Discussion
allergic, inflammation, osteoarthritis, allergy, infection, hypersensitivities, allergies, type-1 allergic reactions, lower musculoskeletal comorbidities, hypersensitivity
METAL ALLERGY, DELAYED TYPE HYPERSENSITIVITY, INFLAMMATION, OSTEOARTHRITIS, ALLERGY, METAL ALLERGY, INFECTION, HYPERSENSITIVITIES, ALLERGIES, HYPERSENSITIVITY, INFLAMMATORY RESPONSE
This study demonstrated no relevant differences in inflammatory response, cytokine expression patterns and PROMs between coated and standard TKA in patients without allergies during mid-term FU.Regarding the inflammatory response there were no differences between the standard and coated treatment group. In comparison to the allergy cohort, we found differences especially for the expression of IL-6 and IFN γ.IL-5, a messenger for type-1 allergic reactions was detectable prior to surgery as well as at the 1year FU. This was unexpected since IL-5 is involved in acute reactions of the immune system modulating the change of antibody class in lymphocytes to IgE causing mast cell degranulation. This however is not a mechanism for metal hypersensitivity [IL-6 is a cytokine involved in the regulation of acute-phase proteins and immune response towards acute inflammation [IL-8 is a proinflammatory cytokine which induces chemotaxis in neutrophils and other granulocytes causing migration to the site of immune reaction [IFN γ has multiple functions. Among these, it works as a proinflammatory cytokine modulating the immune system during infection [IL-10 has a regulatory function. It acts anti-inflammatory and inhibits the expression of other cytokines. Within our study we found measurable levels of IL-10 prior to and during the 1year FU in every patient. At the 3year FU only few patients presented with measurable blood levels. A possible function might be to counteract the inflammatory processes mediated by IL-8 and IFN γ as discussed above. The elevated levels of IL-8 and IL-10 are in contrast to previously published results [The allergy group demonstrated several interesting findings. All patients were allergic to nickel and four concomitantly to cobalt. Metal allergy as delayed type hypersensitivity (DTH) is characterized by predominant Th1-type inflammation with IFN γ being a marker-signaling factor. Correspondingly, detectable IFN γ in blood characterizes the “DTH favouring status” – being visible already in the preoperative blood samples. What affects IFN γ in the serum to finally drop under the detection limit at the 3year FU is difficult to decipher. A transition to counteracting cytokine patterns – at least to Th2 or immune dampening - is not evident from our data, since levels of IL-5 are unchanged and IL-10 is even decreasing. Are (internal) sensitizing allergen and particle contacts decreased thus reducing the generation of new Th1 effector cells? This constellation may be given using surface coated implants and by the disappearance of initial periimplant saw blade/cutting guide derived particles [The elevated serum levels for IL-5, -6, -8 and -10 prior to surgery might resemble the ongoing inflammatory reactions of the underlying osteoarthritis [While hypersensitivities against implant materials have been known for a long time there is an ongoing debate about its importance in TKA. Especially, whether or not hypoallergenic implants are necessary is being discussed controversially [Regardless of these debates, there are patients with a diagnosed metal allergy asking for hypoallergenic implants. Guidelines and legal regulations differ between countries, making either the use of hypoallergenic implants or extensive informed consent a requirement to use standard implants. It is known that these patients are at higher risk for early revision and less satisfactory results. Therefore, refusing them a hypoallergenic implant is often difficult [Even though coated implants have proven a better resistance against wear in vitro and the AS coating used in this study has demonstrated excellent long-term results, data of arthroplasty registries have suggested higher overall revision rates for hypoallergenic implants [To our knowledge, the present study is the first randomized controlled trial reporting longitudinal cytokine patterns after coated and standard TKA. It has, however, some limitations. This is mainly the exclusion of patients with a history of metal allergy and therefore the target population for coated implants. As explained, this was inevitable according to local guidelines. Yet, the allergy group demonstrated similar results, although this group included only a limited number of patients. Excluding patients with any kind of metal implants was necessary to avoid bias through these implants. This may have resulted in a study population with lower musculoskeletal comorbidities, potentially influencing the PROMs. Furthermore, a 3year FU is relatively short for patients following TKA. There might be changes between the groups at a later stage. Another limitation concerns the intake of anti-inflammatory drugs which may influence the serum cytokine levels. The duration and total amount of NSAR intake, however, was not evaluated during the FU. Also, it needs to be mentioned that the expression patterns of cytokines and other inflammatory mediators are fluctuating and not fully understood.