Aims. Wrist arthroscopy is a standard procedure in hand surgery for diagnosis and treatment of wrist injuries. Even though not generally recommended for similar procedures, general administration of perioperative antibiotic prophylaxis (PAP) is still widely used in wrist arthroscopy. Methods. A clinical ambispective dual-centre study was performed to determine whether PAP reduces postoperative infection rates after soft tissue-only wrist arthroscopies. Retrospective and prospective data was collected at two hospitals with departments specialized in hand surgery. During the study period, 464 wrist arthroscopies were performed, of these 178 soft-tissue-only interventions met the study criteria and were included. Signs of postoperative infection and possible adverse drug effects (ADEs) of PAP were monitored. Additionally, risk factors for surgical site infection (SSIs), such as diabetes mellitus and BMI, were obtained. Results. The overall infection rate of SSI was zero. Neither in the PAP group (n = 69) nor in the control group (n = 109) were signs of postoperative infection observed. Observed symptoms of ADEs were three-times higher in the PAP group when compared to the control-group (16.3 vs 5.5%; p = 0.043). No major ADEs were observed, but one in ten patients in the PAP group reported mild to severe intestinal or hypersensitivity symptoms. Conclusion. We demonstrate that the number needed to treat (NNT) with PAP to prevent one postoperative infection in soft-tissue arthroscopies of the wrist is > 109. Conversely, symptoms of ADEs were reported by one out of ten patients given PAP. Considering the high NNT to prevent postoperative infection and the large number of ADEs caused by PAP, we recommend not to use PAP routinely in soft-tissue arthroscopies of the wrist. Subsequent large-scale studies should be conducted to substantiate these results. Cite this article: Bone Jt Open 2023;4(4):219–225

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). Methods. Studies were identified by searching electronic databases: Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and Embase, from their inception to November 2020, for studies evaluating TKA patients with metal hypersensitivity/allergy. All studies reporting on diagnosing or managing metal hypersensitivity in TKA were included. Data were extracted and summarized based on study design, study population, interventions and outcomes. A practical guide is then formulated based on the available evidence. Results. We included 38 heterogeneous studies (two randomized controlled trials, six comparative studies, 19 case series, and 11 case reports). The evidence indicates that metal hypersensitivity is a rare complication with some histopathological features leading to pain and dissatisfaction with no reliable screening tests preoperatively. Hypoallergenic implants are viable alternatives for patients with self-reported/confirmed metal hypersensitivity if declared preoperatively; however, concerns remain over their long-term outcomes with ceramic implants outperforming titanium nitride-coated implants and informed consent is paramount. For patients presenting with painful TKA, metal hypersensitivity is a diagnosis of exclusion where patch skin testing, lymphocyte transformation test, and synovial biopsies are useful adjuncts before revision surgery is undertaken to hypoallergenic implants with shared decision-making and informed consent. Conclusion. Using the limited available evidence in the literature, we provide a practical approach to metal hypersensitivity in TKA patients. Future national/registry-based studies are needed to identify the scale of metal hypersensitivity, agreed diagnostic criteria, and management strategies. Cite this article: Bone Jt Open 2021;2(10):785–795

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

Total Knee Arthroplasty (TKA) patients may present with effusion, pain, stiffness and functional impairment. A positive metal hypersensitivity (positive LTT) may be an indication for a revision surgery with a custom-made implant devoid of any hypersensitivity-related metal or an implant with the least possible ion content of the metal hypersensitivity, if no custom-made is available. The purpose of the current study is to assess the prevalence of metal hypersensitivity in subjects requiring a primary TKA and assess their early functional outcomes. We are recruiting 660 subjects admitted for TKA. Subjects are randomly assigned to 2 groups: oxidized zirconium implant group or cobalt-chrome implant group. Functional outcomes and quality of life (QoL) are measured pre operatively, 3, 6 and 12 months post operatively with WHOQOL-BREF (domain1-Physical Health, domain 2- Psychological, domain 3- Social relationships, domain 4-Environment), KSS, KOOS and pain Visual Analog Scale (VAS). LTT and metal ions are evaluated pre operatively and 12 months post-surgery. One hundred-sixty patients, 98 women, were enrolled in the study. Mean age was 65.6±8.9. Mean follow up (FU) was 7.1±3.8 months. Eighty-one (50.6%) were randomised in the cobalt-chrome group. Infection rate was 1.9%, one patient required debridement. Three patients (1.9%) presented with contracture at three months FU. At 12 months, WHOQOL-BREF domain 1, 2 and 4 improved significantly (p0,05). Overall, all 160 patients improved their functional outcomes and QoL. At 12 months, VAS scores decreased from 7±2.06 at baseline to 1.95±2.79. Furthermore, the high prevalence of positive LTT (27/65) do not seem to affect early functional outcomes and QoL on patients that may have received a potential implant with hypersensitivity (18/27)

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

The evolution of orthopedic implants has witnessed a great evolution and allowed insights into the various metals and alloys compatible with the human body. However, some recent reports have raised concerns regarding hypersensitivity to several metals used in orthopedic implants. These cases are mostly documented in the field of arthroplasty. Metal ion release following hip or knee arthroplasty is a known phenomenon and associated immune reactions to these metal ions have been implicated in the causation of these hypersensitivity reactions. These reactions frequently lead to poor outcome following these implant surgeries. We here present two rare cases of metal induced hypersensitivity reactions following orthopedic surgeries. We have also reviewed the literature in this context to look into the various causes of metal reactions, types of implant involved in hypersensitivity, methods of testing and management options in these cases

Patients with painful metal-on-metal bearings presenting to the orthopaedic surgeon are a difficult diagnostic challenge. The surgeon must go back to basic principles, perform a complete history and physical exam, obtain serial radiographs and basic blood work (ESR, CRP) to rule out common causes of pain and determine if the pain is, or is not, related to the bearing. The Asymptomatic MoM Arthroplasty: Patients will present for either routine follow up, or because of concerns re: their bearing. It is important to emphasise that at this point the vast majority of patients with a MoM bearing are indeed asymptomatic and their bearings are performing well. The surgeon must take into account: a) which specific implant are they dealing with and what is its track record; b) what is the cup position; c) when to perform metal ion testing; d) when to perform further soft tissue imaging (MARS MRI, Ultrasound); e) when to discuss possible surgery. Painful MoM THA causes not related to the bearing couple: These can be broken down into two broad categories. Causes that are Extrinsic to the hip include: spine, vascular, metabolic and malignancy. Causes that are Intrinsic to the hip can either be Extracapsular (iliopsoas tendonitis and trochanteric bursitis) or Intracapsular (sepsis, loosening, thigh pain, prosthetic failure). Painful MoM THA causes related to the bearing couple: There are now described a number of possible clinical scenarios and causes of pain that relate to the metal-on-metal bearing couple itself: a) local hypersensitivity reaction without a significant soft tissue reaction; b) local hypersensitivity reaction with a significant soft tissue reaction; c) impingement and soft tissue pain secondary to large head effect. Metal ions: obtaining serum, or whole blood, cobalt and chromium levels is recommended as a baseline test. However, there is no established cutoff level to determine with certainty if a patient is having a hypersensitivity reaction. A 7 parts per billion cutoff has been suggested. This gives high specificity, but poor sensitivity. Metal ions therefore can be used as a clue, and one more test in the workup, but cannot be relied upon in isolation to make a diagnosis. MARS MRI: a useful tool for demonstrating soft tissue involvement, but there are many painless, well-functioning MoM implants that have soft tissue reactions, that don't require a revision. In the painful MoM hip an MRI, or ultrasound, is recommended to look for soft tissue destruction or a fluid-filled periprosthetic lesion (pseudotumor). Significant soft tissue involvement is concerning and is commonly an indication for revision in the painful MoM hip. Treatment: management of the painful MoM hip is directly related to the etiology of the pain. Unique to MoM bearing is the issue of pain secondary to a local hypersensitivity reaction. All above tests should be utilised to help determine the best course of action in any individual patient. The painful MoM bearing, that is demonstrating significant soft tissue involvement is a concerning scenario. Earlier revision, to prevent massive abductor damage, would seem prudent for these patients. The painful MoM bearing with no significant soft tissue changes can probably be followed and reviewed at regular intervals. If the pain persists and is felt to be secondary to a hypersensitivity reaction, then revision is really the only option, although the patient must be cautioned regarding the unpredictable nature of the pain relief

Metal-on-metal bearings (MoM) saw an increase in global utilisation in the last decade. This peaked in 2008 in the US, with approximately 35% of bearings being hard-on-hard (metal-on-metal, or ceramic-on-ceramic). Beginning in 2008, reports began to surface regarding local soft tissue reactions and hypersensitivity to MoM bearings. A major implant manufacturer recalled a resurfacing device in 2010 after national joint registries demonstrated higher than expected revision rates. Patients with painful MoM bearings are a difficult diagnostic challenge. The surgeon must go back to basic principles, perform a complete history and physical exam, obtain serial radiographs and basic blood work (ESR, CRP) to rule out common causes of pain and determine if the pain is, or is not, related to the bearing. The Asymptomatic MoM Arthroplasty: Patients will present for either routine follow up, or because of concerns regarding their bearing. It is important to emphasise that at this point the vast majority of patients with a MoM bearing are indeed asymptomatic and their bearings are performing well. The surgeon must take into account: a) which specific implant are they dealing with and what is its track record; b) what is the cup position; c) when to perform metal ion testing; d) when to perform further soft tissue imaging (MARS MRI, Ultrasound); e) when to discuss possible surgery. Painful MoM THA causes not related to the bearing couple: These can be broken down into two broad categories. Causes that are Extrinsic to the hip include spine, vascular, metabolic and malignancy. Causes that are Intrinsic to the hip can either be Extracapsular or Intracapsular. Painful MoM THA causes related to the bearing couple: There are now described a number of possible clinical scenarios and causes of pain that relate to the MoM bearing couple itself: A) Local hypersensitivity reaction without a significant soft tissue reaction; B) Local hypersensitivity reaction with a significant soft tissue reaction; C) Impingement and soft tissue pain secondary to large head effect. Factors related to a hypersensitivity reaction: Some patients, and prostheses, seem to be at a higher risk of developing issues following a MoM bearing, although our understanding of the interplay of these factors is still in evolution: patients at risk include all women and patients with smaller component sizes. Implant factors play a role with some implants having higher wear rates and being more prone to corrosion. Special tests: There is ongoing confusion related to the relative value of the various special tests that patients with a painful MoM undergo. A) Metal Ions - obtaining serum, or whole blood, cobalt and chromium levels is recommended as a baseline test. However, there is no established cutoff level to determine with certainty if a patient is having a hypersensitivity reaction. Metal ions therefore can be used as a clue, but cannot be relied upon in isolation to make a diagnosis. B) MARS MRI - a useful tool for demonstrating soft tissue involvement, but there are many painless, well-functioning MoM implants that have soft tissue reactions, that don't require a revision. In the painful MoM hip an MRI, or ultrasound, is recommended to look for soft tissue destruction or a fluid-filled periprosthetic lesion (pseudotumor). Significant soft tissue involvement is concerning and is commonly an indication for revision in the painful MoM hip. C) CT imaging - can be utilised to help determine cup position and combined anteversion, however, plain radiographs can give a rough estimate of this as well, so routine CT scan evaluations are not currently recommended. The painful MoM bearing, that is demonstrating significant soft tissue involvement is a concerning scenario. Earlier revision, to prevent massive abductor damage, would seem prudent for these patients. The painful MoM bearing with no significant soft tissue changes can probably be followed and reviewed at regular intervals. If the pain persists and is felt to be secondary to a hypersensitivity reaction, then revision is really the only option, although the patient must be cautioned regarding the unpredictable nature of the pain relief

Introduction. Metals used for total knee arthroplasty (TKA) are well known for their good biocompatibility, but may be a source of a release of metal ions that can be a cause of local and systemic adverse effects, aseptic loosening, and hypersensitivity reactions. One of the major difficulties in performing TKA is the selection of implants for patients who are preoperatively diagnosed as subject to metal sensitivity. Alternative solutions in cases of hypersensitivity are implants without metal constituents or metallic implants treated with a non-sensitive surface process. The aim of this study was to evaluate clinical results in patients who had been preoperatively diagnosed with metal sensitivity and who subsequently were provided with the zirconia-ceramic LFA-III TKA, and with a minimum 5-year follow-up. Methods. Five patients (8 knees) with metal sensitivity underwent TKA using cemented zirconia-ceramic LFA-III implants. The LFA-III implant (KYOCERA Medical Co., Japan) is composed of a zirconia ceramic femoral component and a titanium-alloy tibial component with a polyethylene insert. All patients were female andthe average age at the time of surgery was 76.1 years. The average follow-up time was 7.2 years. Clinical and radiographic assessments were conducted with the Knee Society scoring system. Results. No patients except one who had palmoplantar pustulosis preoperatively presented systemic or local dermatitis after surgery. The mean preoperative range of motion of 97.6 degrees improved to a mean of 110.7 degrees at the time of the most recent follow-up. The mean postoperative knee and function scores were 77.1 and 66.9, respectively. Subtle periprosthetic radiolucencies were found in 2 knees after the surgery. Discussion. The zirconia-ceramic LFA-III TKA has performed well over a 5-year period in patients with metal hypersensitivity. Although this implant has a metal tibial component made of titanium, no systemic or local adverse events related to metal hypersensitivity were recorded. Ceramic implants can be an attractive alternative solution for patients suffering from hypersensitivity reactions to metals

Background. Pseudotumours have been associated with metal-on-metal (MoM) hip replacements. We define it as a solid mass which may have cystic components that is neither neoplastic nor infectious in aetiology. The cause of a pseudotumour is not fully understood but could be due to excessive wear, metal hypersensitivity or due to an as-yet unknown cause. Aim. We present the retrieval analysis of early failure MoM hips revised for pain, loosening or a symptomatic mass. Tissues and implants were examined for the possible causes of failure and pseudotumour formation. Corrosion as a potential new cause for pseudotumour formation will be presented. Methods. A group of 16 MoM hip replacements were collected for retrieval analysis. Six of which had a pseudotumour. An Artificial Hip Profiler (Redlux Ltd) was used to measure wear. Edge loading was determined using the 3D wear data. Tissues were histologically evaluated using a 10-point ALVAL scoring system, which strongly suggests hypersensitivity (1). Cases were assigned to one of three categories: high wear (rates >5m/yr), hypersensitivity or corrosion. Results. Of the 6 pseudotumours, 3 had edge loading, 2 had high ALVAL scores and one had corrosion at the head taper junction. The high wear group, (3 cases) all demonstrated edge loading. Histology revealed more metal wear particles and macrophages, with a low ALVAL score in these cases. Two cases were found to have hypersensitivity with a high ALVAL score, more lymphocytes with less visible wear debris and macrophages. The wear rates were also lower, <4m/yr. One total hip replacement had corrosion at the junction between the head and adaptor taper for the stem. The bearings had low wear and the tissue had extensive necrosis as well as products of corrosion enclosed in fibrin (2). There was no suggestion of hypersensitivity (low ALVAL score). Conclusion. Pseudotumours can be caused by high wear, but if this is ruled out, a hypersensitivity or corrosion product reaction should be considered

Purposes of the study and background. An increasing number of clinical studies involving a range of chronic pain conditions report widespread mechanical pressure pain hypersensitivity, which is commonly interpreted as resulting from central sensitization (CS). Secondary hyperalgesia (increased pinprick sensitivity surrounding the site of injury) is considered to be a manifestation of central sensitization. However, it has not been rigorously tested whether central sensitization induced by peripheral nociceptive input, involves widespread mechanical pressure pain hypersensitivity. The aim of this study was to assess whether high frequency electrical stimulation (HFS), which induces a robust secondary hyperalgesia, also induces a widespread decrease of pain pressure thresholds (PPTs). Summary of the methods and results. We measured PPTs bilaterally on the temples (temporalis muscles), on the legs (tibialis anterior muscles) and on the ventral forearm (flexor carpi radialis muscles) before, 20 min after, and 45 min after applying HFS on the ventral forearm of sixteen healthy young volunteers. To evaluate the presence of secondary hyperalgesia, mechanical pin-prick sensitivity was assessed on the skin surrounding the site where HFS was applied and also on the contralateral arm. HFS induced a significant increase in mechanical pinprick sensitivity on the HFS-treated arm. However, HFS did not decrease PPTs either in the area of increased pinprick sensitivity nor at more distant sites. Conclusion. The present study provides no evidence for the hypothesis that central sensitization, induced after intense activation of skin nociceptors, involves a widespread decrease of PPTs. No conflicts of interest. Sources of Funding: This study was funded by the Université Catholique de Louvain

Cobalt chrome alloy is commonly used in joint replacement surgery. However, it is recognised that some patients develop lymphocyte mediated delayed type hypersensitivity (DTH) responses to this material, which may result in extensive bone and soft tissue destruction. Phase 1. United Kingdom: From an existing database, we identified extreme phenotype patient groups following metal on metal (MoM) hip resurfacing or THR: ALVAL with low wearing prostheses; ALVAL with high wear; no ALVAL with high wear; and asymptomatic patients with implants in situ for longer than ten years. Class I and II HLA genotype frequency distributions were compared between these patients’ groups, and in silico peptide binding studies were carried out using validated methodology. Phase 2. United Kingdom: We expanded the study to include more patients, including those with intermediary phenotypes to test whether an algorithm could be developed incorporating “risk genotypes”, patient age, sex and metal exposure. This model was trained in phase 3. Phase 3. United Kingdom, Australia, United States. Patients from other centres were invited to give DNA samples. The data set was split in two. 70% was used to develop machine learning models to predict failure secondary to DTH. The predictions were tested using the remaining blinded 30% of data, using time-dependent AUROCs, and integrated calibration index performance statistics. A total of 606 DNA samples, from 397 males and 209 female patients, were typed. This included 176 from patients with failed prostheses, and 430 from asymptomatic patients at a mean of >10 years follow up. C-index and ROC(t) scores suggested a high degree of discrimination, whilst the IBS indicated good calibration and further backed up the indication of high discriminatory ability. At ten years, the weighted mean survival probability error was < 4%. At present, there are no tests in widespread clinical use which use a patient's genetic profile to guide implant selection or inform post-operative management. The algorithm described herein may address this issue and we suggest that the application may not be restricted to the field of MoM hip arthroplasty

Introduction. Metal ion and particle release, particularly cobalt, has become an important subject in total hip arthroplasty, as it has shown to induce metal hypersensitivity, adverse local tissue reactions and systemic ion related diseases. The purpose of the following study was compare the ion release barrier function of a zirconium nitride (ZrN) multilayer coated hip stem for cemented use, designed for patients with metal ion hypersensitivity, against its uncoated version in a test configuration simulating the worst case scenario of a severely debonded hip stem. The ZrN multilayer coating is applied on a CoCrMo hip stem and consists of a thin adhesive chromium layer, five alternating intermediate layers out of chromium nitride (CrN) and chromium carbonitride (CrCN) and a final zirconium nitride (ZrN) shielding layer [1]. Methods. Hip stems with a ZrN multilayer coating (CoreHip AS, Aesculap AG, Germany) were tested in comparison with a cobalt-chrome uncoated version (CoreHip, Aesculap AG, Germany). In order to create a worst case scenario, the smallest stem size with the biggest offset in combination with an XL ceramic head (offset +7 mm) was used. The stems were embedded according to the ISO 7206-6 test in a bone cement sheet. Once the bone cement was bonded, the stem was pulled out and a PMMA grain was placed inside the femoral cavity in order to uprise the hip stem above its embedding line and simulate a debonded cemented hip stem with a severe toggling condition. The dynamic test was performed under bovine serum environment with an axial force of 3.875 kN [2] at 11.6 Hz for 15 million cycles. The test was interrupted after 1, 3, 5, 10 and 15 million cycles and the surfaces of the stems were analyzed through scanning electron microscopy (SEM) with energy dispersive X-Ray (EDX). Moreover, the test medium was analyzed for metal ion concentration (cobalt, chromium and molybdenum) using ICP-MS. Results. The SEM/EDX analysis demonstrated that the ZrN multilayer coating kept its integrity, as no trace of the substrate material (CoCrMo) could be detected. Furthermore, the taper of the ZrN group showed less fretting and corrosion than the taper of the CoCrMo stem (Fig.1). Moreover, the ion concentration analysis showed a reduction of up to two orders of magnitude in the release of cobalt, chromium and molybdenum in the ZrN coated stems in comparison with the uncoated version. Discussion. The results showed that, even in a worst case scenario of high micro-motion due to a severe stem debonding within the cement mantle, the hip stems with a ZrN multilayer coating substantially reduce the release of ions from the substrate material. For any figures or tables, please contact the authors directly

The histopathology of periprosthetic tissues has been important to understanding the relationship between wear debris and arthroplasty outcome. In a landmark 1977paper, Willert and Semlitsch (1) used a semiquantitative rating to show that tissue reactions largely reflected the extent of particulate debris. Notably, small amounts of debris, including metal, could be eliminated without “overstraining the tissues” but excess debris led to deleterious changes. Currently, a plethora of terms is used to describe tissues from metal-on-metal (M-M) hips and corroded modular connections. We reviewed the evaluation and reporting of local tissue reactions over time, and asked if a dose response has been found between metal and tissue features, and how the use of more standardized terms and quantitative methodologies could reduce the current confusion in terminology. Methods. The PubMed database was searchedbetween 2000 and 2015 for papers using “metal sensitivity /allergy /hypersensitivity, Adverse Local Tissue Reaction (ALTR): osteolysis, metallosis, lymphocytic infiltration, Aseptic Lymphocytic Vasculitis-Associated Lesions (ALVAL), Adverse Reaction to Metal Debris (ARMD) or pseudotumor/ pseudotumour” as well as metal-on-metal / metal-metal AND hip arthroplasty/replacement. Reports lacking soft tissue histological analysis were excluded. Results. 131 articles describing M-M tissue histology were found. In earlier studies, the terms metal sensitivity / hypersensitivity /allergy implied or stated the potential for a Type IV delayed type hypersensitivity response as a reason for revision. More recently those terms have largely been replaced by broader terms such as ALTR, ALVAL and ARMD. ALVAL and metal hypersensitivity were often used interchangeably, both as failure modes and histological findings. Several histology scoring systems have been published but were only used in a limited number of studies. Correlations of histological features with metal levels or component wear were inconclusive, typically because of a high degree of variability. Interestingly, there were very few descriptions that concluded that the observed reactions were benign / normal or anticipated i.e. regardless of the histological features, extent of debris or failure mode, the histology was interpreted as showing an adverse reaction. Discussion. There is now an expanded set of terms to describe tissues but they lack clear definitions and typically do not use quantitative histological data to describe a wide range of periprosthetic reactions to metal. Lower limits of inflammation, necrosis or re-organization that represent a “normal” reaction to surgery and/or small amounts of wear debris are not clearly defined and are rarely discussed. The widespread adoption of the term “adverse” in the present tissue lexicon implies a cause and effect relationship between metal wear and corrosion products and histological features even though this has yet to be determined. The use of quantitative histological scores rather than subjective histological descriptions is imperative to improve the understanding and reporting of the range of periprosthetic reactions. In particular, a new lexicon that allows for a level of tissue reaction that is not misinterpreted as adverse is required

Objectives. Modern metal-on-metal (MoM) hip resurfacing arthroplasty (HRA), while achieving good results with well-orientated, well-designed components in ideal patients, is contraindicated in women, men with head size under 50 mm, or metal hypersensitivity. These patients currently have no access to the benefits of HRA. Highly crosslinked polyethylene (XLPE) has demonstrated clinical success in total hip arthroplasty (THA) and, when used in HRA, potentially reduces metal ion-related sequelae. We report the early performance of HRA using a direct-to-bone cementless mono-bloc XLPE component coupled with a cobalt-chrome femoral head, in the patient group for whom HRA is currently contraindicated. Methods. This is a cross-sectional, observational assessment of 88 consecutive metal-on-XLPE HRAs performed in 84 patients between 2015 and 2018 in three centres (three surgeons, including the designer surgeon). Mean follow-up is 1.6 years (0.7 to 3.9). Mean age at operation was 56 years (. sd. 11; 21 to 82), and 73% of implantations were in female patients. All patients were individually counselled, and a detailed informed consent was obtained prior to operation. Primary resurfacing was carried out in 85 hips, and three cases involved revision of previous MoM HRA. Clinical, radiological, and Oxford Hip Score (OHS) assessments were studied, along with implant survival. Results. There was no loss to follow-up and no actual or impending revision or reoperation. Median OHS increased from 24 (interquartile range (IQR) 20 to 28) preoperatively to 48 (IQR 46 to 48) at the latest follow-up (48 being the best possible score). Radiographs showed one patient had a head-neck junction lucency. No other radiolucency, osteolysis, component migration, or femoral neck thinning was noted. Conclusion. The results in this small consecutive cohort suggest that metal-on-monobloc-XLPE HRA is successful in the short term and merits further investigation as a conservative alternative to the current accepted standard of stemmed THA. However, we would stress that survival data with longer-term follow-up are needed prior to widespread adoption. Cite this article: R. B. C. Treacy, J. P. Holland, J. Daniel, H. Ziaee, D. J. W. McMinn. Preliminary report of clinical experience with metal-on-highly-crosslinked-polyethylene hip resurfacing. Bone Joint Res 2019;8:443–450. DOI: 10.1302/2046-3758.810.BJR-2019-0060.R1

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: Metal-on-metal (MoM) articulations for THA are used successfully from CoCr-alloys. Low or high carbon hydride metals contain less or more than 0.2% carbon in the alloy. The systems show encouraging clinical results and lower rates of aseptic loosening in midterm results. Hypersensitivity reactions to high carbide MoM articulations were reported. The immune response is characterized by a perivascular T-/B-lymphocyte infiltration of the capsular tissue around the hip replacement. The present study examines if lymphocytic reactions are present in low carbide MoM THA and if distinct cytokines are released to joint fluids. Retrieval tissues from 28 patients were used. Joint fluids were aspirated at the time of surgery. Materials and Methods: Tissues were collected from 25 patients undergoing 26 aseptic revisions of MoM THA (CoCrMo, Sikomet. ®. , Plus Orthopaedics). The patients had following symptoms: Hip and femoral pain; recurrent dislocation and clicking noises. 8 patients had osteolysis, 12 patients showed a metallosis. The peripros-thetic tissues were examined by standard histology and immunohistochemistry. Joint fluids were frozen at the time of surgery. The control groups were patients with osteoarthritis of the hip (n=10), revisions from Al2O3-UHMWPE articulations (n=6), revisions of MoM with hypersensitivity reaction (n=18), and MoM without hypersensitivity reactions (n=8). The fluids were analyzed for various Interleukins, Il-1 receptor antagonist, G-CSF, GM-CSF, IFN gamma, MIP-1ß, and TNF-α. Results: 18 out of 26 cases showed diffuse and follicular lymphocyte infiltrations in the revision tissues. Perivas-cular T- and B-lymphocytes and few macrophages were also seen. In low and excessive metallosis no lymphocytes were observed. The tissue response in low carbide MoM is similar to high carbide MoM. Analysis of the cytokine profile in the joint fluids showed markers of osteoclast activation (Il-6 and −10) in all MoM articulations. TNF-α increase was increased in all loosening groups but was further increased in MoM. Il-5, IFN gamma, MIP-1ß, and GM-CSF were increased in all fluids from loosening cases but were further increased in MoM with lymphocyte activation. Discussion: Activation of lymphocytes in failed MoM THA’s is not necessarily related to high carbide MoM. Hypersensitivity also occurred in low carbide MoM THA. The cytokine profiles in the joint fluids showed distinct characteristics. Il-6 and Il-10, markers of osteo-clast activation, were elevated in all cases of bone loss and osteolysis. The increase in TNF-α may account for a regulation of the OPG/RANKL system TNF-a which can induce osteolysis. The elevated levels of Il-5, IFN gamma, MIP-1ß, and GM-CSF in MoM failures with hypersensitivity represent markers of chemotaxis and lymphocyte activation may account for index markers of hypersensitivity reaction

Background. Innovative developments for total knee arthroplasty enhanced anatomical design and fixation in order to decrease particle-induced aseptic implant loosening. As hypersensitivity reactions to metallic implant materials have been recognized to possibly cause premature implant failure, ceramic materials might constitute a proper alternative solution. The aim of this prospective short-term study was the initial comparison of a completely metal-free ceramic with a geometrically identical metallic arthroplasty over a one-year follow-up period. Methods. Eighty patients requiring primary total knee arthroplasty were enrolled within this open-label prospective comparative study. Patients were randomly divided among two groups to either undergo implantation of a completely metal-free system using a composite matrix material containing aluminum oxide (Al2O3) and zirconium oxide (ZrO2) (n=40), or an anatomically identical metallic knee system made of a cobalt-chromium alloy (Co28Cr6Mo) (n=40) produced by the same manufacturer. Clinical assessment was performed preoperatively, and during follow-up at three and twelve months using the Knee Society Score, Oxford Knee Score and EQ-5D-VAS. For radiological evaluation, standard preoperative and postoperative standardized radiographs were taken at mentioned follow-up visits. Results. Demographical data were not significantly different among our two study groups, and no patient has been lost to follow-up. The postoperative clinical scores improved significantly at three and twelve month follow-ups, but did not differ statistically among groups. The radiologically evaluated mean postoperative mechanical and anatomical axes showed proper alignment within both groups at all times. Notably, no revision surgery had to be performed, and no complications were recorded whatsoever. Conclusion. To our knowledge, this is the first study comparing a total ceramic metal-free knee system with a geometrically identical metallic TKR. Within the short-term follow-up of minimally one year, no significant differences could be demonstrated clinically or radiologically, therefore making this ceramic knee system a suitable option for patients with a known hypersensitivity to metal. Mid-term and long-term studies will be required to demonstrate the overall efficiency of this TKR to potentially expand its medical indication

Introduction. There has been much controversy around metal on metal hip replacements of late due to adverse metal reactions. There is evidence implicating lymphocyte mediated response (type IV delayed-hypersensitivity) to metal debris generated by the implants as one of the main factors responsible for the reactions. Our understanding of these adverse reactions continues to improve but we also recognize that the majority of patients with MOM implants are asymptomatic with well functioning implants. Studies have shown up to 16% allergy to metal ions on pre-operative allergy patch testing. We set out to determine the incidence of hypersensitivity to Cobalt, Chromium and Molybdenum in a arthroplasty population. Method. We assayed whole blood using a validated optimized lymphocyte transformation test, MELISA as part of a prospective randomized study on large diameter bearing surfaces. We recruited 47 subjects, 19 males, 28 females (35–75 yrs). Specific exclusions included presence of metal implants in the body and industrial exposure to metals. Results. Results were available for 46 patients. Four patients (9%) demonstrated hypersensitivity to Cobalt and none to Chromium or Molybdenum. Two were female and two male. The result was weakly positive in three patients and strongly positive in one female. Conclusion. Hypersensitivity in patients without prior exposure to Cobalt, Chromium and Molybdenum is low. The relevance of a positive hypersensitivity test and implications on the choice of bearings is a subject that requires further research. NO DISCLOSURES

Pathological assessment of periprosthetic tissues is important, not only for diagnosis, but also for understanding the pathobiology of implant failure. The host response to wear particle deposition in periprosthetic tissues is characterised by cell and tissue injury, and a reparative and inflammatory response in which there is an innate and adaptive immune response to the material components of implant wear. Physical and chemical characteristics of implant wear influence the nature of the response in periprosthetic tissues and account for the development of particular complications that lead to implant failure, such as osteolysis which leads to aseptic loosening, and soft-tissue necrosis/inflammation, which can result in pseudotumour formation. The innate response involves phagocytosis of implant-derived wear particles by macrophages; this is determined by pattern recognition receptors and results in expression of cytokines, chemokines and growth factors promoting inflammation and osteoclastogenesis; phagocytosed particles can also be cytotoxic and cause cell and tissue necrosis. The adaptive immune response to wear debris is characterised by the presence of lymphoid cells and most likely occurs as a result of a cell-mediated hypersensitivity reaction to cell and tissue components altered by interaction with the material components of particulate wear, particularly metal ions released from cobalt-chrome wear particles. Cite this article: Professor N. A. Athanasou. The pathobiology and pathology of aseptic implant failure. Bone Joint Res 2016;5:162–168. DOI: 10.1302/2046-3758.55.BJR-2016-0086