Melisa®
MELISA® Pre-Testing prior to surgery
MELISA testing for patients with planned surgery - important consideration
MELISA tests for Type IV hypersensitivity, which is mediated by T-cell memory. This immune response requires prior sensitization - meaning that if the immune system has never encountered a particular metal, it will not have developed a memory response to it. However, complete avoidance of metal exposure is nearly impossible, as metals are present in everyday environments, including food, and cosmetics. Some patients may not realise they are already exposed via dental metals when undergoing pre-testing for orthopedic implants. From an immunological perspective, metals may provoke the same Type IV response, regardless of whether they are used in dental or orthopedic applications.
MELISA can be used for metal hypersensitivity testing prior to surgery if there are inicators that an allergy may be present. For instance, skin reactions to metals, previous failed surgery and repeated unexplained infections following surgery using metal devices, pins or plates.
There are recommendations available on managing patients with potential metal hypersenstivity prior to undergoing joint arthroplasty or implantation surgery. Schalock et al. (1) recommend that patients who report cutaneous metal allergy should be tested prior to device implantation. Granchi et al. (2) also recommend patch testing for any patient with previous signs or symptoms of metal allergy. Granchi et al. further add that patients with positive skin reactions should not have an implant containing the metal allergen if possible (2).
Some orthopaedic surgeons who suspect that a patient may have problems with metals, for instance, nickel, will pre-test for a whole panel of metals. Titanium was traditionally thought of as bio-inert, but there are increasing reports that it may cause problems in hypersensitive patients (3). Studies show that in vitro blood lymphocyte transformation tests such as MELISA are better suited for diagnosing possible metal sensitivity than patch testing (4, 5, 6). Also, the relationship between skin hypersensitivity and systemic hypersensitivity is ill-defined. Lymphocyte transformation test sensitivity is higher than patch testing and provides quantifiable data and is highly reproducible (7).
However, even in a paper that recommends using pre-operative allergy testing in patients with self-reported metal allergy, there are limitations in testing. The authors report that the frequency of allergy increases after the operation (2). The magnitude of exposure differs significantly - a large orthopedic implant introduces a substantially higher and more prolonged exposure than dietary or cosmetic sources of titanium. Granchi et al. say that the frequency of positive tests increases post-operatively, especially in those patients with failing implants or metal-on-metal devices.
The immune system is dynamic, and sensitivity may develop over time with increased exposure. Testing provides a snapshot of immune reactivity at a specific moment but cannot predict how the immune system will respond to prolonged or intensified exposure in the future. Therefore, the MELISA test cannot guarantee that an allergy will not develop during in vivo, long-term, high-level metal exposure post-surgery.
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References
1. Schalock PC, Menne T, Johansen JD, Taylor JS, Maibach HI, Liden C, Bruze M, Thyssen JP. Hypersensitivity reactions to metallic implants-diagnostic algorithm and suggested patch test series for clinical use. Contact Dermatitis. 2012;66:4–19.
2. Granchi D, Cenni E, Giunti A, Baldini N. Metal hypersensitivity testing in patients undergoing joint replacement: a systematic review. J Bone Joint Surg Br. 2012;94:1126–1134.
3. Wood, MM, and E Warshaw. 2015. “Hypersensitivity reactions to titanium: diagnosis and management.” Dermatitis 26:7-25.
4. Carossino, AM, C Carulli, and S Ciuffi. 2016. “Hypersensitivity reactions to metal implants: laboratory options.” BMC Musculoskelet Disord 17:486.
5. Hallab, NJ. 2004. “Lymphocyte transformation testing for quantifying metal-implant-related hypersensitivity responses.” Dermatitis. 15(2):82-90.
6. Ständer, S, E Oppel, P Thomas, and B Summer. 2017. “Evaluation of lymphocyte transformation tests as compared with patch tests in nickel allergy diagnosis.” Contact Dermatitis ;76(4):228-234. doi:10.1111/cod.12751.
7. Saccomanno, M. F., Sircana, G., Masci, G., Cazzato, G., Florio, M., Capasso, L., Passiatore, M., Autore, G., Maccauro, G., Pola, E., 2019. Allergy in total knee replacement surgery: Is it a real problem? World J Orthop. 10, 63-70.