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MElisa

FDA statement & BSEM conference


Center for Devices and Radiological Health (part of the US FDA)  conducted an extensive review of the biological response to metal implants, read it HERE.
You can buy the complete conference proceedings from HERE. Alternatively, recordings of the conference proceedings are available to purchase as a USB flash drive from the BSEM website HERE. More details about conference programme can be found below.

A summary by Dr Shideh Pouria – British Society for Ecological Medicine

On 16 November the British Society for Ecological Medicine held a conference in London exploring the concept of metal toxicity and allergy as a much-overlooked factor in modern diseases. The conference was held jointly and dedicated to the memory of Professor Vera Stejskal, who passed away last year. Prof Stejskal was a pioneering Swedish immunologist and the inventor of the MELISA blood test for diagnosing metal allergy.*

Speaking at the conference were medical, surgical and dental professionals, many of whom have found the MELISA test invaluable in their practice, as well as scientists who have used the test to investigate the mechanisms and effects of metal toxicity. Overall, the day provided an eye-opening series of lectures on what appears to be a frequently overlooked source of ill health and disease.

The conference began with a presentation by Dr Olaf Beckford, a chemist, who together with Prof Stejskal set up the MELISA lab in Neuss, Germany. Dr Beckford gave an overview of the wide range of symptoms that may be caused by metal hypersensitivity, including fibromyalgia, muscle pain, chronic fatigue, autoimmunity, gastrointestinal problems, dermatitis, chemical sensitivity, headaches, cognitive dysfunction, and depression. Metal hypersensitivity causes inflammation, which is a central factor in many chronic diseases, including heart disease, Alzheimer’s, and cancer.

Sources of metal exposure include dental fillings and implants, medicines, cosmetics, foods, vaccines (in which aluminium and mercury are used as adjuvants), smoking, piercings, and medical devices such as pacemakers. Dental restorations alone can include mixtures of various metals such as mercury, gold, palladium, tin, silver, nickel and more. Macrophages act as transporters of metal ions throughout various tissues via the blood and lymphatic systems. Often potentially toxic metals compete with other beneficial minerals or for transport systems – for example, titanium and iron or zinc and nickel. Dr Beckford explained that even though metals may exert toxic effects in biological systems, MELISA testing does not measure such toxicity: instead it is a means of assessing metal allergy or hypersensitivity.

Several speakers presented cases of patients with serious health problems who made remarkable recoveries after the source of metal sensitivity and toxicity was removed. Dr Schroeder is a Washington State-based surgeon who in the last ten years has removed over 1,000 metal medical devices. He presented cases of extraordinary improvements in his patients’ health as a result of his interventions. This included included a patient with fibromyalgia, chronic fatigue, migraines, and rosacea. The onset of symptoms had followed surgery in which stainless steel and subsequently titanium screws were placed in her foot. MELISA testing came back positive for nickel, titanium and vanadium allergenicity. After the hardware was removed, she recovered her health fully, as attested by a voice recording that was played to the conference attendees.

Dr Schroeder also presented evidence, which showed that implants consisting of two different types of metals (e.g. stainless steel and titanium) can be far more problematic when used in the same patient. This is because an electric current is set up between the two metals, leading to corrosion and dispersal of one or both metals throughout the body and resulting in widespread systemic toxicity. This can take place even if the two different metal implants are widely separated within the body.

Dr Jose Mendonça is director of the Head and Neck Surgery Unit, Adult Stem Cell Therapy Unit at POLUSA Hospital, Galicia. He spoke about the shifting paradigm regarding titanium, which has historically been viewed as a biocompatible and safe material for use in dentistry and implants. However, more recently, a growing number of studies document side-effects such as allergy and corrosion. This new perspective has to be seen in the context of the increasing possibility of contact with titanium, via (for example) titanium dioxide in food additives, sunscreens, cookware and medicines as well as to other compounding factors such as exposure to electromagnetic fields (EMF).

Titanium-related issues observed by surgeons and dentists may include infections, allergies, osteolysis, bone resorption and neuropathy. Dr Mendonça explained that toxic metals tend to accumulate in the jaw. From there, the vascular system transports them into the brain, causing neuro-inflammation, cognitive dysfunction and other symptoms. In his practice he showed how the removal of titanium implants from affected patients and replacement with implants made of zirconium improved patient outcomes. He mentioned cases of Alzheimer’s that have been ameliorated after titanium dental implants were replaced with ones made of zirconium.

In cases of patients with reactions to dental implants and as a resultant damage to the jaw, Dr Mendonça has been able to regenerate the affected tissue using adult stem cells derived from bone marrow, along with tissue matrix proteins and growth factors (cytokines). Clearly this therapy should be made widely available to regenerate damaged and necrotic tissue in a number of disease conditions.

Dr Goran Stojanovic is a biological dentist based at the ndu Clinic in London. He spoke of the wide array of metals commonly used in dentistry and said awareness is growing among dentists and patients of the toxic and allergenic potential of such metals within the oral cavity and also systemically. He discussed the case of a teenage girl presenting with fevers, blisters, and excruciating pain while chewing after dental orthodontic treatment. One of the differential diagnoses entertained by her doctors was leukaemia. She was found to be allergic to the nickel in her dental braces. Immediately the braces were removed, her symptoms vanished.

Dr Stojanovic discussed more biocompatible alternative materials available, such as zirconium implants, ceramic inlays, and glass ionomer and composite fillings. He outlined the protocols used to safely remove toxic materials such as mercury amalgam fillings. He emphasized the importance of using barriers and other protective methods to prevent further exposure to the patient and dental staff alike.

Dr John McLaren-Howard, of Acumen laboratories, spoke on the topic of nickel as the “ubiquitous allergen”. He demonstrated how various aspects of nickel sensitivity can be diagnosed in different ways. Dr McLaren-Howard said about 25% of people with skin sensitivity to nickel who pass through his lab show positive responses to both MELISA and ACUMEN.

He highlighted also the important interactions between calcium and nickel: for example, many cell signalling pathways use changes in intracellular calcium as a messenger and nickel is one of a number of potential toxins and allergens that ‘piggy-back’ onto that mechanism. Nickel and intracellular calcium changes affect important cellular mechanisms, including mitosis. Nickel also accumulates on hormone receptor sites.

Nickel has long been recognised as a known carcinogen, but less well known is that it has a strong relationship with heart attacks. Research has found increases in serum nickel following heart attack. It is possible that the nickel is stored in mitochondria in heart muscle and released during the heart attack. In general, urine nickel increases are useful biomarkers, but nickel found in more specific tests shows greater clinical significance, e.g. when it is found as a DNA adducts

Sources of nickel exposure include stainless steel cooking vessels, medical and dental implants and devices, body piercings, smoking, vehicle exhaust, and many foods. Supplementing with vitamin C during meals and a diet high in iron inhibits nickel absorption.

Mrs Rebecca Dutton runs support groups for patients affected by scoliosis (understandingscoliosis.org). In her presentation, she discussed how a significant proportion of patients who undergo scoliosis surgery have been found to be allergic to their spinal hardware. She suggested that one of the underlying causes of scoliosis could be exposure to metals in the first place (the link between misshapen spine in fish and mercury exposure is already known). Sources of mercury exposure include thimerosal, the preservative used in childhood vaccines until it was (mostly) phased out in 2004. She put forward the case for routine preoperative metal allergy testing and gave examples of non-surgical treatments for scoliosis or the use of non-metal spinal hardware (such as carbon-coated implants) as alternatives to metal hardware.

Mr Simon Ellis is an independent consultant in trauma and orthopaedic surgery who specialises in knee surgery. He spoke about the problem of metal allergy in relation to joint replacement. He said that over the last ten years it has become clear that there is a group of patients for whom conventional joint replacement using stainless steel components containing nickel is inappropriate. Negative reactions include synovitis, pain, stiffness, infection, necrosis, and skin problems. However, metal hypersensitivity as an explanation for poor outcomes from knee surgery was highly controversial among surgeons, with the majority denying that it could explain poor functioning of a knee replacement. In spite of this reluctance to acknowledge any problem, there are a growing number of lawsuits following serious reactions such as necrotic tissue at the sites of knee replacements. Mr Ellis uses MELISA testing pre-operatively to identify metal hypersensitivity in patients with indications of sensitivity, for example, a skin nickel allergy. He also uses it post-operatively in patients with implant failure. He favours the use of nitride-coated implants as an alternative to metal.

The final speaker was Christopher Exley, professor in bioinorganic chemistry at the Birchall Centre, Lennard-Jones Laboratories, Keele University (UK) whose research has focused on the ecotoxicity of aluminium.  Prof Exley discussed aluminium, a systemic toxicant, as an adjuvant in vaccines. He pointed out that aluminium adjuvants are not separately tested for safety and approved by regulators. Only the complete vaccine is approved. In addition, aluminium adjuvants are administered to the placebo group in vaccine safety trials. Thus there is no way of identifying potential adverse reactions to these adjuvants in regulatory safety trials.

The day ended with a final tribute to Vera Stejskal in the form of excerpts from a recording of a talk, which summarised rather aptly the topics covered during the course of the day. The take-home messages from this highly inspiring and illuminating day were:

  • Metal hypersensitivity is on the increase due to proliferating sources of exposure and potential co-factors such as EMF exposure
  • Steps should be taken to avoid exposure in the first place
  • Patients showing symptoms that could be due to metal hypersensitivity should be tested using MELISA and other indicated methods
  • Patients who have had reactions to metal hardware or other exposures should be tested for hypersensitivity
  • Metal implants and dental materials that are causing problems should be safely removed, or replaced using non-biologically active materials
  • Toxic metals (e.g. mercury, aluminium) used in vaccines may pose health risks to susceptible individuals
  • Appropriate detoxification methods should be employed to help patients recover their health.

 

Conference Programme: Systemic Effects of Metal Exposure in Clinical Practice: Protecting Patients and Optimising Outcomes

Session 1

Welcome Address, Dr Shideh Pouria MB BS BSc MRCP (UK) PhD CMT
MELISA as a Tool for Identifying Inflammatory Triggers, Olaf Beckord Dipl. Chem. Ing (GER)
Management of Systemic Effects of Metal Implants, Dr Scott Schroeder DPM FACFAS

Session 2

Titanium: Is the Paradigm Shifting? Dr Jose Mendonça Caridad MD DMD PhD
Improving Patient Outcomes with Biological Dentistry, Dr Goran Stojanovich

Session 3

Nickel: The Ubiquitous Allergen, Dr John McLaren-Howard PhD DSc
Scoliosis, Spinal Surgery and Metal Allergy, Rebecca Dutton
Selecting Implants for Metal Allergic Patients, Mr Simon Ellis MA (Cantab) MBBS FRCS (Orth)

Session 4

Systemic Toxicity of Aluminium Adjuvants, Prof Christopher Exley PhD FRSB
Panel Discussion

You can buy the complete conference proceedings from HERE. Alternatively, recordings of the conference proceedings are available to purchase as a USB flash drive from the BSEM website HERE

   

  • Title: Associated diseases
  • Subtitle: Melisa
  • Intro text editor:

    People with metal hypersensitivity may have numerous symptoms associated with an overactive immune system, including chronic fatigue, joint and muscle pain, cognitive impairment, depression, headaches, fibromyalgia and skin rashes.

    The article A comprehensive summary of disease variants implicated in metal allergy lists hundreds of publications describing metal-specific allergy responses, identifying over 50 unique manifestations. According to the authors, metals constitute one of the major classes of allergens responsible for a disproportionately large segment of the total burden of disease associated with allergy. Excerpts are available HERE.

    Another recent review article looks at the connection between metal hypersensitivity and implant failure. You can check the full article here: The contribution of metal allergy to the failure of metal alloy implants, with special reference to titanium: Current knowledge and controversies. A brief excerpt focused on several case reports of clinical reactions to implants is available HERE.

  • List item:
    • List title: Increased reactivity to metals has been found in the following diseases:, List text:

      • Multiple Sclerosis (Prochazkova 2003, 2006, Stejskal 2006)
      • Chronic Fatigue Syndrome (Stejskal 1994, 1999)
      • Rheumatoid Arthritis (Prochazkova 2003, Stejskal 2006)
      • Fibromyalgia (Öckert 2006, Stejskal 2013)
      • Amyotrophic Lateral Sclerosis (Pleva 2000)
      • Cardiovascular disease (Manousek 2016)
      • Lupus Erythematosis (Prochazkova 2003)
      • Oral Lichen Planus (Stejskal 1996)
      • Oral burning and itching (Stejskal 2006)
      • Skin diseases such as eczema or psoriasis (Prochazkova 2003, Venclikova 2003, Kohdera, Ionescu)
      • Sjögren’s syndrome (Prochazkova 2003)
      • Alopecia areata and atopic alopecia (Nakayama and Chen 2018)
      • Autoimmune thyroiditis (Sterzl 1999, Prochazkova 2003, 2010, Hybenova 2010)


      The prevalence of metal hypersensitivity in patients with implants is significantly higher than in the general population, with an even higher rate among patients with failed or failing implanted devices. (Hallab et al. Metal sensitivity in patients with orthopedic implants. The Journal of Bone and Joint Surgery 2001;83:428)

      We are conducting a study to see if metals may be implicated in the development of scoliosis. Read more about the research HERE.

    • List title: Treatment of diseases where metal allergy has played a part, List text:

      As with any allergy, exposure to the offending allergen should be minimized or, if possible, avoided altogether.
      Metals can be found in food and also in medication, such as nickel and titanium dioxide, so in this case, patients might consider diets low in nickel. If a patient is allergic to a metal found in dental fillings or dental implants, it is important to consult a dentist who is experienced in the field of metal-free dentistry. The importance of being protected during the removal of, for example, amalgam fillings, cannot be overstated. Every dentist will have their own protocols, for instance, the SMART protocol from the International Academy of Oral Medicine and Toxicology (IAOMT). For many patients, avoiding metals will be enough for them to feel a significant health improvement.

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  • Title: Implant hypersensitivity
  • Subtitle: metal exposure
  • Intro text editor:

    The MELISA test may be used in two ways for orthopaedic patients. First, prior to surgery, patients whose clinical history suggests metal sensitivity may be pre-tested to ensure that they receive the most suitable implant, more info HERE. Second, post-surgery, MELISA can be used to identify if metal hypersensitivity is responsible for any of the symptoms that have developed.

    Patients suffering from metal hypersensitivity may have numerous local symptoms associated with an overactive immune system, such as localised pain, swelling, cutaneous allergic reactions, joint and muscle pain, implant failure, apparent recurrent infections around the operation site, and possible systemic reactions such as fibromyalgia, chronic fatigue and cognitive impairment. MELISA is a scientifically proven and clinically validated blood test that detects type-IV hypersensitivity to multiple metals at the same time.

  • List item:
    • List title: Metal hypersensitivity and orthopaedics, List text:

      Metal hypersensitivity is a well-documented factor in the failure of implants, and the need for  testing in sensitive patients is well recognized by both implant manufacturers and by surgeons alike. The prevalence of metal hypersensitivity in patients with implants is significantly higher than in the general population, with an even higher rate among patients with failed or failing implanted devices.

    • List title: Implant alloys, List text:

      An exact breakdown, which includes trace amounts of metals present, is needed prior to testing, but below is a guideline. Metals usually found in common medical grade alloys include:

      Cobalt chrome: cobalt, chromium, manganese, molybdenum, nickel, tungsten
      Stainless steel: chromium, manganese, molybdenum, nickel, tungsten
      Titanium alloy (TiAl6V4): titanium, vanadium, aluminium, traces of nickel

      Recently, cases of titanium hypersensitivity have also been described. Titanium is a transition metal and thus may function as a hapten and trigger cellular hypersensitivity. Since titanium, in the form of titanium dioxide (E171), is used as white pigment in toothpaste, cosmetics and medication, the latent sensitization of susceptible individuals is possible. Traces of nickel (0.03%) may be found even in commercially pure titanium due to the production process.

    • List title: Stents, clips and coils, List text:

      Both bare metal and drug eluting stents have been occasionally implicated in the developments of various  hypersensitivity reactions. More information about the metals commonly contained in stents can be found HERE. It is important to establish which metals are contained in your device prior to testing.

  • References:

    References
    Valentine-Thon E, Schiwara HW. Validity of MELISA® for metal sensitivity testing. Neuroendocrinology Letters 2003; 24(1/2):57-64
    Aesculap Implant systems brochure 2009 www.aesculapimplantsystems.com
    Rushinga G, Goretsky M, Gustin T, Morales M, Kelly R, Nuss D. When it is not an infection: metal allergy after the Nuss procedure for repair of pectus excavatum. Journal of Pediatric Surgery 2007;42:93-97
    Adala R, Chakravarthy M, Srinivas V, Pai S. Orthopaedic surgery in a patient with metal sensitivity. J Cutan Aesthet Surg. 2011 Jan-Apr; 4(1): 67-68.
    Hallab, N. PhD, Merritt, K. PhD, Jacobs, J. Metal sensitivity in patients with orthopedic implants. The Journal of Bone and Joint Surgery 2001;83:428.
    Cohen D. How safe are metal-on-metal hip implants? BMJ 2012;344:e1410
    Grammatopolous G, Pandit H, Kwon YM, Gundle R, McLardy-Smith P, Beard DJ, et al. Hip resurfacings revised for inflammatory pseudotumour have a poor outcome. J Bone Joint Surg Br 2009;91:1019-24.
    Stejskal V, et al. Metal-specific lymphocytes: biomarkers of sensitivity in man. Neuroendocrinology Letters 1999;20:289-298
    Prochazkova J, Sterzl I, Kucerova H, Bartova J, Stejskal V. The beneficial effect of amalgam replacement on health in patients with autoimmunity. Neuroendocrinology Letters 2004;25(3):211-218.
    Thomas P, Bandl WD, Maier S, Summer B, Przybilla B. Hypersensitivity to titanium osteosynthesis with impaired fracture healing, eczema, and T-cell hyperresponsiveness in vitro: case report and review of the literature. Contact Dermatitis. 2006.Oct;55(4):199-202.
    Evrard L, Waroquier D, Parent D. Allergies to dental metals. Titanium: a new allergen. Rev Med Brux. 2010 Jan-Feb; 31(1):44-9.
    Schuh A, Thomas P, Kachler W, Goske J, Wagner L, Holzwarth U, Forst R. Allergic potential of titanium implants. Orthopade. 2005. Apr;34(4):327-8, 330-3.
    Niki Y, Matsumoto H, Otani T, Yatabe T, Kondo M, Yoshimine F, Toyama Y. Screening for symptomatic metal sensitivity: a prospective study of 92 patients undergoing total knee arthroplasty. Biomaterials. 2005. Mar;26(9):1019-26.
    Schalock P, Menne T, Johansen J, Taylor J, Maibach H, Liden C, Bruze M, Thyssen J. Hypersensitivity reactions to metallic implants – diagnostic algorithm and suggested patch test series for clinical use. Contact Dermatitis. 2011 July, 66, 4-19.
    Basko-Pilluska J, Thyssen J, Schalock P. Cutaneous and systemic hypersensitivity reactions to metallic implants. Dermatitis. 2011 Mar-Apr;22(2):65-79.
    Syburra T, Schurr U, Rahn M, Graves K, Genoni M. Gold-coated pacemaker implantation after allergic reactions to pacemaker compounds. Europace. 2010 May;12(5):749-50.
    Dörner T, Haas J, Loddenkemper C, von Baehr V, Salama A. Implant-related inflammatory arthritis. Rheumatology. 2006. 2, 53-56.
    Jacobs JJ, Hallab NJ. Loosening and osteolysis associated with metal-on-metal bearings: A local effect of metal hypersensitivity?J Bone Joint Surg Am. 2006 Jun;88(6):1171-2.
    Hallab NJ, Anderson S, Stafford T, Glant T, Jacobs JJ. Lymphocyte responses in patients with total hip arthroplasty. J Orthop Res. 2005. Mar;23(2):384-91.
    Hallab NJ, Anderson S, Caicedo M, Skipor A, Campbell P, Jacobs J. Immune responses correlate with serum-metal in metal-on-metal hip arthroplasty. J Arthroplasty. 2004;19(8 Suppl 3):88-93.
    Ross IB, Warrington RJ, Halliday WC. Cell-mediated allergy to a cerebral aneurysm clip: case report. Neurosurgery. 1998 Nov;43(5):1209-11.

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  • Title: Beryllium
  • Subtitle: Metal exposure
  • List item:
    • List title: Where is Beryllium found?, List text:

      Beryllium is a metal that is used in the manufacturing of products like cars, golf clubs and computers, manufacture of thermal coating, nuclear reactors, rocket heat shields, brakes, x-ray tubes, and dental plates. It is found in some dental crowns and dental plates, but exposure to the dust is highest during the manufacturer so those working in dental laboratories may be exposed.

    • List title: What is beryllium disease?, List text:

      Beryllium-induced lung disease can occur when beryllium dust or fumes are inhaled.  Chronic beryllium disease (CBD, berylliosis) is associated with inhaling beryllium powder or fumes (although inhaling beryllium does not always lead to CBD). An exposed person usually gets sensitized to beryllium prior to progressing to CBD. Sensitization is similar to an allergy; when allergic or sensitized, the body reacts negatively to that particular substance. Beryllium sensitivity (BeS) and CBD can develop soon after exposure or many (30-40) years later. Of those working around beryllium, about 10% get sensitized to it and about half of those progress to develop CBD.

      According to NIOSH (the National Institute for Occupational Safety and Health, 2011), “workers exposed to particles, fumes, mists and solutions from beryllium-containing materials may develop beryllium sensitization or chronic beryllium disease, a potentially disabling or even fatal respiratory disease.”  Depending on how workers are exposed, the diseases can affect different tissues and organs. Breathing in fumes or dusts of beryllium compounds may injure the lungs. While most commonly associated with diseases of the lungs, beryllium may also affect such organs as the liver, kidneys, heart, nervous system, and the lymphatic system.

      The Centers for Disease Control and Prevention (CDC) states that “sensitization has been found in one to ten percent of workers in cross-sectional studies, with chronic beryllium disease diagnosed in ten to 100 percent of the sensitized”. This statement means that between 1 to 10% of workers who work with beryllium may become sensitized. Of those workers who become sensitized, 10% or all may later develop chronic beryllium disease. Another study stated that on average, 1 to 6% of exposed workers may develop sensitivity, but it may be as high as 16% in workplaces with high exposure levels.

    • List title: How can it be diagnosed?, List text:

      A blood test called beryllium lymphocyte proliferation test (BeLPT) can measure how blood cells react to beryllium. This test can be used for medical surveillance programs. NIOSH states that “it is believed that a person must first be sensitized before beryllium in the lungs can cause the lung damage (called granulomas) of chronic beryllium disease. However, the overall proportion of all sensitized individuals who will eventually develop chronic beryllium disease is not known.”
       

      MELISA is involved with a working group that aims to bring standardised beryllium sensitivity testing to Europe to allow exposed workers to be tested for hypersensitivity.
       

      Links for the specification for testing for Beryllium hypersensitivity can be found HERE.
       

  • References:

    Read more:


    Cleveland Clinic 
    Canadian Centre for Occupational Health and Safety

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