HYPERSENSITIVITY TO METALS

Abstract

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.