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Objectives: Chronic low-level metal exposure may result in metal sensitization and undesirable side-effects. The main sources of metal exposure are from the environment or from corrosion of dental metal alloys. Affected patients are routinely diagnosed with the epicutaneous (patch) test. However, such testing may induce false-positive (irritative) reactions and may in itself sensitize or exacerbate symptoms. Alternatively, MELISA (Memory Lymphocyte ImmunoStimulation Assay), an optimized lymphocyte transformation test (LTT), can be used. In this study we analyzed the overall frequency and distribution of metal sensitization among symptomatic, metal-exposed patients. In addition, we determined the reproducibility of the assay and assessed its clinical relevance for detecting and monitoring hypersensitivity to metals., Methods: To analyze the frequency and distribution of metal sensitization, blood from 700 consecutive patients was tested against a total of 26 metals in the validated LTT-MELISA. For reproducibility testing, 391 single metal tests from 63 patients were performed in parallel. Finally, to assess clinical relevance, 14 patients with known metal exposure showing local (dry mouth, Oral Lichen Planus, Burning Mouth Syndrome, eczema) and/or systemic (chronic infections, fatigue, autoimmune disorders, central nervous system disturbances, depression) effects were tested in LTT-MELISA. In 7 cases testing was repeated following removal of the allergy-causing metals or, in 2 additional cases, without therapeutic intervention., Results: Of the 700 patients tested, 74.6% responded to >/= 1 metal in LTT-MELISA, with a subgroup of 17.9% responding to >/= 3 metals. Reactivity was most frequent to nickel (68.2%), followed by cadmium (23.7%), gold (17.8%), palladium (12.7%), inorganic mercury (11.4%), molybdenum (10.8%), beryllium (9.7%), titanium dioxide (4.2%), lead (3.7%), and platinum (3.4%). Reproducibility was 94.9%, with most discordant results in a low-positive range. Removal of the alloys or prostheses containing allergenic metals resulted in remarkable clinical improvement correlating with a significant reduction or complete normalization of specific lymphocyte reactivity. In contrast, both LTT-MELISA reactivity and clinical symptoms remained unchanged in follow-up samples from the 2 patients who did not remove the source of metal exposure., Conclusion: The optimized LTT-MELISA test is a clinically useful and reliable tool for identifying and monitoring metal sensitization in symptomatic metal-exposed individuals.

We report a case in which burning mouth syndrome (BMS) was associated with a strong allergy to mercury. The aim of this case history is to strengthen knowledge of the relationship among allergy to mercury, systemic allergic contact dermatitis, and hypersensitivity of the oral mucosa. We performed series of standard and dental patch tests for screening for contact allergy to dental materials, in accordance with International Contact Dermatitis Research Group guidelines. Positive extreme allergic reactions to mercury (+++) and amalgam (++) were seen at the patch site and caused a flare-up of the systemic erythematous reaction. Full recovery from BMS and complete remission of systemic dermatitis were achieved after the mercury tooth filling was removed. Mercury is thought to be an allergen implicated in BMS as well as in the systemic reactivation of allergic contact dermatitis. Patch testing with dental series seems to have greater sensitivity and relevance in BMS patients.