Metal hypersensitivity and pro-inflammatory cytokine production in patients with failed orthopedic implants: A case-control study.

Orthopedic implants heal well without complications in most patients but fail for unclear reasons in some individuals. This study determined the relevance of metal hypersensitivity in patients with failed orthopedic implants and those requiring orthopedic implant surgery. The study included 35 patients with failed orthopedic implants and 15 subjects scheduled for orthopedic implant surgery. The production of selected pro-inflammatory cytokines was measured in patients with failed orthopedic implants. Metal hypersensitivity was measured in all subjects using the MELISA® test. Of common metals in orthopedic alloys, the patients with failed orthopedic implants responded most frequently to nickel, chromium, titanium, iron, and molybdenum. Hypersensitivity to metals found in implants was measured in 40% of patients with failed implants. The study also showed that titanium exposure in patients with titanium hypersensitivity might lead to implant failure. Metal hypersensitivity testing should be offered to patients before surgery to minimize the risk of implant failure.

Orofacial granulomatosis associated with hypersensitivity to dental amalgam.

Orofacial granulomatosis is a clinicopathologic entity characterized by chronic swelling of the lip and possible soft tissues in the orofacial region owing to granulomatous inflammation of unknown cause. We present 3 cases of orofacial granulomatosis associated with allergic contact dermatitis to dental materials. Previous treatment with corticosteroids did not have any therapeutic effect. Patch testing revealed a positive reaction to several allergens, including dental amalgam and mercury in 2 cases. A lymphocyte transformation test modified for metals was used to evaluate lymphocyte reactivity. After the removal of the suspected allergens, all patients experienced recovery within 1 month, with the exception of the lip swelling, which gradually subsided over several months.

Influence of metals on cytokines production in connection with successful implantation therapy in dentistry.

OBJECTIVES: In most of patients in need of implantation treatment in the oral cavity, implants heal well, nevertheless, there are some individuals, in whom titanium implants fail for reasons, which remain unclear. DESIGN: The aim of our study was to determine if there is a difference between metal influenced IL-1ß, IL-4, IL-6, TNF-α and IFN-γ cytokines production in patients with successfully healed implants compared to those, whose implant therapy was unsuccessful. SETTING: The two study groups included 12 patients with failed dental titanium implants and 9 patients with successfully healed implants. In the subjects, cytokine production was established after lymphocyte cultivation with mercury, nickel and titanium antigens. RESULTS: IL-1ß levels were significantly increased in all patients after stimulation with titanium and in patients with accepted implants compared to patients with failed implants after the stimulation with mercury and titanium. Titanium caused significantly increased IL-6 production in all patients. TNF-α and IFN-γ levels were also significantly increased after the stimulation with titanium. Significantly increased TNF-α levels were found in patients with accepted implants as compared to patients with failed implants. CONCLUSIONS: Increased production of IL-1ß a IL-6 cytokines in reaction to titanium and increased production of TNF-α and IFN-γ cytokines in reaction to mercury, which is very often present in the form of amalgam in the oral cavity of persons in need of implant therapy, can play an important role in immune reactions during implant healing process. In patients with failed titanium implants, decreased production of these cytokines may participate in implant failure.

The role of environmental factors in autoimmune thyroiditis.

Environmental factors can play an important role in the development of autoimmune thyroiditis (AT) and other autoimmune diseases. This article reviews the role of heavy metals and infectious agents in AT. Currently, the genes responsible for a metal-induced pathology are known in experimental animals but similar knowledge is lacking in man. Metals such as nickel or mercury induce delayed type T cell hypersensitivity (allergy) which is relatively common, especially in women. T-cell allergy can be studied with the lymphocyte transformation test, LTT-MELISA. It has been found that patients with AT and other autoimmune diseases, such as multiple sclerosis, psoriasis, systemic lupus erythematosus and atopic eczema, show increased lymphocyte reactivity in vitro to inorganic mercury, nickel and other metals compared to healthy controls. The important source of mercury is dental amalgam. Replacement of amalgam in mercury-allergic subjects resulted in improvement of health in about 70% of patients. Several laboratory parameters such as mercury-specific lymphocyte responses in vitro and anti-thyroid autoantibodies were normalized as well. In contrast, no changes in health and laboratory results were observed in mercury-allergic patients who did not have their amalgams replaced. The same was true for non-allergic patients who underwent amalgam replacement. Infectious agents such as Helicobacter pylori (Hp) may cause chronic inflammation and autoimmune reactivity in susceptible subjects. The results of in vitro experiments performed with lymphocytes from Hp infected patients indicate that Hp can cause immunosuppression which might be eliminated by successful eradication therapy. In conclusion, heavy metals and Hp infection may play an important role in AT. Laboratory tests, such as LTT-MELISA, can help to determine the specific etiological agents causing inflammation in individual patients. The treatment of AT and other autoimmune diseases might be improved if such agents are eliminated and any future exposure restricted.

Removal of dental amalgam decreases anti-TPO and anti-Tg autoantibodies in patients with autoimmune thyroiditis.

OBJECTIVES: The impact of dental amalgam removal on the levels of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies was studied in patients with autoimmune thyroiditis (AT) with and without mercury allergy. METHODS: Thirty-nine patients with AT were tested by an optimized lymphocyte proliferation test MELISA for allergy (hypersensitivity) to inorganic mercury. Patients were divided into two groups: Group I (n = 12) with no hypersensitivity to mercury and Group II (n = 27) with hypersensitivity to mercury. Amalgam fillings were removed from the oral cavities of 15 patients with hypersensitivity to mercury (Group IIA) and left in place in the remaining 12 patients (Group IIB). The laboratory markers of AT, anti-TPO and anti-Tg autoantibodies, were determined in all groups at the beginning of the study and six months later. RESULTS: Compared to levels at the beginning of the study, only patients with mercury hypersensitivity who underwent amalgam replacement (Group IIA) showed a significant decrease in the levels of both anti-Tg (p=0.001) and anti-TPO (p=0.0007) autoantibodies. The levels of autoantibodies in patients with or without mercury hypersensitivity (Group I and Group IIB) who did not replace amalgam did not change. CONCLUSION: Removal of mercury-containing dental amalgam in patients with mercury hypersensitivity may contribute to successful treatment of autoimmune thyroiditis.

The beneficial effect of amalgam replacement on health in patients with autoimmunity.

BACKGROUND: Patients with certain autoimmune and allergic diseases, such as systemic lupus, multiple sclerosis, autoimmune thyroiditis or atopic eczema, often show increased lymphocyte stimulation by low doses of inorganic mercury in vitro. The patients often report clinical metal hypersensitivity, especially to nickel. OBJECTIVE AND METHODS: In this study we examined the health impact of amalgam replacement in mercury-allergic patients with autoimmunity. The suitability of MELISA, an optimized lymphocyte stimulation test, for the selection of susceptible patients and monitoring of sensitization was also examined. Amalgam fillings were replaced with composites and ceramic materials. Follow-up health status and lymphocyte reactivity were assessed and evaluated half a year or later following amalgam removal. RESULTS: Results of lymphocyte reactivity measured with MELISA indicate that in vitro reactivity after the replacement of dental amalgam decreased significantly to inorganic mercury, silver, organic mercury and lead. Out of 35 patients, 25 patients (71%) showed improvement of health. The remaining patients exhibited either unchanged health (6 patients, 17%) or worsening of symptoms (4 patients, 11%). The highest rate of improvement was observed in patients with multiple sclerosis, the lowest rate was noted in patients with eczema. The initial mercury-specific lymphocyte reactivity was significantly higher in the responder group, than in the non-responders, whose health was not improved by amalgam removal. All patients with health improvement after amalgam replacement showed reduced proliferation to inorganic mercury in follow-up MELISA. In vitro responses to phenylmercury and nickel did not differ between the groups. CONCLUSIONS: Mercury-containing amalgam may be an important risk factor for patients with autoimmune diseases. MELISA is a valuable tool for selection of patients for amalgam replacement and also for monitoring of metal allergies.

Dental amalgam as one of the risk factors in autoimmune diseases.

BACKGROUND: Experimental and clinical data published recently show that dental amalgam can give rise to undesirable immunological responses in susceptible individuals. In genetically susceptible strains of experimental animals, mercury and silver can induce autoimmune responses. Sera of patients sensitive to mercury were found to have a higher incidence of autoantibodies relative to controls. OBJECTIVE: The aim of this study was to determine possible presence of antinuclear SSB/La autoantibodies after the in vitro stimulation of peripheral blood lymphocytes with HgCl2. METHODS: Lymphocytes were obtained from patients with autoimmune thyroiditis and increased response to mercury in vitro. Mononuclear cells were cultivated for 6 days with 100 microl HgCl2 solution or with pure medium and the levels of antinuclear autoantibodies SSB/La were assayed by a commercial SSB/La ELISA kit. RESULTS: Increased production of SSB/La autoantibodies in the media following stimulation of peripheral blood lymphocytes with HgCl2 was found in all cases. Using the Student's paired test, the results were significant on the p=0.05 significance level. CONCLUSION: Results imply that, in some patients with thyroiditis, mercury from dental amalgam can stimulate the production of antinuclear antibodies. Dental amalgam may be a risk factor in some patients with autoimmune disease.

Mercury and nickel allergy: risk factors in fatigue and autoimmunity.

This study examined the presence of hypersensitivity to dental and environmental metals in patients with clinical disorders complicated with chronic fatigue syndrome. Three groups of patients were examined through medical history, dental examination, and by using a modified test of blast transformation for metals-MELISA(R). The three groups consisted of the following: 22 patients with autoimmune thyroiditis with or without polyglandular autoimmune activation; 28 fatigued patients free from endocrinopathy; and 22 fatigued professionals without evidence of autoimmunity. As controls, a population sample or 13 healthy subjects without any evidence of metal sensitivity was included. Healthy controls did not complain of marked fatigue and their laboratory tests did not show signs of autoimmunity and endocrinopathy. We have found that fatigue, regardless of the underlying disease, is primarily associated with hypersensitivity to inorganic mercury and nickel. The lymphocyte stimulation by other metals was similar in fatigued and control groups. To evaluate clinical relevance of positive in vitro findings, the replacement of amalgam with metal-free restorations was performed in some of the patients. At a six-month follow-up, patients reported considerably alleviated fatigue and disappearance of many symptoms previously encountered; in parallel, lymphocyte responses to metals decreased as well. We suggest that metal-driven inflammation may affect the hypothalamic-pituitary-adrenal axis (HPA axis) and indirectly trigger psychosomatic multisymptoms characterizing chronic fatigue syndrome, fibromyalgia, and other diseases of unknown etiology.