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      Titanium and Other Metal Hypersensitivity Diagnosed by MELISA® Test: Follow-Up Study

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          Abstract

          This study is aimed at proving the clinical benefit of the MELISA® test in the minimization or complete elimination of health problems in patients with confirmed hypersensitivity to metals used for tissue replacements. A group of 305 patients aged 20-75 years with previously proven metal hypersensitivity (initial MELISA® test), mainly to titanium and then to another fifteen metals, was chosen from the database at the Institute of Dental Medicine. From these patients, a final group of 42 patients agreed to participate in the study, 35 of which were female and 7 were male. The patients completed a special questionnaire aimed at information regarding change of health status from their last visit and determining whether the results of the initial MELISA® test and recommendations based on it were beneficial for patients or not. They were clinically examined, and peripheral blood samples were taken to perform follow-up MELISA® tests. Questionnaire data was processed, and the follow-up MELISA® test results were compared with the results of the initial MELISA® tests. For statistical analysis, the Fisher's exact test and paired T-test were used. Thirty-two patients reported that they followed the recommendations based on the results of the initial MELISA® tests, and of these, 30 patients (94%) confirmed significant health improvement. Six patients did not follow the recommendation, and from these, only one patient reported an improvement in his health problems. By comparison of the initial and follow-up MELISA® test results, it can be stated that the hypersensitivity to the given metal decreased or disappeared after the therapeutic interventions performed based on the initial MELISA® test results. The evaluation of the data obtained from patients in this study confirmed a significant clinical benefit of MELISA® test.

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          Metal sensitivity in patients with orthopaedic implants.

          All metals in contact with biological systems undergo corrosion. This electrochemical process leads to the formation of metal ions, which may activate the immune system by forming complexes with endogenous proteins. Implant degradation products have been shown to be associated with dermatitis, urticaria, and vasculitis. If cutaneous signs of an allergic response appear after implantation of a metal device, metal sensitivity should be considered. Currently, there is no generally accepted test for the clinical determination of metal hypersensitivity to implanted devices. The prevalence of dermal sensitivity in patients with a joint replacement device, particularly those with a failed implant, is substantially higher than that in the general population. Until the roles of delayed hypersensitivity and humoral immune responses to metallic orthopaedic implants are more clearly defined, the risk to patients may be considered minimal. It is currently unclear whether metal sensitivity is a contributing factor to implant failure.
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            General review of titanium toxicity

            Background Titanium is a commonly used inert bio-implant material within the medical and dental fields. Although the use of titanium is thought to be safe with a high success rate, in some cases, there are rare reports of problems caused by titanium. In most of these problematic reports, only individual reports are dominant and comprehensive reporting has not been performed. This comprehensive article has been prepared to review the toxicity of titanium materials within the medical and dental fields. Methods We used online searching tools including MEDLINE (PubMed), Embase, Cochrane Library, and Google Scholar by combining keywords such as “titanium implant toxicity,” “titanium implant corrosion,” “titanium implant allergy,” and “yellow nail syndrome.” Recently updated data has been collected and compiled into one of four categories: “the toxicity of titanium,” “the toxicity of titanium alloys,” “the toxicity of titanium implants,” and “diseases related to titanium.” Results Recent studies with regard to titanium toxicity have been increasing and have now expanded to the medical field in addition to the fields of environmental research and basic science. Problems that may arise in titanium-based dental implants include the generation of titanium and titanium alloy particles and ions deposited into surrounding tissues due to the corrosion and wear of implants, resulting in bone loss due to inflammatory reactions, which may lead to osseointegration failure of the dental implant. These titanium ions and particles are systemically deposited and can lead to toxic reactions in other tissues such as yellow nail syndrome. Additionally, implant failure and allergic reactions can occur due to hypersensitivity reactions. Zirconia implants can be considered as an alternative; however, limitations still exist due to a lack of long-term clinical data. Conclusions Clinicians should pay attention to the use of titanium dental implants and need to be aware of the problems that may arise from the use of titanium implants and should be able to diagnose them, in spite of very rare occurrence. Within the limitation of this study, it was suggested that we should be aware the rare problems of titanium toxicity.
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              Biologic effects of implant debris.

              Biologic response to orthopedic implants debris is central to clinical performance. Eventual implant loosening due to aseptic osteolysis has been attributed to local inflammatory responses to wear and corrosion products that are produced by articulating implant interfaces. The response to implant debris is dominated by local immune activation, e.g. macrophages. Immune reactivity has been shown to depend on the number of particles produced or the dose (i.e., the concentration of phagocytosable particles per tissue volume, which can be characterized by knowing the size distribution and amount of debris). Elongated particles (fbers) are generally more pro-inflammatory than round particles, and there is a growing consensus that metals particles are more proinflammatory than polymers in vivo. Generally, to produce an in vitro inflammatory response, particles need to be less than 10 mum, i.e. phagocytosable. However, both soluble and particulate debris derived from Co-Cr-Mo alloy implants can induce monocyte/macrophage activation and secretion of pro-inflammatory cytokines such as IL-1beta, TNFalpha, IL-6 and IL-8 via up-regulation of transcription factor NFkappabeta, and activation of inflammasome danger signaling in human macrophages. Not only does activation of local (and systemic) inflammation result in decreased osteoblast function but osteoclast activity increases. Some people are more predisposed to implant debris induced inflammation and metal "allergy" testing services are becoming available. New pathways of implant debris-induced inflammatory reactions continue to be discovered, such as the "danger signaling" inflammasome pathway, which provides new targets for pharmaceutical intervention and improved implant performance.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2021
                3 June 2021
                : 2021
                : 5512091
                Affiliations
                Institute of Dental Medicine, First Faculty of Medicine and General University Hospital in Prague, Charles University, Prague 121 11, Czech Republic
                Author notes

                Academic Editor: Victor Feitosa

                Author information
                https://orcid.org/0000-0001-8296-4425
                https://orcid.org/0000-0002-1029-2671
                https://orcid.org/0000-0003-0846-5104
                https://orcid.org/0000-0003-1703-8518
                https://orcid.org/0000-0003-4354-1926
                https://orcid.org/0000-0001-7368-4499
                https://orcid.org/0000-0002-1998-0278
                https://orcid.org/0000-0002-6945-9798
                Article
                10.1155/2021/5512091
                8192180
                532315d9-0240-4380-83cf-8bfea788d7ca
                Copyright © 2021 Radka Vrbova et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 January 2021
                : 7 May 2021
                : 20 May 2021
                Funding
                Funded by: Ministerstvo Zdravotnictví Ceské Republiky
                Award ID: NV19-08-00070
                Categories
                Research Article

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