Diagnosis and treatment of metal-induced side-effects.

Environmental factors are recognized as a cause of the increasing frequency of allergic and autoimmune diseases. In addition to external pollutants, metal ions released from dental restorations or from other body implants might trigger inflammation in susceptible subjects. In humans, genes governing metal-induced inflammation and autoimmunity are not yet known. In clinical praxis, metal-sensitive patients will present various symptoms ranging from oral mucosal changes and skin disease to excessive fatigue and autoimmune diseases. Since genetic markers of genetic susceptibility in man are not known, one has to rely on the phenototypic markers. Such biomarkers might be certain detoxification enzymes but also the presence of metal-specific memory cells in the blood. With the increasing use of metal implants in medicine and dentistry, it is important to have a proper tool for the diagnosis of metal allergy in susceptible subjects. After nickel, gold is now the second most common sensitizer. In addition to patch test, an in vitro blood test, an optimized commercially available lymphocyte transformation test (MELISA) is discussed. Both tests were used for the diagnosis of metal allergy in a selected group of 15 patients who suffered from clinical metal sensitivity in addition to other health problems. The concordance of the two tests was good but MELISA detected more metal allergies than patch test. The removal of incompatible dental material (RID) resulted in long-term health improvement in the majority of patients. We postulate that in vivo, metal ions activate T-cells, initiating systemic inflammation, which, through cytokines, affects the brain and hypothalamus-pituitary-adrenal axis. We postulate that in vivo metal ions will activate T-cells starting systemic inflammation which, through cytokines affect the brain and hypothalamus-pituitary-adrenal (HPA) axis. The treatment and rehabilitation of metal sensitive patients is based on a firm understanding and recognition of individual susceptibility. RID has to be done done with extreme caution and according to standard working protocol. If performed properly, this treatment can result in decreased systemic inflammation and improved health in sensitized patients.

The role of metals in autoimmunity and the link to neuroendocrinology.

Current available literature indicates a risk for metal-induced autoimmunity in man. Metal pathology may be due to toxic or allergic mechanisms where both may play a role. The main factors decisive for disease induced by metals are exposure and genetics which determine the individual detoxifying capacity and sensitivity to metals. This paper reviews the possible mechanisms which may play a role in metal-induced autoimmunity with the emphasis on multiple sclerosis (MS), rheumatoid arthritis (RA) and amyotrophic lateral sclerosis (ALS). We also discuss the role of inflammation-induced changes in the hypothalamus-pituitary-adrenal (HPA) axis as a possible explanation of fatigue, depression and other psychosomatic symptoms observed in these diseases. The increased knowledge about individual sensitivity based on genotype and phenotype variability together with the use of biomarkers for the diagnosis of this individual susceptibility seems to be the key in elucidation of the operating mechanisms. Since metal-induced sensitization may be induced by chronic low-dose exposure, the conventional toxicological approach comparing concentrations of metals in brain autopsies, organ biopsies and body fluids in patients and controls may not provide answers regarding the metal-pathology connection. To address this issue, longitudinal studies of metal-sensitive patients are preferable to the traditional case-control studies.