Sensitivity to implant materials in patients with total knee arthroplasties

Abstract

Materials used for total knee arthroplasty (TKA), may elicit an immune response whose role in the outcome of the arthroplasty is still unclear. The aim of this study was to evaluate the frequency of sensitization in patients who had undergone TKA, and the clinical impact of this event on the outcome of the implant. Ninety-four subjects were recruited, including 20 patients who had not yet undergone arthroplasty, 27 individuals who had a well-functioning TKA, and 47 patients with loosening of TKA components. Sensitization was detected by using patch testing including haptens representative of cobalt-based alloys (CoCrMo), titanium-based alloys (TiAlV), and bone cements. The frequency of positive skin reactions to metals increased significantly after TKA, either stable or loosened (No Implant 20%; Stable TKA 48.1%, p = 0.05; Loosened TKA 59.6%, p = 0.001, respectively). We found a higher frequency of positive patch testing to vanadium in patients who had a Stable TKA with at least one TiAlV component (39.1%, p = 0.01). The medical history for metal allergy seems to be a risk factor, because the TKA failure was fourfold more likely in patients who had symptoms of metal hypersensitivity before TKA. The prognostic value was supported by survival analysis, because in these individuals the outcome of the implant was negatively influenced (the logrank test Chi square 5.1, p = 0.02). This study confirms that in patients with a TKA the frequency of positive patch testing is higher than in the normal population, although no predictive value is attributable to the sensitization because patch testing was not able to discriminate between stable and loose implants. On the contrary, the presence of symptoms of metal allergy before implantation should be taken into account as a potential risk factor for TKA failure.

Introduction

Total knee arthroplasty (TKA) has been a major advance in the treatment of knee disabilities, predictably achieving excellent results at a long-term follow-up with relatively low perioperative morbidity [1], [2]. In over 95% of patients TKA relieves pain, improves functional status, and restores most of their normal activities of daily living. In spite of the excellent outcome, TKA can fail over time, and the revision rate over 5 or more years is 2% of knees and 2.1% of patients [1]. TKA failure is generally multifactorial even though the main reasons may be ascribed to mechanical and biological causes [3], [4]. Chronic inflammation following the generation of wear particles has been recognized as the main biological mechanism leading to implant failure [5]. Moreover, if degradation products are able to interact with the immune system, undesirable immunotoxic effects may be induced, including a delayed-type hypersensitivity reaction (DTH) [6], [7], [8], [9]. Metals and acrylic cements represent the main components of TKA: in contact with biological fluids they undergo corrosion and wear, and metal ions or other molecules may induce a DTH [10]. Nickel, cobalt, and chromium are known to be the most common sensitizers, [9], [11] but also hypersensitivity to titanium and vanadium has been described [12], [13]. Polymeric biomaterials, namely acrylic bone cements, are not easily chemically degraded and immunogenic reactions to poly-methyl-methacrylate or other constituents have been occasionally reported [14]. The possible correlation between hypersensitivity and implant failure has been previously investigated, but the main question about the cause–effect relationship between these events has not yet been solved.

One of the major difficulties in understanding the clinical implications of hypersensitivity to the implant components is the lack of universally accepted testing methods [15]. Several in vitro tests based on the reactivity of immune cells to metal–protein complexes have been proposed in diagnosing a systemic hypersensitivity to the implant components [11], [16], [17], but they have some faults that limit large-scale application, including the high costs and the need to be performed in qualified laboratories. In addition, the number of immune cells recruited from biological samples does not allow an exhaustive assay of all the immunogenic substances contained in metal alloys and bone cements, and the elevated toxicity of some chemicals often hampers their in vitro testing [11], [18]. Alternatively, the in vivo approach, i.e. the epicutaneous skin-testing (patch testing), is cheap and allows to estimate simultaneously several haptens [19]. Although patch testing is the most common method used to diagnose contact allergy to metals, its validity in determining a deep-tissue hypersensitivity lets some doubts [10], [11]. Nevertheless, its usefulness in detecting the sensitization to implant materials may be improved if patients are tested with an appropriate series of haptens according to the prosthesis components [19], [20].

An additional limit in establishing the role of the sensitivity to the implant components is the paucity of clinical studies providing clear data of a connection between metal sensitivity and outcome of the implant [15]. The majority of investigators suggest that hypersensitivity can be a contributing factor to implant failure, because of the high proportion of metal DTH in patients with prosthesis loosening [10], the shorter lifespan of the implant in patients having positive patch testing [19], and the histological findings of hypersensitivity-like reaction in tissue around the artificial joint, especially in metal-on-metal bearings [21], [22], [23], [24], [25]. Most studies have been performed in cohorts of patients undergoing a total hip arthroplasty (THA) [10], while few data are available for patients with TKA [9]. From a theoretical point of view, the proportion of positive skin reactions in patients with TKA could differ from those observed in THA for several reasons, including the biomechanics of the joint influencing the metal ion release.

The main goals of our pilot study were to evaluate (i) the frequency of skin sensitization in patients who had undergone TKA, and (ii) the clinical impact of this event on the outcome of the implant. For this purpose we chose to use patch testing by applying a panel of haptens representative of cobalt-based alloys (CoCrMo), titanium-based alloys (TiAlV), and bone cements.