Oral lichen planus linked to dental mercury amalgam fillings

Allergy to copper derived from dental alloys as a possible cause of oral lesions of lichen planus
Frykholm KO, Frithiof L, Fernström ÅIB, Moberger G, Blohm SG, Björn E
Acta Derm‐Venerol 49 1969 268‐81

2 cases of lichen planus apparently caused by allergy to dental metals
Nakayama H; Oshiro A; Sato S;
Nakano N (Jpn) Jibiinkoka 1972 Apr;44(4):239‐ 47

Lichenoid tattoo hypersensitivity.
Taaffe A; Knight AG; Marks R Br Med J 1978 Mar 11;1(6113):616‐8

Four patients are described who developed granulomatous reactions in the red portions of their tattoos. Histopathological and immunofluorescence studies showed features of lichen planus. Mercury was identified in only one patient's lesion, and hypersensitivity to mercury was shown by patch testing in one other patient. Tattooing may provide a localised antigenic challenge resulting in spontaneously occurring lichen planus.

The red tattoo and lichen planus.
Taaffe A; Wyatt EH Int J Dermatol 1980 Sep;19(7):394‐6

Toxicity of metal ions to alveolar macrophages.
Castranova V; Bowman L; Miles PR; Reasor MJ Am J
Ind Med 1980;1(3‐4):349‐57
Significant concentrations of metals are found in the respirable particulate effluents associated with metallurgical smelters. In this investigation the effects of the metallic ions lead, cadmium, iron, mercury, aluminum, chromium, and nickel on various aspects of alveolar macrophage function were studied. The production of antibacterial substances (ie, reactive forms of oxygen) by these cells and oxygen consumption are very sensitive to the metals. Particle uptake displays moderate sensitivity, while lysosomal enzyme activity and membrane integrity are fairly resistant to metals. In addition, the effects of the organic solvents carbon tetrachloride, toluene, and xylene on alveolar macrophage function were tested. These solvents were found to inhibit oxygen consumption and the release of antibacterial substances while not greatly affecting membrane integrity. The results of these experiments indicate that some metals and some organic substances are toxic to alveolar macrophage function.

Oral lichen planus and contact allergy to mercury.
Finne K; Goransson K; Winckler L Int J Oral Surg
1982 Aug;11(4):236‐9
29 patients with oral lichen planus and amalgam fillings were patch tested for contact allergy to dental materials. 18 of these patients (62%) had a contact allergy to mercury. In a control material, the frequency of mercury allergy was 3.2%. In 3 of the patients the lesions healed completely after removal of the amalgam fillings. On the basis of these findings it is recommended that all amalgam fillings be removed after a positive patch test to mercury, as a step in the treatment of oral lichen planus.

Salivary gland function and changes in patients with oral lichen planus.
Lundström I.M.C. Scand J Dent Res 90:443‐458 1982

Allergy to the mercury in dental amalgam
Allergie au mercure dans l'amalgame dentaire. Duxbury AJ;
Watts DC; Wastell EA (Review) (Fre) Med Hyg (Geneve) 1982 Oct 13;40(1487):3416‐8

The role of dental restorative metals in the pathogenesis of oral lichen planus
Eversole LR, Ringer M
Oral Surg 57 1984 383‐387 (AD48)

Allergy and corrosion of dental materials in patients with oral lichen planus.
Int J Oral Surg. 1984 Feb;13(1):16-24.
Abstract
Patients with histologically verified oral lichen planus (OLP) were studied regarding allergic reactions to substances in dental materials, presence of clinical corrosion orally and factors influencing corrosion, such as mixed gold and amalgam therapy, non-precious pin-constructions or complete dentures. The material consisted of 48 OLP patients (33 female, 15 male) and the results were compared with those of a control group (40 patients) and/or general population samples. When patch tested, 39% of the OLP patients reacted to one or more components in dental materials. Reaction to mercury was most common, being noted in 26%. Clinical signs of corrosion were significantly more frequent in the OLP group (72%) than in the control cases (28%). Patients with atrophic-erosive OLP exhibited a significantly higher frequency of corrosion (83%) than those with reticular type (46%). Mixed gold and amalgam therapy and screwposts were equally present in both the OLP and control group and the frequency of complete dentures corresponded to that reported for general populations. A change of dental materials in 8 patients with positive patch tests led to marked oral improvement in 6 cases, 2 of which became completely cured. The frequencies recorded for allergic reactions and corrosion as well as the result of treatment indicate that substances in dental materials may be of significance in cases of OLP.

Electrogalvanically‐induced contact allergy of the oral mucosa. Report of a case.
Lind PO; Hurlen B; Stromme Koppang H Int J Oral Surg 1984 Aug;13(4): 339‐45
A 69‐year‐old white female presented bilateral lesions of the oral mucosa possibly related to electrogalvanism. The lesions were histologically characterized as lichen planus and as mild epithelial dysplasia on the left and right sides, respectively. They disappeared after removing amalgam restorations opposing the lesions. Epicutaneous patch tests and lymphocyte3 transformation tests showed that the patient suffered from a contact allergy to mercury compounds, indicating this as a mechanism by which electrogalvanism may induce lesions of the oral mucosa.

Oral lichen planus: hypersensitivity to dental restoration material.
Mobacken H; Hersle K; Sloberg K; Thilander H Contact Dermatitis 1984 Jan; 10(1):11‐5
67 patients with oral lichen planus of the atrophic‐erosive or reticular plaque type were
examined. Dental amalgam in contact with mucosal lesions was present in 64 patients, and gold fillings in 33. Patch testing with a standard procedure was performed with components of dental fillings. 11 patients (16%) reacted to at least one of the mercury compounds compared to 8% in a reference group. Most positive reactions were caused by elemental mercury and ammoniated mercury. No patient reacted to gold or copper. Readings at days 10‐14 did not increase the number of responders. 13 patients were patch tested with palladium; all were negative. It is not clear whether in the mercury‐ positive patients allergy to dental amalgam is a causative or aggravating factor, or merely on epiphenomenon.

Amalgam-related oral lichenoid reaction.
Scand J Dent Res. 1986 Oct;94(5):448-51.
Lind PO, Hurlen B, Lyberg T, Aas E.

Abstract
In 52 patients with oral lichen planus topographically related to amalgam restorations, the fillings were replaced by other materials in 18, 16 of whom experienced complete remission of the lesions within 1-12 months. These results are discussed in relation to the results of epicutaneous patch tests for possible allergy to a number of mercury compounds. The term "oral lichenoid reaction", is suggested to describe these lesions.

Oral lichenoid reactions related to mercury sensitivity.
Br J Oral Maxillofac Surg. 1987 Dec;25(6):474-80.
James J, Ferguson MM, Forsyth A, Tulloch N, Lamey PJ.
Department of Oral Surgery, Glasgow Dental Hospital and School.

Abstract
Lichen planus is a common disorder of unknown aetiology. It has been proposed that in some cases it represents a form of allergic reaction to the metals contained in dental amalgam, particularly mercury. Twenty-nine consecutive dentate patients who had lichen planus of the oral mucosa were patch-tested to the range of metals contained in dental amalgam. Ten out of 29 (34%) showed an allergic reaction to mercury and all of these patients had amalgams greater than 5 years old. The amalgams were poorly contoured and had corroded, resulting in continued release of mercury ions. Six patients had their amalgams replaced with composite or glass ionomer materials resulting in resolution of ulcerated lesions. In a follow-up of 3-24 months, one patient had a recurrence of ulcerated areas and another, despite resolution of the oral lesions had persistent discomfort.

Lymphocytes, Langerhans cells and HLA‐DR expression on keratinocytes in oral lesions associated with amalgam restorations.
Bolewska J Reibel J T
J Oral Pathol Med (1989 Oct) 18(9):525‐8

It has been shown recently that patients with mucosal lesions confined to areas opposing amalgam restorations (contact lesions) show a high rate of allergic reaction towards mercury. These lesions may, therefore, represent a contact hypersensitivity reaction. Contact lesions often have a lichenoid appearance. From a pathogenetic and differential diagnostic point of view we therefore evaluated the presence of lymphocyte subpopulations, Langerhans cells (LC) and the expression of HLA‐DR antigens on mucosal keratinocytes in biopsies of contact lesions (Group 1) and in lichen planus lesions with (Group 2) and without (Group 3) partial contact with amalgam restorations. T lymphocytes dominated in all three groups and LC counts were similar. HLA‐DR positive keratinocytes were found in 18‐ 36% of lesions in all three groups. Thus, the immunologic parameters examined are not of value in discriminating between the types of lesions studied. Rather, it seems that the pattern observed is a common reaction of the oral mucosa to known (amalgam restorations) and unknown factors

Mucosal reactions to amalgam restorations.

J Oral Rehabil. 1990 Jul;17(4):293-301.
Jameson MW, Kardos TB, Kirk EE, Ferguson MM.
Department of Restorative Dentistry, School of Dentistry, University of Otago Dunedin, New Zealand.

Abstract
Amalgam restorations have been implicated both in contact sensitivity reactions and in lichenoid reactions. This appears to be related principally to the mercury content, although other metals cannot be discounted. The cases of two patients are reported who showed features of lichenoid reactions of the oral mucosa, in addition to features of a contact hypersensitivity to mercury. The mucosal lesions resolved following replacement of the amalgams with non-metallic restorations. Consideration is given to the selection of materials and procedures currently available for treatment of these patients. This paper supports the view that sensitivity to heavy metals must be considered as a possible cause of erythematous and lichenoid reactions of the oral mucosa.

Resolution of oral lichenoid lesions after replacement of amalgam restorations in patients allergic to mercury compounds

JUHANI LAINE1, KIRSTI KALIMO2, HELI FORSSELL1, RISTO-PEKKA HAPPONEN1,*
British Journal of Dermatology
Volume 126, Issue 1, pages 10–15, January 1992

Summary
The significance of contact allergy in patients with various oral symptoms was studied. Positive patchtest reactions to mercury compounds were found in 21/91 patients. Of these, 18 had lichenoid lesions in oral mucosa in close contact to amalgam fillings, and three patients with contact allergy had neither amalgam fillings in their teeth nor visible oral lesions. Amalgam replacement was carried out in 15/18 symptomatic patients. The fillings were replaced with gold in three cases, composite resin fillings in six, glass ionomer in three and both gold and composite materials in three cases. In 10 patients there was complete replacement and in five it was restricted to the fillings adjacent to the mucosal lesions. After a mean follow-up period of 3.2 years a complete cure was seen in seven patients, each of whom had had all their fillings changed. A marked improvement occurred in six patients, and there was no change in two.

Oral mucosa and skin reactions related to amalgam.
Adv Dent Res. 1992 Sep;6:120-4.
Holmstrup P.
Department of Periodontology, Royal Dental College, Copenhagen, Denmark.

Abstract
Documented cases of oral mucosa and skin affections related to amalgam restorations are rare, although the exact incidence is unknown. Lesions of the oral mucosa may be due to specific immunologic or non-specific toxic reactions toward products generated from restorations. The immunologic reaction most probably involved in mucosal affections related to amalgam is the delayed or cell-mediated (type IV) reaction. Such reactions are seen in contact allergy, and the term "contact lesions of the oral mucosa" has been used. There is a much lower tendency of sensitization through mucous membranes than through skin, and it is questionable whether mercury released from amalgam restorations is able to sensitize a patient. A chronic toxic reaction may be established due to repeated or constant influence to toxic agents in low concentrations over long periods. Such reactions are most frequently localized to the contact zone with the toxic agent. Chronic toxic reactions may possibly be seen in areas of the oral mucosa in direct contact with amalgam fillings. Since the clinical features of these lesions do not differ from those of lesions due to contact hypersensitivity, the diagnosis is obtained by exclusion based on a negative patch test.

Patch test reactions to metal salts in patients with oral mucosal lesions associated with amalgam restorations.

Contact Dermatitis. 1992 Sep;27(3):157-60.
Nordlind K, Lidén S.
Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.

Abstract

Patch testing with various metal salts was performed in patients with oral mucosal lesions associated with amalgam restorations, by using polypropylene-coated aluminium discs. Positive reactions to mercuric chloride were obtained in 5/12 (42%) of these patients, but only in 1/11 patients (9%) with oral mucosal lesions unassociated with amalgam restorations and in 3/36 patients (8%) in a control group without mucosal lesions. The difference between the former group and the control patients is statistically significant (p less than 0.05). In addition, a positive test reaction to copper sulfate was obtained in 2 patients (16%) with amalgam-associated mucosal lesions and negative reactions to mercuric chloride. 2 of the 5 positive test reactions to mercuric chloride, in the patients with lichenoid mucosal lesions associated with amalgam, became lichenoid and persisted for at least 3 weeks. The patients with these reactions were also positive at a concentration of 0.05% mercuric chloride, but were negative to metallic mercury, in contrast to 2 other patients in the same group. This indicates the necessity of including mercuric chloride when patch testing such patients.

Oral lichenoid lesions and mercury sensitivity.

Contact Dermatitis. 1993 Nov;29(5):275-6.
Bircher AJ, von Schulthess A, Henning G.
Department of Dermatology, University Hospital, Basel, Switzerland.

Healing of lichenoid reactions following removal of amalgam. A clinical follow-up.

J Clin Periodontol. 1995 Apr;22(4):287-94.
Henriksson E, Mattsson U, Håkansson J.
Department of Oral and Maxillofacial Surgery, Central Hospital, Karlstad, Sweden.

Abstract

174 patients referred to the Department of Oral and Maxillofacial Surgery, Central Hospital, Karlstad, Sweden during 1987 to 1989 for lichenoid lesions and evaluation of a possible connection with amalgam restorations were invited to a clinical re-examination. 159 of the patients were re-examined with the purpose of evaluating the long-term effect upon performed substitution therapy. Partial or total removal of amalgam had been recommended according to a set of given criteria. The re-examination showed that 62 patients had performed partial and 69 patients total removal of amalgam fillings. 28 patients had not performed any substitution therapy. There was a difference between recommended and performed therapy. The results demonstrated that 92% of patients with lichenoid lesions only in contact with amalgam fillings healed or improved clinically following removal of amalgam. No statistical difference was found in healing between patients who only removed fillings in contact and those who had removed all amalgam restorations. More than 60% of buccal lichenoid lesions without contact with amalgam at time of referral disappeared following amalgam substitution. Gingival lichenoid lesions did not respond to substitution of amalgam to another material. 3 out of 17 patch-tested patients demonstrated a hypersensitivity reaction to mercury. All lichenoid lesions in these patients healed following total substitution. Partial or total removal of amalgam fillings was also performed on 10 patients with completely negative patch-tests. 6 out of these patients demonstrated complete healing of their lichenoid reactions at re-examination.

The histopathology of oral mucosal lesions associated with amalgam or porcelain-fused-to-metal restorations.

Oral Dis. 1995 Sep;1(3):152-8.
Larsson A, Warfvinge G.
Department of Oral Pathology, Centre for Oral Health Sciences, Lund University, Malmö, Sweden.

Abstract

OBJECTIVES:
To analyse the interface stomatitis patterns of oral lichenoid lesions in contact with amalgam and to compare these with the histologic changes in oral lesions clinically associated with porcelain-fused-to-metal (PFM) restorations. To relate these features to the presence of tissue-bound mercury (Hg).

DESIGN:
A retrospective analysis of tissue biopsies, with clinical data collected via a complementary questionnaire.

SUBJECTS AND METHODS:
479 biopsies diagnosed in 1987 as 'lichenoid reactions'. From these, we retrieved all with amalgam contact and without candida or medication. From 1990-91, all mucosal lesions stated to be associated with PFM restorations were then retrieved for comparative analysis. The biopsies were examined with routine histologic and autometallographic methods.

RESULTS:
77 amalgam-associated lesions were found and could be subdivided into five pre-defined interface stomatitis types. We found 22 lesions associated with PFM and 20 showed histopathologic features similar to those associated with amalgam. Hg accumulations were detected in the majority of amalgam-associated but only in part of the PFM-associated lesions.

CONCLUSIONS:
Amalgam-associated lichenoid lesions present a wide spectrum of histopathologic patterns, corresponding to similar patterns in dermatopathology but with no evidence of association with specific disease. PFM-associated lesions tend to display similar lichenoid features, suggestive of common pathogenetic mechanisms. Hg accumulations may play a role to maintain the chronicity of such lichenoid lesions.

Oral lichenoid lesions, mercury hypersensitivity and combined hypersensitivity to mercury and other metals: histologically-proven reproduction of the reaction by patch testing with metal salts.
Contact Dermatitis. 1995 Nov;33(5):323-8.
Koch P, Bahmer FA.
Hautklinik der Universität des Saarlandes, Homburg/Saar, Germany.

Abstract
We report 11 patients seen between 1991 and 1994 with oral lichenoid lesions (OLL). In 10 cases, there was contact with dental amalgam fillings, and in patient no. 10 with both amalgam restorations and a gold crown. The last patient had, in addition to her OLL, lichen planus of the skin and genital mucosa. In 5 cases, combined sensitization to mercury and other metal salts, particularly gold sodium thiosulfate (GST) and palladium chloride (PDC), was observed. In 10 patients, the lesions considerably improved or totally cleared within 1 to 9 months of replacement of restoration materials. Histological examination of biopsies from the test sites of amalgam, mercuric chloride, GST and PDC, taken 10 or 17 days after application of patch tests, showed lichenoid changes in 7 patients with at least 1 of the allergens. As at least 2 patients had inflammatory lesions of the oral mucosa related to both amalgam and gold restorations, combined sensitization to inorganic and organic mercury derivatives, GST and, in 1 case, PDC, a "dental restoration metal intolerance syndrome" is proposed.

Oral lichenoid lesions caused by allergy to mercury in amalgam fillings.
Contact Dermatitis. 1995 Dec;33(6):423-7.
Pang BK, Freeman S.
Contact & Occupational Dermatitis Clinic, Skin & Cancer Foundation, NSW, Australia.
Erratum in Contact Dermatitis 1996 Jul;35(1):70.

Abstract
Oral lichenoid lesions (OLL) or lichen-planus-like lesions are often idiopathic. Our aim was to determine whether OLL can be caused by allergy to mercury in amalgam fillings, and whether resolution of OLL occurs after replacement of amalgam with other dental fillings. Patients with only OLL (except for 1 case with cutaneous lichen planus) referred for patch testing during 1985-1994 to the Contact and Occupational Dermatitis Clinic of the Skin & Cancer Foundation, Darlinghurst, were reviewed. Patch tests were performed with 1% mercury, 1% ammoniated mercury, 0.1% thimerosal, 0.1% mercuric chloride, 0.05% phenylmercuric nitrate and an amalgam disc, using Finn Chambers occluded for 2 days, 19 patients (17 women and 2 men; age range: 28-72 years) had OLL in close contact with amalgam fillings and showed positive patch test reactions to mercury compounds, 16 out of 19 patients had their amalgam fillings replaced. In 13 patients, the OLL healed. 1 patient had marked improvement. 1 patient had no improvement and developed multiple oral squamous cell carcinoma. In conclusion, OLL can be caused by allergy to mercury in amalgam fillings. Replacement of amalgam with other dental fillings usually results in resolution of OLL and is recommended for cases with positive patch test reactions to mercury compounds.

The relevance and effect of amalgam replacement in subjects with oral lichenoid reactions

S. H. IBBOTSON1, E. L. SPEIGHT1, R. I. MACLEOD2, E. R. SMART2, C. M. LAWRENCE1
British Journal of Dermatology
Volume 134, Issue 3, pages 420–423, March 1996

Summary
In this study we examined the prevalence of mercury hypersensitivity in patients with oral lichenoid reactions (OLR) and the effect of amalgam replacement in subjects with amalgams adjacent to OLR irrespective of their mercury sensitivity status. One hundred and ninety-seven patients with oral problems were examined: 109 with OLR. 22 with oral and generalized lichen planus. and 66 with other oral diagnoses, including aphthous ulcers and orofacial granulomatosis. Nineteen per cent of patients with OLR reacted to mercury on patch testing, significantly more than in those with generalized lichen planus (0%) and in those with other oral diagnoses (3%). Twenty-two patients with OLR and adjacent amalgams had amalgam replacement and. in 16 of 17 mercury-positive subjects and three of four mercury-negative subjects, the OLR resolved after amalgam removal. In conclusion, we found a significantly increased prevalence of mercury hypersensitivity in patients with localized OLR in comparison to subjects with other oral problems. Amalgam replacement resulted in resolution of OLR in the majority of patients with amalgams adjacent to OLR irrespective of their mercury sensitivity status.

Amalgam-associated oral lichenoid reactions. Clinical and histologic changes after removal of amalgam fillings.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996 Apr;81(4):459-65.
Ostman PO, Anneroth G, Skoglund A.
Department of Oral Pathology, University of Umea, Sweden.

Abstract
OBJECTIVE AND STUDY DESIGN:
Forty-nine consecutive patients with clinically diagnosed oral lichenoid reactions in contact with amalgam fillings were studied clinically and histologically. The long-term effect of replacement of these fillings was also examined.

RESULTS:
Seventeen (35%) patients showed positive reactions to mercury at the epicutaneous patch test that was carried out before treatment. After treatment, total regression of the lesions was found clinically in 33 (69%) and histologically in 26 (55%) patients. Most of the remaining lesions changed clinically and histologically to a less pronounced tissue reaction. Lesions in direct contact with amalgam fillings (group I) showed significantly better healing results than lesions that exceeded the contact area (group II). No difference in healing capacity was noted in the two groups between patients with positive patch reactions to mercury compared with those with negative reactions. Lesions that histologically were classified as benign oral keratosis showed a similar healing pattern as those classified as oral lichen planus.

CONCLUSION:
In group I all lesions changed histologically and clinically to a normal mucosa or to a less affected tissue reaction. In group II this change was less pronounced, which suggests that the fillings themselves were not the only factor involved in the cause of these lesions. The results suggest that various etiologic factors are involved in lichenoid reactions and that the effect of removal of amalgam fillings cannot be predicted by epicutaneous patch testing and biopsies.

In vitro lymphocyte proliferation test in the diagnosis of oral mucosal hypersensitivity reactions to dental amalgam.
J Oral Pathol Med. 1997 Sep;26(8):362-6.
Laine J, Happonen RP, Vainio O, Kalimo K.
Department of Oral Diseases, University Central Hospital of Turku, Finland.

Abstract
Patch testing was carried out in 23 patients with oral lichenoid lesions (OLL) topographically related to dental amalgam fillings. Twelve patients displayed positive reactions to several mercury compounds, whereas 11 patients were negative. An in vitro lymphocyte proliferation (LyPro) test was carried out using different mercury compounds and other metal salts. Mercuric chloride and phenyl mercuric acetate caused positive proliferation in 3/12 patch test-positive and in 5/11 negative patients. One out of seven healthy control subjects had a positive LyPro result. The mean stimulation index (SI) values between the patient groups or compared with the control subjects did not differ significantly. Zinc, tin, copper or silver salts caused in vitro lymphocyte stimulation in most of the patients and in healthy control people. Total (14) or partial (4) replacement of amalgam fillings was carried out in 18 patients. Complete healing of lichenoid lesions was seen in 4/6 LyPro test-positive and in 5/10 patch test-positive patients at follow-up examinations 12 months after the replacement of amalgam fillings. The in vitro proliferation assay seems not to be a specific test for identifying the patients who would benefit from amalgam replacement.

Contact hypersensitivity to mercury in amalgam restorations may mimic oral lichen planus.
Cutis. 1999 Mar;63(3):189-92.
Camisa C, Taylor JS, Bernat JR Jr, Helm TN.
Section of Clinical Dermatology, Cleveland Clinic Foundation, Ohio, USA.

Abstract
Oral lichenoid lesions caused by hypersensitivity to mercury in amalgam fillings may mimic oral lichen planus on clinical and histologic examination. A positive patch test reaction to more than one mercurial allergen increases confidence in the diagnosis and justifies the removal and replacement of all amalgam fillings with those made of other materials. A complete remission may be expected about 3 months after the last amalgam filling is removed.

Immunocompetent cells in amalgam-associated oral lichenoid contact lesions.
J Oral Pathol Med. 1999 Mar;28(3):117-21.
Laine J, Konttinen YT, Beliaev N, Happonen RP.
Department of Oral Diseases, University Central Hospital of Turku, Finland.

Abstract
Inflammatory cells in amalgam-associated, oral lichenoid contact lesions (OLL) were studied in 19 patients by immunocytochemistry using monoclonal antibodies. Ten of the patients displayed allergic patch test (PT) reactions to several mercury compounds and nine were negative. The immunocytochemical quantification showed a uniform composition of the inflammatory mononuclear cells in the two study groups. The number of HLA-D/DR-positive dendritic cells (P<0.001) and CD1a-positive Langerhans cells (P=0.035) was significantly lower in the PT-negative than PT-positive patients. HLA-D/DR expression on keratinocytes varied from negative to full thickness staining of the epithelium. HLA-D/DR expression in the full thickness of epithelium (3) or through the basal and spinous cell layers (2) was seen in 5 of 8 PT-positive patients, whereas none of the PT-negative patients had this staining pattern (P=0.045). These patients also showed a good clinical response after amalgam removal. Consequently, OLL may represent a true delayed hypersensitivity reaction with a trans-epithelial route of entrance of the metal haptens released from dental restorative materials.

Oral lesions and symptoms related to metals used in dental restorations: a clinical, allergological, and histologic study.
Journal of the American Academy of Dermatology. 1999 Sep;41(3 Pt 1):422-30.
Koch P, Bahmer FA.
Department of Dermatology, University of the Saarland, Homburg/Saar, Germany.

Abstract
BACKGROUND:
Allergy to mercury as a cause of oral lichenoid lesions (OLL) remains controversial. Some authors reported high frequency of sensitization to mercury and beneficial effect from removal of amalgam fillings in such patients, whereas others state that this procedure affects favorably all OLL, whether patients are sensitized to inorganic mercury or not.

OBJECTIVE:
Our purpose was to determine the frequency of sensitization to metal salts in 194 patients (patients with OLL partly adjacent to amalgam fillings: 19, oral lichen planus (OLP) without close contact to amalgam: 42, other oral diseases: 28, oral complaints: 46, control group: 59). We further studied the histologic changes of biopsy specimens from positive patch tests to metal salts, and investigated the effect of removal of amalgam in OLL, to clarify whether it is possible to identify patients who will benefit from this procedure.

METHODS:
Patch testing was performed with the German standard series, a dental prosthesis series, and a metal salt series including gold, mercury, and palladium salts as well as other salts of metals used in dental restorations. Late readings (10 and 17 days after application of the patch tests) were performed in all patients.

RESULTS:
Of 19 patients with OLL adjacent to amalgam fillings, 15 (78.9%) were sensitized to inorganic mercury (INM), significantly more than those with OLL not adjacent to amalgam, other oral diseases or complaints, and the control group. In 5 of 15 (33.3%) of the patients with OLL, a positive patch test to INM was observed only at D10 or D17. Amalgam was removed in 18 patients with OLL (sensitization to INM: 15), and in 11 patients with OLP (sensitization to INM: 2). After removal, the lesions of 13 of 15 of the INM-sensitized patients with OLL (86. 7%) and 2 with OLP healed or improved significantly, but this was not observed with the INM negative patients. Frequency of sensitization to gold sodium thiosulfate (GST) and palladium chloride 1% pet (PDC) was high in all groups. This was partly because readings were performed late. Lesions of 2 patients with allergic contact stomatitis caused by gold and 1 caused by palladium healed completely after removal of these restorations. Histologically, lichenoid changes were observed in 14 of 36 biopsy specimens of positive patch tests from INM (9/21), GST (2/10), and PDC (3/5) in all patient groups, mainly in persistent patch tests at D10 or D17. This was not observed in 12 biopsy specimens taken from persistent patch tests from other substances, including nickel sulfate.

CONCLUSION:
Our results suggest that sensitization to mercury is an important cause of OLL, whether all lesions or only a part of them are adjacent to amalgam fillings. Sensitization to GST may reflect true gold allergy and should be considered as a cause of oral diseases in some patients. Sensitization to PDC is frequent but has yet only little clinical relevance. Patch tests may be positive only at D10 or D17. This suggests the importance of additional readings of GST, PDC, and mercury salts at this time.

Delayed and immediate hypersensitivity reactions associated with the use of amalgam.

Br Dent J. 2000 Jan 22;188(2):73-6.
McGivern B, Pemberton M, Theaker ED, Buchanan JA, Thornhill MH.
University Dental Hospital of Manchester.

Abstract
Hypersensitivity to the constituents of dental amalgam is uncommon. When it occurs it typically manifests itself as a lichenoid reaction involving a delayed, type IV, cell-mediated hypersensitivity response. Rarely, a more acute and generalised response can occur involving both the oral mucosa and skin. We describe two cases that illustrate the presentation and management of these two types of reaction.

Activation of oral keratinocytes by mercuric chloride: relevance to dental amalgam-induced oral lichenoid reactions
M.C. Little1,2, R.E.B. Watson1, M.N. Pemberton2, C.E.M. Griffiths1, M.H. Thornhill3
British Journal of Dermatology
Volume 144, Issue 5, pages 1024–1032, May 2001

Background
Despite the benefits of mercury-containing amalgam dental fillings there are growing concerns regarding the potential adverse health effects arising from exposure to mercury released from fillings. In some individuals this process may result in a local lichenoid reaction of the oral mucosa.

Objectives
The aim of this study was to investigate the possibility that mercury salts released from amalgam fillings might act directly on oral keratinocytes to induce changes that could promote the development of such lesions.

Methods
In vitro experiments were performed in which normal oral and cutaneous keratinocytes were cultured in the presence of mercuric chloride (HgCl2). ICAM-1 expression and the release of cytokines was determined by enzyme-linked immunosorbent assay techniques. T-cell binding to HgCl2-pretreated keratinocytes was assessed using a colorimetric method.

Results
Subcytotoxic concentrations of HgCl2 induced a concentration-related increase in ICAM-1 expression and consequent T-cell binding on oral, but not cutaneous, keratinocytes. HgCl2 also stimulated the release of low levels of tumour necrosis factor-a and interleukin-8 (but not RANTES), and inhibited the release of interleukin-1a by oral keratinocytes.

Conclusions
This study provides evidence that oral keratinocytes may play an integral part in initiating the pathogenesis of amalgam-induced lichenoid reactions.

Oral lichenoid reactions associated with amalgam: improvement after amalgam removal

A. Dunsche1, I. Kästel1, H. Terheyden1, I.N.G. Springer1, E. Christophers2, J. Brasch2
British Journal of Dermatology
Volume 148, Issue 1, pages 70–76, January 2003

Summary
Background
The pathogenetic relationship between oral lichenoid reactions (OLR) and dental amalgam fillings is still a matter of controversy.

Objectives
To determine the diagnostic value of patch tests with amalgam and inorganic mercury (INM) and the effect of amalgam removal in OLR associated with amalgam fillings.

Methods
In 134 consecutive patients 467 OLR were classified according to clinical criteria. One hundred and fifty-nine biopsies from OLR lesions were histologically diagnosed according to the World Health Organization criteria for oral lichen planus (OLP) and compared with 47 OLP lesions from edentulous patients without amalgam exposure. One hundred and nineteen patients were patch tested with an amalgam series. In 105 patients (357 of 467 lesions) the amalgam fillings were removed regardless of the patch test results and OLR were re-examined within a follow-up period of about 3 years. Twenty-nine patients refused amalgam removal and were taken as a control group.

Results
Eleven patients with OLR (8·2%) had skin lesions of lichen planus (LP). Histologically, the lesions in the OLR group could not be distinguished from those seen in the OLP group. Thirty-three patients (27·7%) showed a positive patch test to INM or amalgam. Amalgam removal led to benefit in 102 of 105 patients (97·1%), of whom 31 (29·5%) were cured completely. Of 357 lesions, 213 (59·7%) cleared after removal of amalgam, whereas 65 (18·2%) did not improve. In the control group without amalgam removal (n = 29) only two patients (6·9%) showed an improvement (P < 0·05). Amalgam removal had the strongest impact on lesions of the tongue compared with lesions at other sites (P < 0·05), but had very little impact on intraoral lesions in patients with cutaneous LP compared with patients without cutaneous lesions (P < 0·05). Patients with a positive patch test reaction to amalgam showed complete healing more frequently than the amalgam-negative group (P < 0·05). After an initial cure following amalgam removal, 13 lesions (3·6%) in eight patients (7·6%) recurred after a mean of 14·6 months.

Conclusions
Of all patients with OLR associated with dental amalgam fillings, 97·1% benefited from amalgam removal regardless of patch test results with amalgam or INM. We suggest that the removal of amalgam fillings can be recommended in all patients with symptomatic OLR associated with amalgam fillings if no cutaneous LP is present.

Oral lichenoid lesions (OLL) and mercury in amalgam fillings.

Contact Dermatitis. 2003 Feb;48(2):74-9.
Wong L, Freeman S.
Skin and Cancer Foundation, Darlinghurst NSW, Australia.

Abstract
84 patients with oral lichenoid lesions (OLL) were seen in the contact dermatitis clinic. All these patients had reticulate, lacy, plaque-like or erosive lichenoid changes adjacent to amalgam fillings. Patch testing to metallic mercury, 0.1% thimerosal, 1% ammoniated mercury, 0.1% mercuric chloride, and in some cases 0.05% phenylmercuric nitrate and amalgam discs was undertaken. 33 (39%) patients had positive patch test findings. 30/33 patch test positive patients had replacement of their amalgam fillings, with 28 (87%) patients experiencing improvement of symptoms and signs within 3 months. This confirms that mercury allergy is a factor in the pathogenesis of OLL in some cases. In cases where patch test negative patients improve with amalgam replacement, mercury may be acting as an irritant in the pathogenesis of OLL.

Amalgam-contact hypersensitivity lesions and oral lichen planus.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 Mar;95(3):291-9.
Thornhill MH, Pemberton MN, Simmons RK, Theaker ED.
Department of Dental Diagnostic Science, University of Texas Health Science Center San Antonio, 78229-3900, USA.

Abstract
OBJECTIVE:
The purpose of this study was to investigate the relationship between amalgam restorations and oral lichen planus.

STUDY DESIGN:
Eighty-one patients with oral lichenoid lesions were characterized clinically and skin patch tested for amalgam or mercury hypersensitivity. Thirty-three of these patients had amalgam fillings in contact with oral lesions replaced and were followed to determine the outcome.

RESULTS:
Clinically, 2 patient groups were identified: (1) 30 patients with probable amalgam-contact hypersensitivity lesions (ACHLs) and (2) 51 patients with oral lichen planus (OLP) but no clear relationship with amalgam. Seventy percent of ACHL cases were patch test positive for amalgam or mercury compared with only 3.9% of OLP cases (P < .0001). Amalgam replacement resulted in lesion improvement in 93% of ACHL cases. No such improvement was observed in the OLP cases treated (P < .001).

CONCLUSION:
OLP is a heterogeneous condition within which an ACHL subgroup can be identified. ACHLs, but not other OLP lesions, respond favorably to amalgam replacement. A strong clinical association between lesions and amalgam restorations plus a positive patch test result was a good predictor of lesion improvement on amalgam replacement.

Lichenoid reactions of murine mucosa associated with amalgam

A. Dunsche1, M.P. Frank2, J. Lüttges3, Y. Açil1, J. Brasch4, E. Christophers4, I.N.G. Springer1
British Journal of Dermatology
Volume 148, Issue 4, pages 741–748, April 2003

Summary
Background In 97% of all patients with oral lichenoid reactions (OLR) associated with dental amalgam a removal of the fillings leads to a decline of the lesions, as a minimum.

Objectives
The aim of this study was to determine if contact allergic or local toxic effects or both may contribute to OLR using an animal model with mercury-sensitive and non-sensitive rats.

Methods
Twenty Brown Norway rats, which have a genetic predisposition for an autoimmune syndrome after exposure to mercury and 20 Lewis rats, not mercury sensitive, were treated as follows: 10 animals of each group were sensitized with a low dose of mercuric chloride. Half of all animals received local exposure of the right buccal mucosa to amalgam (left: control), the others to amalgam alloy free of mercury. All rats were patch tested with an amalgam series.

Results
After 20 days of exposure 96% of all animals showed white mucosal lesions restricted to the contact zone of the alloy on the treated side, but only up to 25% had a positive patch test reaction to amalgam or inorganic mercury (INM). The lesions showed no relation to species, alloy, sensitization or patch test reaction.

Conclusions
While allergic mechanisms may contribute to mucosal contact lesions in Brown Norway rats, this is less probable in Lewis rats. Mercury in general appears to be irrelevant in the development of ORL in this study. If this holds true for humans as well, patch testing with an amalgam series may be helpful in a minor fraction of all patients with OLR.

A case of lichen planus caused by mercury allergy

British Journal of Dermatology
Y. Kato1, R. Hayakawa1, R. Shiraki1, K. Ozeki2
Volume 148, Issue 6, pages 1268–1269, June 2003

Oral lichenoid lesions and contact allergy to dental mercury and gold.

Contact Dermatitis. 2003 Nov;49(5):264-5.
Athavale PN, Shum KW, Yeoman CM, Gawkrodger DJ.
Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK.

Oral Lichen Planus and Allergy to Dental Amalgam Restorations

Archives of Dermatology. 2004;140:1434-1438.
Ronald Laeijendecker, MD; Sybren K. Dekker, MD, PhD; Piet M. Burger, MD; Paul G. H. Mulder, PhD; Theodoor Van Joost, MD, PhD; Martino H. A. Neumann, MD, PhD

ABSTRACT

Objectives
To determine contact allergies in patients with oral lichen planus and to monitor the effect of partial or complete replacement of amalgam fillings following a positive patch test reaction to ammoniated mercury, metallic mercury, or amalgam.

Design
In group A (20 patients), the oral lesions were confined to areas in close contact with amalgam fillings. In group B (20 patients), the lesions extended 1 cm beyond the area of contact with amalgam fillings. In group C (20 patients), the oral lesions had no topographic relationship with amalgam fillings. Partial or complete replacement of amalgam fillings was recommended if there was a positive patch test reaction to ammoniated mercury, metallic mercury, or amalgam. Control group D (20 patients) had signs of allergic contact dermatitis.

Results
Amalgam fillings were replaced in 13 patients of group A, with significant improvement. Dental amalgam was replaced in 8 patients of group B, with significant improvement. In group C, amalgam replacement in 2 patients resulted in improvement in 1 patient. These results were evaluated after 3 months. No positive patch test reactions to mercury compounds were found in patients with concomitant cutaneous lichen planus and in group D.

Conclusions
Contact allergy to mercury compounds is important in the pathogenesis of oral lichen planus, especially if there is close contact with amalgam fillings and if no concomitant cutaneous lichen planus is present. In cases of positive patch test reactions to mercury compounds, partial or complete replacement of amalgam fillings will lead to a significant improvement in nearly all patients.

Healing of oral lichenoid lesions after replacing amalgam restorations: a systematic review.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004 Nov;98(5):553-65.
Issa Y, Brunton PA, Glenny AM, Duxbury AJ.
University Dental Hospital of Manchester, England, UK.

Abstract
OBJECTIVE:
We sought to systematically review the literature related to oral lichenoid lesions (OLLs) and amalgam restorations.

STUDY DESIGN:
Cohort and case-controlled studies (no randomized controlled trials or controlled clinical trials available) were reviewed with respect to inclusion criteria and data on patients with OLLs, treatment interventions, and the measurement of outcomes.

RESULTS:
Fourteen cohort and 5 case-controlled trials met the criteria. The study population consisted of 1158 patients (27% male and 73% female; age range, 23-79 years). From 16% to 91% of patients had positive patch test results for at least 1 mercury compound. Of 1158 patients, 636 had to have their restorations replaced. The follow-up period ranged from 2 months to 9 1/2 years. Complete healing ranged from 37.5% to 100%. The greatest improvements were seen in lesions in close contact with amalgam.

CONCLUSIONS:
Protocols must be standardized to obtain valid results. The replacement of amalgam restorations can result in the resolution or improvement of OLLs. Patch testing seems to be of limited value. The topographic relationship between an OLL and an amalgam restoration is a useful--but not conclusive--marker.

Lichenoid reaction associated to amalgam restoration.
Med Oral Patol Oral Cir Bucal. 2004 Nov-Dec;9(5):423-4; 421-3.
Segura-Egea JJ, Bullón-Fernández P.

Abstract
Hypersensitivity to mercury associated with amalgam restorations may occur and present in one of two different ways. Most commonly it presents as an oral lichenoid reaction affecting oral mucosa in direct contact with an amalgam restoration and represents a delayed, type IV, cell mediated immune response to mercury or one of the other constituents of the dental amalgam. We report a case of oral lichenoid reaction associated to amalgam restoration. A 38 year-old woman presented a caries lesion of tooth #37. A Blacks class I preparation was performed and filled with amalgam. After 19 months, intra-oral examination revealed atrophic lesion, lightly erythematous, affecting the left buccal mucous. The lesion contacted directly with the amalgam restoration in the lower first molar. The right buccal mucosa was normal. His medical history was unremarkable, he was taking no medication and had no known allergies. However, the patient had felt certain rare sensation in that zone when eating sharp meals. Biopsy showed histological changes compatible with oral lichen planus. The patient decided not to change again the restoration, because she did not have important annoyances and she did not wish to be treated again. Other restorations were performed with composite resins, and no reaction was evidenced in the mucosa.

Oral lichenoid lesions and allergy to dental materials.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007 Dec;151(2):333-9.
Ditrichova D, Kapralova S, Tichy M, Ticha V, Dobesova J, Justova E, Eber M, Pirek P.
Department of Dermatology and Venereology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.

Abstract

BACKGROUND:
Dental materials, oral hygiene products and food additives may cause contact allergic reactions in the mouth with varied clinical presentation. Oral lichenoid lesions (lichen planus-like lesions) can be induced by hypersensitivity to dental restorative metals, acrylates, flavorings and other substances.

AIM:
The aim of this study was to demonstrate contact allergy to dental materials in patients with oral lichenoid lesions using patch tests.

PATIENTS AND METHODS:
Routine patch tests with two sets of allergens - "European Standard" and "Dental Screening" (Chemotechnique Diagnostics, Sweden) supplemented with pulverized amalgam, iridium, indium, menthol, sorbic acid and platinum were done on a set of 25 patients with lichenoid lesions located on the buccal mucosa, tongue and lips. Application and interpretation of the tests were conducted according to ICDRG (International Contact Dermatitis Research Group).

RESULTS:
15 (60 %) patients showed sensitization to 1 or more allergens, with a total of 31 positive reactions. The greatest frequency of positive reactions was to dental metals, with a total of 27 positive reactions. The order of tested metals according to frequency of positive reactions was mercury (6/25/24 %), amalgam (6/25/24 %), nickel (4/25/16 %), palladium (4/25/16 %), cobalt (3/25/12 %), gold (2/25/8 %), chrome (1/25/4 %), indium (1/25/4 %). The clinical relevance of the results with regard to the material's presence in the mouth was demonstrated in 11 (44 %) patients. In 9 patients, replacement of the positively tested materials led to healing or to significant regression of mucosal changes.

CONCLUSIONS:
The results of the patch tests showed the possible contribution of contact sensitization in the pathogenesis of lichenoid manifestations in the oral cavity. Due to the premalignant character of these lesions, replacement of positively tested materials and follow up of these patients is advised.

Association between oral lichenoid reactions and amalgam restorations.
Journal of the European Academy of Dermatology and Venereology. 2008 Nov;22(10):1163-7. Epub 2008 Apr 3.
Pezelj-Ribaric S, Prpic J, Miletic I, Brumini G, Soskic MS, Anic I.
Medical Faculty, University of Rijeka, Department of Oral pathology, Rijeka, Croatia.

This study examined the association between oral lichenoid reactions (OLR) and amalgam restorations in 20 patients with OLR compared to 20 healthy volunteers. Study subjects were skin patch tested and salivary levels of IL-6 and IL-8 were measured. Sixteen out of 20 patients demonstrated a contact allergy to inorganic mercury or amalgam. IL-6 and IL-8 levels were significantly elevated in the OLR group compared to the health volunteer group. The authors did not report exposure to any other drugs which may have caused the localized allergic reaction. All patients with OLR had their amalgam restorations replaced. The authors report that 16 patients experienced complete healing of their lesions, 3 showed a marked improvement and 1 showed no improvement. IL-6 and IL-8 levels reportedly dropped significantly following amalgam replacement. The follow-up was from 3 months to 3.5 years after amalgam replacement. The subjects all had their fillings replaced (there was no control group with OLR and no treatment). Therefore it's possible that the lesions resolved on their own and not as a result of amalgam removal. The authors concluded that OLR is associated with a localized allergic reaction to the mercury in amalgam fillings.

Abstract
BACKGROUND:
The aim of this study was to perform a clinical assessment of the association between oral lichenoid reactions (OLR) and amalgam restorations and to determine the salivary concentrations of interleukin-6 (IL-6) and IL-8 before and after replacement of the amalgam restorations.

METHODS:
The study included 20 patients with OLR and 20 healthy volunteers, who were examined between 2001 and 2005 at the Oral Medicine Unit of the Medical Faculty University of Rijeka. All patients were skin patch tested by an experienced physician. Saliva samples were collected, prepared and analysed for IL-6 and IL-8 concentrations using enzyme-linked immunosorbent assay.

RESULTS:
Sixteen out of 20 patch-tested patients showed a sensitization to inorganic mercury or amalgam. Total replacement of all amalgam fillings was carried out on 20 patients with fillings based on composite resin, gold, porcelain or a combination of these. Sixteen out of 20 patients showed complete healing of OLR; three patients had marked improvement, whereas one patient showed no improvement. Levels of IL-6 detected before replacement were significantly higher than IL-6 levels following the replacement (P = 0.003). The IL-8 levels measured before replacement procedure were significantly higher than the IL-8 levels after replacement of the fillings (P < 0.001).

CONCLUSIONS:
On the basis of clinical observations, restorative therapy resulted in tissue healing. Following the replacement of amalgam fillings with fillings based on other restorative materials, levels of both IL-6 and IL-8 shifted towards normal, as measured in healthy subjects.

Local adverse effects of amalgam restorations.
McCullough MJ Tyas MJ
Int Dent J (2008 Feb) 58(1):3‐

Amalgam has been used for the restoration of teeth for well over 100 years, and is the most successful of the direct restorative materials with respect to longevity. Despite the increasing use of tooth‐ coloured materials, with advantages of aesthetics and adhesion, amalgam is one of the most widely used dental restorative materials. One of the principal disadvantages of amalgam, apart from aesthetics, is that it may have adverse biological effects, both locally and systemically. Locally, it can cause an erythematous lesion on the adjacent oral soft tissues (tongue and buccal mucosa), and systemically free mercury in the amalgam may give rise to a hypersensitivity reaction. The purpose of this paper is to review the literature concerning the local adverse reactions to dental amalgam. The focus will be on the reactions of the oral mucosa, and brief consideration will be given to laboratory cytotoxicity of dental amalgam and its components, and to the 'amalgam tattoo'.

Oral allergies to dental materials.
Evrard L Parent D
Bull Group Int Rech Sci Stomatol Odontol (2010) 49(1):14‐8

Oral allergies represent a pathological entity not well known nor diagnosed by dental health
professionals. The purpose of this work is to present an information relative to the
multidisciplinary steps to be done to solve allergy problems. Three clinical examples of contact oral allergies (to mercury, or gold, or methacrylates) are presented, as to illustrate signs and symptoms of an oral allergy to the more frequent dental materials implied.We discuss the problem of oral allergies from what is known from the scientific literature. We stress the importance of a multidisciplinary approach to take into account patients with an oral allergy, with participation of specialists from dental and dermatologic fields.

Relationship between mercury levels in blood and urine and complaints of chronic mercury toxicity from amalgam restorations.
Eyeson J House I Yang YH Warnakulasuriya KA
Br Dent J (2010 Feb 27) 208(4):E7; discussion 162‐3

AIM: To determine whether patients complaining of oral and medical symptoms perceived to be associated with chronic mercury toxicity have elevated mercury levels in their blood and urine. METHODS: The study group in this audit were 56 patients presenting to an oral medicine unit with complaints perceived to be related to chronic mercury toxicity. Their symptoms and comorbidity were charted and mercury levels in blood and urine were biochemically tested by atomic absorption spectrophotometry. RESULTS: None had elevated mercury levels in blood or urine above the normal threshold level. Subgroup analysis showed subjects with oral lesions, autoimmune disorders and multiple sclerosis had relatively and significantly higher mercury levels within this cohort, but within the threshold values. When tested by multiple logistic regression adjusted for age and gender, mercury levels in blood or urine, numbers of amalgams were not significant for multiple sclerosis or previously diagnosed autoimmune disease. CONCLUSION: Mercury levels in blood and urine of this cohort of patients with perceived chronic mercury toxicity were within the normal range in accordance with a national laboratory threshold value.

Oral lichenoid reaction associated with tin component of amalgam restorations: a case report.

The American Journal of Dermatopathology 2010 Feb;32(1):46-8.
Aggarwal V, Jain A, Kabi D.
Department of Dental Surgery, Safdarjung Hospital, New Delhi, India.

This case report describes a twenty three year old man with bilateral oral lichenoid reaction. Histopathological features were compatible with lichenoid mucositis. Patch test resulted in positive response to amalgam powder and tin. The amalgam restorations were removed and the teeth were restored with a temporary material which was eventually replaced with a light-cured composite resin. The lesion was resolved after one month and was still absent at the six month review.

Abstract

Amalgam or its components may cause type IV hypersensitivity reactions on the oral mucosa. Majority of the reported cases involved a delayed hypersensitivity to mercury. A case of bilateral oral lichenoid reaction is presented, which was present in relation to amalgam restorations. Histopathological features were compatible with lichenoid mucositis. Patch test was positive with pulverized amalgam and tin. The lesion healed up after replacement of restorations with an intermediate restorative material. The clinician should be aware of all possible pathological etiologies of white lesions. If there is any doubt about the nature or management of an unusual oral lesion, referral to appropriate specialists is mandatory.

Oral lichenoid reaction, dental amalgam, and tin allergy.
Pigatto PD Bombeccari G Spadari F Guzzi G
Am J Dermatopathol (2011 Jun) 33(4):414‐5

Diagnosing oral lichenoid contact reaction: clinical judgment versus skin‐patch test.
Luiz AC Hirota SK Dal Vechio A Reis VM Spina R Migliari DA
Minerva Stomatol (2012 Jul‐Aug) 61(7‐8):311‐7

AIM: Objective of this study was to compare the skin‐patch test with the clinical diagnosis of oral lichenoid contact reaction (OLCR) as indicators for amalgam replacement.METHODS: Of 53 patients (38 female and 15 male; mean age 48.7) with oral lichen planus (OLP), 26 were identified as having OLCR, and clinically graded according to the proximity of their lesions with amalgam fillings: class I (weak association), class II (moderate association), and class III (strong association). All OLCR patients were skin‐patch tested for both standard (Brazilian) and specific allergens (TROLAB, Germany). Patients were considered skin‐patch positive only if they developed positive skin reactions for thimerosal and/or amalgam components. Amalgam replacement was indicated in all class II and III patients. For class‐I patients, amalgam replacement was indicated only if they were skin‐patch test positive. Readings for the skin‐patch test were made at 48h and 96h.RESULTS: Of the 26 patients with OLCR, two missed the followup and were excluded, leaving 24 cases. Of these, four were class‐I, and all were negative for the skin‐patch test. Twelve were class‐II, of whom seven were skin‐patch positive. Eight were class‐ III, of whom six were skin‐patch positive. Following amalgam replacement in the 12 class‐II patients, six showed improvement and six had complete resolution, while in the eight class‐III patients, two showed improvement and six a complete resolution.
CONCLUSION: Clinical diagnosis of OLCR lesions is a more reliable indicator for the question of amalgam replacement
than is the skin‐patch test.

Oral lichenoid lesions associated with amalgam restorations: a prospective pilot study addressing the adult population of the Basque Country.
Lartitegui‐Sebastián MJ MartÃnez‐Revilla B Saiz‐Garcia C Eguizabal‐Saracho S Aguirre‐Urizar JM
Med Oral Patol Oral Cir Bucal (2012 Jul) 17(4):e545‐9

Oral lichenoid lesions (OLLs) are linked to a heterogeneous group of pathologies involving the oral mucosa that cannot be distinguished from the oral lichen planus excepting the fact that direct causal factors such as silver amalgam restorations (SARs) can be allocated to them.
PURPOSE: To analyze the prevalence of mucosal lesions associated with SAR in a group of SAR carrying patients in the Basque Country.
STUDY DESIGN: A clinical prospective study was carried out on 100 adult patients over 30 years of age at the UPV/EHU Clinical Odontology Service whose rear teeth had at least one SAR. Patients were identified and mucosal lesions and amalgam restorations were characterized. Patch tests were performed on patients with lesions and amalgams were replaced with composite material. A statistical and comparative analysis was performed with the resulting data.
RESULTS: OLLs were found in 7 patients whose predominant lesion was bilateral, asymmetrical and asymptomatic white papule‐macule. Lesions were related to old and corroded SARs. Patch testing was positive in two cases. SAR substitution produced an improvement in 5 cases.
CONCLUSIONS: The presence of lichenoid lesions associated with SARs is infrequent in our environment and is preferentially related to old and corroded restorations.

Oral lichenoid contact lesions to mercury and dental amalgam: a review.
McParland H Warnakulasuriya S
J Biomed Biotechnol (2012) 2012:589569

Human oral mucosa is subjected to many noxious stimuli. One of these substances, in those who have restorations, is dental amalgam which contains mercury. This paper focuses on the local toxic effects of amalgam and mercury from dental restorations. Components of amalgam may, in rare instances, cause local side effects or allergic reactions referred to as oral lichenoid lesions (OLLs). OLLs to amalgams are recognised as hypersensitivity reactions to low‐level mercury exposure. The use of patch testing to identify those susceptible from OLL is explored, and recommendations for removing amalgam fillings, when indicated are outlined. We conclude that evidence does not show that exposure to mercury from amalgam restorations poses a serious health risk in humans, except for an exceedingly small number of hypersensitivity reactions that are discussed.

Diagnosing oral lichenoid contact reaction: clinical judgment versus skin-patch test.
Luiz AC, Hirota SK, Dal Vechio A, Reis VM, Spina R, Migliari DA.
Minerva Stomatol. 2012 Jul-Aug;61(7-8):311-7. English, Italian.

AIM:
Objective of this study was to compare the skin-patch test with the clinical diagnosis of oral lichenoid contact reaction (OLCR) as indicators for amalgam replacement.
METHODS:
Of 53 patients (38 female and 15 male; mean age 48.7) with oral lichen planus (OLP), 26 were identified as having OLCR, and clinically graded according to the proximity of their lesions with amalgam fillings: class I (weak association), class II (moderate association), and class III (strong association). All OLCR patients were skin-patch tested for both standard (Brazilian) and specific allergens (TROLAB, Germany). Patients were considered skin-patch positive only if they developed positive skin reactions for thimerosal and/or amalgam components. Amalgam replacement was indicated in all class II and III patients. For class-I patients, amalgam replacement was indicated only if they were skin-patch test positive. Readings for the skin-patch test were made at 48h and 96h.
RESULTS:
Of the 26 patients with OLCR, two missed the follow-up and were excluded, leaving 24 cases. Of these, four were class-I, and all were negative for the skin-patch test. Twelve were class-II, of whom seven were skin-patch positive. Eight were class-III, of whom six were skin-patch positive. Following amalgam replacement in the 12 class-II patients, six showed improvement and six had complete resolution, while in the eight class-III patients, two showed improvement and six a complete resolution.
CONCLUSION:
Clinical diagnosis of OLCR lesions is a more reliable indicator for the question of amalgam replacement than is the skin-patch test.

Diagnosing oral lichenoid contact reaction: clinical judgment versus skin-patch test.
Luiz AC, Hirota SK, Dal Vechio A, Reis VM, Spina R, Migliari DA.
Minerva Stomatol. 2012 Jul-Aug;61(7-8):311-7. English, Italian.

Etiogenic study on oral lichenoid reactions among Tamil Nadu population: a prospective cohort study.
Nagaraj E, Eswar P, Kaur RP.
Indian J Dent Res. 2013 May-Jun;24(3):309-15. doi: 10.4103/0970-9290.117992.
PMID: 24025876 Free Article

Abstract
BACKGROUND:
Most of the clinical, epidemiological, and etiogenic studies on oral lichenoid reactions (OLRs) have been undertaken in the United States, UK, Scandinavia, and other European countries. So far, very few cohort studies on a small population have been documented from South Asian region to implicate the role of various causative agents in the precipitation of OLR.
OBJECTIVES:
To implicate the role of various allopathic, alternate medicinal drugs, dental materials, etc., in the precipitation OLRs; to evaluate the pattern of remission; and to estimate the time period for the remission of lesions following the discontinuance of the suspected agents in the population of Tamil Nadu.
MATERIALS AND METHODS:
A total of 102 patients were included, of whom 51 (mean age 43.3 years, SD 14.59) formed the study group, who possessed a positive drug history to the intake of either potential allopathic or alternate drugs or had recent dental metallic fillings/restorations, and 51 were (mean age 47.86 years, SD14.67) in the control group possessing oral lichen planus (OLP). The patients were followed up at a monthly interval period for a period of 18 months.
RESULTS:
Complete remission of signs and symptoms was noticed in 41 patients, partial remission in 6, no change in 2, newer lesions in 1, and flaredup lesions were observed in 1 participant in the study group. The mean onset time for lichenoid eruptions was found to be 2.5 months (SD 58.82) and the mean remission time after discontinuing the drug was 9.1 months (SD 4.7).
CONCLUSION:
OLR could be implicated to documented lichenoid agents like calcium channel blockers, ACE inhibitors, atarvastatin, metformin, glibenclamide, dapsone, carbimazole, silver amalgam fillings, etc.in southSouth Indian population. Furthermore, the drugs like oflaxacin, arsenical album, and yellow orpimentumwere also found to have strong implication in the precipitation of OLR. Discontinuance of the suspected agents resulted in healing in the majority of cases.

Regression of oral lichenoid lesions after replacement of dental restorations.
Mårell L, Tillberg A, Widman L, Bergdahl J, Berglund A.
J Oral Rehabil. 2014 May;41(5):381-91.
PMID: 24843865

Amalgam contact hypersensitivity lesion: an unusual presentation-report of a rare case.
Ramnarayan B, Maligi P, Smitha T, Patil U.
Ann Med Health Sci Res. 2014 Sep;4(Suppl 3):S320-3. doi: 10.4103/2141-9248.141981.
PMID: 25364611 Free PMC Article

Patch testing in oral lichenoid lesions of uncertain etiology.
Lynch M, Ryan A, Galvin S, Flint S, Healy CM, O'Rourke N, Lynch K, Rogers S, Collins P.
Dermatitis. 2015 Mar-Apr;26(2):89-93. doi: 10.1097/DER.0000000000000109.
PMID: 25757080

The role of patch testing in the management of oral lichenoid reactions.
Suter VG, Warnakulasuriya S.
J Oral Pathol Med. 2015 May 20. doi: 10.1111/jop.12328. [Epub ahead of print]
PMID: 25990286

Role of dental restoration materials in oral mucosal lichenoid lesions.
Sharma R, Handa S, De D, Radotra BD, Rattan V.
Indian J Dermatol Venereol Leprol. 2015 Sep-Oct;81(5):478-84. doi: 10.4103/0378-6323.162341.
PMID: 26261149 Free Article

Oral lichenoid reactions, patch tests, and mercury dental amalgam.
Pigatto PD, Spadari F, Bombeccari GP, Guzzi G.
J Oral Pathol Med. 2015 Aug 26. doi: 10.1111/jop.12352. [Epub ahead of print] No abstract available.
PMID: 26308960

Allergic Reactions to Dental Materials-A Systematic Review.
Syed M, Chopra R, Sachdev V.
J Clin Diagn Res. 2015 Oct;9(10):ZE04-9. doi: 10.7860/JCDR/2015/15640.6589. Epub 2015 Oct
PMID: 26557634 Free PMC Article

Correlation of corrosion resistance of dental alloy restorations with oral lichen planus pathology.
M. Andrei, S. Tovaru, I. Parlatescu, C. Gheorghe and C. Pirvu*
Materials and Corrosion 2015

In this article, the corrosion processes that occur in metallic fixed dental restorations from a group of patients with oral lichen planus are investigated throughout electrochemical characterizations. Oral lichen planus (OLP) is a non-infectious, chronic, autoimmune disorder, of unknown aetiology, which involves the oral mucosa and sometimes, it has a malignant transformation. The presence of oral metals is incriminated as a trigger factor in the pathology of OLP. In order to emphasise this influence, the alloys recovered after the removal
of some old metal restorations in OLP patients were analysed. Their composition was determined by energy dispersive X-ray spectroscopy. Open circuit potential measurements, Tafel analysis and electrochemical impedance spectroscopy were also carried out. The studied alloys were high copper alloys and chromium–nickel base alloys with different electrochemical behaviour. The
results suggested a correlation between corrosion process in the oral environment and oral lichen planus pathology.

A comparative analysis of metal allergens associated with dental alloy prostheses and the expression of HLA-DR in gingival tissue

XIN ZHANG,1,* LI-CHENG WEI,2,* BIN WU,1 LI-YING YU,1,* XIAO-PING WANG,3 and YUE LIU1
Mol Med Rep. 2016 Jan; 13(1): 91–98.

Abstract
The present study aimed to provide guidance for the selection of prosthodontic materials and the management of patients with a suspected metal allergy. This included a comparison of the sensitivity of patients to alloys used in prescribed metal-containing prostheses, and correlation analysis between metal allergy and accompanying clinical symptoms of sensitized patients using a patch test. The results from the patch test and metal component analyses were processed to reach a final diagnosis. In the present study, four dental alloys were assessed. Subsequent to polishing the surface of a metal restoration, the components were analyzed using an X-ray fluorescence microscopy and spectrometry. Immunohistochemical analysis, reverse transcription-polymerase chain reaction and western blotting were used to detect the expression levels of human leukocyte antigen (HLA)-DR in gingival tissues affected by alloy restoration, and in normal gingival tissue samples. Positive allergens identified in the patch test were consistent with the components of the metal prostheses. The prevalence of nickel (Ni) allergy was highest (22.8%), and women were significantly more allergic to palladium and Ni than men (P<0.05). The protein and gene expression levels of HLA-DR in the Ni-chromium (Cr) prosthesis group were significantly higher, compared with those in the other groups (P<0.01); followed by cobalt-Cr alloy, gold alloy and titanium alloy. In conclusion, dentists require an understanding of the corrosion and allergy rates of prescribed alloys, in order to reduce the risk of allergic reactions. Patch testing for hypersensitive patients is recommended and caution is required when planning to use different alloys in the mouth.

PMCID: PMC4686053

Molecular Mechanisms of Nickel Allergy

Masako Saito, Rieko Arakaki, Akiko Yamada, Takaaki Tsunematsu, Yasusei Kudo, and Naozumi Ishimaru*
Int J Mol Sci. 2016 Feb; 17(2): 202.

Abstract
Allergic contact hypersensitivity to metals is a delayed-type allergy. Although various metals are known to produce an allergic reaction, nickel is the most frequent cause of metal allergy. Researchers have attempted to elucidate the mechanisms of metal allergy using animal models and human patients. Here, the immunological and molecular mechanisms of metal allergy are described based on the findings of previous studies, including those that were recently published. In addition, the adsorption and excretion of various metals, in particular nickel, is discussed to further understand the pathogenesis of metal allergy.

Conclusions and Perspectives
The incidence of allergic diseases has been increasing worldwide. The pathogenesis and mechanisms of the allergic response is highly complex, and many patients develop refractory disease. Because metal allergy is caused by materials used in products that are common in our daily life, chances of triggering the onset of allergic reactions are high. The clinical symptoms of metal allergy include rashes, swelling, and pain. Molecular pathogenesis of a metal allergy suggests that excess responses to metals occur via the complicated process of the interactions among the immune system, epithelial barrier, and homeostatic mechanism. The unique features, adsorption, and the excretion of metals in the human body complicate the pathogenesis and symptoms of metal allergy. Molecular mechanisms of metal allergy need to be determined to develop novel therapeutic strategies. Analysis and characterization of the precise mechanisms could have clinical implications leading to the development of new diagnostic or treatment methods for metal allergy.

PMCID: PMC4783936

Lichenoid reaction associated with silver amalgam restoration in a Bombay blood group patient: A case report

Rohini Rangarao Pawar, Sudha S. Mattigatti, Rushikesh R. Mahaparale, and Amit P. Kamble
J Conserv Dent. 2016 May-Jun; 19(3): 289–292.

Abstract
The pathogenic relationship between the oral lichenoid reaction (OLR) and dental restorative materials has been confirmed many times. An OLR affecting oral mucosa in direct contact with an amalgam restoration represents a delayed, type IV, cell mediated immune response to mercury or one of the other constituents of the dental amalgam. Bombay blood group patients are more prone to this. A case of bilateral OLR is presented, which is present in relation to amalgam restoration. The lesion healed up after the replacement of restorations with an intermediate restorative material. The clinician should be aware of all the possible pathological etiologies of white lesions. If there is any doubt about the nature or management of a usual oral lesion, a referral to an appropriate specialist is mandatory.

CONCLUSION
From this case report, it is evident that amalgam restorations may induce lichenoid reactions in susceptible individuals such as Bombay blood group patients. The typical appearance of these lesions usually confirms diagnosis in most cases. Clinical features as well as the results of skin patch testing against Hg and Silver alloy can help in the diagnosis. Several studies have shown the benefit of replacing restorations on the healing of lichenoid reactions.

Para functional habits may also exacerbate lesions close to restorations. Psychological aspects, lifestyle of patient, and genetic susceptibility have also been proposed to be the predisposing factors. Complete healing of lichenoid lesions after the replacement of dental amalgam in 28/62 (42%) patients with positive patch tests results and 3/15 (20%) patients with negative patch test results was reported by Laine et al.[12]

These lesions are rarely symptomatic, and many patients are unaware of their existence. The removal of the offending fillings may result in clearing of the lesions. Patients whose lesions are in direct contact with the fillings have a better prognosis. Amalgam removal, whenever it is necessary, should always be done using absolute isolation with rubber dam, abundant irrigation, and high-volume suction. This avoids ingestion, minimizes inhalation of mercury vapor, and largely eliminates the risk of an exacerbation of the lesion during the amalgam removal.

PMCID: PMC4872588

Amalgam Contact Allergy in Oral Lichenoid Lesions.

Thanyavuthi A, Boonchai W, Kasemsarn P.
Dermatitis. 2016 Jul-Aug;27(4):215-21. doi: 10.1097/DER.0000000000000204.

PMID: 27323234

Conclusions: The prevalence of amalgam contact allergy in patients with OLLs was 58.5%. Mercury was the most common allergen, followed by copper sulfate. An association between clinical, topographic relation, and positive patch test results would be a useful predictor for favorable outcome after amalgam removal.

Allergen-getriggerte lichenoide Mundschleimhautläsionen: Diagnose und Therapie anhand eines Fallbeispiels.

Olms C, Remmerbach TW.
Swiss Dent J. 2017;127(1):27-37.

PMID: 28134970

Allelic loss in amalgam-associated oral lichenoid lesions compared to oral lichen planus and mucosa.

Rodrigues LN, Sousa SF, Silva R, Abreu M, Pires FR, Mesquita RA, Bastos-Rodrigues L, De Marco L, Gomes CC, Gomez RS, Bernardes VF.
Oral Dis. 2017 May;23(4):471-476. doi: 10.1111/odi.12627. Epub 2017 Feb 8.

PMID: 28028908

Differential metallothionein expression in oral lichen planus and amalgam-associated oral lichenoid lesions.

Mendes GG, Servato JP, Borges FC, Rosa RR, Siqueira CS, de Faria PR, Loyola AM, Cardoso SV.
Med Oral Patol Oral Cir Bucal. 2018 May 1;23(3):e262-e268. doi: 10.4317/medoral.22144.

PMID: 29680841

Can We Separate Oral Lichen Planus from Allergic Contact Dermatitis and Should We Patch Test? A Systematic Review of Chronic Oral Lichenoid Lesions.

Rahat S, Kashetsky N, Bagit A, Sachdeva M, Lytvyn Y, Mufti A, Maibach HI, Yeung J.
Dermatitis. 2021 May-Jun 01;32(3):144-150. doi: 10.1097/DER.0000000000000703.

PMID: 33273245

Abstract
This systematic review summarizes characteristics and treatment outcomes of dental amalgam-associated oral lichenoid lesions (OLLs) and oral lichen planus (OLP). Embase and MEDLINE were searched for original studies on OLLs or OLP associated with dental amalgam. Data extraction was completed from 44 studies representing 1855 patients. Removal of amalgam restorations led to complete resolution in 54.2% (n = 423/781), partial resolution in 34.8% (n = 272/781), and no resolution in 11.0% (n = 86/781) of the patients with OLLs, whereas complete resolution occurred in 37.1% (n = 72/194), partial resolution in 26.3% (n = 51/194), and no resolution in 36.6% (n = 71/194) of the patients with OLP. For patients with OLLs, 91.6% of the patients with positive patch tests and 82.9% with negative patch tests had improvement with removal of amalgam, whereas for patients with OLP, 89.2% of the patients with positive patch tests and 78.9% with negative patch tests had improvement with removal of amalgam. Our results suggest improvement occurs, regardless of patch testing status.