Diagnostic classification of spondylarthropathy and rheumatoid arthritis by synovial histopathology: a prospective study in 154 consecutive patients

Arthritis Rheum. 2004 Sep;50(9):2931-41. doi: 10.1002/art.20476.


Objective: To explore prospectively the value of synovial histopathology in comparison with the value of classic parameters for diagnostic classification of spondylarthropathy (SpA) and rheumatoid arthritis (RA) in patients with an atypical disease presentation.

Methods: Synovial biopsy samples were obtained from 154 consecutive patients presenting for diagnostic evaluation; 67 patients fulfilled the classification criteria for RA, SpA, or other well-defined disease at the time of arthroscopy (cohort 1), and an additional 53 patients were classified after a full diagnostic reevaluation at 6 months (cohort 2). Synovial parameters with diagnostic value were identified in cohort 1 and were compared prospectively with classic diagnostic parameters in cohort 2.

Results: Staining with anticitrulline, staining with monoclonal antibody 12A (recognizing HLA-DR shared epitope-human cartilage glycoprotein 39(263-275) complexes), and crystal deposition had positive predictive values (PPVs) for diagnosis of >90% in patients with an atypical disease presentation (cohort 2). Using these 3 parameters, a diagnosis was predicted by synovial histopathology in 39.6% of cohort 2 patients and turned out to be correct in 90.5% of these patients at 6 months of followup. Using a multiparameter model rather than single histopathologic parameters, even better results were obtained, with a diagnostic prediction in 79.2% of samples and a PPV of 81.0%. In comparison, a similar multiparameter model using classic diagnostic criteria rather than synovial histopathology performed poorly in cohort 2; the sensitivity was 56.6% and the PPV was 73.3%, with an inferior capacity to predict SpA. Especially for the presence of crystals and anticitrulline staining, the analysis of synovial tissue had a clear added value to the analysis of synovial fluid or serum in patients with an atypical presentation.

Conclusion: This proof-of-concept study indicates that synovial histopathology can contribute to the multiparametric diagnostic classification of inflammatory arthritis in patients with an atypical presentation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / immunology
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Biomarkers / blood
  • Biopsy
  • Blood Sedimentation
  • C-Reactive Protein / analysis
  • C-Reactive Protein / immunology
  • Cohort Studies
  • HLA Antigens / blood
  • HLA Antigens / immunology
  • Humans
  • Middle Aged
  • Models, Biological
  • Pilot Projects
  • Predictive Value of Tests
  • Prospective Studies
  • Rheumatoid Factor / blood
  • Rheumatoid Factor / immunology
  • Spondylarthropathies / blood
  • Spondylarthropathies / diagnosis*
  • Spondylarthropathies / immunology
  • Spondylarthropathies / pathology
  • Synovial Membrane / pathology*


  • Antibodies, Monoclonal
  • Biomarkers
  • HLA Antigens
  • C-Reactive Protein
  • Rheumatoid Factor