Skip to main content
PMC home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2004 Nov 26;64(6):899–905. doi: 10.1136/ard.2004.025585

Rheumatoid and psoriatic knee synovitis: clinical, grey scale, and power Doppler ultrasound assessment of the response to etanercept

U Fiocco 1, F Ferro 1, M Vezzu 1, L Cozzi 1, C Checchetto 1, P Sfriso 1, C Botsios 1, L Ciprian 1, G Armellin 1, R Nardacchione 1, A Piccoli 1, S Todesco 1, L Rubaltelli 1
PMCID: PMC1755540  PMID: 15567814

Abstract

Objective: To determine the effect of tumour necrosis factor α (TNFα) blockade with etanercept in refractory knee joint synovitis (KJS) in rheumatoid and psoriatic arthritis, by local and systemic disease activity assessment and combined grey scale and power Doppler ultrasonographic monitoring.

Methods: 27 knees affected by rheumatoid KJS (n = 12) and psoriatic KJS (n = 8) were assessed before receiving treatment and at 3 and 12 months' follow up. Time dependent clinical changes in disease activity were monitored by C reactive protein, erythrocyte sedimentation rate (ESR), global health status (GHS), and Ritchie (RAI) and knee joint articular (KJAI) indices; synovial changes were monitored by ultrasonographic and power Doppler indices for grey scale synovial thickening and for distinct intrasynovial vessel power Doppler flow configurations (fluid/synovium interface (F/SI-PD) and pannus/cartilage interface (P/CI-PD)). Interobserver and intraobserver variability of grey scale and power Doppler ultrasonographic was evaluated. Response to treatment was assessed by analysis of variance for repeated measures on clinical and ultrasonographic variables.

Results: Rapid (3 months) reduction in F/SI-PD flow (p<0.001), parallel to reductions of C reactive protein (p<0.05), ESR (p<0.001), KJAI (p<0.002), RAI, and GHS (p<0.001), was sustained at 12 months when it was accompanied by reduction in both synovial thickening and P/CI-PD flow (p<0.001). No differences (ANOVA) were noted at baseline or at 12 months in clinical and ultrasonographic variables between either the rheumatoid or the psoriatic KJS groups.

Conclusion: Grey scale and power Doppler ultrasonography are reliable measures of long term change in rheumatoid and psoriatic KJS disease activity in response to anti-TNFα treatment with etanercept.

Full Text

The Full Text of this article is available as a PDF (112.0 KB).

Figure 1.

Figure 1

Open in a new tab

 Mean changes in disease activity and ultrasonographic variables over time in rheumatoid and psoriatic refractory knee joint synovitis (KJS). (A) systemic disease activity measurements. (B) local disease activity and ultrasonographic measurements. CRP, C reactive protein; ESR, erythrocyte sedimentation rate; F/SI-PD, fluid/synovium interface power Doppler flow configuration; GHS, global health status; KJAI, knee joint articular index; P/CI-PD, pannus/cartilage interface power Doppler flow configuration; RAI, Ritchie articular index; ST–US, synovial thickness measured by ultrasound.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antoni Christian, Dechant Claudia, Hanns-Martin Lorenz P. D., Wendler Joerg, Ogilvie Alexandra, Lueftl Mathias, Kalden-Nemeth Dolores, Kalden Joachim R., Manger Bernhard. Open-label study of infliximab treatment for psoriatic arthritis: clinical and magnetic resonance imaging measurements of reduction of inflammation. Arthritis Rheum. 2002 Oct 15;47(5):506–512. doi: 10.1002/art.10671. [DOI] [PubMed] [Google Scholar]
  2. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  3. Bathon J. M., Martin R. W., Fleischmann R. M., Tesser J. R., Schiff M. H., Keystone E. C., Genovese M. C., Wasko M. C., Moreland L. W., Weaver A. L. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000 Nov 30;343(22):1586–1593. doi: 10.1056/NEJM200011303432201. [DOI] [PubMed] [Google Scholar]
  4. Carotti M., Salaffi F., Manganelli P., Salera D., Simonetti B., Grassi W. Power Doppler sonography in the assessment of synovial tissue of the knee joint in rheumatoid arthritis: a preliminary experience. Ann Rheum Dis. 2002 Oct;61(10):877–882. doi: 10.1136/ard.61.10.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Conaghan Philip G., O'Connor Philip, McGonagle Dennis, Astin Paul, Wakefield Richard J., Gibbon Wayne W., Quinn Mark, Karim Zunaid, Green Michael J., Proudman Susanna. Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis. Arthritis Rheum. 2003 Jan;48(1):64–71. doi: 10.1002/art.10747. [DOI] [PubMed] [Google Scholar]
  6. Emery Paul. Evidence supporting the benefit of early intervention in rheumatoid arthritis. J Rheumatol Suppl. 2002 Nov;66:3–8. [PubMed] [Google Scholar]
  7. Filippucci E., Farina A., Carotti M., Salaffi F., Grassi W. Grey scale and power Doppler sonographic changes induced by intra-articular steroid injection treatment. Ann Rheum Dis. 2004 Jun;63(6):740–743. doi: 10.1136/ard.2003.007971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fiocco U., Cozzi L., Chieco-Bianchi F., Rigon C., Vezzù M., Favero E., Ferro F., Sfriso P., Rubaltelli L., Nardacchione R. Vascular changes in psoriatic knee joint synovitis. J Rheumatol. 2001 Nov;28(11):2480–2486. [PubMed] [Google Scholar]
  9. Fiocco U., Cozzi L., Rigon C., Chieco-Bianchi F., Baldovin M., Cassisi G. A., Gallo C., Doria A., Favaro M. A., Piccoli A. Arthroscopic synovectomy in rheumatoid and psoriatic knee joint synovitis: long-term outcome. Br J Rheumatol. 1996 May;35(5):463–470. doi: 10.1093/rheumatology/35.5.463. [DOI] [PubMed] [Google Scholar]
  10. Fiocco U., Cozzi L., Rubaltelli L., Rigon C., De Candia A., Tregnaghi A., Gallo C., Favaro M. A., Chieco-Bianchi F., Baldovin M. Long-term sonographic follow-up of rheumatoid and psoriatic proliferative knee joint synovitis. Br J Rheumatol. 1996 Feb;35(2):155–163. doi: 10.1093/rheumatology/35.2.155. [DOI] [PubMed] [Google Scholar]
  11. Fiocco Ugo, Ferro Federica, Cozzi Luisella, Vezzù Maristella, Sfriso Paolo, Checchetto Carlo, Bianchi Fulvia Chieco, Nardacchione Roberto, Piccoli Antonio, Todesco Silvano. Contrast medium in power Doppler ultrasound for assessment of synovial vascularity: comparison with arthroscopy. J Rheumatol. 2003 Oct;30(10):2170–2176. [PubMed] [Google Scholar]
  12. Gladman D. D., Farewell V. T., Nadeau C. Clinical indicators of progression in psoriatic arthritis: multivariate relative risk model. J Rheumatol. 1995 Apr;22(4):675–679. [PubMed] [Google Scholar]
  13. Gladman Dafna D. Effectiveness of psoriatic arthritis therapies. Semin Arthritis Rheum. 2003 Aug;33(1):29–37. doi: 10.1053/sarh.2002.50024. [DOI] [PubMed] [Google Scholar]
  14. Gladman Dafna D., Helliwell Philip, Mease Philip J., Nash Peter, Ritchlin Christopher, Taylor William. Assessment of patients with psoriatic arthritis: a review of currently available measures. Arthritis Rheum. 2004 Jan;50(1):24–35. doi: 10.1002/art.11417. [DOI] [PubMed] [Google Scholar]
  15. Hau M., Kneitz C., Tony H-P, Keberle M., Jahns R., Jenett M. High resolution ultrasound detects a decrease in pannus vascularisation of small finger joints in patients with rheumatoid arthritis receiving treatment with soluble tumour necrosis factor alpha receptor (etanercept). Ann Rheum Dis. 2002 Jan;61(1):55–58. doi: 10.1136/ard.61.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hau M., Schultz H., Tony H. P., Keberle M., Jahns R., Haerten R., Jenett M. Evaluation of pannus and vascularization of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis by high-resolution ultrasound (multidimensional linear array). Arthritis Rheum. 1999 Nov;42(11):2303–2308. doi: 10.1002/1529-0131(199911)42:11<2303::AID-ANR7>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
  17. Helliwell P. S., Hetthen J., Sokoll K., Green M., Marchesoni A., Lubrano E., Veale D., Emery P. Joint symmetry in early and late rheumatoid and psoriatic arthritis: comparison with a mathematical model. Arthritis Rheum. 2000 Apr;43(4):865–871. doi: 10.1002/1529-0131(200004)43:4<865::AID-ANR18>3.0.CO;2-W. [DOI] [PubMed] [Google Scholar]
  18. Karim Z., Wakefield R. J., Quinn M., Conaghan P. G., Brown A. K., Veale D. J., O'Connor P., Reece R., Emery P. Validation and reproducibility of ultrasonography in the detection of synovitis in the knee: a comparison with arthroscopy and clinical examination. Arthritis Rheum. 2004 Feb;50(2):387–394. doi: 10.1002/art.20054. [DOI] [PubMed] [Google Scholar]
  19. Klauser Andrea, Frauscher Ferdinand, Schirmer Michael, Halpern Ethan, Pallwein Leo, Herold Manfred, Helweg Gernot, ZurNedden Dieter. The value of contrast-enhanced color Doppler ultrasound in the detection of vascularization of finger joints in patients with rheumatoid arthritis. Arthritis Rheum. 2002 Mar;46(3):647–653. doi: 10.1002/art.10136. [DOI] [PubMed] [Google Scholar]
  20. Marguerie Laurent, Flipo René-Marc, Grardel Bruno, Beaurain Didier, Duquesnoy Bernard, Delcambre Bernard. Use of disease-modifying antirheumatic drugs in patients with psoriatic arthritis. Joint Bone Spine. 2002 May;69(3):275–281. doi: 10.1016/s1297-319x(02)00396-2. [DOI] [PubMed] [Google Scholar]
  21. Marks G. C., Habicht J. P., Mueller W. H. Reliability, dependability, and precision of anthropometric measurements. The Second National Health and Nutrition Examination Survey 1976-1980. Am J Epidemiol. 1989 Sep;130(3):578–587. doi: 10.1093/oxfordjournals.aje.a115372. [DOI] [PubMed] [Google Scholar]
  22. Marzo-Ortega H., McGonagle D., O'Connor P., Emery P. Efficacy of etanercept in the treatment of the entheseal pathology in resistant spondylarthropathy: a clinical and magnetic resonance imaging study. Arthritis Rheum. 2001 Sep;44(9):2112–2117. doi: 10.1002/1529-0131(200109)44:9<2112::AID-ART363>3.0.CO;2-H. [DOI] [PubMed] [Google Scholar]
  23. Massardo Loreto, Gabriel Sherine E., Crowson Cynthia S., O'Fallon W. Michael, Matteson Eric L. A population based assessment of the use of orthopedic surgery in patients with rheumatoid arthritis. J Rheumatol. 2002 Jan;29(1):52–56. [PubMed] [Google Scholar]
  24. McGonagle D., Gibbon W., O'Connor P., Green M., Pease C., Emery P. Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy. Arthritis Rheum. 1998 Apr;41(4):694–700. doi: 10.1002/1529-0131(199804)41:4<694::AID-ART17>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  25. Mease P. J., Goffe B. S., Metz J., VanderStoep A., Finck B., Burge D. J. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet. 2000 Jul 29;356(9227):385–390. doi: 10.1016/S0140-6736(00)02530-7. [DOI] [PubMed] [Google Scholar]
  26. Moll J. M., Wright V. Psoriatic arthritis. Semin Arthritis Rheum. 1973;3(1):55–78. doi: 10.1016/0049-0172(73)90035-8. [DOI] [PubMed] [Google Scholar]
  27. Newman J. S., Laing T. J., McCarthy C. J., Adler R. S. Power Doppler sonography of synovitis: assessment of therapeutic response--preliminary observations. Radiology. 1996 Feb;198(2):582–584. doi: 10.1148/radiology.198.2.8596870. [DOI] [PubMed] [Google Scholar]
  28. Ostergaard M., Ejbjerg B., Stoltenberg M., Gideon P., Volck B., Skov K., Jensen C. H., Lorenzen I. Quantitative magnetic resonance imaging as marker of synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy: a one year follow up study. Ann Rheum Dis. 2001 Mar;60(3):233–236. doi: 10.1136/ard.60.3.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ostergaard M., Ejbjerg B., Stoltenberg M., Gideon P., Volck B., Skov K., Jensen C. H., Lorenzen I. Quantitative magnetic resonance imaging as marker of synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy: a one year follow up study. Ann Rheum Dis. 2001 Mar;60(3):233–236. doi: 10.1136/ard.60.3.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ostergaard M., Hansen M., Stoltenberg M., Gideon P., Klarlund M., Jensen K. E., Lorenzen I. Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis. Arthritis Rheum. 1999 May;42(5):918–929. doi: 10.1002/1529-0131(199905)42:5<918::AID-ANR10>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  31. Ostergaard M., Stoltenberg M., Løvgreen-Nielsen P., Volck B., Jensen C. H., Lorenzen I. Magnetic resonance imaging-determined synovial membrane and joint effusion volumes in rheumatoid arthritis and osteoarthritis: comparison with the macroscopic and microscopic appearance of the synovium. Arthritis Rheum. 1997 Oct;40(10):1856–1867. doi: 10.1002/art.1780401020. [DOI] [PubMed] [Google Scholar]
  32. Peterfy Charles G. New developments in imaging in rheumatoid arthritis. Curr Opin Rheumatol. 2003 May;15(3):288–295. doi: 10.1097/00002281-200305000-00017. [DOI] [PubMed] [Google Scholar]
  33. Rahman P., Nguyen E., Cheung C., Schentag C. T., Gladman D. D. Comparison of radiological severity in psoriatic arthritis and rheumatoid arthritis. J Rheumatol. 2001 May;28(5):1041–1044. [PubMed] [Google Scholar]
  34. Rhodes Laura A., Tan Ai Lyn, Tanner Steven F., Radjenovic Aleksandra, Hensor Elizabeth M. A., Reece Richard, O'Connor Philip, Emery Paul, McGonagle Dennis. Regional variation and differential response to therapy for knee synovitis adjacent to the cartilage-pannus junction and suprapatellar pouch in inflammatory arthritis: implications for pathogenesis and treatment. Arthritis Rheum. 2004 Aug;50(8):2428–2432. doi: 10.1002/art.20444. [DOI] [PubMed] [Google Scholar]
  35. Ribbens Clio, André Béatrice, Marcelis Stefaan, Kaye Olivier, Mathy Luc, Bonnet Valérie, Beckers Catherine, Malaise Michel G. Rheumatoid hand joint synovitis: gray-scale and power Doppler US quantifications following anti-tumor necrosis factor-alpha treatment: pilot study. Radiology. 2003 Sep 11;229(2):562–569. doi: 10.1148/radiol.2292020206. [DOI] [PubMed] [Google Scholar]
  36. Rubaltelli L., Fiocco U., Cozzi L., Baldovin M., Rigon C., Bortoletto P., Tregnaghi A., Melanotte P. L., di Maggio C., Todesco S. Prospective sonographic and arthroscopic evaluation of proliferative knee joint synovitis. J Ultrasound Med. 1994 Nov;13(11):855–862. doi: 10.7863/jum.1994.13.11.855. [DOI] [PubMed] [Google Scholar]
  37. Sokoll K. B., Helliwell P. S. Comparison of disability and quality of life in rheumatoid and psoriatic arthritis. J Rheumatol. 2001 Aug;28(8):1842–1846. [PubMed] [Google Scholar]
  38. Stone M., Bergin D., Whelan B., Maher M., Murray J., McCarthy C. Power Doppler ultrasound assessment of rheumatoid hand synovitis. J Rheumatol. 2001 Sep;28(9):1979–1982. [PubMed] [Google Scholar]
  39. Szkudlarek M., Court-Payen M., Strandberg C., Klarlund M., Klausen T., Ostergaard M. Power Doppler ultrasonography for assessment of synovitis in the metacarpophalangeal joints of patients with rheumatoid arthritis: a comparison with dynamic magnetic resonance imaging. Arthritis Rheum. 2001 Sep;44(9):2018–2023. doi: 10.1002/1529-0131(200109)44:9<2018::AID-ART350>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  40. Taylor P. C., Steuer A., Gruber J., Cosgrove D. O., Blomley M. J. K., Marsters P. A., Wagner C. L., McClinton C., Maini R. N. Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo-controlled study of infliximab therapy in early rheumatoid arthritis. Arthritis Rheum. 2004 Apr;50(4):1107–1116. doi: 10.1002/art.20123. [DOI] [PubMed] [Google Scholar]
  41. Terslev L., Torp-Pedersen S., Qvistgaard E., Kristoffersen H., Røgind H., Danneskiold-Samsøe B., Bliddal H. Effects of treatment with etanercept (Enbrel, TNRF:Fc) on rheumatoid arthritis evaluated by Doppler ultrasonography. Ann Rheum Dis. 2003 Feb;62(2):178–181. doi: 10.1136/ard.62.2.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wakefield Richard J., Brown Andrew K., O'Connor Philip J., Emery Paul. Power Doppler sonography: improving disease activity assessment in inflammatory musculoskeletal disease. Arthritis Rheum. 2003 Feb;48(2):285–288. doi: 10.1002/art.10818. [DOI] [PubMed] [Google Scholar]
  43. Walther M., Harms H., Krenn V., Radke S., Faehndrich T. P., Gohlke F. Correlation of power Doppler sonography with vascularity of the synovial tissue of the knee joint in patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 2001 Feb;44(2):331–338. doi: 10.1002/1529-0131(200102)44:2<331::AID-ANR50>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  44. Weidekamm C., Köller M., Weber M., Kainberger F. Diagnostic value of high-resolution B-mode and doppler sonography for imaging of hand and finger joints in rheumatoid arthritis. Arthritis Rheum. 2003 Feb;48(2):325–333. doi: 10.1002/art.10784. [DOI] [PubMed] [Google Scholar]
  45. Weinblatt M. E., Kremer J. M., Bankhurst A. D., Bulpitt K. J., Fleischmann R. M., Fox R. I., Jackson C. G., Lange M., Burge D. J. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999 Jan 28;340(4):253–259. doi: 10.1056/NEJM199901283400401. [DOI] [PubMed] [Google Scholar]
  46. Yazici Y., Erkan D., Lockshin M. D. A preliminary study of etanercept in the treatment of severe, resistant psoriatic arthritis. Clin Exp Rheumatol. 2000 Nov-Dec;18(6):732–734. [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES