Diagnosis of Metal Hypersensitivity in Orthopedics

The pathology of early aseptic implant failure has been linked in basic science, case, and group studies to metal implant debris-induced delayed-type hypersensitivity (DTH) responses (or metal allergy). However, a precondition of metal DTH does not always result in implant failure. The methods of diagnosing metal DTH responses measure cell-mediated adaptive immunity, where conditioned lymphocytes respond to specific stimuli. Metal-sensitivity testing is a direct test of an individual's immune response to metal challenge, which has been in use for over the past half century to measure delayed-type responses to drugs (such as antibiotics) where the results indicate levels of immune reactivity. Currently approved methods for human diagnostic testing for metal DTH include both skin testing (patch testing) and in vitro blood testing using lymphocyte transformation testing (LTT). LTT testing may be better suited for diagnosing implant-related sensitivity, given the ability of dermal exposure to metals to induce DTH responses. Metal sensitivity among the general population has been well established with a rate of 10%-15%, where hypersensitivity to nickel is the most common. However, it remains unknown about the exact percentage of these presensitized people that will go on to develop pathogenic metal-sensitivity responses to their implant. Recent studies show that when exposure to metal implant debris is minimized, the chances of metal DTH reactivity are also minimized. Further, past basic science studies, case studies, and cohort studies indicate the clinical utility of metal-sensitivity testing in specific patient populations. Continuing clinical outcome studies are needed to relate positive patch and metal-LTT test results with other clinical determinants to more definitively predict and prevent pathologic reactivity to implants.