• 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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• Title: Mercury allergy
• Subtitle: Metal exposure
• Intro text editor:

  There are different forms of mercury, MELISA testing can differentiate between allergy to each form. Each type has its different properties and is therefore utilized in different ways in dentistry, medicine and industry or is present in the environment. Allergy to mercury is specific, so an individual can be allergic to inorganic mercury and not to phenylmercury. This is because the cells involved in Type IV allergic reaction –  memory T cells – will recognise a specific form of mercury. Naturally, it is possible that an individual can be allergic to all four types of mercury. In many cases it is important to locate the source of exposure to mercury that causes inflammation in the body, so that exposure can be stopped.

• List item:
  • List text:

    Inorganic mercury, or ‘metallic mercury’, is a frequent source of metal allergy. It constitutes 50% of dental amalgam fillings. Dental authorities accept that mercury vapour constantly evaporates from the fillings, but argue this is below a safe limit. However, for hypersensitive patients, there is no safe limit.

    In 2020 The FDA issued the following statement: “The FDA has found that certain groups may be at greater risk for potential harmful health effects of mercury vapor released from the device. As a result, the agency is recommending certain high-risk groups avoid getting dental amalgam whenever possible and appropriate.” For more information, please check HERE.

    One of the groups at greater risk for potential harmful health effects is “People with known heightened sensitivity (allergy) to mercury or other components of dental amalgam.”

    Replacing amalgam fillings with non-metallic alternatives has delivered radical health improvements in patients who tested MELISA-positive for mercury. 71% of patients showed health improvements in this study.

  • List text:

    Methylmercury is the most toxic form of mercury. It affects the immune system, alters genetic and enzyme systems, and damages the nervous system, including coordination and the senses of touch, taste, and sight. Methylmercury is particularly damaging to developing embryos, which are five to ten times more sensitive than adults. Methylmercury becomes concentrated as it move up the food chain, so the large predator fish such as shark and swordfish have the highest concentrations. Bacteria in the body can transform inorganic mercury into methylmercury.

  • List text:

    Phenylmercury is the organic mercury most commonly found in dental root fillings. While it has been phased out in many countries, it is also used as a preservative in eye drops and nose drops. Phenylmercury is used to control the growth of fungus in some interior latex paints manufactured before 1991, some exterior and oil base paints, some caulks, eye-area cosmetics, toiletries and other products.

  • List text:

    Ethylmercury is a form of organic mercury. It forms a part of thimerosal, which is used as a preservative in some vaccines, eye drops and nasal sprays.

  • List text:

    Thimerosal is one of the most controversial substances is modern medicine. Its main component is ethyl mercury (49.6% by weight), yet it is still used as a preservative in some childhood vaccines, most flu vaccines and some eye drops and contact lens solution. It is being withdrawn from vaccines in many countries.

  • List title: Full body autoradiograph, List text:

    A special form of mercury can be used to demonstrate that mercury binds to the body proteins. The distribution of mercury in various organs of the body can be traced by sensitive photographic emulsion. Below are four pictures of mice that were injected with mercury labelled with a radioactive isotope. Then, using autoradiography, a special picture was produced. The areas where the mercury is deposited are shown in white.

    The pictures demonstrate widespread distribution of mercury in the body of the mice. Organs rich in fat – such as brain and collagen – are very prone to mercury binding. One of the reasons for this is that mercury is particularly keen to bind to two amino acids; methionine and cysteine. Both amino acids contain sulphur hydrogen (SH)-groups. This is a particularly attractive target for mercury. Fat tissues and collagen tissues are rich in SH-groups.

• References:

  Figure 1. Distribution of radioactivity in male mouse 6 hours after intravenous injection of 203HgCl2. Magnification 2x.

  Figure 2. Distribution of radioactivity in male mouse 24 hours after intravenous injection of 203HgCl2. Magnification 2x.

  Figure 3 and 4. Distribution of radioactivity in male mouse 2 days after intravenous injection of 203HgCl2. Magnification 2x and 9x (right).

   

   

   

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• Title: Titanium hypersensitivity
• Subtitle: Metal exposure
• Intro text editor:

  Titanium hypersensitivity is uncommon and titanium is generally described as a bio-compatible material – yet laboratories using the MELISA technology have reported that about 4% of all patients tested to titanium will have titanium sensitivity (HERE). Recent data from a single MELISA laboratory shows 6% positive responses from 100 consecutive tests.

  Titanium and its main alloy (Ti 6Al 4V) are used in  orthopaedic and spinal surgery, in pacemakers and clips and coils as well as in dental titanium implants. It is generally seen as a bio compatible alternative to traditional alloys like stainless steel and cobalt chromium. Titanium dioxide is also used in food manufacturing, toothpaste and in the coating of some medications.

  Like all metals, titanium releases particles and ions through corrosion. These metals ions bind to proteins in the body. For those who react, the body’s immune system will attack this new protein/metal structure. This may start an immune reaction. The MELISA test a scientifically-proven test which can objectively test for the presence of titanium hypersensitivity and measure its severity.

• List item:
  • List title: Testing for titanium hypersensitivity, List text:

    Blood based testing may give an more accurate measurement of titanium reactions than patch testing. Titanium particles are too large to penetrate the skin and the relationship between skin sensitivity and systemic hypersensitivity is ill-defined. The Mayo Clinic conducted a decade of patch testing and found no positive reactions to titanium despite published cases of titanium hypersensitivity.

  • List title: Do you suspect you have titanium hypersensitivity?, List text:

    If a health problem start after you have received a titanium implant it is possible that you are hypersensitive to titanium. You can take a MELISA test for titanium hypersensitivity through one of the clinics we cooperate with or send a sample to a laboratory. If you are planning to have a test before receiving a titanium implant it is advised to find out the exact composition of the implant. Vanadium, aluminium and other metals are sometimes added to improve the properties of titanium implants, and allergy to these metals can also be tested.

  • List title: Titanium: where to find it, List text:
    • Orthopedic and surgical implants.
    • Pacemakers and implanted defibrillators.
    • Dentistry: in dental implants and as a colour pigment in composites.
    • Sunscreen agents: finely ground titanium dioxide blocks the harmful ultraviolet rays from the sun.
    • Confectionery: makes candy look brighter and adds a crunchy coat to, for example, chewing gum.
    • Cosmetics: used to brighten and intensify the colour of make-up. It is regularly found in eyeshadow, blusher, nail polish, lotions, lipstick and powder.
    • Toothpaste: used as a pigment agent to make the toothpaste whiter.
    • Medication and vitamin supplements may also get their white coating from titanium dioxide.
    • Piercing & jewellery: for example watches and all types of body piercing. Fewer people are allergic to titanium than, for instance, to nickel.
  • List title: How about patients’ stories?, List text:

    You can check our Patient testimonials page HERE and read about people who recovered from their serious health problems after being diagnosed with titanium hypersensitivity and having their titanium implants removed.

  • List title: Titanium impurities, List text:

    Some researchers believe that titanium allergy does not exist and patients are reacting to the impurities in titanium, for instance nickel, chromium and cadmium. Several studies show that titanium alloys contain traces of nickel (0.03%) as a result of the production process. This can pose trigger health problems in patients with nickel allergy, and also mean that a reaction may be falsely attributed to titanium itself. You can read more about nickel in titanium implants HERE.

  • List title: How about studies?, List text:

    The articles Hypersensitivity to titanium: Clinical and laboratory evidence and LTT-MELISA is clinically relevant for detecting and monitoring metal sensitivity published in 2006 can be downloaded from our Article page HERE.

    In the former article fifty-six (56) patients who had developed clinical symptoms after receiving titanium-based implants were tested in MELISA against 10 metals including titanium. Out of 56 patients, 54 were patch-tested with titanium as well as with other metals. The implants were removed in 54 patients (2 declined explantation), and 15 patients were retested in MELISA.

    Of the 56 patients, 21 (37.5%) were positive, 16 (28.6%) ambiguous, and 19 (33.9%) negative to titanium. In the latter group, 11 (57.9%) showed lymphocyte reactivity to other metals, including nickel. All 54 patch-tested patients were negative to titanium. Following removal of the implants, all 54 patients showed remarkable clinical improvement. In the 15 retested patients, this clinical improvement correlated with normalization in MELISA reactivity.

    The conclusion of the article is that these data clearly demonstrate that titanium can induce clinically relevant hypersensitivity in a subgroup of patients chronically exposed via dental or endoprosthetic implants. Below, you will also find several articles which discuss the issue of corrosion of titanium implants and possible reactions due to hypersensitivity.

• References:

  Publications dealing with titanium

  A list of references can be found in our brochures:
  Titanium implants – testing for allergy (dental)
  Titanium in orthopedics

  Further studies

  • Metal Allergens of Growing Significance: Epidemiology, Immunotoxicology, Strategies for Testing and Prevention, Forte G. et al. Inflamm Allergy Drug Targets. 2008 Sep;7(3):145-62.
  • Full-mouth oral rehabilitation in a titanium allergy patient using zirconium oxide dental implants and zirconium oxide restorations. A case report from an ongoing clinical study.
    Oliva X. et al. Eur J Esthet Dent. 2010 Summer;5(2):190-203.
  • Study on patch test reagent for titanium. Nakajima K. Kokubyo Gakkai Zasshi. 2007 Jun;74(2):92-8.
  • Allergies to dental metals. Titanium: a new allergen. Evrard L, Waroquier D, Parent D. Rev Med Brux. 2010 Jan-Feb;31(1):44-9.
  • Implant failure due to Titanium hypersensitivity/allergy? – Report of a case SADJ February 2007
  • Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells Toxicology 2005
  • Titanium particles stimulate bone resorption by inducing differentiation of murine osteoclast J Bone Joint Surg Am. 2001
  • Immunohistochemical study of the soft tissue around long-term skin-penetrating titanium implants Biomaterials 1995
  • In vitro corrosion of titanium Biomaterials. 1998
  • Sensitivity to titanium. A cause of implant failure? Bone Joint Surg Br. 1991
  • A case of allergic reaction to surgical metal clips inserted for postoperative boost irradiation in a patient undergoing breast-conserving therapy Breast Cancer. 2001
  • Biocompatibility of dental casting alloys Crit Rev Oral Biol Med. 2002
  • Validity of MELISA® for metal sensitivity testing^®Validity of MELISA® for metal sensitivity testingg Neuro Endocrinol Lett. 2003
  • Das Allergiepotenzial von Implantatwerkstoffen auf Titanbasis A. Schuh, et al. Der Orthopäde Volume 34, Number 4, 327-33
  • Tissue reaction to bone plates made of pure titanium: a prospective, quantitative clinical study. A. Ungersboeck, et al. Journal of Materials Science: Materials in Medicine Volume 6, Number 4, 223-229
  • Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. M Shimizu et al.Particle and Fibre Toxicology 2009, 6:20

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