title: No conclusive evidence that histologically found granulomas and acute local reactions following hylan G-F 20 injections are related or have clinical significance.
abstract: Osteoarthritic (OA) knee pain can be successfully treated with hylan G-F 20 (Synvisc, Sanofi Biosurgery, Cambridge, MA) with few local adverse events. However, a few studies have identified hyaluronate positive (HA+) granulomas in the synovial tissue of patients treated with hylan G-F 20 raising the question of their relationship and clinical significance. To understand the potential relationship of HA+ granulomas with the occurrence of acute local reactions (ALRs), we evaluated the synovial tissue of OA patients undergoing total knee replacement that had previously been treated with hylan G-F 20 (n = 101) or had not been treated (n = 20). Granulomas were observed in nine patients, of which eight were in the hylan G-F 20 group (7.9%); HA+ granulomas were identified in six of these eight patients (5.9%). Three of the six patients with HA+ granulomas experienced an ALR within 30 days of administering an injection. Overall, we found no consistent relationship between histologically found HA+ granulomas and the occurrence of an ALR following hylan G-F 20 treatment. These microscopic granulomas were not associated with any symptoms and likely have little clinical significance. The low occurrence of granulomas and/or ALRs should not preclude use of hylan G-F 20 for the treatment of knee pain associated with OA.
authors.affiliation: Department of Orthopedics, Orthopedic Specialists of Louisiana, Shreveport, Louisiana.
authors.forename: David D
authors.initials: DD
authors.lastname: Waddell
authors.affiliation: Department of Orthopedics, Newport Orthopedic Institute, Newport Beach, California.
authors.forename: Alan
authors.initials: A
authors.lastname: Beyer
authors.affiliation: Department of Orthopedics, Howard University Hospital, Washington, District of Columbia.
authors.forename: Terry L
authors.initials: TL
authors.lastname: Thompson
authors.affiliation: Department of Clinical Research, Genzyme Biosurgery, Cambridge, Massachusetts.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Morawiak
authors.affiliation: Department of Biostatistics, Genzyme Biosurgery, Cambridge, Massachusetts.
authors.forename: Clare
authors.initials: C
authors.lastname: Elkins
authors.affiliation: Department of Anatomic Pathology, University of Miami Hospital, Miami, Florida.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rosenberg
authors.affiliation: Department of Orthopedics, Cedars-Sinai Orthopedics, San Francisco, California.
authors.forename: Andrew
authors.initials: A
authors.lastname: Spitzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D015745:Granuloma, Foreign-Body / Q000209:etiology* / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D007267:Injections; D007719:Knee Joint / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D001672:Biocompatible Materials; C049816:hylan; D006820:Hyaluronic Acid