Titanium hypersensitivy

Phlebotomy service options in the US

Clinics providing access to MELISA testing



Phlebotomy service options in the US

Clinics providing access to MELISA testing




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 bodys 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.

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.

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. Read moreNickel in titanium 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.

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 theclinicswe cooperate with or send a sample to alaboratory. 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.

The articlesHypersensitivity to titanium: Clinical and laboratory evidenceandLTT-MELISA is clinically relevant for detecting and monitoring metal sensitivitypublished in 2006 can be downloaded from ourArticle page.

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.

On ourPatient testimonialspage, you can read about two young people who recovered from their serious health problems after being diagnosed with titanium hypersensitivity and having their titanium implants removed.

A list of references can be found in our brochures:

Titanium implants testing for allergy (dental)

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 caseSADJ February 2007

Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells

Titanium particles stimulate bone resorption by inducing differentiation of murine osteoclastJ Bone Joint Surg Am. 2001

Immunohistochemical study of the soft tissue around long-term skin-penetrating titanium implantsBiomaterials 1995

In vitro corrosion of titaniumBiomaterials. 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 alloysCrit Rev Oral Biol Med. 2002

Das Allergiepotenzial von Implantatwerkstoffen auf TitanbasisA. 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

MELISAis a blood test to aid the diagnosis of metal hypersensitivity. It is used worldwide by healthcare professionals to help determine whether patients are hypersensitive to metals commonly used in dental restorations or medical implants. Further test applications include Lyme disease.

On InternationalwomeninscienceDay we remember Prof Vera Stejskal who is sadly no longer with us. We miss her unquenchable optimism, can-do attitude, thirst for knowledge and burning desire to bring about change so that people who are suffering from metal hypersensitivity get the support and treatment they need. Vera, we do our best to follow in your footsteps but your shoes are hard to fill.Dr Vera Stejskal, inventor of MELISA testing, has passed away after a brief period of illness. A pioneer in the field of immunotoxicology, her groundbreaking research into the connection between metal induced inflammation and chronic disease has helped hundreds of patients regain their health. She was born in Prague and fled to Sweden after the 1968 invasion of Czechoslovakia.

She started work at the Department of Immunology at the University of Stockholm where she became Associated Professor of Immunology in 1976. She then joined Astra, running its immunotoxicology division where one of her first assignments was to have a final look at a new drug that was being tested: omeprazole. Studies had showed necrotizing vasculitis in the small intestine of some dogs, and the project looked set to be terminated. The group she led was able to prove that the drug had no such side effects and the drug went on to become Losec, the best-selling drug in the world.

As a next project, Dr Stejskal was asked to develop a test for the diagnosis of drug allergy among workers in Astras pharmaceutical factories. They had noticed that some workers complained of allergy related symptoms while working in the factories symptoms that would completely disappear during holidays. Dr Stejskal applied the lymphocyte transformation test, originally developed in the 1960s for evaluating histocompatible class II HLA antigens. She modified it for class II antigen typing and also applied it extensively to detecting type IV allergies to drugs. As of today, Astra is still using this blood test to ensure workers are not exposed to drugs that might be inducing sensitivities.

In 1990 a colleague of Dr Stejskal, dermatologist Dr Margit Forsbeck, asked to try the new test on patients who suspected their symptoms were caused by their dental metal fillings, mainly amalgam. At the time, the only option was patch testing as a skin test not very reliable for testing metal allergy. Dr Stejskal compared lymphocyte reactions between patients and healthy controls and found to her surprise that patients lymphocytes reacted more frequently and strongly to mercury salts than controls. The results were published in The Journal of Clinical Immunology in 1996 (Mercury-specific lymphocytes: An indication of mercury allergy in man).

In 1999, Astra and Zeneca group merged to form AstraZeneca. Since there were now three immunotoxicological departments, Dr Stejskal decided to leave the company and pursue the test on her own. Astra was a pharmaceutical rather than a diagnostic company, and had no interest in developing the test further. She patented it under the name MELISA, and acronym for Memory Lymphocyte Immuno Stimulation Assay.

She then devoted her life to the test, and was affiliated with the Karolinska Institute, Stockholm. From 2004 to 2012 she was an associated professor at the Department of Immunology and Microbiology, First Medical faculty at Charles University, Prague, Czech Republic, where she directed research on the pathological role of metals in chronic diseases.

Dr Stejskal and colleagues worked tirelessly to prove the validity of the MELISA, and that its test results were repeatable, reliable and useful. The test promised to open a new field of medicine, investigating the link between chronic disease and an allergy to an everyday metal exposure. The allergies were rare, but for those affected they could be debilitating yet once their condition was diagnosed, the patients health could improve with removal or replacement of allergy causing metals. Dr Stejskal organised conferences to educate and facilitate cooperation between researchers, doctors and dentist, and dentistry especially was a key part of the treatment protocol. Many professional relationships turned into close friendships.

MELISA started to be performed under license by certified laboratories worldwide and university researchers were using the test in their work. In total, Dr Stejskal published more than 100 scientific articles and was frequently a speaker on the subject of immunotoxicity of heavy and transitional metals and the link to the development/aggravation of allergy and autoimmunity. She was also board member of European Academy of Environmental Medicine and scientific member of ESAAM and I-GAP.

Dr Stejskal never planned to retire for her, her work was her passion in life. She believed rigorous scientific studies would bring a better, healthier world. The MELISA test is her medical legacy, and will now continue without her. She has left us to go on to further discoveries and adventures....See MoreSee Less

Allergy to gold is a rare condition, but in some it can play an important role in the development of health issues. In this case, a 64-year-old female was reevaluated for contact dermatitis; she had developed rashes after starting a new medication and had oral lichenoid lesions in the mouth. Patch testing showed a positive allergic reaction to gold and it turned out that her dental metal crowns has a significant gold content. Her dentist recommended removal of the gold-containing crowns. Previous studies on patients with oral lichen planus and amalgam fillings concluded that there is a likely therapeutic benefit in removal of the amalgam in most situations.

Gold Dental Implant-Induced Oral Lichen Planus

Lichen planus is a chronic inflammatory cutaneous and mucosal disease mostly affecting middle-aged individuals. The etiology of lichen planus is unknown, but current literature suggests that it is an ...

This article makes it absolutely clear why manufacturers of medical devices must fully disclose all metals used. These surgeons knew about their patients nickel allergy and chose a stainless steel stent. It was only when the patient experienced a reoccurrence of his previous symptoms that the vascular surgeons discovered that stainless steel is made up of between 10-16% nickel. The stent was removed and the patients symptoms resolved. The surgeons say Each manufacturer of vascular stents has used proprietary metallurgy in the production of its stent. Checking with the manufacturer as to the stent metallurgy and considering alternatives to treatment need to be addressed before use of stainless steel stents in those patients with nickel or other metal allergies.. Although this is true, it would save a great deal of suffering if manufacturers clearly listed the exact composition in the first place....See MoreSee Less

Systemic hypersensitivity reaction to endovascular stainless steel stent

Endovascular intervention has become the mainstay for treatment of most patients suffering from peripheral vascular disease. We describe a patient wit...

This article about devices that are implanted to control pain suggests that prior to testing a simple screening question about metal hypersensitivity and skin reactions to metals should be asked.

The authors reviewed 13 case reports of hypersensitivity to neuromodulatory devices (mainly spinal cord stimulators) and found that in addition to polyurethane, nickel, platinum and silicone were identified as potential allergens.

pubmed.ncbi.nlm.nih.gov/33428821/...See MoreSee Less

Metal hypersensitivity: the consequences of overlooking its possibility can be disastrous.

After two cobalt chromium knee replacements this patient was left with pain, swelling and weakness in his thigh muscles. Infection was ruled out. A double revision was performed again using cobalt chromium (alloyed with nickel). For 2 months after the revision his symptoms improved and then the pain and swelling returned. After 10 months he had developed pain in and a burning sensation in both his hands and feet. After 2 years he had swelling, pain, a rash had spread all over the whole of his body and he developed issues with swallowing. MELISA testing showed a positive result for nickel hypersensitivity and further knee surgery was performed: this time with oxidized zirconium alloy. After 10 years follow up the patients swelling and eczema have been significantly alleviated. The authors add The complex clinical course observed after routine TKA in this patient demonstrates the importance of integrating metal hypersensitivity diagnostics into clinical decision-making, with advisability that tests for metal hypersensitivity perhaps should have been performed before the first revision....See MoreSee Less

Metal Hypersensitivity and Complex Regional Pain Syndrome After Bilateral Total Knee Arthroplasty: A Case Report - PubMed

Metal hypersensitivity should be considered after the exclusion of infection; however, the concurrent development of complex regional pain syndrome may mask the clinical presentation.