6th MELISA Study Group - résumé During the weekend 14-16 August, 1998 I participated in the meeting organized by the International MELISA Study Group under the leadership of Prof. Vera Stejskal. The theme was "Dental Materials and Psychoneuroimmunology". The meeting place this time was Sjövillan (the Lake Villa) at the Danderyd hospital, which houses the MELISA Medica foundation in really beautiful surroundings by the lake Edsviken. There were about 30 participants from several countries, Italy, Austria, Germany, Belgium, Holland, Finland, France, Switzerland, Japan and Sweden. The majority of the participants were dentists. It was a friendly and quite informal seminar with several important contributions. I shall not comment on the details from all contributions, but only from those that I felt had particular scientific news value. Psychoneuroimmunology is a new discipline, but scientifically very "hot". It deals not only with issues directly relevant to the amalgam problem. Thus, it has been found that various signs of inflammation and an activated immune system occur regularly in various psychiatric diseases, such as depressions, schizophrenia and Alzheimer's. Conceivably, psychosomatic reactions can be precipitated by psychological overload if this creates an immune system disequilibrium, but the same end result can also be brought about by many purely somatic factors that tend to cause malaise and sickness behaviour. Anybody who ever had influenza knows this, but there is now a novel insight that some diseases or symptoms may be due to chronic and hidden inflammations, which are not of infectious origin, but may possibly be caused by metal-induced immune responses. MELISA® is a laboratory test that may play an important role also in this new field. The seminar did not cover only psychoneuroimmunology connections but immunology was of course the underlying theme. Romuald Hudecek, a dentist from Uppsala and a member of the MELISA MEDICA foundation was the first speaker. He presented a study of the factors that determine the quantity of mercury (mercury vapour and amalgam particles) absorbed by patients and dental personnel during amalgam removal. Vera Stejskal presented data on MELISA® test results in 3,156 patients tested during the last 10 years in 3 different laboratories (Södertälje, Uppsala and Munich). The most common sensitizer was nickel, followed by mercury, cadmium, palladium and gold. The lymphocytes from females responded significantly more often to nickel, as compared to males while the reactivity to mercury was sex-independent. These results indicate that mercury released from amalgam or from other external sources may result in sensitization, which is relatively common in patients claiming dental metal intolerance. Titanium reactivity at the lymphocyte level was quite common and titanium, a member of the transition metal family, is physico-chemically very reactive. Titanium dioxide (E 171) is present in many dental materials (cements, composites etcetera), and also in a majority of tooth-pastes, often together with sodium lauryl sulfate, a very common tenside. Sodium lauryl sulfate (maximum allowance in tooth-pastes is 6%) increases the permeability of the oral mucosa and facilitates the entrance of not only titanium dioxide but also of all other chemicals through the mucosal barrier. 105 patients with a CFS-like syndrome and suspected metal-hypersensitivity were tested with MELISA®. Amalgam and other dental metal replacement was performed in 86 of those patients. Sixty-seven patients experienced long-term health improvement, and decreased reactivity to metals was detected at the lymphocyte level. The patients who did not improve, or in a few cases got worse, were either non-reactive at the beginning of the study before the metal removal, or were still reactive after the metal replacement. In several case reports it was shown that patients with Sjögren´s syndrome do often react to gold and palladium. Metal reactivity of patients with multiple sclerosis (MS) patients is individually specific; often the reactivity is directed against mercury, palladium, lead, cadmium and nickel. Michael Maes, professor of psychiatry at the University of Antwerp gave a lecture entitled "Activation of the immune system may cause depression and other systemic symptoms". Since I am a psychiatrist myself, I was particularly fascinated by the revolutionary developments he told us about. In "major depression" there are several markers which indicate that "the inflammatory response system" (IRS) is activated. The number of white blood cells is increased in the blood, and so are cortisol levels. Different substances, so called cytokines, known for their role in inflammation and immunity are also increased: some of the interleukines (IL-1 beta, IL-2, IL-6), interferon-gamma, so called acute-phase-proteins (haptoglobin, alpha 1-antitrypsin, C-reactive protein). In addition, there are signs of a certain type of anaemia that is common in chronic disease, and serum zinc is low. Blood tryptophan levels are also below normal. None of these changes in the immune system, or even the mental symtoms are specific for depression but they should be regarded as general inflammatory reactions that can be caused by various agents such as viruses, bacteria or metals. Influenza, for instance, induces a state of general malaise including psychomotor retardation, irritability, anhedonia (inability to feel pleasure), loss of appetite, weight reduction, sleep disturbances. All these symptoms occur also during major depression and are then called vegetative symptoms. They may in fact be induced by cytokines, such as IL1, IL6 and interferon. Depressive symptoms occur in various diseases such as in MS, following stroke, in Alzheimer's disease, but most commonly they appear on their own and without any known cause. Hence, there is the exciting possibility that heavy metals can induce such symptoms as well. Anti-depressive medicines also have an effect on the IRS which agrees with such theories. Prozac decreases IL-6 and interferon-gamma. Tsunetoshi Kohdera, an allergist from Kyoto, talked about dental metals and the connection to psoriasis, atopic eczema and other skin diseases. He has studied the lymphocyte transformation test (LTT) in psoriasis. LTT is similar to MELISA® and can demonstrate the presence of memory cells to metals in psoriatic patients. T-cells play a decisive role in both psoriasis and atopic eczema. In 40 cases of psoriasis, 34 patients showed positive reactions to one or more dental metals. All 40 patients were also sensitive to house dust mites. Following dental metal removal and purchasing of mite-free bed linen, the symptoms improved dramatically without using corticosteroids. In 1-3 months, 83% of patients improved, 67% of them markedly . Psoriasis is difficult disease to treat and this protocol seems to give surprisingly good results. Dr Kohdera also demonstrated pictures of a number of cases with atopic eczema that was resistant to conventional treatment, all of which improved following allergen elimination. Fisher's textbook "Contact Dermatitis" recommends amalgam removal in certain cases. Here a laboratory test could directly indicate the existence of hypersensitivity to one or more metals in the individual patient. Birgitta Brunes, a physician and MS patient herself, explained her model of MS treatment which includes dental metal removal and which she has described in her book "From MS diagnosis to better health" (1996, with co-author Adima Bergli). Antero Danersund, physician at the unit for Clinical Metal Biology in Uppsala reported laboratory findings with MELISA® and PIXE in 25 patients suffering from chronic fatigue and dental metal intolerance. MELISA® detected reactivity against mercury, cadmium, palladium and gold. Reactions to titanium occurred in 5 cases, and this is not uncommon in patients with titanium implants, or where titanium dioxide has penetrated the mucosal barrier. PIXE is also called nuclear microscopy and gives us information about the concentrations of various elements inside cells. Amalgam patients had increased levels of mercury in red blood cells and in the plasma as compared with the control group. Following metal replacement, the levels became normalized, and even lower than in the control group! Johann Lechner, a dentist from Munich reported on his experience with "chronic jaw osteitis", which is a condition that is difficult to diagnose. The so called cavitation (or "NICO") in the jaw bone may develop in the wake of dental infections and extractions. It is nearly impossible to detect on x-ray pictures. The bone tissue is transformed to a soft pulp that can be sucked away after uncovering the cavitation. Dr. Lechner has injected radio-opaque fluid into the cavities after the operation in some cases, and could therefore demonstrate the amazing extent of bone destruction that is possible in these states. If such a lesion is located in the lower jaw, nervus mandibularis may lose its protecting bone channel and lie practically unprotected in the pulpy contents of the cavity, which may contain heavy metals and other toxic substances that may perpetuate chronic inflammation in sensitized patients. This may be the origin of some cases of neuralgia, a condition with terrible pain. One of the pictures shown originated from a patient who committed suicide by jumping from a window, since she couldn't live with her pain. This phenomenon of chronic jaw osteitis has several names but many dentists and physicians find it hard to believe that it actually exists, since it is difficult to document by x-rays. In any case, it is hardly good for your health to have such deposits of dead, decomposed tissue in your head. At the end of the day Dagmar Magnusson (dentist) gave us an excellent picture review of the use of different modern metal-free dental materials. In conclusion, it is more and more obvious that the problems connected with chronic heavy metal exposure cannot be fully understood without the help of immunology. In the future much research will have to be devoted to the problems of individual metal sensitivity. Per Dalén

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