Mechanism
The MELISA test measures type-IV delayed hypersensitivity reaction. Type-IV reactions are mediated by T-lymphocytes (or memory lymphocytes) that have had prior contact with a given allergen.Stejskal V, Forsbeck M, Nilsson R. Lymphocyte transformation test for diagnosis of isothiazolinone allergy in man. J Invest Dermatol 1990; 94: 798–802. This is in contrast to a type-I allergy, which is mediated by IgEApplications
Dentistry
MELISA was further developed to help to assess the impact of hypersensitivity to metals used in dentistry. Hypersensitivity to dental metals may be associated with local oral reactions including oral lichen planus, stomatitis and ulceration.Laiendecker R, Van Joost T. Oral manifestation of gold allergy. J Am Acad Dermatol 1994; 30: 205-209.Bruce G, Hall W. Nickel hypersensitivity-related periodontitis. Compend Contin Educ Dent 1995; 178: 180-184.Tosti A, Piraccini BM, Peluso AM. Contact and irritant stomatitis. Semin Cutan Med Surg 1997; 16: 314-319.Issa Y, Brunton P, Glenny A, Duxbury A. Healing of oral lichenoid lesions after replacing amalgam restorations: a systemic review. Oral Surg Med Oral Pathol Oral Radiol Endod 2004; 98: 553-565. The frequency of metal-induced lymphocyte responses was examined in 3,162 dental patients in three European laboratories using the MELISA test.Stejskal V, Danersund A, Lindvall A, Hudecek R. Metal-specific lymphocytes: biomarkers of sensitivity in man. Neuroendocrinology Letters 1999; 20: 289-298. The patients suffered from local and systemic symptoms attributed to their dental restorations. The effect of dental metal removal was studied in 111 patients with metal hypersensitivity and symptoms resemblingOrthopaedics and surgery
Type IV hypersensitivity to metals is common, particularly to nickel, however hypersensitivity related complications associated with metal implants are less frequently reported. Potential hypersensitivity complications include skin rashes, chronic joint pain, swelling, aseptic loosening, and joint failure. Willert H, Buchhorn G, Fayyazi A. Metal-on-metal bearings and hypersensitivity in patients with artificial hip joints: a clinical and histomorphological study. J Bone Joint Surg Am. 2005; 87(1):28-36.Niki Y, Matsumoto H, Otani T, Yatabe T, Kondo M, Yoshimine F, Toyama Y. Screening for symptomatic metal sensitivity: a prospective study of 92 patients undergoing total knee arthroplasty. Biomaterials 2005; 26: 1019-1026. Many authors conclude that LTT-based blood tests like MELISA may be a better option for detecting systemic allergies from implants, while patch testing is better suited to detecting dermal hypersensitivity. They add that LTT based testing may also be a good option in cases of indeterminate hypersensitivity or in patients with joint failure of an unknown cause since it has higher sensitivity than patch testing Carossino A, Carulli C, Ciuffi S. Hypersensitivity reactions to metal implants: laboratory options. BMC Musculoskelet Disord 2016; 17: 486. doi: 10.1186/s12891-016-1342-y.Hallab N, Merritt K, Jacobs JJ. Metal sensitivity in patients with orthopedic implants. J Bone Joint Surg Am 2001; 83: 428-436. Some surgeons and researchers suggest LTT testing prior to surgery in patients with suspected/self-reported metal allergy Lionberger D, Samorajski J, Wilson C, Rivera A. What role does metal allergy sensitization play in total knee arthroplasty revision? J Exp Orthop 2018; 5(1):30. doi: 10.1186/s40634-018-0146-4.Granchi D, Cenni E, Giunti A, Baldini N. Metal hypersensitivity testing in patients undergoing joint replacement. J Bone Joint Surg Br 2012; 94(8): 1126-1134. doi: 10.1302/0301-620X.94B8.28135.Dodd M, Begley A. 2019. The utility of MELISA testing for metal allergy in patients requiring TMJ replacement. Br J Oral Maxillofac Surg 2019; 57(10). doi: 10.1016/j.bjoms.2019.10.254.McMinn D, Zaiee H. 2013. The Ceramic BMHR. nlineAvailable at: http://www.mcminncentre.co.uk/ceramic-birmingham-mid-head-resection.htmlTitanium hypersensitivity
Titanium and its main alloy (Ti6Al4V) are generally seen as hypoallergenic options for arthroplasty and for dental implants. Although uncommon, with a prevalence estimated at between 0.6-6.3%,Sicilia A., e. a., 2008. Titanium allergy in dental implant patients: a clinical study on 1500 consecutive patients. Clinical Oral Implants Research, pp. Aug;19(8):823-35.Hosoki, M. et al., 2018. Cross-sectional observational study exploring the clinical risk of titanium allergy caused by dental implants. Journal of Prosthodontic Research, Vol 62(4), pp. 426-431. titanium hypersensitivity has been reported post-implantation with symptoms including impaired fracture healing, local eczema, pain, swelling, systemic dermatitis, implant loosening, and failure, all of which have been reported to resolve with implant removal and replacement with a non-titanium implant Wood, M. & Warshaw, E., 2015. Hypersensitivity reactions to titanium: diagnosis and management. Dermatitis, pp. 26:7-25.Thomas, P. et al., 2006. Hypersensitivity to titanium osteosynthesis with impaired fracture healing, eczema, and T-cell hyperresponsiveness in vitro: case report and review of the literature. Contact Dermatitis, p. 55: 199–202.Opstal, N. F., 2011. Revision of a tibial baseplate using a customized oxinium component in a case of suspected metal allergy: a case report. Acta Orthop Belg., pp. 77:691-695.Goto, M., Mitsui, Y., Tanesue, R. & Okawa, T., 2013. Hypersensitivity to Suture Anchors. Case reports in Orthopedics. In spinal surgery, microscopic titanium particles are present in the tissues surrounding the implant.Richardson, T. e. a., 2008. Serum titanium levels after instrumented spinal arthrodesis. Spine, p. 33:792–796. These particles activate macrophages that increase bone absorption and inflammatory reactions.Ramachandran, R. e. a., 2006. The effects of titanium and polymethylmethacrylate particles on osteoblast phenotypic stability. J Biomed Mater Res A. p. 77:512–517. Released nanoparticles will circulate in the body fluids, eventually accumulating in remote organs.Hallab, N., 2009. A review of the biologic effects of spine implant debris: fact from fiction. SAS J, p. 3:143–160. Titanium has been shown to induce clinically relevant hypersensitivity which can be detected with MELISA testing.Müller, K. & Valentine-Thon, E., 2006. Hypersensitivity to titanium: clinical and laboratory evidence. Neuro Endocrinol Lett, pp. 1:31-5. The accuracy of patch testing for titanium allergy, in particular, seems to be variable; the Mayo clinic failed to find any positive reactions to titanium in over a decade,Davis, M., Wang, M., Yiannias, K. & Keeling, K., 2011. Patch testing with a large series of metal allergens: findings from more than 1,000 patients in one decade at Mayo Clinic. Dermatitis, pp. 22(5):256-71. despite several published cases of titanium allergy.Evrard, L., Waroquier, D. & Parent, D., 2010. Allergies to dental metals. Titanium: a new allergen. Rev Med Brux, pp. 31(1):44-49.Chronic diseases
The test is also used to determine whether metal allergy is a contributing factor in the development of chronic diseases such asOccupational medicine
The MELISA test is used inValidity
Whilst two articles have concluded that the MELISA test may give false positive (Cederbrant, et al., 1999) (Cederbrant, et al., 1997) reactions, a subsequent study concluded the MELISA test is "reproducible, sensitive, specific, and reliable for detecting metal sensitivity in metal-sensitive patients." (Valentine-Thon & Schiawara, 2003) The developers of the MELISA test argue that the critical articles calculated the sensitivity and specificity of in vitro lymphocyte proliferation tests using patch testing as its reference. It is well-known that patch testing can cause irritative local reactions. It is generally agreed that LTT based tests like MELISA are better suited for diagnosing implant-related metals sensitivity than patch testing as the relationship between skin hypersensitivity and systemic hypersensitivity (Ständer, et al., 2017) is ill-defined. Performing the LTT under optimised stimulating conditions might be a useful additional tool for the diagnosis of hypersensitivity (Ständer, et al., 2017) (FDA, 2019). To test whether patients with symptoms attributed to dental amalgam differed from healthy controls, a study compared 23 amalgam patients, 30 subjects who considered themselves healthy with amalgams and 10 subjects without amalgam using MELISA and other tests. The researchers found that a high frequency of positive results was obtained among healthy subjects with or without dental amalgam, and concluded that the test cannot be used as an objective test for mercury allergy (Cederbrant, et al., 1999). Another study by the same critical author used 34 patients to test the sensitivity and specificity if the MELISA test, and concluded that it is not useful for diagnosis of contact allergy to the metals gold, palladium and nickel, since many false-positive results will be obtained (Cederbrant, et al., 1997). The clinical relevance of the test has been shown by the decrease of patient-reported metal-specific responses following the removal of the allergy-causing metals (however the trial did not have a placebo control). (Stejskal, et al., 2006) (Valentine-Thon, et al., 2006)References
{{DEFAULTSORT:Melisa Immunologic tests Allergology Blood tests