Skip to main content

Advertisement

SpringerLink
Log in

Spondyloarthritis at the crossroads of imaging, pathology, and structural damage in the era of biologics

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Ankylosing spondylitis (AS) is characterized by two key pathologic findings: sacroiliac joint and spinal inflammation and new bone formation with possible bone fusion, usually in the axial skeleton. Thus, structural damage in AS must be viewed differently than that in rheumatoid arthritis. Tumor necrosis factor blockers effectively inhibit inflammation, as shown by signs and symptoms, function, C-reactive protein, and MRI, and will probably prevent erosive structural damage. However, the ossification of already-damaged bone cannot be influenced by tumor necrosis factor blockade, because these drugs do not inhibit osteoblasts. It remains to be seen whether additional targeting of new bone formation is clinically meaningful in advanced AS. The most important action to prevent structural damage is probably an early diagnosis and effective anti-inflammatory treatment of AS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Sieper J, Rudwaleit M, Khan MA, Braun J: Concepts and epidemiology of spondyloarthritis. Best Pract Res Clin Rheumatol 2006, 20:401–417.

    Article  PubMed  Google Scholar 

  2. Braun J, Sieper J: Ankylosing spondylitis. Lancet 2007, 369:1379–1390.

    Article  PubMed  Google Scholar 

  3. Rudwaleit M, Metter A, Listing J, et al.: Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria. Arthritis Rheum 2006, 54:569–578.

    Article  PubMed  Google Scholar 

  4. van der Linden SM, Valkenburg HA, de Jongh BM, Cats A: The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum 1984, 27:241–249.

    Article  PubMed  Google Scholar 

  5. Rudwaleit M, Khan MA, Sieper J: The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 2005, 52:1000–1008.

    Article  PubMed  Google Scholar 

  6. Feldtkeller E, Khan MA, van der Heijde D, et al.: Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int 2003, 23:61–66.

    PubMed  Google Scholar 

  7. Brandt HC, Spiller I, Song IH, et al.: Performance of referral recommendations in patients with chronic back pain and suspected axial spondyloarthritis. Ann Rheum Dis 2007, 66:1479–1484.

    Article  PubMed  Google Scholar 

  8. Song IH, Poddubnyy DA, Rudwaleit M, Sieper J: Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs. Arthritis Rheum 2008, 58:929–938.

    Article  PubMed  CAS  Google Scholar 

  9. Braun J, Brandt J, Listing J, et al.: Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002, 359:1187–1193.

    Article  PubMed  CAS  Google Scholar 

  10. Davis JC Jr, Van Der Heijde D, Braun J, et al.: Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 2003, 48:3230–3236.

    Article  PubMed  CAS  Google Scholar 

  11. van der Heijde D, Kivitz A, Schiff MH, et al.: Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebocontrolled trial. Arthritis Rheum 2006, 54:2136–2146.

    Article  PubMed  CAS  Google Scholar 

  12. Braun J, Landewe R, Hermann KG, et al.: Major reduction in spinal inflammation in patients with ankylosing spondylitis after treatment with infliximab: results of a multicenter, randomized, double-blind, placebo-controlled magnetic resonance imaging study. Arthritis Rheum 2006, 54:1646–1652.

    Article  PubMed  CAS  Google Scholar 

  13. Calin A, Mackay K, Santos H, Brophy S: A new dimension to outcome: application of the Bath Ankylosing Spondylitis Radiology Index. J Rheumatol 1999, 26:988–992.

    PubMed  CAS  Google Scholar 

  14. Creemers MC, Franssen MJ, van’t Hof MA, et al.: Assessment of outcome in ankylosing spondylitis: an extended radiographic scoring system. Ann Rheum Dis 2005, 64:127–129.

    Article  PubMed  CAS  Google Scholar 

  15. van der Heijde D, Landewé R, van der Linden S: How should treatment effect on spinal radiographic progression in patients with ankylosing spondylitis be measured? Arthritis Rheum 2005, 52:1979–1985.

    Article  PubMed  CAS  Google Scholar 

  16. Braun J, Sieper J, Bollow M: Imaging of sacroiliitis. Clin Rheumatol 2000, 19:51–57.

    PubMed  CAS  Google Scholar 

  17. Hermann KG, Althoff CE, Schneider U, et al.: Spinal changes in patients with spondyloarthritis: comparison of MR imaging and radiographic appearances. Radiographics 2005, 25:559–569.

    Article  PubMed  Google Scholar 

  18. Maksymowych WP, Inman RD, Salonen D, et al.: Spondyloarthritis research Consortium of Canada magnetic resonance imaging index for assessment of sacroiliac joint inflammation in ankylosing spondylitis. Arthritis Rheum 2005, 53:703–709.

    Article  PubMed  Google Scholar 

  19. Haibel H, Rudwaleit M, Brandt HC, et al.: Adalimumab reduces spinal symptoms in active ankylosing spondylitis: clinical and magnetic resonance imaging results of a fifty-two-week open-label trial. Arthritis Rheum 2006, 54:678–681.

    Article  PubMed  CAS  Google Scholar 

  20. Maksymowych WP, Dhillon SS, Park R, et al.: Validation of the spondyloarthritis research consortium of Canada magnetic resonance imaging spinal inflammation index: is it necessary to score the entire spine? Arthritis Rheum 2007, 57:501–507.

    Article  PubMed  Google Scholar 

  21. Weber U, Pfirrmann CW, Kissling RO, et al.: Whole body MR imaging in ankylosing spondylitis: a descriptive pilot study in patients with suspected early and active confirmed ankylosing spondylitis. BMC Musculoskelet Disord 2007, 8:20.

    Article  PubMed  Google Scholar 

  22. Althoff CE, Appel H, Rudwaleit M, et al.: Whole-body MRI as a new screening tool for detecting axial and peripheral manifestations of spondyloarthritis. Ann Rheum Dis 2007, 66:983–985.

    Article  PubMed  CAS  Google Scholar 

  23. Appel H, Hermann KG, Althoff CE, et al.: Whole-body magnetic resonance imaging evaluation of widespread inflammatory lesions in a patient with ankylosing spondylitis before and after 1 year of treatment with infliximab. J Rheumatol 2007, 34:2497–2498.

    PubMed  Google Scholar 

  24. Weber U, Kissling RO, Holder J: Advances in musculoskeletal imaging and their clinical utility in the early diagnosis of spondyloarthritis. Curr Rheumatol Rep 2007, 9:353–360.

    Article  PubMed  Google Scholar 

  25. Weber U, Pfirrmann CWA, Kissling RO, et al.: Early spondyloarthritis in HLA-B27 positive monozygotic twin pair: A highly concordant onset, sites of involvement, and disease course. J Rheumatol 2008, 35:1464–1466.

    PubMed  Google Scholar 

  26. Poole AR: The histopathology of ankylosing spondylitis: are there unifying hypotheses? Am J Med Sci 1998, 316:228–233.

    Article  PubMed  CAS  Google Scholar 

  27. Maksymowych WP: Ankylosing spondylitis—at the interface of bone and cartilage. J Rheumatol 2000, 27:2295–2301.

    PubMed  CAS  Google Scholar 

  28. McGonagle D, Gibbon W, Emery P: Classification of inflammatory arthritis by enthesitis. Lancet 1998, 352:1137–1140.

    Article  PubMed  CAS  Google Scholar 

  29. Ball J: Pathology and pathogenesis. In: Ankylosing spondylitis. Edited by Moll JM. Edinburgh: Churchill Livingstone; 1980: 96–112.

    Google Scholar 

  30. Cruickshank B: Lesions of cartilaginous joints in ankylosing spondylitis. J Pathol Bacteriol 1956, 71:73–84.

    Article  PubMed  CAS  Google Scholar 

  31. Bywaters EGL, Olsen E: A case of early ankylosing spondylitis with fatal secondary amyloidosis: demonstrated at the Royal Postgraduate Medical School. BMJ 1968, 2:412–416.

    Article  Google Scholar 

  32. Francois RJ, Gardner DL, Degrave EJ, Bywaters EG: Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not merely enthesitis. Arthritis Rheum 2000, 43:2011–2024.

    Article  PubMed  CAS  Google Scholar 

  33. Braun J, Bollow M, Neure L, et al.: Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 1995, 38:499–505.

    Article  PubMed  CAS  Google Scholar 

  34. Savill DL: The manubrio-sternal joint in ankylosing spondylitis. J Bone Joint Surg Br 1951, 33:56–64.

    PubMed  Google Scholar 

  35. Appel H, Kuhne M, Spiekermann S, et al.: Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow. Arthritis Rheum 2006, 54:1805–1813.

    Article  PubMed  Google Scholar 

  36. Braun J, Bollow M, Eggens U, et al.: Use of dynamic magnetic resonance imaging with fast imaging in the detection of early and advanced sacroiliitis in spondylarthropathy patients. Arthritis Rheum 1994, 37:1039–1045.

    Article  PubMed  CAS  Google Scholar 

  37. Bollow M, Fischer T, Reisshauer H, et al.: Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis—cellularity correlates with the degree of enhancement detected by magnetic resonance imaging. Ann Rheum Dis 2000, 59:135–140.

    Article  PubMed  CAS  Google Scholar 

  38. Golder W, Karberg K, Sieper J: Fluoroscopy-guided application of corticosteroids for local control of manubriosternal joint pain in patients with spondyloarthropathies. Clin Rheumatol 2004, 23:481–484.

    Article  PubMed  Google Scholar 

  39. McGonagle D, Gibbon W, O’Connor P, et al.: Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy. Arthritis Rheum 1998, 41:694–700.

    Article  PubMed  CAS  Google Scholar 

  40. Lambert RG, Dhillon SS, Jhangri GS, et al.: High prevalence of symptomatic enthesopathy of the shoulder in ankylosing spondylitis: deltoid origin involvement constitutes a hallmark of disease. Arthritis Rheum 2004, 51:681–690.

    Article  PubMed  Google Scholar 

  41. Appel H, Kuhne M, Spiekermann S, et al.: Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis. Arthritis Rheum 2006, 54:2845–2851.

    Article  PubMed  Google Scholar 

  42. Appel H, Loddenkemper C, Grozdanovic Z, et al.: Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis. Arthritis Res Ther 2006, 8:R143.

    Article  PubMed  CAS  Google Scholar 

  43. Brandt J, Haibel H, Cornely D, et al.: Successful treatment of active ankylosing spondylitis with the anti-tumor necrosis factor alpha monoclonal antibody infliximab. Arthritis Rheum 2000, 43:1346–1352.

    Article  PubMed  CAS  Google Scholar 

  44. Appel H, Loddenkemper C, Heydrich R, et al.: Immunohistochemical analysis of osteoblasts in zygapophyseal joints of patients with anyklosing spondylitis reveal repair functions similar to osteoarthritis. Ann Rheum Dis 2008, 67(Suppl II):59.

    Google Scholar 

  45. de Vlam K, Lories RJ, Luyten FP: Mechanisms of pathologic new bone formation. Curr Rheumatol Rep 2006, 8:332–337.

    Article  PubMed  Google Scholar 

  46. Lories RJ, Derese I, de Bari C, Luyten FP: Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis. Arthritis Rheum 2007, 56:489–497.

    Article  PubMed  Google Scholar 

  47. Ball J: Enthesopathy of rheumatoid and ankylosing spondylitis. Ann Rheum Dis 1971, 30:213–223.

    Article  PubMed  CAS  Google Scholar 

  48. Zwerina J, Tuerk B, Redlich K, et al.: Imbalance of local bone metabolism in inflammatory arthritis and its reversal upon tumor necrosis factor blockade: direct analysis of bone turnover in murine arthritis. Arthritis Res Ther 2006, 8:R22.

    Article  PubMed  CAS  Google Scholar 

  49. Walsh NC, Manning CA, Boch JA, et al.: Wnt signalling antagonists are candidates for the suppression of osteoblast differentiation in inflammatory arthritis. Arthritis Rheum 2006, 54(Suppl):S511.

    Google Scholar 

  50. Diarra D, Stolina M, Polzer K, et al.: Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007, 13:156–163.

    Article  PubMed  CAS  Google Scholar 

  51. Lacey DL, Timms E, Tan HL, et al.: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998, 93:165–176.

    Article  PubMed  CAS  Google Scholar 

  52. Sieper J, Appel H, Braun J, Rudwaleit M: Critical appraisal of assessment of structural damage in ankylosing spondylitis: implications for treatment outcomes. Arthritis Rheum 2008, 58:649–656.

    Article  PubMed  Google Scholar 

  53. Maksymowych WP, Chiowchanwisawakit P, Clare T, Lambert RG: Inflammatory lesions of the spine on MRI predict the development of new syndesmophytes in ankylosing spondylitis: Evidence for coupling between inflammation and new bone formation. Ann Rheum Dis 2008, 67(Suppl II):130.

    Google Scholar 

  54. Baraliakos X, Listing J, Rudwaleit M, et al.: Evidence for a link between inflammation and new bone formation in ankylosing spondylitis—a detailed analysis. Ann Rheum Dis 2008, 67(Suppl II):130.

    Google Scholar 

  55. Van der Heijde D, Landewe R, Baraliakos X, et al.: MRI inflammation of the vertebral unit (VU) only marginally contributes to new syndesmophyte formation in that unit: a multi-level analysis. Ann Rheum Dis 2008, 67(Suppl II):130.

    Google Scholar 

  56. Schett G, Landewé R, van der Heijde D: Tumour necrosis factor blockers and structural remodelling in ankylosing spondylitis: what is reality and what is fiction? Ann Rheum Dis 2007, 66:709–711.

    Article  PubMed  CAS  Google Scholar 

  57. Rudwaleit M, Schwarzlose S, Hilgert ES, et al.: Magnetic resonance imaging (MRI) in predicting a major clinical response to anti-TNF-treatment in ankylosing spondylitis. Ann Rheum Dis 2007, (Nov 15 Epub ahead of print).

  58. Haibel H, Rudwaleit M, Listing J, et al.: Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: Results of a twelveweek randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Arthritis Rheum 2008, 58:1981–1991.

    Article  PubMed  CAS  Google Scholar 

  59. Barkham N, Keen HI, Coates LC, et al.: A randomized controlled trial of infliximab shows clinical and MRI efficacy in HLA-B27 positive very early ankylosing spondylitis. Ann Rheum Dis 2008, 67(Suppl II):382.

    Google Scholar 

  60. Sieper J, Baraliakos X, Listing J, et al.: Persistent reduction of spinal inflammation as assessed by magnetic resonance imaging in patients with ankylosing spondylitis after 2 yrs of treatment with the anti-tumour necrosis factor agent infliximab. Rheumatology (Oxford) 2005, 44:1525–1530.

    Article  CAS  Google Scholar 

  61. Braun J, Baraliakos X, Listing J, et al.: Persistent clinical efficacy and safety of anti-tumour necrosis factor alpha therapy with infliximab in patients with ankylosing spondylitis over 5 years: evidence for different types of response. Ann Rheum Dis 2008, 67:340–345.

    Article  PubMed  CAS  Google Scholar 

  62. Heiberg MS, Koldingsnes W, Mikkelsen K, et al.: The comparative one-year performance of anti-tumor necrosis factor alpha drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: results from a longitudinal, observational, multicenter study. Arthritis Rheum 2008, 59:234–240.

    Article  PubMed  CAS  Google Scholar 

  63. van der Heijde D, Landewé R, Einstein S, et al.: Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008, 58:1324–1331.

    Article  PubMed  CAS  Google Scholar 

  64. van der Heijde D, Landewe R, Deoadar A, et al.: Radiographic progression in patients with ankylosing spondylitis after 2 years of treatment not inhibited with infliximab. Ann Rheum Dis 2007, 66(Suppl II):85–86; OP0111.

    Google Scholar 

  65. Braun J, Han C, Kellner H, et al.: Infliximab improves spinal mobility in patients with ankylosing spondylitis: two year findings from the ASSERT clinical trial. Ann Rheum Dis 2007, 66(Suppl II):390.

    Google Scholar 

  66. Braun J, Sieper J: What is the most important outcome parameter in ankylosing spondylitis? Rheumatology 2008 (in press).

  67. Lories RJ, Derese I, Luyten FP: Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest 2005, 115:1571–1579.

    Article  PubMed  CAS  Google Scholar 

  68. Lories RJ, Daans M, Derese I, et al.: Noggin haploinsufficiency differentially affects tissue responses in destructive and remodeling arthritis. Arthritis Rheum 2006, 54:1736–1746.

    Article  PubMed  CAS  Google Scholar 

  69. Wanders A, Heijde D, Landewé R, et al.: Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum 2005, 52:1756–1765.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Infectiology, and Rheumatology, Charité Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Joachim Sieper

Authors
  1. Heiner Appel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joachim Sieper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joachim Sieper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Appel, H., Sieper, J. Spondyloarthritis at the crossroads of imaging, pathology, and structural damage in the era of biologics. Curr Rheumatol Rep 10, 356–363 (2008). https://doi.org/10.1007/s11926-008-0058-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-008-0058-x

Keywords

Search

Navigation