Abstract. Introduction. The aims of our systematic review were to assess the Nickel sensitising potential of total knee arthroplasty (TKA), explore the relationship between Nickel hypersensitivity and clinical outcomes, and evaluate the utility of skin patch testing pre- and/or post-operatively. Methodology. A literature search was performed through EMBASE, Medline and PubMed databases. Articles were screened independently by two investigators. Levels of Evidence were assessed using Oxford CEBM criteria and quality was assessed using MINORS and Cochrane risk-of-bias tools. Results. Twenty studies met the eligibility criteria, reporting on 1354 TKAs. Prevalence of Nickel hypersensitivity ranged from 0% to 87.5%. Only one study which compared prevalence of hypersensitivity in the same patient group before and after surgery noted newly positive patch test reactions in 4.1%. Three studies reported lower prevalence of hypersensitivity in post-operative patients compared to pre-operative patients. Seven studies suggested hypersensitivity might cause complications; six studies did not support any relationship. Seven studies recommended pre-operative patch testing in patients with history of metal allergy; nine studies concluded testing may be valuable post-operatively. Conclusions. Patients undergoing TKA do not seem to be at increased risk of developing Nickel hypersensitivity, and there is conflicting evidence that patients with established hypersensitivity are more likely to experience adverse clinical outcomes. The evidence suggests performing patch testing pre-operatively in patients with history of metal allergy to aid selection of the most appropriate prosthesis, and post-operatively once common causes of implant failure have been excluded, since implant removal or revision with hypoallergenic implants may alleviate symptoms

INTRODUCTION: Metal-on-metal alloarthroplasty of the hip is gaining popularity in order to avoid complications associated with polyethylene wear. On the other hand, metal-on-metal articulations release metal ions, the biological effects of which remain unclear. Genetic and immunological changes have been associated with increased metal ion levels in arthroplasty patients. We intended to study the outcome after metal-on-metal arthroplasty of the hip with a focus on the toxicologically and immunologically relevant metal ions chromium, cobalt, nickel, and manganese. PATIENTS AND METHODS: A prospective, randomised study was designed where all patients received a cemented arthroplasty of the hip, either with a metal-on-metal bearing (Metasul ®; 28 patients) or with a metal-on-polyethylene bearing (Protasul ®, 26 patients). Only patients with primary osteoarthritis of the hip and without other metallic implants were included (mean age 65 years, range 45–74). Follow-up was performed after a minimum of two years. Clinical outcome was measured by the Harris hip score and the SF36, and radiographic analysis was undertaken by plain radiography. Metal ion concentrations in patient serum were analysed by high-resolution plasma mass spectrometry. RESULTS: It was found that the clinical outcome was almost identical in both groups with respect to Harris hip score and SF36, and radiographic signs of osteolyses or loosening did not occur in any group. In the metal-on-metal group, chromium concentrations increased 4.1 fold and cobalt concentrations increased 7.6 fold when compared to preoperative values (p< 0.05; Wilcoxon Mann Whitney Test), whereas nickel and manganese concentrations did not change significantly. In the metal-on-polyethylene group, no significant increase in the concentration of any ion occurred. DISCUSSION: In conclusion, metal-on-metal and metal-on-polyethylene arthroplasties of the hip provide equal clinical and radiographic outcomes in the medium term, but the concentrations of chromium and cobalt increase considerably after metal-on-metal arthroplasty. Importantly, the allergogenic and previously not assessed ions nickel and manganese show no significant changes in the medium term after any type of hip alloarthroplasty. To our knowledge, this is the first study that addresses manganese and nickel concentrations in a prospective, randomized setting, and our patients will be followed further with respect to possible immunological and genetic changes

The role of metal sensitivity or allergy in causing persistent symptoms or failure and need for a revision of a total joint replacement has been the topic of debate and controversy for decades. There was renewed interest in this area with the rise of metal-on-metal hip arthroplasty and the advent of adverse local tissue reactions. This led to an increase in metal ion testing as well as metal sensitivity testing. With the decline of the use of metal-on-metal hip components, this is now mostly an issue in knee arthroplasty. It is well known that a substantial percentage of patients have persistent symptoms following knee replacement. What remains in question is whether allergy to metal or other materials such as PMMA may be a contributing factor. It is accepted that the incidence of positive skin patch tests is higher in symptomatic failed joint replacements. Nickel sensitivity is most common as a positive skin test with up to 15% of patients demonstrating this followed by chromium and cobalt. A recent review by Lachiewicz et al. concluded that there was insufficient evidence to recommend routine or widespread cutaneous or in vitro hypersensitivity testing before primary TKA, that there is no evidence-based rationale to recommend a routine metal allergy screening questionnaire, that there is only anecdotal support for Ni-free implants, and that local dermatitis should be treated with topical steroids. In another article, routine screening for metal allergy was not recommended, however, selective screening for history of sensitivity or unexplained pain or early loosening was suggested. Other experts have recommended a role for utilizing a commercially available alternative to components containing nickel or cobalt in patients thought to be hypersensitive. A recent study, however, concluded that there was no difference in complications, revisions, or reoperations among patients who tested positive with patch testing whether they were treated with standard components or nickel free components. Likewise, a consensus panel published results from the United Kingdom in which cobalt chrome implants were recommended regardless of the patients metal allergy status. Patient perception is important, however, and among patients who report multiple allergies of any kind, a higher percentage are likely to be dissatisfied with their knee replacement. Of more importance are those reporting a specific allergy to metal are substantially more likely to express some dissatisfaction with their components. Metal allergy as a cause of chronic pain and/or early failure of joint replacement is rare if it exists at all. It is always a diagnosis of exclusion. Patients who think they are allergic are probably more likely to be more symptomatic following joint replacement. Whether or not to use a nickel free or hypoallergenic component in such patients remains an area of controversy

Wear debris from metal on metal (M/M) hip resurfacing and metal on polyethylene (M/P) total hip replacements have different biocompatibilities. M/P wear particles have a foreign body effect. 1. M/M wear particles cause hypersensitivity. 2. , DNA damage. 3. ,. 4. and white blood cell suppression. 5. . M/P wear debris contains nickel and M/M wear debris contains cobalt. Nickel and cobalt are both heavy metals, required as trace elements for some bacteria but potentially toxic to bacteria in high concentrations. Cobalt kills Helicobacter Pylori at concentrations as low as 30 ppb. 6. , substantially lower than the concentration in prosthetic joints. Nickel/cobalt permease membrane transporters are found in a wide range of microorganisms. 7. including Staphylococcus Aureus and Coagulase Negative Staphylococci, which commonly infect prosthetic joints. The purpose was to investigate the effects of nanoparticulate wear debris and their heavy metal constituents on bacterial growth. Samples of Coagulase Negative Staphylococci (CNS), Staphylococcus Aureus and MRSA were cultivated to compare their growth in M/M wear debris, M/P wear debris, nickel, cobalt and control culture mediums over 48 hours. Nickel was toxic to CNS (p=0.006) and MRSA (p=0.048). Cobalt also retarded the growth of all three bacteria. M/M wear debris increased the growth of CNS 183 times at 48 hours (p=0.044), Staphylococcus Aureus and MRSA. M/P wear increased the growth of Staphylococcus Aureus 120 times at 48 hours (p=0.021), CNS and MRSA. M/M and M/P nanoparticulate wear debris accelerate the rate of growth of common organisms that infect prosthetic hip joints, the clinical significance of which is uncertain. In isolation, the heavy metals contained within wear debris retard bacterial growth, particularly nickel. Nanoparticulate wear debris does not possess the toxic effects of its constituent metals on bacteria. This reinforces the safety of wear debris but also shows the potential for anti-bacterial effects to be harnessed

Total knee arthroplasty is a well-established treatment for degenerative joint disease, on the other hand metal ion release of cobalt or chromium and particle formation can trigger intolerance reactions. Biotribological examinations can help to assess the metal ion release in different settings. The purpose of this study was the evaluation of inter-laboratory differences in the metal ion concentration analysis. Samples were generated in a 3+1 station knee wear simulator (EndoLab GmbH, Thansau, Germany) with a medium size Columbus Knee System with or without AS multilayer coating. The wear simulation was performed under highly demanding activity (HDA) profile and samples were taken after 0.5, 5.0, 5.5. and 8.0 million cycles. The samples were blinded and sent to three different laboratories and the content of chromium, cobalt, molybdenum, nickel, and zirconium was assessed by inductively coupled plasma mass spectrometry (ICP-MS). The AS multilayer coating clearly reduced the release of chromium, cobalt and molybdenum. Mean levels were: Chromium 9329.78µg/l ± 985.44 vs 503.75µg/l ± 54.19, cobalt 10419.00µg/l ± 15.517.53 vs 2.60µg/l ± 1.35, molybdenum 2496.33µg/l ± 102.62 vs 2.46µg/l ± 2.31. Interestingly we found especially for nickel and zirconium big inter-laboratory differences in the metal assessment. There were up to 10-fold higher values in comparison of one laboratory to another. The data demonstrate that results of metal ion assessment should be evaluated by interlaboratory comparison and should be critically interpreted

Introduction. The utilization of lymphocyte transformation testing (LTT) has increased for diagnosing metal sensitivity associated with TKA, but its validity for the diagnosis of TKA failure due to an immune reaction has not been established. Methods. We performed a retrospective study of 27 well-fixed, aseptic primary TKAs with persistent pain and/or stiffness, revised by a single, experienced surgeon for suspected metal allergy to nickel based on a positive LTT. Periprosthetic tissue samples obtained at the time of revision surgery were scored using the aseptic lymphocytic vasculitis-associated lesion (ALVAL) scoring system. Results. Eight patients were categorized as mildly reactive, 8 reactive, and 11 highly reactive to nickel by LTT. The predominant findings on routine histology were fibrosis and varying degrees of lymphocytic infiltration in 17/27 (63%) of the cases. The average ALVAL score of the cohort was 3.1 ± 1.9, out of a maximum score of 10. Average Knee Society Scores (KSS) improved post-revision, as did range of motion (all p<0.01). Neither LTT stimulation index as a continuous variable nor as a categorical variable (mild, moderate, high) was correlated with ALVAL score, pre-operative function, or change in function at last follow-up (0.015 < r < 0.30, 0.13 < p < 0.95) as measured by KSS. In addition, the ALVAL score did not correlate significantly with either pre-operative or post-operative KSS or range of motion (0.061 < r < 0.365, 0.09 < p < 0.88). Conclusions. Based on this analysis including histopathology, LTT results alone are insufficient for the diagnosis of TKA failure due to an immune reaction. A positive LTT may not indicate that an immune reaction is the cause of pain and stiffness post-TKA. The role of LTT in assessing immune failure of TKA needs further investigation. Diagnostic criteria for immune failure of a TKA need to be established

Summary. Metal-on-metal hip replacements have been associated with adverse reactions including inflammatory pseudotumours and soft tissue necrosis. We have shown that cobalt can directly activate toll-like receptor 4, an immune receptor causing pro-inflammatory interleukin-8 secretion. This may contribute to adverse reaction development. Introduction. Metal-on-metal hips have the highest failure rate of any joint arthroplasty material. Reasons for failure include the development of pseudotumours, soft tissue necrosis and pain around the affected joint. The adverse reactions appear to be inflammatory as failing joints are often infiltrated by immune cells such as lymphocytes. However the exact cellular and biological mechanisms underlying this inflammation are unknown. Toll-like receptor 4 (TLR4) is found on the surface of immune cells including macrophages and dendritic cells. It is activated by lipopolysaccharide (LPS) from Gram negative bacteria, inducing an immune response against the pathogen through increased secretion of pro-inflammatory cytokines. It has recently been shown that nickel can activate TLR4, causing inflammation. Cobalt, a component of many metal-on-metal joints, is adjacent to nickel in the periodic table and shares a number of nickel's properties. Consequently we hypothesised that cobalt ions from metal-on-metal joints can activate TLR4. Methods. An in vitro cell culture model was developed using human and murine TLR4 reporter cell lines to investigate the effects of metal ions, including cobalt, on TLR4. Real-time PCR was used to examine the effect of cobalt on inflammatory gene expression, including IL-8, CCL-2 and IRAK-2, while an ELISA assay was conducted to investigate IL-8 protein expression in a human macrophage cell line (MonoMac 6). The TLR4 agonist LPS was included as a positive control and as a negative control TLR4 activation was blocked using the chemical agonist CLI-095 (Invivogen, UK). Results. Using human TLR4 reporter cells we show that cobalt at clinically-relevant concentrations can activate human TLR4. This effect appears unique to humans as murine TLR4 is unresponsive to cobalt but still responds to LPS. We also demonstrate that in human macrophages physiologically-relevant concentrations of cobalt cause increased pro-inflammatory IL-8 secretion (p<0.001). IL-8 is involved in perpetuating the immune response by recruiting more inflammatory cells to the site of inflammation. Cobalt-induced IL-8 secretion can be blocked using a TLR4 antagonist (p<0.001) showing that the effect is due to cobalt activation. Cobalt ions also alter gene expression in human macrophages. Cobalt upregulates expression of IL-8 and IRAK2 genes; IRAK2 is a key component of the TLR4 signalling pathway. Interestingly, cobalt causes downregulation of the CCL2 gene whereas it is upregulated in response to LPS. Discussion. In this study we have demonstrated that cobalt ions can activate human TLR4 signalling and in human macrophages this can increase expression of pro-inflammatory IL-8. We have also developed a robust series of assays for determining the effects of metal ions and other orthopaedic materials on the TLR4 signalling pathway. These methods will be used to investigate the immunological effects of additional orthopaedic metals (e.g. chromium, titanium and molybdenum). This work has identified a key pathway involved in the immune response to metal ions which can now be investigated for genetic variability and as a potential therapeutic target

Total joint arthroplasty has proven to be efficient to relieve pain and regain mobility. In fact, most patients undergoing a total knee arthroplasty (TKA) are satisfied with their surgery (80 to 90%), yet 4 to 7% still complain of unexplainable pain and stiffness. Several authors have proposed that reactivity to the implant could explain this phenomenon. Still, no strong evidence supports this theory as of today. We aimed to determine the prevalence of metal and cement hypersensitivity in a cohort of patients with unexplained pain and stiffness after TKA. We retrieved data for a group of patients presenting unexplained pain and stiffness. We excluded all other potential known causes of pain. All patients were tested with a Lymphocyte Transformation Test from whole blood taps. We analysed data of hypersensitivity to metals (alloy particles of titanium and cobalt, aluminum, cobalt, nickel, zirconium, vanadium, molybdenum, cobalt, chromium and iron) and PMMA cement (bone cement monomer and particles). Fifty-three patients underwent a LTT for unexplained pain and stiffness after total knee arthroplasty between May 2012 and May 2015. The cohort consisted of 26 men and 27 women with a mean age of 66.3(±8.0) years. Six patients had no hypersensitivity (11.3%), leaving 88.7% of the cohort with hypersensitivity to metal and/or cement. Almost half the cohort of patients tested for PMMA was hypersensitive to cement (44.0%). The most common metal hypersensitivity was nickel (69.8%). Twelve patients presented sensitivity to only one metal (22.6%), whereas 35 patients were hypersensitive to more than one metal (66.0%). Eleven patients had revision surgery with a hypoallergenic prosthesis. Patients reported a significant diminution of pain as well as better knee function compared to preoperative status as early as 6 weeks postop, although some reported residual stiffness. The results of this study suggest that metal and/or cement hypersensitivity could play a role in cases of total knee arthroplasty with unexplained pain and stiffness. Randomised controlled clinical trials on the subject will be initiated by our team to further investigate this phenomenon

Introduction Patients who have undergone total joint arthroplasty have demonstrated elevated postoperative levels of the component metal ions (cobalt, chrome, titanium) in blood and urine. The metal ion release is due to wear particles produced by fretting and corrosion of the metal surfaces and interfaces. Postoperative levels may be many-fold greater than preoperative and normal population levels. The postoperative levels depend on a number of factors including component metals, implant design, and fixation. Fretting corrosion of spinal implants has been previously demonstrated. Elevated metal ion levels in tissue fluids might be expected, however there are significant differences in stress on the spinal implant when compared with a mobile joint bearing. The aim of this study is to determine whether component metal ions can be measured in the blood and urine of patients who have previously undergone surgery with spinal instrumentation. Methods Patients who had undergone surgery which included spinal instrumentation were recruited to the study. All had stainless steel implants. These cohorts were subdivided into two groups: those who had retained implants and those who had spinal implants which had been removed. A cohort of volunteers who had no metal implants served as controls. All subjects provide blood for serum nickel and serum chromium assays and (random) urine for measurement of chromium and creatinine. Serum chromium and nickel and urinary chromium/creatinine ratio were compared between groups. Non-parametric statistical analysis was used to test differences (MWU) and correlations (Spearman). A p-value less than 0.05 was considered significant. Results The study group consisted of 44 patients who had undergone surgery 5–25 years previously. The implants had been removed in 12 patients. The mean number of spinal levels at operation was 10 (range 3–18) and the mean number of couplings was 10 (range 2–18). The average age at follow-up was 36 years (range18–75). There was no difference in levels of serum nickel and blood chromium between controls and study cohorts. A significant difference between the controls and study groups was noted with the mean urinary chromium/ creatinine ratio being in the order of 100 times greater in the implant group. The mean level in the implant-retained group was1.6 times greater than in patients in whom the implants had been removed. The random urinary chromium/creatinine ratios correlated with the length of the instrumentation and the number of couplings in the spinal instrumentation. Conclusions A raised level of chromium excretion in patients with spinal implants suggests that metal ions are released from the implants by electrolytic and fretting-corrosion. Removal of the implant reduces the excretion levels but not to base-line levels. The blood levels of both metal ions tested were no different from controls suggesting that the kidney was able to adequately handle the release of chromium from the implant without a build-up of chromium in the blood

Metal-on-metal arthroplasties are being inserted in increasing numbers of younger patients due to the increased durability and reduced requirement for revision in these implants. Recent studies have raised many concerns over possible genotoxicity of MoM implants. This is a prospective study of patients who have undergone elective total hip replacement, they were selected and then randomised into two groups. Group A received a MoP implant and group B received a MoM implant. Patients are reviewed pre-operatively (control group), at 3 months, 6 months, 1 year and 2 years post-operatively. On each occasion blood tests are taken to quantify metal ion levels (chromium, cobalt, titanium, nickel and vanadium) using HR-ICPMS method and chromosome aberrations in T lymphocytes using 24 colour fluorescent in situ hybridisation (FISH). Fiffty three patients have been recruited to date, 24 of whom had MoP prosthesis and 29 a MoM. 25 of these have had their one-year follow-up with blood analysis. Cobalt and chromium concentration increased during the first 6 months in both MoM and MoP groups, in the MoM group the chromium levels were twice that of MoP group and 12x that of the preoperative samples. There was no difference with the levels of titanium, nickel and vanadium. Chromosome aberrations occurred in both groups. At 6 months both the MoM and MoP groups showed increase frequency of aneuploidy aberrations with further increases after one year. Structural damage in the form of translocations occurred in the MoM group after one year, but not in the MoP group. Preliminary results of this study show that the levels of chromium and cobalt are significantly higher in the MoM group compared to the MoP group. This corresponds to increases in chromosome aberrations between the groups particularly in translocations present in the MoM group at 1 year

Introduction: The aim of this study is to investigate whether MoM implants result in more chromosome aberrations and increased blood metal ions post-operatively when compared to MoP implants. Large head metal-on-metal articulating surfaces of the hip are being used in increasing numbers of patients for oncological purposes due to the increased stability and reduced dislocation rate. Recent studies have raised many concerns over possible genotoxicity of MoM implants. Methods: This is a prospective study of patients who have undergone elective total hip replacement. Patients were randomised into two groups (MoP and MoM). Patients are reviewed pre-operatively (control group), at 3 months, 6 months, 1 year and 2 years post-operatively. On each occasion blood tests are taken to quantify metal ion levels (chromium, cobalt, titanium, nickel and vanadium) using HR-ICPMS and chromosome aberrations in T lymphocytes using 24 colour fluorescent in situ hybridisation (FISH). Results: 24 patients had MoP prosthesis and 29 a MoM. Cobalt and chromium concentration increased during the first 6 months in both MoM and MoP groups, in the MoM group the chromium levels were twice that of MoP group and 12x that of the preoperative samples. There was no difference with the levels of titanium, nickel and vanadium. Chromosome aberrations occurred in both groups. At 6 months both the MoM and MoP groups showed increase frequency of aneuploidy aberrations with further increases after one year. Structural damage in the form of translocations occurred in the MoM group after one year, but not in the MoP group. Discussion: Results of this study show that the levels of chromium and cobalt are significantly higher in the MoM group compared to the MoP group. This corresponds to increases in chromosome aberrations between the groups particularly in aneuploidy and translocations present in the MoM group at 1 year

Introduction. Adverse Local Tissue Reactions (ALTR) have been reported in association with both wear and corrosion. Tissue reactions have been reported in association with corrosion at CoCr head-CoCr neck, CoCr head-TiAl6V4 neck, and CoCr modular neck on beta-titanium (TMZF) stem junctions. The current abstract reports on 3 cases of ALTR in association with CoCr modular necks on convention titanium (TiAl6V4) stem junctions. Case 1. A 67 year old male (87 kg, 1.73 m, BMI 29.1) presented with new onset hip irritation 11 months after surgery. Radiographs show no abnormalities. Further investigation revealed the following: ESR = 95, CRP = 5, Cr level = 1.0, Co level = 4.1, leukocyte transformation testing = highly reactive to nickel. Hip aspiration was culture negative with 11,250 wbc. Metal artifact reduction MR showed cystic local reaction in the region of the greater trochanter. Case 2. A 52 year old male (89 kg, 1.83 m, BMI 26.5) presented with new onset hip irritation 30 months after surgery. Radiographs show no abnormalities. Further investigation revealed the following: ESR = 7, CRP = 5.4, Cr level = 2.1, Co level = 4.8, leukocyte transformation testing = reactive to nickel. Hip aspiration was culture negative with 3995 wbc. Metal artifact reduction MR showed cystic local reaction in the region of the iliopsoas. Case 3. A 52 year old male (104 kg, 1.85 m, BMI 30.1) presented with new onset hip irritation 26 months after surgery. Radiographs show no abnormalities. Further investigation revealed the following: ESR = 33, CRP = 34.9, Cr level = 1.0, Co level = 3.7, leukocyte transformation testing = no reactivity to any of the biomaterials. Hip aspiration was culture negative with 3,780 wbc. Metal artifact reduction MR showed cystic local reaction in the region of the iliopsoas. Discussion. All three of these patients are scheduled for revision surgery. All three had ceramic-ceramic bearings. We have experience with 1029 ceramic-ceramic THA with fixed neck conventional titanium and modular titanium neck implants with minimum 2 yr f/u and have never diagnosed an adverse reaction in any of these patients. It is possible that corrosion at the CoCr neck on TiAl6V4 stem junction is the root cause of these reactions. Although the incidence of diagnosed reactions is roughly 1%, it appears that the use of CoCr at any junction under significant mechanical stress can result in adverse local tissue reaction and therefore should either be avoided or used with great caution and compelling indications

Metals represent the main components of orthopaedic implants. Being in contact with biological fluids, the metallic alloys used for the fabrication of artificial joints undergo corrosion or degradation, therefore they release ions and molecules. Although these do not have antigenic properties, they bind to protein carriers and may act as haptens eliciting a delayed-type hypersensitivity reaction (DTH). Biomaterial-related hypersensitivity is considered as an immunotoxic effect, although little is known about its clinical incidence and its impact on implant failure. The main question about the sensitivity against metals used in the joint prosthesis concern the cause-effect relation with the implant failure. In metal-exposed workers, the diagnosis of DTH is made in vivo by patch testing. For the occupational exposure standard patch-testing protocols are available, but some concerns exist about their applicability to study the hypersensitivity to metal implants. In this case-control study, a panel of representative haptens was used to assess the incidence of positive patch testing in patients undergoing ‘total hip replacement’ (THR) and ‘total knee replacement’ (TKR). The main goal of this study was to evaluate the validity of this relatively simple and safe procedure in the diagnosis of the hypersensitivity reactions to the implant components. A consecutive series of 286 individuals was enrolled in the study. Five groups of patients were evaluated: Group A included 75 patients (20 M; 55 F; median age 59) candidates to primary THR or TKR; Group B included 98 patients with loosening of THR (27 M; 71 F; median age 67; median follow up: 102 months); Group C included 53 patients with stable THR (13 M; 40 F; median age 68; median follow up: 60 months); Group D included 40 patients with failed TKR (14 M; 26 F; median age 68; median follow up: 24 months); Group E included 20 patients with stable TKR (4 M; 16 F; median age 70; median follow up: 16 months). Osteoarthritis was the most frequent disease that led to joint replacement (59%), followed by hip dysplasia (19%), and trauma (13%). Patients with rheumatoid arthritis were excluded from the study, as well as patients who assumed cortico-steroids or other immunosuppressive drugs. Fifty-eight patients (21%) had an additional implant at another site. Hypersensitivity to metals was tested by using the most relevant components of Cobalt-Chromium based alloys (CoCrMo), Ti-based alloys (TiAlV), and bone cements. A drop of each hapten was smeared on the Haye’s chamber test, which was applied to the dorsum of the patient. After 48–72 hours, skin reactions were evaluated and graded as 0 (no reaction), 1 (erythema), 2 (edema), 3 (vesicles), or 4 (bulla). All patients with a medical history of metal DTH showed positive skin reaction. The incidence of positive patch testing to at least one hapten, as well as the frequency of DTH to metal, resulted significantly higher in patients with TKR, while the incidence of positive skin testing to bone cements was similar in all groups. Group B patients with CoCrMo-THR showed a low frequency of nickel-DTH in comparison to Group A (9% and 22%, respectively). In patients with TiAlV-THR the immune status seemed to be unaffected, and these individuals showed a high incidence of vanadium-DTH (Group A: 8%; Group B: 21%; Group C: 19%; p= 0.04). A high incidence of vanadium hypersensitivity was found also in patients with TKR (Group D: 33%; Group E: 20%). The median duration of the implant resulted significantly lower in patients who had a positive patch testing to metals (71 vs 106 months; p= 0.008). Our results demonstrated the reliability of the panel used for skin testing, which was able to identify a systemic hypersensitivity status. A remarkable finding concerned the prevalence of DTH related to the metal composition of the implant. A significant low frequency of metal DTH, namely nickel, was found in patients with CoCrMo-failed implant. Because nickel is the most common metal sensitizer and its amount in both CoCrMo and TiAlV alloys is very low, we may consider the incidence of nickel DTH as informative for the immune status of the examined group. In the TiAlV group the immune status seems to be unaffected; on the contrary, theese patients showed a high prevalence of vanadium skin reaction. These results confirm the conclusion of previous studies, where the immunocompromised status of patients who had a CoCrMo had been shown and related to the high serum level of chromium and cobalt. Although the cause-effect relation between DTH and implant failure cannot be established, the hypersensitivity should be considered when deciding what type of prosthesis to use. Either if the sensitization precedes or follows the loosening, it participates in the network of events that are responsible for prosthetic loosening, because contributes to mantain the inflammatory process

Introduction The first ceramic knee implant in a human patient was used by Dr. G. Langer of the Orthopaedic Clinic at the University of Jena, Germany in 1972. In 1980, Drs. Oonishi and Hasegave began using a alumina femoral component on a polyethylene tibial component. These early attempts all involve the search for solutions to the wear and degradation problems. The application of ceramics was limited by:. polyethylene wear and degradation. demand of thin components. Excellent Scratch resistance AMC Ceramics is much harder than most surgical instruments. In comparison, metal components are easily scratched and damaged during surgery with the consequence of increasing wear. Surface quality: Surface quality of the articulation surfaces components made from AMC Ceramics provide excellent articulation surfaces. Low Friction: Knee Components made of AMC Ceramics show a low coefficient of friction. The resulting frictional forces on the prostheses are lower and offer the option for a reduction of aseptic loosening. Low Allergic Potential: Ceramics are generally not considered as elicitors of allergic reactions. Hypersensitive reactions – especially to nickel – in total joint replacement are discussed as one possible reason for postoperative syndromes. Surface Lubrication: AMC is a material with a very good surface lubrication capability. A low wetting angle is exhibited by the material. Conclusion: Knee implants have become an area of great interest in the past years. For more than 10 years ceramic femoral components are used in Japan. Published follow-up data in scientifically journals are promising. Leading orthopaedic surgeons are interested in this option today to reduce the risk of pitting and delamination of Polyethylene. Material improvements are required for young active patients and nickel sensitive patients. The novel AMC Ceramic offers a solution to minimise the allergic and wear related problems of knee implants. New concepts on the basis of hard on hard combination are technically already realised. The use of knee endoprosthesis with ceramic on ceramic combination is an option for ”zero” wear bearings in the knee

Recently, a series of locally destructive soft tissue pseudotumour has been reported in patients following metal-on-metal hip resurfacing arthroplasty (MoMHRA), requiring revision surgery in a high percentage of patients. Based on the histological evidence of lymphocytic infiltration, a delayed hypersensitivity reaction to nickel (Ni), chromium (Cr) or cobalt (Co) has been suggested to play a role in its aetiology. The aim of this study was to investigate the incidence and level of hypersensitivity reaction to metals in patients with pseudotumour. Materials and Methods: 25 patients were investigated in this Ethics approved study:. Group 1: MoMHRA patients with pseudotumours, detected on the ultrasound and confirmed with MRI (n=6, 5 F:1 M, mean age 53 years);. Group 2: MoMHRA patients without pseudotumours (n=13, 7 F:6 M, mean age 55 years); and. Group 3: age-matched control subjects without metal implants (n=6, 4 F:2 M, mean age 54 years). Lymphocyte transformation tests (LTT) were used to measure lymphocyte proliferation responses to metals. Peripheral blood mononuclear cells were isolated from heparinized blood samples using standard Ficoll–Hypaque® (Pharmacia). The PBMC were cultured at a cell density of 106 cells/mL. Culture was set up in the presence of either:. medium alone;. nickel chloride (Sigma; 10-4M-10-6M);. cobalt chloride (10-4M-10-6M); and. chromium chloride (10-4M-10-6M). After 5 days of culture, cells were pulsed with [3H]-thymidine and proliferation was assessed by scintillation counting. The stimulation index (SI) was calculated by the ratio of mean counts per minute of stimulated to unstimulated cultures. A SI value of greater than 2.0 was interpreted as a positive result. Results: A clinical history of metal allergy was reported in 2/6 in Group 1, 2/13 in Group 2, and none in Group 3. In pseudotumour group, the incidence of reactivity to Ni, Co and Cr was 60%, 17% and 0%, respectively. Within Group 2, the reactivity to Ni, Co and Cr was 69%, 8% and 15%, respectively. One control subject had reactivity to Ni. Inter-group comparisons of mean SI values (Kruskal-Wallis non-parametric analysis of variance) showed no significant differences (p> 0.05). Discussion: The incidence of enhanced lymphocyte response to metals in patients with MoMHRA was more common than the control group. However, in comparison with non-pseudotumour patients, there was no significant difference in the incidence or the level of lymphocyte reactivity in patients with pseudotumour. We conclude that patients with MoMHRA have an enhanced lymphocyte response to metal ions, reflecting exposure and immune reactivity. However, patients with pseudotumours have a similar proliferative response to those without pseudotumours, which suggests that type IV hypersensitivity may not be the cause of the pseudotumours

To further extend the longevity of total hip replacement, bearings with better wear characteristics are desirable. Despite generally inferior clinical results with metal-on- metal total hip replacements, many metal-on-metal implants lasted over two decades or are still functioning in patients who received the implant at a young age. Acetabular component wear and loosening limit the survival of hips. Because of this, long-term survival rates of the Charnley hip and the McKee-Farrar are similar. Consequently, there is renewed interest in metal-on- metal bearings for total hip arthroplasty. Aseptic loosening of early metal-on-metal prostheses was not uniform due to the metal-on-metal bearings or due to wear. There is evidence indicating that some metal-on-metal bearing couples were poorly designed and/or manufactured leading to high frictional torque and/or excessive wear which could have been the cause of failure. Very low wear has been observed on metal-on- metal bearings retrieved after more than 20 years of use. The wear characteristics are a function of materials, design, and manufacturing. Polar bearing is preferred to reduce frictional torque, but excessive radial clearance is associated with higher wear. As has been demonstrated in hips with metal-on-plastic bearings, clinical success and failure are multifactorial. The chance of success with new metal-on-metal bearings is increased when the bearing is combined with well-established femoral stems and acetabular shells. As has been seen in hips, which have metal-on-polyethylene bearings, loosening of hips with metal-on-metal bearings can occur due to other factors such as suboptimal stem and/or cup design, manufacturing or implantation technique. Studies of the levels of cobalt and chromium in the hair, blood, and urine have shown that metallic content in patients with metal-metal total hips are generally higher than in patients with metal-UHMWPE articulations. While the release of cobalt and chromium ions from metal-metal total hips has been verified, the clinical significance of this finding is still unclear. Cobalt and chromium wear particles have been shown to induce carcinoma in animal models, giving rise to the concern that such alloys could have the same effect if present in sufficient amounts in human tissue for a sufficient length of time. Overall, the available epidemiological data do not demonstrate an increase in cancer risk following total hip replacement. At the same time, it is important to recognise the limitations of the available data with regard to sample size, length of follow-up and lack of stratification for other co-morbidities. The issue of delayed-type hypersensitivity (DTH) to the main elements in metal-metal total hips – cobalt, chromium, and nickel. Skin patch testing is unreliable for the assessment of hypersensitivity to implants, however, this type of testing has shown that cobalt, chromium, and nickel are associated with contact dermatitis. Because there is a higher reported incidence of metal sensitivity in patients with loose components, the association between metal sensitivity and loose implants has fuelled a long-standing debate: does hypersensitivity cause loosening or does loosening cause hypersensitivity? A small number of patients with metal-metal total hips develop an adverse local tissue response and present with unexplained pain and chronic effusions that resolve when the metal-metal bearings are exchanged for metal-UHMWPE hips. The histology of abundant lymphocytes and plasma cells is highly suggestive of an immune response. Caution should be taken in the implantation of a metal-metal bearing in patients with a known sensitivity to metals. Further investigations of the local and systemic effects related to the wear of the primary articulating surfaces are needed. It should be emphasised, however, that clinical success is multifactorial. Patient selection, surgical technique, component fixation, and the other aspects of the prosthetic joint will influence the clinical performance of any articulation

Aims

Revision total knee arthroplasty (rTKA) is a technically challenging and costly procedure. It is well-documented that primary TKA (pTKA) have better survivorship than rTKA; however, we were unable to identify any studies explicitly investigating previous rTKA as a risk factor for failure following rTKA. The purpose of this study is to compare the outcomes following rTKA between patients undergoing index rTKA and those who had been previously revised.

Aims

Metal allergy in knee arthroplasty patients is a controversial topic. We aimed to conduct a scoping review to clarify the management of metal allergy in primary and revision total knee arthroplasty (TKA).

It is estimated that 15 % of the population is allergic to metal, most commonly to Nickel, which is a common component of the alloys in most knee and hip arthroplasties. It would therefore be expected that allergy to metal is a frequent form of implant failure – but very little is reported in the literature. With the recent concerns about metal-on-metal bearings and metal ion issues, there has been renewed interest in metal allergy – with the Australian Joint Registry 2010 reporting it as a causative factor in 7 % of Hip Resurfacing revisions. With over 200 BHR and 571 ASR Hip Resurfacing arthroplasties in my series from 2001, I have identified only 1 patient with implant failure due to metal allergy. In 2010 two Total Knee Arthroplasty patients presented with pain and strongly positive Melisa allergy tests – these patients were revised to Titanium coated implants resulting in a complete relief of symptoms. This paper will analyse the problem of metal sensitivity, the investigation and management of the allergic patient who has, or requires, joint arthroplasty

Background. When reversing the hard-soft articulation in inverse shoulder replacement, i.e. hard inlay and soft glenosphere (cf. Figure 1), the tribological behaviour of such a pairing has to be tested thoroughly. Therefore, two hard materials for the inlay, CoCr alloy and alumina toughened zirconia ceramic (ceramys®) articulating on two soft materials, conventional UHMWPE and vitamin E stabilised, highly cross-linked PE (vitamys®) were tested in a joint simulator. Methods. The simulator tests were performed at Endolab GmbH, Rosenheim, Germany, analogue to standardised gravimetric wear tests for hip prosthesis (ISO 14242-1) with load and motion curves adapted to the shoulder. The test parameters differing from the standard were the maximum force (1.0 kN) and the range of motion. A servo-hydraulic six station joint simulator (EndoLab) was used to run the tests up to 5*106 cycles with diluted calf serum at 37° C as lubricant. Visual inspection and mass measurements were done at 0.1, 0.5, 1, 2, 3, 4 and 5 million cycles using a high precision scale and a stereo microscope, respectivly. Results. The wear rates measured in the simulator are summarised in the table below and illustrated in Figure 2. The simulator wear rate of the standard articulation CoCr – UHMWPE is similar to that found in the corresponding pairing for hip endoprosthesis, although the articulation diameter of the glenospheres tested is larger (42 mm compared to 28 – 32 mm in hip joints). Replacing UHMWPE by the cross-linked vitamys®, the wear rate is reduced to about 1/3 for both hard counterparts, CoCr and ceramys®, respectively. Replacing the CoCr inlay by a part made from ceramys® lowers wear by about 37 % in articulation against UHMWPE. This difference is significant (p = 0.002, significance level 5 %). And comparing CoCr and ceramys® against vitamys®, yields a reduction of about 44 %. Which is significant again (p = 0.015, significance level 5 %). The lowest wear rate, with a reduction of about 80 % compared to the standard CoCr – UHMWPE, exhibits the pairing of both advanced materials, ceramys® – vitamys®. Conclusions. Long-term clinical follow-up will confirm if this in-vitro wear reduction leads to longer in-vivo survival of reverse total shoulder arthroplasty. Such a study is under ethic approval, currently. However, the ceramys® inlay offers the benefits of a nickel free inverse shoulder replacement with less x-ray opacity, compared to CoCr. To view tables/figures, please contact authors directly