Testing
-
Metal allergy – a possible cause of health problems
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. MELISA is a scientifically proven and clinically validated blood test that detects type-IV allergy to multiple metals, such as mercury, gold, palladium and titanium.(1)
-
Why use MELISA?
Exposure to metals in dental fillings and crowns, surgical implants, joint prostheses and environmental pollutants can lead to health problems in sensitive individuals (if they cause an allergic reaction). MELISA can identify the individuals who may suffer side effects from metal exposure. The test indicates which metals the immune system will tolerate and which will cause an immune reaction. This information may be useful prior to surgery or to dental work to establish the optimal type of materials the body will tolerate.
-
High success rates
Seventy-six percent of chronic fatigue patients in a clinical trial experienced health improvement after removing dental restorations containing allergenic metals, as identified by the MELISA test (2). An additional study of patients with autoimmune diseases showed that 71% of those with positive responses in MELISA improved after having their fillings removed (3). In a further study, patients with fibromyalgia were tested for allergy to metals with MELISA. By reducing their exposure to metals identified as problematic, significant health benefits were seen. 50% of patients no longer fulfilled the criteria for fibromyalgia diagnosis; the remaining 50% all reported an improvement in their symptoms (4).
-
Allergy vs. toxicity
MELISA measures whether the immune system reacts to specific metals: it does not measure the levels of metals in the body. Other tests, such as hair analysis, quantify excreted or current levels of mercury or other metals, but these are usually found to be below the official “safe limit”. For hypersensitive individuals, there may be no “safe” level; even trace amounts may trigger symptoms if the immune system reacts (5). This reaction will be on-going unless the source of exposure is removed.
-
Metal allergy and orthopaedics
Metal allergy is a well-documented factor in the failure of implants. The need for allergy testing in sensitive patients is 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 prevalence rate among patients with failing implanted devices (6). Studies show that lymphocyte transformation tests are better suited for diagnosing possible metal sensitivity in patients with implants than traditional patch testing (7). Implant-related hypersensitivity reactions are mediated by sensitized T cells and the relationship between skin hypersensitivity and systemic hypersensitivity is ill defined. Lack of standardization, subjective evaluation and irritative reactions also contribute to reduced reliability.
-
MELISA is particularly useful in diagnosing titanium allergy
The Mayo clinic found no positive reactions to titanium in over a decade of patch testing despite many published cases of titanium allergy (8). In a 2006 study, 56 symptomatic patients exposed to titanium through dental implants were tested with MELISA. Of the 56 patients tested, 21 (37.5%) were positive to titanium. Conversely all patients were patch test negative to titanium. Following the removal of titanium implants in hypersensitive patients showed remarkable clinical improvement (9). It is important to remember that traces of other metals such as nickel and aluminium are found even in commercially pure titanium due to the production process (5, 10).
Recent studies have shown that allergy to the constituents in bone cements (11, 12) may be a causal factor in joint failure. MELISA is able to test for certain constituents of bone cements to determine whether an individual is hypersensitive.
-
Additional uses
Lyme Disease: MELISA testing is has been clinically validated for the diagnosis of Lyme disease (13). MELISA testing is a particularly useful tool in diagnosing Lyme in serologically and clinically unclear cases (14).
Gluten: An additional application for MELISA is in furthering the diagnosis of non-coeliac gluten sensitivity.
-
How the MELISA test works
MELISA tests the patient’s white blood cells against a panel of suspected allergens based on the patient’s medical and dental history. The reaction is measured by two separate methods: uptake of radioisotope by dividing lymphocytes and evaluation by microscope. The test report shows the strength of the reaction as a Stimulation Index and lists the most common sources of exposure.
-
How to get tested
Before testing it is helpful to establish which metals the patient is currently exposed to. A pre-test questionnaire can be used to establish this. A blood sample may be sent to any licensed MELISA laboratory as long as it arrives within 48 hours (ideally 24). The blood should be kept at room temperature and sent in special tubes, which will be provided by the lab. The amount of blood required depends on how many antigens are to be tested. For a screening of 10 metals, 36 ml blood, or 4 large tubes of blood, is needed. Steroids or other immuno-suppressant drugs may affect the test result, as well as any ongoing systemic infections (Staphylococcus etc).
References
1. Valentine-Thon E, Schiwara HW. Validity of MELISA for metal sensitivity testing. Neuroendocrinology Letters 2003;24(1/2):5764. Article
2. Stejskal V, et al. Metal-specific lymphocytes: biomarkers of sensitivity in man. Neuroendocrinology Letters 1999; 20:289-298. Article
3. 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. Article
4. Stejskal V, Ockert K, Bjørklund G. Metal-induced inflammation triggers fibromyalgia in metal-allergic patients. Neuroendocrinology Letters 2013;34(6):559-65. Article
5. Harloff et al. Titanium allergy or not? “Impurity” of titanium implant materials. Health 2010(2);4;306-310 Article
6. Hallab N, Merritt K, Jacobs, J. Metal sensitivity in patients with orthopedic implants. The Journal of Bone and Joint Surgery 2001;83:428. Abstract
7. Hallab NJ, Anderson S, Stafford T, Glant T, Jacobs JJ. Lymphocyte responses in patients with total hip arthroplasty. J Orthop Res. 2005;23(2):384-91. Abstract
8. Davis M et al. Patch testing with a large series of metal allergens: findings from more than 1,000 patients in one decade at Mayo Clinic. Dermatitis 2011;22(5):256-71. Abstract
9. Müller K, Valentine-Thon E. Hypersensitivity to titanium: Clinical and laboratory evidence.
Neuro Endocrinol Lett 2006; 27(Suppl 1):31-35. Article
10. Schuh A, Thomas P, Kachler W, Göske J, Wagner L, Holzwarth U, Forst R. [Allergic potential of titanium implants]. Orthopade 2005;34(4):327-8, 330-3. Abstract
11. Thomas P. et al. Allergy towards bone cement. Orthopade 2006;35(9):956, 958-60. Abstract
12.Thomas B. et al. High frequency of contact allergy to implant and bone cement components, in particular gentamicin, in cemented arthroplasty with complications: usefulness of late patch test reading. Contact Dermatitis 2015;73(6):343-9. Abstract
13. Valentine-Thon E, Ilsemann K, Sandkamp M. A novel lymphocyte transformation test (LTT-MELISA) for Lyme borreliosis.Diagn Microbiol Infect Dis 2007;57:27-34. Article
14. Puri B, Segal D, Monro J. Diagnostic use of the lymphocyte transformation test-memory lymphocyte immunostimulation assay in confirming active Lyme borreliosis in clinically and serologically ambiguous cases.Int J Clin Exp Med 2014;7(12):5890-5892. Article
- Title: Metal hypersensitivity
- Subtitle: Melisa
- List item:
- List title:
What is metal hypersensitivity?, List text:
Metal hypersensitivity (also called metal sensitivity or metal allergy) is a disorder of the immune system that affects 10% to 15% of the population. In susceptible people, exposure to certain metals is followed by a cell-mediated immune reaction (type IV hypersensitivity, also called delayed-type hypersensitivity).
A type IV hypersensitivity reaction is mediated by T-lymphocytes (white blood cells) that have had prior contact with a given allergen. These cells respond by enlarging (lymphoblast transformation) and dividing (proliferation) when exposed to the sensitising allergen. The newly formed effector cells, together with their secreted cytokines, mediate the resulting allergic reaction.
Inflammation activated by metal allergy may be one of the causes of ill health in patients. Type IV metal allergy is often overlooked as a culprit in many of today’s chronic illnesses, more info HERE.
- List title:
How can a metal hypersensitivity be diagnosed?, List text:
With a skin test or, more objectively and safely, with a lymphocyte transformation test (also referred to as “LTT” or “LPT” test). MELISA is an optimised and validated lymphocyte transformation test.
- List title:
Which symptoms may indicate metal hypersensitivity?, List text:
The classic symptom of metal hypersensitivity is allergic contact dermatitis. In addition to local symptoms, chronic exposure to metals may cause numerous symptoms associated with an overactive immune system in susceptible people. Patients with metal hypersensitivity report symptoms such as inflammation, joint and muscle pain, cognitive impairment (brain fog), depression and headaches. Metal hypersensitivity has been implicated in the aetiology of chronic fatigue syndrome, autoimmune disease, fibromyalgia and multiple chemical sensitivity.
- List title:
What is the main difference between standard LTT and MELISA testing?, List text:
By optimising the methodology of LTT, MELISA has improved both the specificity and the sensitivity of the test. Below are the four major changes that MELISA implements, in contrast with LTT.
1. MELISA uses a higher number of lymphocytes per test
2. The metal concentrations used have been chosen so that they are non-mitogenic and non-toxic
3. The test uses partial depletion of macrophages which restores the lymphocyte-monocyte balance so that it is similar to that in the blood
4. In addition to objective determination of lymphocyte proliferation by radiolabeled thymidine, morphological examination gives an additional reading directly on the level of stimulated lymphocytes
The MELISA test was validated on 250 patients in 2003 and found to be reproducible, sensitive, specific and reliable for detecting metal sensitivity. Further validation on a larger group of patients was published in 2016. In 2021, a university study wrote about the “significant benefits of MELISA testing”.
To our knowledge, no other LTT except the widely published beryllium-LTT has been validated.
- List title:
Which metals cause hypersensitivity?, List text:
The most frequently allergenic metals are nickel, gold, palladium, cadmium, various mercury compounds, cobalt, chromium and molybdenum. Other metals can induce positive responses in MELISA as well. Everyone has a unique immune system and basically, any substance could trigger an immune response in susceptible individuals.
- List title:
What is metal hypersensitivity?, List text:
Improving patient health through personalised testing


Latest news
-
Dr Scott Schroeder, Podiatric Physician and Surgeon
Foot & Ankle Center, Wenatchee, WA, USA“I have many patients that are interested in this type of testing associated with implants. Thank you for the great work you have done.”
-
Dr Toril Jelter MD, General Practitioner & Pediatrician
Mount Diablo Integrated Wellness Center, Walnut Creek, CA, USA“A type IV metal allergy is often overlooked as a culprit in many of today's chronic illnesses. MELISA testing gives targeted information on what needs to be avoided. Many patients get their life back with this information instead of remaining chronically ill for the rest of their days.”
-
Dr Goran D. Stojanovic, Dental Surgeon
The Ella Clinic, London, UK“Working in holistic dentistry I use an integrated approach and treat the patient as a whole, focusing on the dental need in the larger context of the person’s overall well-being. MELISA provides me with invaluable information for the most suitable materials to be used.”
-
MUDr. Jan Maňoušek
Cardiologist, University Hospital Brno, Czechia“In daily practice, I see how dental metal fillings (eg amalgam), as well as dental or orthopedic implants, can have an adverse effects on arrhythmias (eg atrial fibrillation). For many patients, establishing a timeline between a dental or orthopaedic procedure and their symptoms developing will aid diagnosis."