MELISA Test for Hypersensitivity to Metals: Should This Be Routine Prior to Implant Surgery?

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Alison, a patient, asks:
Regarding the implant “intolerance” issue, a plethora of scientific, peer reviewed articles seem to provide information on the increasing awareness, and need for treatment, for those with hyper-sensitivity/reactions to titanium. MELISA is a blood test which gives valuable information on a patient’s sensitivity to a variety of metals based on lymnphoblast activity (very condensed explanation). Considering the possibility of people experiencing adverse reactions to implant metals, should testing for intolerance, with MELISA, routinely be done prior to implant placement?

OsseoNews.com Editor’s Note: For more information on MELISA please visit, http://www.melisa.org/

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13 Responses to “ MELISA Test for Hypersensitivity to Metals: Should This Be Routine Prior to Implant Surgery? ”

• charles Schlesinger, DDS June 30th, 2008

  
  

  The prevelance of true Ti allergy is estimated at 0.6% of the population (Sicilia A, Cuesta S, Coma G, Arregui I, Guisasola C, Ruiz E.Section of Periodontology, Medical & Dental School.University of Oviedo.SPAIN) .

  Most of the incidence of reported Ti allergy has been to either Titanium particulate in the lungs or dermal contact to Ti alloys- namely nickel-titanium used in jewelry. Approx. 15% of the population has a nickel sensitivity. Medical grade titanium alloy is a compltely different animal.

  To answer the original question- Since the incidence is so very low, routine testing would not be indicated. If there was a patient who had a past history of metallic allergy, then it may be a good adjunct to treatment.

• anon July 1st, 2008

  
  

  Grade IV titanium, is what implants use, is an alloy. Traces of various other metals are in it making it much stronger as pure titanium is structurally quite weak. Most allergies are with the alloyed components and not titanium

• charles Schlesinger, DDS July 1st, 2008

  
  

  6/4 Ti alloy which is most common in medical uses contains Ti, vanadium and aluminum. With most of the product being composed of Ti. There is work going on currently to produce pure Ti with improved strengths in order to overcome the issues with its alloyed components.

• Dr. Ben Eby July 1st, 2008

  
  

  If in doubt about sensitivity issues, it is good to test. My experience has not shown a need for testing in most cases. I have tested twice, because of known sensitivity to a variety of metals and didn’t have a problem in either case. If the incidence of sensitivity is fairly high in certain hands, I would take a hard look at the surgical techniques used.

• Gary D Kitzis, DMD July 2nd, 2008

  
  

  Grades I, II, III and IV are CP titanium. Grade V is an alloy (Ti6Al4V).

  While grades I-IV contain very small traces of other materials, the titanium is still considered to be CP–commercially pure. The “impurities” include nitrogen, carbon, hydrogen iron and oxygen. The biggest difference between the four CP grades, is in the amounts of oxygen and iron. Grades I & II, are similar (about 99.5% Ti) and grades III & IV are very similar to each other (over 99% Ti), but all are considered pure.

  I do not think you can compare people who have sensitivity to, for example, silver or base metal jewelry used in earrings or bracelets, with sensitivity to solid titanium used in implants.

  In all my years in dentistry, I have had one patient about 25 years ago who was noticeably allergic to metal. We used plastic retractors and mirrors when treating her, covered the handpiece and other instruments with dermacell tape and generally had a hard time treating her because she had to be insulated from metal. Scaling her teeth was done quickly so ultrasonic curettes (partly insulated from her tissues by water) did not remain in contact with any gingival area more than a few seconds. She ate with plastic utensils, wore no jewelry that touched her skin and had to cover the clasps in her bra with dermacell tape. Contact dermatitis was seen after any continued base metal contact. Fortunately, we were able to treat her with composite resins and gold posterior crowns that were 89% gold and 9% platinum alloys. My point in this example, is she knew she was allergic to metals and in the same sense, potential implant patients who are highly allergic to metals also know that they are. If there is a problem with metals, patients are aware of them from their daily living activities.

  General metal allergy testing for high noble gold alloys or titanium is not necessary unless the patient demonstrates a history of extreme metal sensitivity.

• mike stanley, asst. July 2nd, 2008

  
  

  A reading of the abstracts listied on the MELISA site confirm Dr. Schlesinger’s observation that reactions seem to be confined to particulates and alloy components and at very low rates. Other reactions seem more related to the fact that the skin was broken, not that it was titanium that penetrated it. None of the abstracts mentioned details of the tested “titanium” components or particulate sizes, so full text might be in order.
  “Routine” testing seems excessive given the low rate of positives n the general population.

• Pieter Boshoff July 3rd, 2008

  
  

  Prof Vera Stejskal who developed melisa test should be asked for her comment. There is more incidence of Titanium sensitivity than previously believed and especially in those people with toxic heavy metal overload In such cases I would recommend a melisa test and a urine challenge test PRIOR to placing titanium. Remember that anaphylactic shock with penicillin is scarce but if it happens to you it seems like 100% incidence !

• Vera Stejskal, Associated Professor of Immunology July 3rd, 2008

  
  

  Regarding titanium hypersensitivty, the fact is that the occurrence might be far higher as recognized. The reason is that the conventional patch test, which is a golden standard for the detection of metal hypersensitivity, has not been developed for testing of titanium allergy.

  Usually, tests are performed by placing a titanium dioxide suspension on the skin under occlusion for 1-2 days. Under these conditions the absorption through the skin is quite low, if it is happening at all. The reason is that titanium is not soluble and the particles are too big to penetrate the skin. If one uses titanium chloride salt for patch testing one can sensitize the majority of patients, as shown by Japanese dermatologists. Also, physico-chemically, titanium is a transition metal, which indicates that is has the capacity to bind to proteins and function as a hapten (a small molecule that can induce allergy).

  Those interested in titanium allergy might read the following articles Hypersensitivity to titanium: Clinical and laboratory evidence and LTT-MELISA® is clinically relevant for detecting and monitoring metal sensitivity which can be downloaded from www.melisa.org/articles.php

• anon July 3rd, 2008

  
  

  I could not find any published studies specifically on implants and a suggested replacement at the above website. Did I overlook this information?

• Linda Nelson July 5th, 2008

  
  

  The link to the articles are here

  Hypersensitivity to titanium: Clinical and laboratory evidence
  http://www.melisa.org/pdf/Hypersensitivity%20to%20titanium.pdf

  Clinical and laboratory evidence and LTT-MELISA® is clinically relevant for detecting and monitoring metal sensitivity
  http://www.melisa.org/pdf/MELISA%20is%20clinically%20relevant.pdf

• David Cotant DDS July 8th, 2008

  
  

  The medical literature indicates that the MELISA tests has “so many false positives and negatives to render it as not effective in medical decision making”. I have used it once, and the patient showed no allergy to Titanium. It requires 8 to 11 tubes of blood, and must be overnighted to the testing site. The cost and bother of a test that is of questionable results, makes it of limited value.

• Dr. Mehdi Jafari July 11th, 2008

  
  

  Hypersensitivity reactions to titanium seem to be a cause of implant failure in orthopedic surgery rather than dentistry. A proof of sensitivity to titanium is by the local presence of abundant macrophages and T–lymphocytes and the absence of B -lymphocytes indicating Type IV hypersensitivity. Titanium ions inhibit osteoclastic activity and reduce osteoblastic protein synthesis. In a study using the human osteoblast cell line MG-63 (proliferating osteoblasts), titanium ions showed to induce IL-6 production and activate osteoclastogenesis. Titanium cytotoxicity is dependent on the particle size; the smaller the size, the more toxic it is. Patients who have had an allergic reaction to a metallic device or jewelry are more likely to show a reaction to a titanium implant than those with no history at all. Up to the present time, there is no evidence that there is an increased risk of a reaction to an implanted device in patients who have skin patch sensitivity but no history of reaction to metallic materials. A number of cases of local skin reaction secondary to implantation of a cardiac pacemaker appeared in the literature. The causal allergen was a combination of both their metallic and plastic components. There is evidence of granulomatous reaction due to titanium alloy used in body piercing, broken screws of an orthopedic implant and clips used during vascular surgery procedures. MELISA (memory lymphocyte immunostimulation assay) reactivity is directly dependent on lymphocyte concentration; the higher the lymphocyte concentration per test, the stronger the reactivity.

• vera stejskal July 11th, 2008

  
  

  In response to David Cotant, DDS I would like to mention the following: the so called false-positivity of LTT_MELISA is due to the fact that patch test is usually used as “golden standard”, not the clinical relevance of the test. The low sensitivity of the patch test and the false-positive reactions (due to irritative reactions) are well known.
  The most important proof that LTT_MELISA is clinically relevant is that the in vitro reactivity to titanium or other metals in question usually decreases following the removal of the implant and at the same time the clinical side-effects subside. In patients where the metal exposure persists,specific lymphocyte reactivity remains the same. Read Valentine et al 2006 on our website.
  For titanium testing one needs ca 20 ml of blood (2-3 x 8 ml).

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Mon September 08 2008

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