Female, 51 years old, presented with central nervous system (CNS) disturbances, concentration difficulties, loss of memory, and coordination problems. She also suffered from fatigue, depression, muscle weakness, and chronic infections. She has been exposed to amalgam fillings and Au/Pd crowns but also to pentachlorophenol and lindane in her home. All skin tests in standard and metal series were negative. In MELISA, she showed strong multiple metal sensitization, especially to HgCl2 and Ni. She underwent complete amalgam and Au/Pd crown removal, followed by metal elimination therapy with glutathione, sodiumthiosulfate (10%), and thiopronine. She also changed her place of residence. After 6 months, significant improvement of all symptoms occurred. At the same time, MELISA to most metals became negative. In this case, MELISA initially showed strong sensitization especially to HgCl2 and Ni, despite negative patch test results; clinical relevance of this sensitivity was confirmed by its significant reduction upon removal of the relevant dental metals. Such cases demonstrate a major advantage of LTTs compared to skin testing in their ability to detect systemically- as well as dermally-induced sensitizations. In addition, because heavy metals (particularly HgCl2) and pentachlorophenol are both detoxified by the glutathione system, complete recovery of this patient required not only removal of dental metal and avoidance of pentachlorophenol but also metal elimination therapy.

Male, 70 years old, with amalgam fillings and Au crowns, presented with seronegative oligoarthritis. MELISA® was strongly positive to Be but negative to all other metals including Ni. Four months after complete dental metal replacement and metal elimination therapy, significant improvement of clinical symptoms and normalization of Be-specific reactivity occurred. As this patient reported no occupational exposure to Be, exposure was most likely due to Be-contaminated dental metals.

Female, 77 years old, presented early 2003 with stomatitis and extremely dry mouth. She had Pd-containing Au crowns, and her lymphocytes reacted to Pd and Ni. One year after removal of crowns, her symptoms did not improve. Her metal-induced reactivity also persisted, and she became positive to Au as well. The patient reported that she had had two Ni-containing screws inserted into her kneecap in December 2003 and, in addition, used an electric razor daily. The rotating head of the razor was subsequently found to contain Pd (175 mg/kg). No Pd was found in her blood (MELISA in mid-2005 showed still very strong responses to Pd (SI = 119.5), which could be caused by her razor, higher responses to Ni than previously (SI = 7.9), perhaps due to the screws, and now lower responses to Au (SI = 2.9), probably due to Au crown replacement. The patient’s symptoms remained unchanged. This case demonstrates that a thorough and ongoing anamnesis of the patient is required to identify all, often obscure, sources of metal exposure.

Female, 46 years old, presented with acute polyarthritis 10 days, after implantation of a Ti pin. She had amalgam fillings as well as Ti implants. Multiple metal reactivities were found at the lymphocyte level, in particular to TiO2 (SI = 14.8) and HgCl2 (SI= 6.8). 17 months after complete dental metal removal as well as chelation with 2,3-dimercapto-propane sulfonate (DMPS) and 2,3-dimercaptosuccinic acid (DMSA), significant clinical improvement and normalization of all metal reactivities was observed.This case strongly suggests that the patient developed sensitivity not only to HgCl2 due to Hg-containing amalgams but also to Ti due to chronic exposure to Ti-containing implants. The insertion of a Ti pin possibly provided a booster effect leading to the acute clinical symptoms.

Female, 13 years old, developed severe acne, fatigue, and headaches after implantation of Ni-containing orthodontic brackets. Her lymphocytes reacted strongly to Ni (SI = 34.2) only, while the patch test to Ni was negative. The patient also had high interleukin-2 (IL-2) in blood (127 pg/ml, normal value <15 pg/ml). Six months after removal of brackets, acne and other symptoms significantly improved, in vitro reactivity to Ni significantly decreased (SI = 17.1), and the IL-2 level returned to normal. Further therapy, including Nifree diet, is ongoing.

Female, 65 years old, presented at the end of 2004 with chronic excruciating pain in her knee six months after implantation of a knee endoprosthesis. As she was patch test positive for Ni, she was assured that her implant was a Ni-free Ti alloy. Because of her pain, she contacted the laboratory for testing of possible Ti allergy. In MELISA tests of two consecutive blood samples, she was found to have no sensitization to the common components of Ti alloys but showed a strong sensitization to Ni (SI = 25.8 in the first test, 27.8 in the second test). Her orthopedic clinic assured her that this had no clinical relevance as her implant did not contain Ni and advised her to continue her palliative treatment of physiotherapy and pain medication. After 10 more months of chronic pain, the patient insisted on removal of the implant, one portion of which was subsequently found to contain no Ti but primarily Co, Cr, and Mo (> 99%) and a small amount of Ni (0.124%), the other portion containing primarily Ti (96%), V (4%), and spurious amounts of other metals including Ni (0.014%). The clinic admitted its regrettable mistake and replaced both parts with a “pure” Ti prosthesis. One week later (!) the patient was free of pain, and her Ni reactivity had dropped to SI = 17.8.

Female, 56 year-old entertainer, presented with eczema and bone and join pain. She had only amalgam fillings but massive occupational exposure to TiO2via daily cosmetics (up to 854 mg/kg in some products). She exhibited strong reactivity to TiO2 (SI = 24.9) and weak reactivity to Be and Pt (both SI = 3.8). Five months after avoiding TiO2-containing cosmetics, in addition to metal elimination therapy, significant clinical improvement and normalization of lymphocyte reactivity was observed. The patient continued avoiding TiO2, and three years later, lymphocyte reactivity remained in a normal range, and the patient was still in good health. This case demonstrates not only the potential risk of developing hypersensitization to TiO2 in cosmetics but also the stability of negative MELISA reactivity during consequent exposure avoidance. On the other hand, strong lymphocyte reactivity to metals persisted in follow-up samples from 2 patients with multiple Pd-containing Au crowns who did not undergo dental replacement.

Female, 69 years had been suffering from steroid resistant oral lichen planus for for 4 years. Both patch testing and MELISA detected allergies to nickel, gold and cobalt. Additional MELISA detected allergy to palladium and platinum among others. Following removal of all amalgams and partial removal of gold crown her OLP resolved after 18 months.

A female suffered from burning mouth syndrome, severe chronic dry coughing, and multiple allergies. She responded strongly to Ni (SI = 70.9), less strongly to Pd (SI = 11.4), and weakly to Co (SI = 3.6) in 2003 and nearly identically 2 years later. Lymphocyte responses to HgCl2, PhHg, Au, Sn, Cd, and TiO2 remained negative. Similarly, another patient, who complained of Quincke’s edema of the tongue, vulvitis, and eczema of the hands, responded strongly to Ni (SI = 52.2), less strongly to Au (SI = 14.6) and Pd (SI = 10.3), and weakly to Cd (SI = 4.2) and Pb (SI = 3.5) in 2005. Her metal-induced lymphocyte responses were similar one year later, with only an insignificant decrease in reactivity to Cd and Pb. Interestingly, skin tests with this patient were positive for Ni, Pd, and Co as well as for Au in the form of sodium thiosulfate aurate but not for Au in the form of Au Degunorm discs obtained from the dentist. In both cases clinical symptoms, as well as lymphocyte reactivity, remained unchanged.