Assessment of immunologic mechanisms for flare reactions to Synvisc

Intraarticular injection of Synvisc for treatment of knee pain sometimes results in an acute local reaction (flare). We tested the hypothesis that the flare was a Type-1 hypersensitivity reaction as manifested by the presence of Synvisc antibodies in the synovial fluid and serum and by an increase in the concentration of the mast-cell enzyme tryptase in the synovial fluid. Our second objective was to determine whether the ratio of CD4+ to CD8+ lymphocytes in the synovial fluid was increased, as would be expected in a Type-4 hypersensitivity reaction. The study population was a prospective, consecutive series of 16 patients who had a flare, and 20 control patients. We found no differences in product-specific antibodies in the synovial fluid or serum between patients with flares and patients without flares. The mean tryptase level in the synovial fluid of patients with flares, 3.8 +/- 0.8 microg/L, was not different from the corresponding level in the control patients. The CD4+/CD8+ ratio in the synovial fluid was more than eight times greater in patients with flares. Flares that sometimes occur after treatment with Synvisc are probably not Type-1 (antibody-mediated) hypersensitivity reactions, but may be Type-4 (cell-mediated) hypersensitivity reactions.