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

posted in Patient Questions on Dental Implants

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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/

19 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).

• Kim Hovey September 10th, 2008

  
  

  Hello! I found this thread while searching for implant allergies. I have just had surgery on both feet, and screws implanted. The left one, done in March, did fine. The right one, however is now 3 months post-op and will not heal completely. It drains constantly. At my last appointment, the doctor did a thorough review of all my records, and a metal allergy test.

  It appears that I AM one of the few that is allergic to Titanium. Go Figure!

  I had cervical surgery, but no cage was used, so there was never a problem.

  It is a strong possibility that I will be needing knee replacements in the not-so-distant future. I do have a medic alert ID and carry it all the time. I have added “surgical metal allergy” to the information on it. For now this is all the protection I have if I am unable to speak for myself.

  Are there any ways to do implants that do NOT require the use of metal? Can someone direct me to more information on this idea? I cannot seem to find anything.

  Thank you!

• Mary B January 24th, 2009

  
  

  I had two dental implants on Nov. 5, 2008. Four days later I began to experience a herpes simplex prodrome in the side of my head. It is now 10 WEEKS later…and in spite of antivirals (Valtrex) almost continuously, my lips still break out with pain and the typical things herpes does when you take the valtrex late (past 72 hrs of onset). The diagnosis of herpes is confirmed, immune system checked by bloodwork (results in soon). The point is that I’ve NEVER had this happen…I may have had 5 cold sores in my entire life (I am 48). I get a few days’ peace, then it flares up again. Very painful. The periodontist who did the implants cannot see any correlation with the HSV, but the timing to me is very suspicious. Is it possible that the presence of these dental implants is stimulating the herpes virus continuously? Help!

• Mary B February 25th, 2009

  
  

  Update on herpes simlex (cold sores) flare-up–it is now Feb. 25, 2009, and the flare-ups are still going strong. We are in week 15. Valtrex dose has been doubled & zovirax cream added; still breaking thru with firey pain and, if medication is taken late, some blistering & flaking. I have found some articles* implicating titanium in the development of arthritis (stimulating the nervous system, not my problem of suppression!) and one by the NIH re: effects of metals onthe immune system**, and another (sorry, lost medical site) on the toxicity of titanium implants varying with the form of Titanium…who’s to know the form isn’t changing in my mouth, due to chemical reactions? Has ANYONE else had a patient with unprecedented, continuous herpes flare-up after dental implants??

  *http://www.nature.com/ncprheum/journal/v2/n1/full/ncprheum0087.html
  **http://www.ncbi.nlm.nih.gov/pubmed/15487704?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=4&log$=relatedarticles&logdbfrom=pubmed

• A. Branson September 2nd, 2009

  
  

  The most significant need is to educate dental professionals that titanium allergies do exist. For 3 years after I had several implants placed, there were multiple problems which were dismissed by the surgeon who also refused to discuss or look at the MELISA test results with the end result that 2/3’s of my mandible had to be removed when the implants were finally removed-by a different surgeon although he listed the reason for removal as “patient preference.” Who in the world would choose to have their jaw removed?
  A. Branson

• Judi September 23rd, 2009

  
  

  OMG, the last comment I posted on here was removed. I would like to hear more about your case Brandon.
  I’m going through something semilar.

• Karen October 2nd, 2009

  
  

  Interesting that I’ve stumbled on this! Sept 23 I rec’d BMP under anesthesia and 2 implants (to replace a failing one) and 2 days later started with the herpes! Of course I didn’t know why the unbelievable sore throat, difficulty swalling etc. Yesterday, Oct 1, my surgeon said “herpes” and I’ve got a mouth full of sores! Now is affecting my tongue and having problems swallowing again. Have dr appt this afternoon to get on the antibiotic for this. Any doctors willing to respond to this? What is the connection? There has to be. Have never had anything like this EVER.

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