Diagnostic tests for titanium hypersensitivity in implant dentistry: a systematic review of the literature

Abstract

Purpose There are rising concerns about titanium hypersensitivity reaction regarding dental endosseous implants. This review aims to summarize and compare the validity and reliability of the available dermatological and laboratory diagnostic tests regarding titanium hypersensitivity. The following PICO design was used: In Patients with titanium dental implants (P) does epicutaneous testing (ECT) (I), compared to lymphocyte transformation test (LTT) or Memory Lymphocyte Immunostimulation Assay (MELISA) (C) detect hypersensitivity reactions (O)? A literature search was performed including all studies dealing with this topic. Studies regarding orthopedic implants were excluded. Methods Three databases (MEDLINE PubMed, Cochrane Library, SciELO) were screened for suitable studies and an additional manual search was also performed. Literature regarding hypersensitivity reactions in orthopedic implants, hypersensitivity reactions regarding implants not related to dental or maxillofacial surgery, animal studies and in vitro studies were excluded. A quality assessment of all selected full-text articles was performed. Randomized, controlled trials were evaluated with the Cochrane Risk of Bias Tool I. Cohort studies were assessed according to the New Castle–Ottawa Scale and case series according to Moga et al. (Development of a quality appraisal tool for case series studies using a modified Delphi technique. 2012). Results 10 studies were included in the quantitative synthesis and available for the endpoint diagnostics of intolerance reactions to titanium dental implants: 2 clinical studies, 7 cohort studies and 1 case series. The potential for bias (internal validity) for these studies was overall rated as high. Conclusions The study of the available literature regarding ECT and MELISA or LTT in patients with suspected titanium hypersensitivity showed inconsistent results in terms of reliability and validity and thus, those tests should be regarded cautiously. There is strong evidence that titanium hypersensitivity in dental implants is associated with innate immunity: unspecific pro-inflammatory responses due to particle induced hyperreactivity of macrophages or toxicological responses especially towards nanoparticles rather than activation of the adaptive immune system. Therefore, tests detecting allergies do not seem expedient and inflammatory clinical signs should be regarded as leading parameters. Graphical Abstract

Metal Allergy: State-of-the-Art Mechanisms, Biomarkers, Hypersensitivity to Implants

“…This could suggest that implants which were containing Ti caused inflammation and cytotoxicity due to localized irritation and corrosion rather than metal hypersensitivity [ 80 ]. This is confirmed by the studies where Ti hypersensitivity in dental implants was linked with innate immunity induced by hyperreactivity macrophages to Ti particles [ 81 ].…”

Early bone formation around immediately placed two-piece tissue-level zirconia implants with a modified surface: an experimental study in the miniature pig mandible

“…Although cp Ti exhibits high biocompatibility and favorable mechanical properties, a disadvantage is the grayish color, which can lead to undesirable esthetics when mucosal tissue retracts and the Ti surface becomes exposed. In addition, the potential accumulation of Ti particles in local lymph nodes is a limitation [ 12 , 13 , 14 , 15 ].…”

S3 Guidelines on Ceramic Dental Implants and Titanium Hypersensitivity: Statements and Recommendations for the Worldwide Implant Dentistry Community

“…There are different diagnostic tests to determine titanium hypersensitivity. 35 The aim is to determine if patients would profit from dermatological of laboratory tests if they are suspected to intolerance or hypersensitivity towards titanium. The latter seems to play a role in the growing manifestation of periimplantitis.…”