARAT

Introduction

“Nickel is with you and does things for you from the time you get up in the morning until you go to sleep at night.” This phrase from the brochure “The Romance of Nickel” clearly shows that this metal is present in a large variety of products,

1,2and therefore is almost impossible to avoid.

Nickel is an important cause of allergic contact dermatitis in the general population, both among children and adults, with

3a worldwide prevalence of around 8.6%. The prevalence 4among young females is even higher, around 17%.

Sensitization to nickel can occur from skin contact with jewelry and consumer products, from occupational exposure and experimentally. It can occur either by exogenous (skin contact) or endogenous exposure (oral, inhalation).

Nickel-containing dental alloys continue to be used successfully in the provision of various forms of dental care. Many of these alloys have applications in the construction of restorations designed to remain in clinical service for many years, including crowns, fixed bridgework, and removable partial dentures. Furthermore, nickel-containing alloys find extensive application in orthodontics, including metallic brackets, arch wires, bands, springs and ligature wires. Many instruments and devices, for example, endodontic instruments also contain nickel.

An international workshop was held in Michigan, USA in 1985 on the biocompatibility, toxicity and hypersensitivity to alloy

systems used in dentistry. The workshop summary concluded that despite the apparent lack of data on the biocompatibility of many cast and wrought dental alloys, their clinical efficacy is established.

Given the importance of nickel in the development of optimal qualities of alloys used in dentistry, it is considered important to periodically provide a comprehensive, evidence based review of the existing knowledge and understanding of the biological reactions to and the biocompatibility of nickel containing dental alloys as the possible adverse effects have concerned both the people who have these alloys intraorally and the clinicians and dental technologists who work with them.

Immune response to nickel

a) Allergy to nickel-containing dental alloys

Although many common allergens are found in dental materials, few allergic reactions are associated with the use of them.

Mucosal allergy to metals may be rare for several reasons:

• saliva is constantly washing away potential allergens, which are swallowed;

• the vascularity of the oral mucosa allows for rapid dispersion of potential allergens;

• particulate metals may have a suppressive effect on chemotaxis, phagocytosis and immune response in

5

6

Abstract

Nickel is very widely used in various applications in dentistry i.e. crown and bridge, cast partial dentures and orthodontic appliances to name a few. However, nickel is an important cause of allergic contact dermatitis in general population and as a result there have been a concern about the safety of both the people who have these alloys intraorally and the clinicians and dental technologists who work with them.

The purpose of this article is to review the information regarding the biologic reactions to nickel in dentistry.

Nickel is an allergen, but there is no evidence that individual patients are at a significant risk of developing sensitivity solely due to contact with nickel-containing dental appliances and restorations. Hypersensitivity reactions to nickel are only likely to occur with prior sensitization from non-dental contacts and even these are rare. Clinical evidence has been presented to show that small doses of nickel, e.g. from dental appliances,may induce tolerance to this allergen. The papers reviewed report low rates of release of nickel from dental alloys. Some nickel compounds, which are mildly cytotoxic, have been implicated as carcinogens by inhalation in industrial settings, but these compounds are not present in dentistry-related operations, including dental technology procedures. Nickel-containing alloys and compounds have not been associated with increased cancer risk by oral or dermal routes of exposure. It is concluded that, subject to use according to established techniques, nickel-containing dental alloys do not pose a risk to patients or members of the dental team.

Key words - Nickel, Alloys, Dental appliances, Biomaterials, Toxicology, Allergy, Oral Lichen Planus, Hyposensitization

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JOURNAL OF DENTAL SCIENCES Volume 2 Issue 1

some systems and the paucity of the stratum corneum on mucous membranes may reduce the availability of carrier proteins to combine with metallic haptens to form

complete antigens.

Case reports of allergic reactions to intraoral nickel have 8,9,10,11occasionally been reported in the literature. The reports

are generally of patients with presensitisation to nickel who then, post-insertion of a nickel-containing orthodontic device, developed a form of dermatitis. The clinical signs and symptoms seen included oral oedema, perioral stomatitis, gingivitis, and extraoral manifestations such as eczematous rashes. The time taken for the dermatitis to resolve was from

8,9,10,11two days to several months, after removal of the device. With these reports in mind, it has been suggested that high content nickel–titanium wires should be avoided in nickel-sensitive patients, nickel-free alternatives being available for

12use in such cases.

Renewed interest in nickel allergy occurred when it was shown that a low incidence of both hypersensitivity and partial

13tolerance followed oral exposure to nickel.

b) Toxic reactions to nickel-containing dental alloys

An investigation of the effect on human epithelial cells of non-precious dental casting alloys containing up to 84% nickel showed that the concentration of nickel liberated from the

14metals did not reach cytotoxic levels. Orthodontic arch wires 15 that contained up to 54% nickel caused no cytotoxic effect.

Similarly, it has been determined that the maximum amount of nickel released from orthodontic arch wires was 700 times lower than the amount necessary to elicit cytotoxic reaction in

16a human peripheral blood mononuclear cell culture. These findings are important as the use of high level nickel-containing 'shape-memory' wires is increasing in orthodontics.

c) Oral lichen planus & lichenoid reactions to nickel-containing dental alloys

Metals like nickel, gold, palladium, cobalt or copper released from certain dental cast alloys are thought to be the cause of reactions such as lichenoid reactions and gingival inflammation. The most common reported metal is nickel. Dental materials in direct contact with the oral mucosa may directly alter the antigenicity of basal keratinocytes by the release of corrosion products. Contact allergy to dental materials (presented as lichenoid reactions) mostly involved

17type IV /delayed hypersensitivity reaction. Type IV hypersensitivity involved cell mediated immunity primarily macrophages and T lymphocytes which are sensitized to antigen (haptens), but it is unknown how metallic haptens released from dental materials are capable of triggering immune reactions.

d) Carcinogenic reactions to nickel and nickel-containing dental alloys

Laboratory investigations into the carcinogenicity of dental and orthopaedic alloys were undertaken decades ago, when it was noticed that workers in nickel and chromate refining

18had higher risks of nasal and lung tumors. These findings raised questions as to whether there may be risks to industrial and laboratory personnel exposed to forms of nickel in dust or

7

vapors during casting and grinding procedures. Since exposure is to nickel alloys, which are not carcinogens, these risks are not considered to exist in the dental laboratory. This is ensured when nickel-containing alloys are cast according to manufacturer's directions and the grinding and polishing of nickel-containing castings is accomplished using ducted air evacuation at the workbench. No reports of carcinogenicity associated with the intraoral use of dental alloys have been found.

Diagnosis

The diagnosis of a response to nickel in the oral mucosa is more difficult than on the skin. A known allergy to nickel should be determined when the patient completes the medical history. The patient should then be forewarned of a possible response to the nickel in dental appliances or prosthesis. If a nickel allergy is still in question, a diagnosis can be confirmed by a dermatologist by conducting a cutaneous sensitivity test called a patch test using 5% nickel

19sulphate in petroleum jelly.

Oral clinical signs and symptoms of nickel allergy can include 20the following: a burning sensation, gingival hyperplasia ,

labial desquamation, angular chelitis, erythema multiforme, periodontitis, stomatitis with mild to sever erythema, papular peri-oral rash, loss of taste or metallic taste, numbness,

21,22,23,24,25,26soreness at side of the tongue. It should be noted that symptoms can occur without signs. Extraoral

27manifestations of nickel allergy may have an intraoral origin. Before the diagnosis of nickel hypersensitivity can be made, other lesions should be eliminated including candidiasis, herpetic stomatitis, ulcers due to mechanical irritation and

28allergies to other materials including acrylic.

The nickel leachability test consists of solutions of 1% dimethylglyoxime and 10% ammonium hydroxide solutions which are mixed just prior to use. A moistened Q-tip with the combined solution is used for swabbing the appliance in vitro or samples can be immersed in the mixed solution. A positive test for nickel leachability is a colour change to red. While a positive result can be supportive of nickel leachability from the suspected dental material, a negative test is always

29overriden by the clinical response to removal of the material.

Treatment

If intra- oral signs and symptoms are present and a diagnosis of nickel hypersensitivity is established, the fixed or removable prosthesis should be replaced with another nickel free alloy. The nickel titanium archwire should be removed and replaced with a stainless steel archwire which is low in nickel content or preferably a titanium molybdenum alloy (TMA), hereafter known as “TMA”, which does not contain

30nickel.

Most patients who develop a reaction to Ni-Ti archwires 31subsequently tolerate stainless steel without a reaction.

This is believed to be a result of the nickel being tightly bound to the crystal lattice of the alloy, rendering them unable to be leached into the oral cavity. Stainless steel has been shown to release low amount of nickel in artificial saliva or sweat which

32could help account for its low allerginicity. In the rare event that the patient continues to manifest an allergic reaction, all stainless steel archwires and brackets should be removed. If

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any severe allergic reaction develops, the patient should be referred to a physician to be treated with antihistamines,

33anesthetics or topical corticosteriods. Attempts should be made to complete orthodontic treatment with TMA, fibre reinforced composite, pure Ti or gold-plate wires.

The most commonly used orthodontic brackets that do not contain nickel include ceramic brackets, products using polycrystalline alumna, single crystal sapphire and zirconia. Other nickel-free alternative brackets include polycarbonate brackets made from plastic polymers, titanium brackets and

29gold brackets.

Nickel hyposensitization

Since nickel sensitization is a hapten-specific immunological process, it is possible to induce immune tolerance to this metal. It had been shown that oral exposure to nickel through dental braces prior to ear piercing reduces the risk of

34, 35developing nickel allergy.

Oral administration of nickel sulfate 5.0mg once a week for 6 weeks in nickel-allergy patients significantly reduced the degree of contact allergy, as measured by patch test

36reactions before and after nickel administration.

Although “nickel vaccination” using oral hyposensitizing treatment is commercially available in some countries its

37efficacy is still to be definitely proven.

Discussion The current classification system for dental casting alloys is

broken down into Types I through IV based on the alloy's mechanical and physical properties. Before an alloy can be

classified according to its mechanical and physical properties, however, it first must be evaluated for its reactivity

in the oral cavity, which is governed by thermodynamic principles and electrochemical reaction kinetics. The

potential for corrosion is important in the bio-compatibility of an alloy. Corrosion can produce ionized elements that

interact with biological tissues. Therefore, corrosion increases the risk of toxicity, making it desirable to balance

corrosion against clinical performance when choosing an alloy.

Alloys used in dentistry usually contain at least four metalsand often more, making the issue of bio-compatibility

complex. Elements making up an alloy are not necessarily released in proportion to their percent weight; other factors

38can influence how much of a particular element is released. For example, the structure of an alloy may be single-phase

(homogeneous) or multiphase (heterogeneous). This phase structure can be important to the corrosive properties of an

alloy. Other factors found to affect corrosion are pH and the presence of proteins. For example, nickel is released from

nickel-chromium alloys to a much greater extent in an acidic 39 environment, and the presence of proteins in saline was

found to enhance the release of silver, copper, palladium and zinc compared with a saline solution alone (the opposite was

40found for nickel).

The objectives of this report are to present a review of the literature to cutaneous and mucosal nickel allergy arising after the placement of dental appliances.

Oral nickel contact allergy is rare. An extensive literature

search found only a few reports. 15 patients with lichenoid oral manifestations showed positive reactions when patch tested and the positivity to Ni represented the 12.9% of all positive reactions. The substitution of the fixed replacements of white metal and crowns and dental bridges improved the

41 42healing of the disease. Er and colleagues reported a case of localized gingival recession thought to be related to oral piercing of the lower lip. Oral allergic contact dermatitis from nickel has been associated with oral lichenoid eruptions.

43Scalf and colleagues reported on a series of 51 patients with oral lichen planus, 15.7% of whom reacted positively to

44nickel. Temesvari and Racz reported three adolescent girls who developed chelitis and edema of the face and lips 1 to 12 weeks after exposure to dental appliances. All three girls had +++ patch-test reactions to 5% nickel sulfate, and their symptoms resolved after they ceased wearing the dental

45appliances. Trombelli and colleagues reported the case of a woman who developed eczema on her hands and feet 6 months after having had dental braces placed. The patient had no signs of stomatitis and had a ++ patch-test reaction to nickel. Her dermatitis clinically improved after the removal of

46all dental braces. Wilson and Gould reported the case of an adolescent girl who had a history of patch-test-positive contact dermatitis from nickel and who moreover had a recall reaction of her dermatitis on her hips, forearms, and abdomen 2 weeks after having had dental braces placed. There was no oral involvement. The dermatitis resolved after

47the removal of the dental braces. Veien and colleagues reported on five girls with dermatitis or stomatitis related to orthodontic appliances. Four of the five girls developed extraoral dermatitis after the placement of dental appliances. The four girls had negative reactions on patch tests for nickel but tested positively to nickel on oral challenge. One of the five girls had developed pruritic oral discomfort after the placement of an orthodontic appliance. She had a ++ patch-test reaction to nickel; however, she had a negative reaction to nickel on oral challenge. After her dental appliance was

48removed, her discomfort resolved. Counts and colleagues reported a case of gingival hypertrophy secondary to a nickel-containing transpalatal arch appliance in an adolescent. The patient also had a positive patch-test reaction to 5% nickel sulfate.

In general, nickel-sensitive patients are not at an increased risk of developing an oral eruption after dental work when

49compared with patients who are not sensitive to nickel. It has been proposed that oral nickel exposure may actually protect

50patients from cutaneous nickel allergy. Van Hoogstraten 51and colleagues suggested that oral exposure to nickel

induces a specific T-cell tolerance, preventing subsequent 52cutaneous hypersensitivity. Marigo and colleagues reported

that continuous oral exposure to nickel might modulate nickel sensitivity through oral tolerance, which they demonstrated through in vitro cell proliferation assays. Working with 132

49nickel-sensitive adolescents, Kerosuo and colleagues found that dental braces may reduce nickel sensitivity and that there may be a protective threshold for oral tolerance to

53nickel. Haudrechy and colleagues reported that previous oral nickel exposure through dental appliances prevented 51 patients from developing allergic contact dermatitis from

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52nickel after ear piercing. Marigo and colleagues suggested that continuous oral exposure to nickel may lead to oral tolerance and may modulate nickel sensitivity.

Conclusion

Nickel is found in many alloys used in the practice of dentistry. These alloys have a long-standing history of successful use in dentistry, with no significant reports of biological effects. Nickel is a moderate allergen, as detected by patch testing for contact allergies, but there is no evidence that individual patients are at a significant risk of developing nickel sensitivity solely attributable to contact with nickel-containing dental appliances and restorations. There is no evidence of carcinogenicity associated with the intraoral use of nickel-containing dental alloys.

On the contrary, the frequency of Prosthodontic and Orthodontic treatment and the common use of nickel containing dental materials raise the interesting question of whether dental treatment may act to increase or decrease the burden of nickel hypersensitivity in the population. There is evidence that oral exposure to nickel may induce immunologic tolerance to nickel and thereby reduce the incidence of nickel allergies. Nevertheless when clinical signs or symptoms presumed to be due to nickel hypersensitivity are distressing to patients there are many choices of materials available to the dentist as alternatives.

References

1. The International Nickel Company. Romance of nickel. New York; 1960.

2. Liden C. Nickel in jewelry and associated products. Contact Dermatitis. 1992;26:73–75.

3. Thyssen JP, Linneberg A, Menne T, Johansen JD. The epidemiology of contact allergy in the general population – prevalence and main fi ndings. Contact Dermatitis. 2007;57:287–299.

4. Nielsen NH, Menne T. Allergic contact sensitization in an unselected Danish population. The Glostrup Allergy Study, Denmark. 1992 Acta Derm Venereol Suppl (Stockh). 1992;72:456–460.

5. Lang B, Morris H, Razzoog M. Proceedings of the international workshop: biocompatibility, toxicity and hypersensitivity to alloy systems used in dentistry. 1986.

6. Mj¨ or I. A summary. In: Lang B, Morris H, Razzoog M, editors. Proceedings of the international workshop: biocompatibility, toxicity and hypersensitivity to alloy systems used in dentistry. 1986. p. 319–26. Epidemiology

7. Haberman A, Pratt M, Storrs F. Contact dermatitis from beryllium in dental alloys. Contact Dermatitis 1993;28:157–62.

8. Trombelli L, Virgili A, Corazza M, Lucci R. Systemic contact dermatitis from an orthodontic appliance. Contact Dermatitis 1992;27:259–60.

9. Kerosuo H, Kanerva L. Systemic contact dermatitis caused by nickel in a stainless steel orthodontic appliance. Contact Dermatitis 1997;36:112–3.

10. Veien NK, Borchorst E, Hattel T, Laurberg G. Stomatitis

or systemically induced contact dermatitis from metal wire in orthodontic materials. Contact Dermatitis 1994;30:210–3.

11. Temesvari E, Racz I. Nickel sensitivity from dental prosthesis. Contact Dermatitis 1988;18:50–1.

12. Rahilly G, Price N. Nickel allergy and orthodontics. J Orthod 2003;30:171–4.

13. Vreeburg KJ, de Groot K, von Blomberg M, Scheper RJ. Induction of immunological tolerance by oral administration of nickel and chromium. J Dent Res 1984;63:124–8.

14. Gjerdet NR, Hero H. Metal release from heat-treated orthodont ic archwires. Acta Odontol Scan 1987;45:409–14.

15. Grimsdottir MR, Hensten-Pettersen A, Kullmann A. Cytotoxic effect of orthodontic appliances. Eur J Orthod 1992;14:47–53.

16. Jia W, Beatty MW, Reinhardt RA, Petro TM, Cohen DM, Maze CR, et al. Nickel release from orthodontic arch wires and cellular immune response to various nickel concentrations. J Biomed Mater Res 1999;48:488–95.

17. Bolewska J, Reibel J. T lymphocytes, Langerhans cells and HLA-DR expression on keratinocytes in oral lesions associated with amalgam restorations. J Oral Pathol Med1989;18:525-528.

18. Lodi G, Giuliani M, Majorana A, Sardella A, Bez C, Demarosi F, Carrassi A. Lichen planus and hepatitis C virus: a multicentre study of patients wit oral lesions and a systematic review. Br J Dermatol 2004; 151: 1172-1181.

19. Menne T, Brandup F, Thestrup-Pedersen K, Veien N K et al. Patch test reactivity to nickel alloys. Contact Dermatitis 1987; 16 : 255-259

20. Shelley B W. Gingival hyperplasia from dental braces. Cutis 1981; 28:149-150

21. Lamster I B, Kalfus D I, Steigerward P J, Chasens A I. Rapid loss of alveolar bone association with nonprecious alloy crowns in two patients with nickel hypersensitivity. J Periodontol 1987; 58:486-492.

22. Starkjaer L, Menne T. Nickel allergy and orthodontic treatment . Eur J Orthod 1990; 12:284-289.

23. Bruce G J, Hall H B. Nickel hypersensitivity – related periodontitis. Compend Contin Educ Dent 1995; 12:178, 180-184.

24. Lindsten R, Kurol J. Orthodintic appliances in relation to nickel hypersensitivity: a review. J Orofac Orthop 1997; 58:100-108

25. Cohen L M, Cohen J L. erythema multiform associated with contact dermatitis to poison ivy:three cases and review of literature. Cutis 1998; 62:139-142.

26. Janson G R P, Dainesi E A, Consolaro A, Woodside D G, Freitas M R. Nickel hypersensitivity reaction before, during and after orthodontic therapy. Am J Orthod Dentofacial Orthop 1998; 113 : 655-660.

27. Schultz J C, Connelly E, Glesne , Warshaw E M.

Page 5: 9.Biocompatibility of Nickel Containing Dental Alloys a Review of Literature

35

JOURNAL OF DENTAL SCIENCES Volume 2 Issue 1

Cutaneous and oral eruption from oral exposure to nickel in dental braces. Dermatitis 2004; 15: 154-157.

28. Rahilly G, Price N. Nickel allergy and orthodontics. J Orthod 2003; 30:171-174.

29. J. Noble, S. I. Ahing, N. E. Karaiskos, W. A. Wiltshire. Nickel allergy and orthodontics, a review and report of two cases. Br Dent J 2008;204:297-300.

30. Kim H, Johnson J. Corrosion of stainless steel, nickel-titanium, coated nickel-titanium and titanium orthodontic wire. Angel Orthod 1999; 69:39-44.

31. Toms AP.The corrosion of orthodontic wire. Eur J orthod 1988; 10:87-97.

32. Jensen C S, Lisby S, Baadsgaard O, Byrialsen K, Menne T. Release of nickel ions from stainless steel alloys used in dental braces and their patch test reactivity in nickel –sensitive individuals. Contact Dermatitis 2003; 48: 300-304.

33. Dou X, Liu L, Zhu X J. Nickel – elicited systemic contact dermatitis. Contact Dermatitis 2003; 48: 126-129.

34. Mortz CG, Lauritsen JM, Bindslev-Jensen C, Andeersen KE. Nickel sensitization in adolescents and association with ear piercing, use of dental braces and hand eczema. Acta Derm Venereol Suppl (Stockh). 2002;82:359–364.

35. Van Hoogstraten IMW, Andersen KE, von Blomberg BME, et al. Reduced prevalence of nickel allergy upon oral nickel contact at an early age. Clin Exp Immunol. 1991;85:441–445.

36. Sjovall P, Christensen OB, Moller H. Oral Hyposensitization in nickel allergy. J Am Acad Dermatol. 1987;17:774–778.

37. Minelli M. Nickel vaccination: today and tomorrow. Int J Immunopathol Pharmacol. 2005;18(4 Suppl):19–20.

38. Wataha JC. Biocompatibility of dental casting alloys: a review. J Prosthet Dent 2000;83:223–234.

39. Brune D. Metal release from dental biomaterials. Biomaterials 1986;7:163–75.40. Wataha JC, Nelson SK, Lockwood PE. Elemental release from dental casting alloys into biological media with and without protein. Dent Mater 2001;17:409–14

41. Ditrichova, D.; Kapralova, S.; Tichy, M.; Ticha, V.; Dobesova, J.; Justova, E.; Eber, M.; Pirek, P. Oral lichenoid lesions and allergy to dental materials. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech. Repub., 2007, 151, 333.

42. Er N, Ozkavaf A, Berberoglu A, Yamalik N. An unusual case of gingival recession: oral piercing. J Periodontol 2000;71:1767-9.

43. Scalf L, Fowler J, Morgan K, et al. Dental metal allergy in patients with oral, cutaneous, and genital lichenoid reactions. Am J Contact Dermat 2001;12:146-50.

44. Temesvari E, Racz I. Nickel sensitivity from dental prosthesis. Contact Dermatitis 1988;18:50-1.

45. Trombelli L, Virgili A, Corazza M, et al. Systemic contact dermatitis from an orthodontic appliance. Contact Dermatitis 1992;27:259-60.

46. Wilson A, Gould D. Nickel dermatitis from a dental prosthesis without buccal involvement. Contact Dermatitis 1989;21:53.

47. Veien N, Borchorst E, Hattel T, et al. Stomatitis or systemicallyinduced contact dermatitis from metal wire in orthodontic materials. Contact Dermatitis 1994;30:210-3.

48. Counts AL, Miller MA, Khakhria ML, Strange S. Nickel allergy associated with tranpalatal arch appliance. J Orofac Orthop 2002; 63:509-15.

49. Kerosuo H, Kullaa A, Kerosuo E, et al. Nickel allergy in adolescents in relation to orthodontic treatment and piercing of ears. Am J Orthod Dentofacial Orthop 1996;109:148-54.

50. Mortz C, Lauritsen J, Bindslev-Jensen C, et al. Nickel sensitization in adolescents and association with ear piercing, use of dental braces and hand eczema. Acta Derm Venereol 2002;82:359-64.

51. Van Hoogstraten I, Andersen K, Von Blomberg B, et al. Reduced frequency of nickel allergy upon oral nickel contact at an early age. Clin Exp Immunol 1991;85:441-5.

52. Marigo M, Nouer DF, Genelhu MC, et al. Evaluation of immunologic profile in patients with nickel sensitivity due to use of fixed orthodontic appliances. Am J Orthod Dentofacial Orthop 2003;124:46-52.

53. Haudrechy P, Mantout B, Frappaz A, et al. Nickel release from stainless steels. Contact Dermatitis 1997;37:113-7.