Current Metal Sensitivity Testing Not Adequate for Diagnosing Immune-Related Knee Replacement Failure

Metal sensitivity test results, including lymphocyte transformation testing (LTT), are insufficient to diagnose knee replacement failure due to an immune reaction, according to a study published Feb. 6 in the Journal of Bone and Joint Surgery. The authors say the findings highlight the need to establish diagnostic criteria for total knee arthroplasty (TKA) failure due to an immune reaction.

While TKA is usually successful, an estimated 20 percent of patients are dissatisfied due to chronic pain and/or stiffness, which can be a result of a local immune reaction to the metal. However. A hypersensitivity reaction can be considered in cases with low prosthetic wear and a high aseptic lymphocyte vasculitis-associated lesion (ALVAL) histopathology score, however, it remains a topic of debate for how to definitively diagnose metal sensitivity test as the cause of TKA failure.

Previous research shows that while an estimated 10 to 15 percent of the general population is reactive to skin patch testing for metal sensitivity—most commonly, nickel—skin patch testing is not useful for predicting clinical results with TKA.

It is important to understand the role of metal sensitivity in necessitating TKA revision surgery, as the average cost of the hypoallergenic revision implants is $5,669, or 37 percent more than the standard revision implants, the authors say. Additionally, LTT testing costs nearly $400 per patient.

The present study sought to characterize the relationship of a positive LTT result to histopathologic findings and clinical outcomes among patients undergoing TKA revision. All 27 patients (21 female; mean age, 64.0 years) had a negative infection work-up based upon erythrocyte sedimentation rate, C-reactive protein, and synovial fluid analysis and culture results. All patients had persistent pain and/or stiffness and underwent revision due to a suspected metal allergy to nickel, based on positive LTT results. Periprosthetic tissue samples (synovial tissue directly adjacent to the anterolateral flange of the femoral component) were collected at the time of revision surgery and were scored using the aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) scoring system by a single blinded pathologist.

The researchers found that over an average of 3.6 years from primary to revision surgery, LTT results categorized eight patients as mildly reactive, eight patients as moderately reactive, and 11 patients as highly reactive to nickel. Additionally, one patient was moderately reactive and three were mildly reactive to cobalt, while one patient was moderately reactive and four were mildly reactive to chromium.

Routine histopathologic analysis predominately found fibrosis and varying degrees of lymphocytic infiltration in 63 percent of the cases, with an average ALVAL score of 3.1 out of 10, leading the authors to conclude the histopathology results were “generally nonspecific and nondiagnostic of an immune reaction.”

Post-revision, knee function scores improved significantly. However, neither LTT stimulation index as a continuous variable nor as a categorical variable (mildly reactive, moderately reactive, highly reactive) was correlated with ALVAL score, pre-revision function, or change in function post-revision. Further, AVAL scores did not correlate significantly with either pre-revision or post-revision knee function.

“A distinction should be made between a positive LTT-diagnosed metal sensitivity and TKA failure due to an immune reaction,” write the authors led by Steven Yang, M.D., from Harbor-UCLA Medical Center in Torrance, Calif. “A positive LTT result may not indicate that an immune reaction is the cause of pain and stiffness post-TKA.”

Takeaway: Histopathologic evidence does not support the connection between positive LTT results and TKA failure due to an immune reaction. Better diagnostic criteria are needed to identify metal sensitivity as a cause of TKA failure.