Why is the question of metal allergy relevant today?

As the incidence of osteoarthritic joint disease continues to increase, an ever-growing percentage of the affected population will need to undergo total joint replacement (TJR)1-4.

These upward trends are also expected to be more important for knees compared to hips 2,5. Longer life spans, rising obesity rates, and increasing physical demands among older people are all examples of health factors significantly contributing to joint wear. Analysis of recent projection figures suggested that by 2030, the number of knee replacements will have increased by 117% for first time replacement and by 332% for redo-replacement6. Given these projections, there is definitely a need for clearer understanding of the issues surrounding metal allergy.


What do we know about allergy to metals used in orthopaedic implants?

A knee replacement implant is made of components which aim to recreate the person’s own joint. The material used are: metal alloys, polyethylene which is a high-grade plastic and bone cement. It is the different metal materials found in the alloys which have been linked to the issue of allergy. Allergy comprises a complex variety of hypersensitivity conditions resulting from a variety of immune reactions. Metal in itself and in its natural form does not produce a true allergic reaction7,8. In contrast people who have been sensitised to a product can develop what is known as Type IV hypersensitivity reaction which is mediated by the person’s immune system9. In other terms the immune system can create a memory response to a material it had previously reacted with. The reaction to metals used in orthopaedic implant has been reported with varying frequency between 10% and 50%10-12. The bulk of these studies used skin patch testing to diagnose allergy, however a skin reaction is in fact different to how the body reacts to deeply implanted devices13,14. We also know that the risk of testing positive for an allergic reaction increases when there is a problem with the knee replacement but the other way around has not been proven15.


Is there definitive evidence-based guidance on metal allergy and knee replacement?

Despite a relatively large number of research articles dedicated to the impact of metal allergy or hypersensitivity reaction on joint replacements several questions remain unanswered and there are no definitive guidelines. A recent review article concluded that there is no evidence to support the existence of allergy with total knee replacement and that surgeons should continue to use implants of standard materials with proven track record instead of hypoallergenic implants16. This situation is confirmed in a number of other studies including surveys of experts who recommend using standard implants when faced with a patient who tests positive on skin patch test17-20,21.


What will my surgeon do if I am suspected of having metal allergy?

The most common material in knee replacements implant metal which is linked to hypersensitivity is Nickel. Some patients mostly through prior skin reaction to Nickel found in Jewelry present as potentially having an allergy. Most companies who make knee replacements will offer the option of having a coated component which means that the Nickel in the implant is not in contact with the patient’s own tissue. The issue here is that these implants cost significantly more, there is simply no telling how long this coating will last in real life and these implants do not have the same track record as standard implants. This has led surgeons to still go ahead with standard implants even when someone presents with a suspected Nickel allergy. This approach is considered safe by many and proven in previous studies21-22. It is for the same reasons that most surgeons would not advocate routine screening for allergy with skin patch testing. 


Will I need additional or special tests if metal hypersensitivity is suspected prior to having a knee replacement?

As mentioned above, to date the association between metal allergy and joint replacement has been mainly investigated using skin patch testing23,24. There is limited accuracy of skin patch testing as explained due to the type of immune reaction, this is also limited by the short exposure time to the material tested of 48 to 96 hours25,26.  In addition, with well-functioning knee replacement implants, having a positive skin patch test for nickel has not been linked with an increased reaction  the joint implant27,28. Because of the limitations of this test another approach has been adopted where the person suspected of having a metal allergy has a blood test and the immune reaction of the person is tested against any potential allergic material. This is known as “lymphocyte transformation test (LTT)”. It is not yet widely available and subject to ongoing studies in our centres but it likely will help answer some of the questions about immune reaction to possible materials used in orthopaedic implants. 


What did you learn so far about metal hypersensitivity?

Our group has been studying the question of metal allergy and knee replacements for several years in order to find out more and follow up patients with implants and matched allergic profile. One of our initial studies was to identify how frequent these so-called reactions were. We identified a large number of patients about to have knee replacement and were voluntarily offered blood tests to investigate potential hypersensitivity reactions for knee replacement materials. Our studies also aimed to identify preoperative factors, including prior metallic implant exposure, which could predict susceptibility to hypersensitivity reactions among these patients.   We are in the process of preparing the first report for peer publication of our results. One of the key elements here was the ability to investigate potential prior metallic exposure factors and link those to the risk of testing positive for one or more material used in knee replacement. 


What else do we expect to learn in the future about metal hypersensitivity and knee replacement?

Our research efforts are aimed at finding out answers to some of the key questions in this subject. Part of the ongoing research will be to investigate how a person not known to have an allergic reaction but tests positive is likely to progress with a standard knee replacement. In other terms whether finding out a positive allergy test is likely to affect the results of a standard knee replacement. This also leads us to other questions we are actively trying to answer, whereby investigating the possible link between having a problematic knee replacement and developing hypersensitivity to the material used in knee replacement. Most orthopaedic surgeons will also be interested in finding this out. Since a small proportion of 10 to 20% of patients with knee replacement can potentially continue to have problems despite a well-functioning knee. Testing for metal hypersensitivity among these patients will be a useful additional tool in ruling out problems with knee replacement. At the same time, we are continuing to test patients who have had a redo knee replacement after developing problems with their original knee replacement and testing positive on the allergy blood tests. This will hopefully give us answers on whether removing a problematic knee replacement solves the issue of allergic reaction. All in all, we are very enthusiastic about the work being carried out, and look forward to the completion of the studies and sharing results with the orthopaedic community and knee replacement patients.


Authors bio:
Tarek Boutefnouchet
MBChB MRCS MSc FRCS (Tr&Orth). Is a consultant orthopaedic surgeon with a specialist interest in knee surgery including replacement and joint preservation surgery. He is currently completing a subspecialisation fellowship in Montreal Canada with Prof Julio C Fernandes and Dr Pierre Ranger.
Julio C Fernandes
MD, M Sc, Ph D, MBA, FRCSC.  is an orthopaedic Surgeon, Full Tenure Track Professor, Director of Orthopaedic Research Laboratory Head, Endowed Research Chair in Orthopaedics. Hopital du Sacré Coeur de Montreal, University of Montréal. One of his  areas of research is metal hypersensitivity to orthopaedic implants.



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