Diagnosis of Metal Hypersensitivity in Total Knee Arthroplasty: A Case Report

Delayed type hypersensitivity (DTH) reactions are considered infrequent complications in arthroplasty, but have been recognized to be associated with devastating morbidity and substantial decrease in quality of life of affected patients. Chronic inflammation of artificial joints and associated loss of peri-implant bone often require revision surgery. Methods for the diagnosis of implant-related DTH are available but infrequently considered to the full extent. Sequential diagnostics based on exclusion of septic complications, local and systemic metal level determination, lymphocyte transformation testing (LTT), and local T cell subset analysis are required for an unequivocal DTH diagnosis. Here, we report on a patient with a history of chronic rheumatoid arthritis and an unfavorable outcome of unilateral knee arthroplasty. This case illustrates pitfalls and difficulties in the course of recurrent inflammation following joint replacement. In the early course, suspicion of low-grade bacterial infection led to three two-stage revisions. Afterwards, the joint was proven to be sterile. However, metal level quantification revealed release of especially cobalt and chromium from the joint, LTT indicated persisting cobalt and nickel sensitization and subset analysis of T cells from the synovium suggested DTH as a root cause for the inflammatory symptoms. This report aims to recommend the depicted diagnostic algorithm as an adequate tool for future DTH detection. Yet, systemic to local subset ratios for effector memory and regulatory T cells should be derived from sufficient patient numbers to establish it as a diagnostic marker. Moreover, future prospects regarding implant-related DTH diagnostics are discussed. Therapeutic options for the portrayed patient are proposed, considering pharmaceutical, cell-therapeutic and surgical aspects. Patients who experience peri-implant inflammation but do not have obvious mechanical or infectious problems remain a diagnostic challenge and are at high risk of being treated inadequately. Since potentially sensitizing materials are regularly used in arthroplasty, it is essential to detect cases of acute DTH-derived inflammation of an artificial joint at early postoperative stages. This would reduce the severity of inflammation-related long-term consequences for affected patients and may avoid unnecessary revision surgery

Total Hip Joint Replacement Biotelemetry System

The development of a biotelemetry system that is hermetically sealed within a total hip replacement implant is reported. The telemetry system transmits six channels of stress data to reconstruct the major forces acting on the neck of the prosthesis and uses an induction power coupling technique to eliminate the need for internal batteries. The activities associated with the telemetry microminiaturization, data recovery console, hardware fabrications, power induction systems, electrical and mechanical testing and hermetic sealing test results are discussed

Blood titanium levels in patients with large and sliding titanium implants

Background: Titanium, which is known to be a highly biologically inert element, is one of the most commonly used metals in orthopaedic implants. While cobalt and chromium blood metal ion testing is routinely used in the clinical monitoring of patients with metal-on-metal hip implants, much less is known about the levels of titanium in patients with other implant types. The aim of this study was to better understand the normal ranges of blood titanium levels in patients implanted with large and sliding titanium constructs by comparison with reference levels from conventional titanium hips. Methods: This study examined data collected from 136 patients. Over a period of 24 months, whole blood samples were collected from 41 patients implanted with large titanium implants: long (range 15 to 30 cm) spine rods with a sliding mechanism (“spine rods”, n = 18), long bone tumour implants (“tumour implants”, n = 13) and 3D-printed customised massive acetabular defect implants (“massive acetabular implants”, n = 10). This data was compared with standard, uncemented primary titanium hip implants (“standard hips”, 15 cm long) (n = 95). Clinical, imaging and blood titanium levels data were collected for all patients and compared statistically between the different groups. Results: The median (range) of blood titanium levels of the standard hip, spine rods, femoral tumour implants and massive acetabular implants were 1.2 ppb (0.6–4.9), 9.7 ppb (4.0–25.4), 2.6 ppb (0.4–104.4) and 5.7 ppb (1.6–31.5) respectively. Spine rods and massive acetabular implants had significantly greater blood titanium levels compared to the standard hips group (p < 0.001). Conclusion: This study showed that titanium orthopaedic implants that are large and/or have a sliding mechanism have higher blood titanium levels compared to well-functioning, conventionally sized titanium hips. Reassuringly, the increased levels did not appear to induce adverse metal reactions. This study provides useful baseline data for future studies aimed at assessing blood titanium levels as a biomarker for implant function

Toxicity of metal debris from hip implants

Hip implants are commonly made of cobalt-chromium and titanium alloys. Once inside the body, implants wear and corrode, releasing metal particles and ions into the local tissue and blood. Metal debris can cause local adverse effects, such as bone loss and tissue necrosis, ultimately leading to implant failure. More recently, systemic cobalt toxicity has gained publicity as reports of neurotoxicity, cardiomyopathy and hypothyroidism increased among recipients of metal hip implants. Widespread dissemination of metal debris, and its accumulation in organ tissue, is of a particular concern. The aim of this thesis is to better understand how metallic implant debris affects the body, and how blood metal levels relate to any toxicity symptoms. Prevalence of neurotoxicity and cognitive decline among patients with a history of highly elevated blood cobalt was assessed, using a set of validated questionnaires. Although a number of statistically significant differences were detected between the high cobalt group and controls, clinically relevant neuro-cognitive adverse effects were not observed. Distribution and chemical speciation of cobalt, chromium and titanium deposits were investigated in cadaveric samples of organs from hip replacement patients. Though synchrotron analysis identified the presence of highly oxidised chromium, further work is needed to assess if the results can be extrapolated to the in vivo situation. Genetic factors that might predispose some patients to the adverse effects of cobalt were explored in vitro, using CRISPR/Cas9 gene editing technology. Results of the feasibility study identified several candidate genes for further investigation. Blood titanium was measured in a large group of patients with titanium-based implants, using high resolution ICP-MS. This allowed a reliable laboratory reference range to be defined for use in future patient monitoring. Results from this thesis inform on potential consequences of implant degradation, and demonstrate the clinical utility of blood metal measurements to monitor implant performance

Understanding why metal-on-metal hip arthroplasties fail: a comparison between patients with well-functioning and revised birmingham hip resurfacing arthroplasties. AAOS exhibit selection.

A large proportion of metal-on-metal hip arthroplasty failures are due to unexplained pain. The mechanism of failure has been thought to be associated with factors that increase material loss, including specific design features and surgical positioning of components. However, recent evidence suggests that there is not a simple dose-response relationship. An analysis of failed metal-on-metal hip arthroplasties involving a single design was performed in an attempt to help resolve this issue. Our aim was to identify the clinical and component variables associated with failure of metal-on-metal hip arthroplasties, particularly in patients undergoing revision arthroplasty because of unexplained hip pain, and to clarify the role of material loss

Release of Chromium from Orthopaedic Arthroplasties

Many orthopaedic implants are composed of alloys containing chromium. Of particular relevance is the increasing number of Cobalt Chromium bearing arthroplasies being inserted into young patients with osteoarthritis. Such implants will release chromium ions. These patients will be exposed to the released chromium for over 50 years in some cases. The subsequent chromium ion metabolism and redistribution in fluid and tissue compartments is complex. In addition, the potential biological effects of chromium are also controversial, including DNA and chromosomal damage, reduction in CD8 lymphocyte levels and possible hypersensitivity reactions (ALVAL). The establishment of these issues and the measurement of chromium in biological fluids is the subject of this review

Self-Reported Neurotoxic Symptoms in Hip Arthroplasty Patients With Highly Elevated Blood Cobalt: A Case-Control Study

OBJECTIVES: This study aimed to investigate the prevalence of self-reported neurotoxicity and cognitive defects in hip replacement patients with markedly raised blood cobalt. METHODS: Case group comprised 53 patients with metal-on-metal (MoM) implants and a history of blood Co ≥20 μg/L for a median of 3 years (interquartile range, 2-5 years). The control group comprised 53 patients with ceramic-on-ceramic prostheses and blood Co <1 μg/L. Median age was 67 years (interquartile range, 60-74 years). The participants completed the Neurotoxic Symptom Checklist-60, Diabetic Neuropathy Score, Douleur Neuropathique-10, and Systemic Symptom Checklist, and underwent the Mini-Mental State Examination. RESULTS: The MoM and ceramic-on-ceramic groups were compared, the results were as follows: Neurotoxic Symptom Checklist-60 (median): cognitive defects (2.0 versus 1.9; P = 0.002), chest complaints (1.3 versus 1.3; P = 0.042), balance disturbances (1.3 versus 1.0; P < 0.001), sleep disturbances (2.7 versus 2.0; P = 0.004), mood disorders (2.0 versus 1.5; P = 0.001), sensorimotor disorders (1.6 versus 1.2; P < 0.001), physical complaints (2.0 versus 1.4; P = 0.009), fatigue (2.0 versus 1.6; P = 0.001), and total score (108 versus 90; P < 0.001); abnormal Diabetic Neuropathy Score/Douleur Neuropathique-10 (%): 60.3/13.2 versus 24.5/1.9 (P < 0.001/P = 0.028). Systemic Symptom Checklist (in percent): feeling cold (37.7 versus 17; P = 0.01), weight gain (18.9 versus 1.9; P = 0.008), metallic taste (26.4 versus 3.8; P = 0.002), worsening eyesight (37.7 versus 15.1; P = 0.008) and hearing (24.5 versus 7.5; 0.032), ankle swelling (32.1 versus 7.5; P = 0.002), shortness of breath on exertion (9.4 versus 5.7; P = 0.015), and generalized rash (28.3 versus 7.5; P = 0.01); and Mini-Mental State Examination (median): 29 versus 30 (P = 0.017). Patients in the MoM group were aware of their high cobalt levels and displayed a higher tendency to overreport symptoms (P < 0.001), which could have contributed to the higher scores. CONCLUSIONS: Frequency of reporting a number of symptoms was markedly higher in MoM patients, but clinically significant neurotoxicity was not observed (possibly due to the short exposure to elevated cobalt). Patients with repeated blood Co ≥20 μg/L measurements should be questioned about possible systemic health complaints at follow-up

Inflammatory tissue reactions around aseptically loose cemented hip prostheses: A retrieval study of the Spectron EF stem with Reflection All-Poly acetabular cup

The cemented Spectron EF stem in combination with the cemented non-crosslinked Reflection All-Poly cup showed a high rate of mid-term aseptic loosening. However, the failure mechanisms are not fully known. We assessed the inflammatory tissue reactions and wear particles in periprosthetic tissues, implant wear and blood metal ion levels in 28 patients with failed implants. Histological analysis showed a macrophage pre-dominant pattern with randomly distributed lymphocytes, with various amounts of neutrophils and giant cells. The number of different cell types in the tissue samples from patients in the cup group and in the stem group was similar. Wear particles, mainly ZrO2, CoCrMo, and polyethylene particles of different sizes and shapes, were associated with macrophages/giant cells, and total particle load/mm2 was higher in cases of stem loosening. The Spectron EF stems were heavily worn, abraded, and polished. Stem abrasion correlated with metal ion concentrations in blood. The median polyethylene wear rate of the Reflection cups was 0.23 mm/year. The high proximal roughness of the Spectron EF stem resulted in excessive cement wear during loosening. The resulting inflammatory tissue responses to the degradation products both from the cup and the stem led to massive osteolysis and subsequent implant loosening.publishedVersio