title: Acute inflammation with induction of anaphylatoxin C5a and terminal complement complex C5b-9 associated with multiple intra-articular injections of hylan G-F 20: a case report.
abstract: OBJECTIVE
  The purpose of this case report was to investigate local immune mechanisms present during an acute inflammatory flare initiated by viscosupplementation with hylan G-F 20 in a patient with osteoarthritis (OA) and past meniscectomy.
  
  
  METHODS
  A patient with a history of bilateral OA and partial left knee meniscectomy, who had received three injections of hylan G-F 20, was diagnosed with an acute flare reaction in the left knee. Her chart was evaluated for clinical, radiological, and laboratory findings and for clinical follow-up. Histopathological synovial examination and real-time polymerase chain reaction (RT-PCR) for genes with major roles in local inflammation and enzyme-linked immunosorbent assays (ELISAs) for markers of complement activation and cytokines were performed. To study the impact of the inflammatory and immune features we compared the case patient with groups of three representative OA and three rheumatoid arthritis (RA) patients.
  
  
  RESULTS
  The patient exhibited evidence of highly increased acute phase reactant C-reactive protein (CRP) in the blood. The pathological examination of the synovial membrane identified abundant fibrinous exudate with numerous particles of hyaluronan surrounded by a dense infiltrate of neutrophils and eosinophils. The synovium had moderate hypertrophy and sclerosis as well as an inflammatory infiltrate predominantly composed of T lymphocytes and macrophages with scattered perivascular eosinophils and neutrophils. Immunoperoxidase staining identified numerous deposits of C5b-9 in the fibrinous exudates and the synovial membrane of the patient. Similar findings were observed in the RA patients, whereas deposits were rare in OA synovial samples. In addition, both anaphylatoxin C5a and the terminal complement complex C5b-9 were present at high levels, comparable to those in RA patients. The levels of mRNA for interleukin-1 beta (IL-1β), IL-6, and the neutrophil marker myeloperoxidase (MPO) were markedly increased compared to those in the RA and OA patients.
  
  
  CONCLUSIONS
  This present study is indicative of a pseudo-septic acute inflammatory reaction in response to local accumulation of hylan G-F 20 with the activation of complement and local invasion of pro-inflammatory cells.
authors.affiliation: Tissue Engineering, Repair and Regeneration Program, Hospital for Special Surgery, New York, NY 10021, USA. dragomirc@hss.edu
authors.forename: C L
authors.initials: CL
authors.lastname: Dragomir
authors.forename: J L
authors.initials: JL
authors.lastname: Scott
authors.forename: G
authors.initials: G
authors.lastname: Perino
authors.forename: R
authors.initials: R
authors.lastname: Adler
authors.forename: S
authors.initials: S
authors.lastname: Fealy
authors.forename: M B
authors.initials: MB
authors.lastname: Goldring
mesh_terms: D000208:Acute Disease; D001168:Arthritis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D001672:Biocompatible Materials; D002097:C-Reactive Protein / Q000378:metabolism; D015936:Complement C5a / Q000096:biosynthesis*; D015938:Complement Membrane Attack Complex / Q000096:biosynthesis*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy; D055676:Viscosupplementation / Q000009:adverse effects / Q000379:methods; D055675:Viscosupplements / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D001672:Biocompatible Materials; D015938:Complement Membrane Attack Complex; D055675:Viscosupplements; C049816:hylan; D015936:Complement C5a; D006820:Hyaluronic Acid; D002097:C-Reactive Protein