Granulomatous Inflammation After Hylan G-F 20 Viscosupplementation of the Knee

Background: Recently, intra-articular viscosupplementation with hyaluronate-derived products has gained popularity as a palliative modality for the treatment of osteoarthritis of the knee. Mild pain or swelling at the site of injection may occur in up to 20% of patients, although severe local inflammation, warmth, and joint effusion are rare. We present a series of six cases in which granulomatous inflammation of the synovium was observed after hyaluronate viscosupplementation of the knee. Methods: Six knees (five patients) treated with intra-articular Hylan G-F 20 viscosupplementation underwent a surgical procedure because of persistent symptoms. Routine histopathological evaluation, supplemented by alcian-blue staining and hyaluronidase digestion, was performed in each case. Results: Chronically inflamed synovium with areas of histiocytic and foreign-body giant-cell reaction was observed surrounding acellular, amorphous material. The material stained with alcian blue, a stain for hyaluronate, which disappeared after hyaluronidase digestion. Conclusions: We believe that the injected hyaluronate (Hylan G-F 20) may have been responsible for the synovitis in our patients and thus may be a pathological cause of recalcitrant symptoms after such injection. It is not known whether the responsible pathological agent was the hyaluronate derivative, a contaminant of the purification process, or a component of the carrier substance. Importantly, it appears that the findings in these patients most likely represent a previously unreported pathological response to a viscosupplementation product. This report should raise clinical awareness about this potential complication.