Ankylosing Spondylitis

  • Juergen Braun
  • David Tak Yan Yu


Ankylosing spondylitis (AS) is the prototypical form of the spondyloarthritides, a group of disorders that involves inflammation of the sacroiliac joints, spine, joints, and entheses, as well as extraspinal lesions of the eye, bowel, and heart. Human leukocyte antigen (HLA) B27 is a strong genetic risk factor for AS. However, this gene is neither necessary nor sufficient to cause the disease. Other recently recognized genes are also involved in the pathophysiology of this condition. The principal musculoskeletal lesions of AS are sacro-iliitis, spondylitis, synovitis, and enthesitis. Enthesitis consists of inflammation at the site of tendinous insertions into bone. Sacroiliitis causes inflammatory back pain often localized to the buttocks that can be uni- or bilateral and typically alternates between the left and right side. Spondylitis begins characteristically in the lumbosacral region and proceeds cephalad. The most common extraspinal joints involved are the hips, knees, ankles, and metatarsophalangeal joints. The pattern of arthritis is typically an asymmetric oligoarthri-tis that involves the large joints of the lower extremities. Acute anterior uveitis usually occurs in one eye at a time, although either eye can be involved in any given episode. Patients usually present with a red, painful, photophobic eye.


Inflammatory Bowel Disease Ankylose Spondylitis Human Leukocyte Antigen Sacroiliac Joint Reactive Arthritis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Appel H, Kuhne M, Spiekermann S, Ebhardt H, Grozdanovic Z, Kohler D, et al Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis. Arthritis Rheum 2006; 54(9):2845–2851PubMedCrossRefGoogle Scholar
  2. Baraliakos X, Listing J, Brandt J, Haibel H, Rudwaleit M, Sieper J, et al Radiographic progression in patients with ankylosing spondylitis after 4 yrs of treatment with the anti-TNF-alpha antibody inflix-imab. Rheumatol (Oxford) 2007a; 46(9):1450–1453CrossRefGoogle Scholar
  3. Baraliakos X, Listing J, Rudwaleit M, Haibel H, Brandt J, Sieper J, Braun J. Progression of radiographic damage in patients with anky-losing spondylitis — Defining the central role of syndesmophytes. Ann Rheum Dis 2007; 66(7):910–5PubMedCrossRefGoogle Scholar
  4. Baraliakos X, Listing J, Rudwaleit M, Sieper J, Braun J. The relationship between inflammation and new bone formation in patients with ankylosing spondylitis. Arthritis Res Ther 2008 Sep 1; 10(5):R104PubMedCrossRefGoogle Scholar
  5. Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007; 369:1379–1390PubMedCrossRefGoogle Scholar
  6. Braun J, Bollow M, Seyrekbasan F, et al Computed tomography guided corticosteroid injection of the sacroiliac joint in patients with spon-dyloarthropathy with sacroiliitis: Clinical outcome and followup by dynamic magnetic resonance imaging. J Rheumatol 1996; 23(4): 659–664PubMedGoogle Scholar
  7. Braun J, Tuszewski M, Ehlers S, et al Nested polymerase chain reaction strategy simultaneously targeting DNA sequences of multiple bacterial species in inflammatory joint diseases. II. Examination of sac-roiliac and knee joint biopsies of patients with spondyloarthropathies and other arthritides. J Rheumatol 1997a; 24(6):1101–1105Google Scholar
  8. Braun J, Tuszewski M, Eggens U, et al Nested polymerase chain reaction strategy simultaneously targeting DNA sequences of multiple bacterial species in inflammatory joint diseases. I. Screening of synovial fluid samples of patients with spondyloarthropathies and other arthritides. J Rheumatol 1997b; 24(6):1092–1100Google Scholar
  9. Braun J, Bollow M, Remlinger G, et al Prevalence of spondylarthropa-thies in HLA-B27 positive and negative blood donors. Arthritis Rheum 1998; 41(1):58–67PubMedCrossRefGoogle Scholar
  10. Braun J, Brandt J, Listing J, et al Treatment of active ankylosing spon-dylitis with infliximab — a double-blind placebo controlled multicenter trial. Lancet 2002; 359:1187–1193PubMedCrossRefGoogle Scholar
  11. Braun J, Davis J, Dougados M, Sieper J, van der Linden S, van der Heijde D. First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis. Ann Rheum Dis 2005 Aug 11 [Epub ahead of print]Google Scholar
  12. Braun J, Landewe R, Hermann KG, Han J, Yan S, Williamson P, van der Heijde D. 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 2006a; 54(5):1646–1652CrossRefGoogle Scholar
  13. Braun J, Zochling J, Baraliakos X, et al Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondy-loarthritis and early ankylosing spondylitis: A multicentre randomized controlled trial. Ann Rheum Dis 2006bGoogle Scholar
  14. Breban M, Ravaud P, Claudepierre P, et al Maintenance of infliximab treatment in ankylosing spondylitis: Results of a one-year randomized controlled trial comparing systematic versus on-demand treatment. Arthritis Rheum 2008; 58(1):88–97PubMedCrossRefGoogle Scholar
  15. Brown MA. Human leukocyte antigen-B27 and ankylosing spondylitis. Int Med J 2007; 37:739–740CrossRefGoogle Scholar
  16. Carette S, Graham D, Little H, Rubenstein J, Rosen P. The natural disease course of ankylosing spondylitis. Arthritis Rheum 1983; 26(2):186–190PubMedCrossRefGoogle Scholar
  17. Coates LC, Cawkwell LS, Ng NW, et al Real life experience confirms sustained response to long-term biologics and switching in ankylos-ing spondylitis. Rheumatology (Oxford) 2008; 47(6):897–900CrossRefGoogle Scholar
  18. Dougados M, Luo MP, Maksymowych WP, et al Evaluation of the patient acceptable symptom state as an outcome measure in patients with ankylosing spondylitis: Data from a randomized controlled trial. Arthritis Rheum 2008; 59(4):553–560PubMedCrossRefGoogle Scholar
  19. Garrett S, Jenkinson T, Kennedy LG, et al A new approach to defining disease status in ankylosing spondylitis: The bath ankylosing spon-dylitis disease activity index. J Rheumatol 1994; 21(12):2286–2291PubMedGoogle Scholar
  20. Haibel H, Brandt HC, Song IH, et al No efficacy of subcutaneous meth-otrexate in active ankylosing spondylitis: A 16-week open-label trial. Ann Rheum Dis 2007; 66(3):419–421PubMedCrossRefGoogle Scholar
  21. 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(2):234–240PubMedCrossRefGoogle Scholar
  22. Henderson C, Davis JC. Drug insight: Anti-tumor-necrosis-factor therapy for ankylosing spondylitis. Nat Clin Pract Rheumatol 2006; 2(4):211–218PubMedCrossRefGoogle Scholar
  23. Karberg K, Zochling J, Sieper J, Felsenberg D, Braun J. Bone loss is detected more frequently in patients with ankylosing spondylitis with syndesmophytes. J Rheumatol 2005; 32(7):1290–1298PubMedGoogle Scholar
  24. Landewé R, Dougados M, Mielants H et al Physical function in anky-losing spondylitis is independently determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis 2009; 68(6):863–7PubMedCrossRefGoogle Scholar
  25. Li EK, Griffith JF, Lee VW, et al Short-term efficacy of combination methotrexate and infliximab in patients with ankylosing spondylitis: A clinical and magnetic resonance imaging correlation. Rheumatology (Oxford) 2008 Sept; 47(9):1358–1363 [Epub 2008 Jun 23]CrossRefGoogle Scholar
  26. Lopez-Larrea C, Sujirachato K, Mehra NK, et al HLA-B27 subtypes in Asian patients with ankylosing spondylitis. Evidence for new associations. Tissue Antigens 1995; 45(3):169–176PubMedCrossRefGoogle Scholar
  27. Lories RJ, Derese I, de Bari C, Luyten FP. Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylar-thritis. Arthritis Rheum 2007; 56(2):489–497PubMedCrossRefGoogle Scholar
  28. Mader R. Diffuse idiopathic skeletal hyperostosis: Time for a change. J Rheumatol 2008; 35(3):377–379PubMedGoogle Scholar
  29. Maertens M, Mielants H, Verstraete K, Veys EM. Simultaneous occurrence of diffuse idiopathic skeletal hyperostosis and ankylosing spon-dylitis in the same patient. J Rheumatol 1992; 19(12):1978–1983PubMedGoogle Scholar
  30. Maksymowych WP, Jhangri GS, Fitzgerald AA, et al A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug-refractory ankylosing spondyli-tis. Arthritis Rheum 2002; 46(3):766–773PubMedCrossRefGoogle Scholar
  31. Maksymowych WP, Richardson R, Mallon C, et al Evaluation and validation of the patient acceptable symptom state (PASS) in patients with ankylosing spondylitis. Arthritis Rheum 2007; 57(1):133–139PubMedCrossRefGoogle Scholar
  32. Muche B, Bollow M, François RJ, Sieper J, Hamm B, Braun J. Which anatomical structures are involved in early and late sacroiliitis in spondylo arthritis — a detailed analysis by contrast enhanced magnetic resonance imaging. Arthritis Rheum 2003; 48(5):1374–1384PubMedCrossRefGoogle Scholar
  33. Neidhart M, Baraliakos X, Seemayer C, et al Expression of cathepsin K and MMP-1indicate persistent osteodestructive activity in longstanding ankylosing spondylitis. Ann Rheum Dis 2008 Aug 4 [Epub ahead of print]Google Scholar
  34. Olivieri I, D'Angelo S, Cutro MS, et al Diffuse idiopathic skeletal hyper-ostosis may give the typical postural abnormalities of advanced anky-losing spondylitis. Rheumatology (Oxford) 2007; 46(11):1709–1711CrossRefGoogle Scholar
  35. Robertson LP, Davis MJ. A longitudinal study of disease activity and functional status in a hospital cohort of patients with ankylosing spondylitis. Rheumatology (Oxford) 2004; 43(12):1565–1568CrossRefGoogle Scholar
  36. Rudwaleit M, Metter A, Listing J, Sieper J, Braun J. Inflammatory back pain in ankylosing spondylitis — a reassessment of the clinical history for classification and diagnosis. Arthritis Rheum 2006; 54(2): 569–578PubMedCrossRefGoogle Scholar
  37. Rudwaleit M, Haibel H, Baraliakos X et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum 2009a; 60(3):717–27CrossRefGoogle Scholar
  38. Rudwaleit M, Landewé R, van der Heijde D et al The development of Assessment of Spondylo Arthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis 2009b; 68(6):770–6CrossRefGoogle Scholar
  39. Rudwaleit M, van der Heijde D, Landewé R et al The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009c; 68(6):777–83CrossRefGoogle Scholar
  40. Saraux A, Guillemin F, Guggenbuhl P, et al Prevalence of spondyloar-thropathies in France: 2001. Ann Rheum Dis 2005; 64(10):1431–1435PubMedCrossRefGoogle Scholar
  41. Song IH, Poddubnyy DA, Rudwaleit M, Sieper J. Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflamma-tory drugs. Arthritis Rheum 2008; 58(4):929–938PubMedCrossRefGoogle Scholar
  42. Spoorenberg A, van der Heijde D, de Klerk E, et al Relative value of eryth-rocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis. J Rheumatol 1999; 26(4):980–984PubMedGoogle Scholar
  43. Spoorenberg A, van Tubergen A, Landewe R, et al Measuring disease activity in ankylosing spondylitis: Patient and physician have different perspectives. Rheumatology (Oxford) 2005; 44(6):789–795CrossRefGoogle Scholar
  44. Underwood MR, Dawes P. Inflammatory back pain in primary care. Br J Rheumatol 1995; 34(11):1074–1077PubMedCrossRefGoogle Scholar
  45. 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, placebo-controlled trial. Arthritis Rheum 2006; 54(7):2136–2146PubMedCrossRefGoogle Scholar
  46. van der Heijde D, Landewe R, Einstein S, et al Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008; 58(5):1324–1331PubMedCrossRefGoogle Scholar
  47. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984; 27(4):361–368PubMedCrossRefGoogle Scholar
  48. Ward MM, Reveille JD, Learch TJ, Davis JC Jr, Weisman MH. Occupational physical activities and long-term functional and radiographic outcomes in patients with ankylosing spondylitis. Arthritis Rheum 2008; 59(6):822–832PubMedCrossRefGoogle Scholar
  49. Zink A, Braun J, Listing J, Wollenhaupt J. Disability and handicap in rheumatoid arthritis and ankylosing spondylitis— results from the German rheumatological database. German Collaborative Arthritis Centers. J Rheumatol 2000; 27(3):613–622PubMedGoogle Scholar
  50. Zochling J, van der Heijde D, Burgos-Vargas R, et al ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2006 Aug 26 [Epub ahead of print]Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Juergen Braun
    • 1
  • David Tak Yan Yu
    • 2
  1. 1.Ruhr University Bochum, Rheumazentrum RuhrgebietHerneGermany
  2. 2.UCLA Medical SchoolLos AngelesUSA

Personalised recommendations