IS THE LYMPHOCYTE PROLIFERATION RESPONSE INCREASED IN PATIENTS WITH PSEUDOTUMOURS FOLLOWING METAL-ON-METAL HIP RESURFACINGS?

Abstract

Recently, a series of locally destructive soft tissue pseudotumour has been reported in patients following metal-on-metal hip resurfacing arthroplasty (MoMHRA), requiring revision surgery in a high percentage of patients. Based on the histological evidence of lymphocytic infiltration, a delayed hypersensitivity reaction to nickel (Ni), chromium (Cr) or cobalt (Co) has been suggested to play a role in its aetiology. The aim of this study was to investigate the incidence and level of hypersensitivity reaction to metals in patients with pseudotumour.

Materials and Methods: 25 patients were investigated in this Ethics approved study:

1. Group 1: MoMHRA patients with pseudotumours, detected on the ultrasound and confirmed with MRI (n=6, 5 F:1 M, mean age 53 years);

2. Group 2: MoMHRA patients without pseudotumours (n=13, 7 F:6 M, mean age 55 years); and

3. Group 3: age-matched control subjects without metal implants (n=6, 4 F:2 M, mean age 54 years).

Lymphocyte transformation tests (LTT) were used to measure lymphocyte proliferation responses to metals. Peripheral blood mononuclear cells were isolated from heparinized blood samples using standard Ficoll–Hypaque® (Pharmacia). The PBMC were cultured at a cell density of 106 cells/mL. Culture was set up in the presence of either:

1. medium alone;

2. nickel chloride (Sigma; 10-4M-10-6M);

3. cobalt chloride (10-4M-10-6M); and

4. chromium chloride (10-4M-10-6M).

After 5 days of culture, cells were pulsed with [3H]-thymidine and proliferation was assessed by scintillation counting. The stimulation index (SI) was calculated by the ratio of mean counts per minute of stimulated to unstimulated cultures. A SI value of greater than 2.0 was interpreted as a positive result.

Results: A clinical history of metal allergy was reported in 2/6 in Group 1, 2/13 in Group 2, and none in Group 3. In pseudotumour group, the incidence of reactivity to Ni, Co and Cr was 60%, 17% and 0%, respectively. Within Group 2, the reactivity to Ni, Co and Cr was 69%, 8% and 15%, respectively. One control subject had reactivity to Ni. Inter-group comparisons of mean SI values (Kruskal-Wallis non-parametric analysis of variance) showed no significant differences (p> 0.05).

Discussion: The incidence of enhanced lymphocyte response to metals in patients with MoMHRA was more common than the control group. However, in comparison with non-pseudotumour patients, there was no significant difference in the incidence or the level of lymphocyte reactivity in patients with pseudotumour. We conclude that patients with MoMHRA have an enhanced lymphocyte response to metal ions, reflecting exposure and immune reactivity. However, patients with pseudotumours have a similar proliferative response to those without pseudotumours, which suggests that type IV hypersensitivity may not be the cause of the pseudotumours.