Abstract
The spectrum of HLA-B27-associated inflammatory spine diseases is referred to as axial spondyloarthritis (axSpA). AxSpA encompasses established ankylosing spondylitis (AS) but also nonradiographic axSpA, and can be classified according to the Assessment of SpondyloArthritis international Society classification criteria for axSpA. Specific and effective therapy for axSpA includes education, physiotherapy, NSAIDs and biologic agents, as appropriate. Patients with axSpA, however, are often diagnosed late in the course of the disease. As specific therapy is available, the effective identification of those individuals who are likely to have axSpA among patients with chronic back pain in primary care and their subsequent referral to a rheumatologist for establishing a correct diagnosis is worth pursuing. Candidate referral parameters that can easily be applied to patients with chronic back pain and age at onset ≤45 years (the target population) include inflammatory back pain (IBP) and positivity for HLA-B27. Following diagnostic work-up by a rheumatologist, these referral parameters, either alone or in combination, have led to the diagnosis of as many as 33–45% of patients within this target population with axSpA, 41–62% of whom had undiagnosed AS. Thus, educating primary care physicians on the value of IBP and HLA-B27 testing within this target population, and referral to a rheumatologist if one of these parameters is positive, is a promising approach to reduce the long delay in diagnosing patients with axSpA.
Key Points
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The long delay of several years in diagnosing ankylosing spondylitis (AS) is unacceptable, as specific therapy is available
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Inflammatory back pain (IBP) is the key clinical symptom of patients with axial spondyloarthritis (axSpA), including AS and nonradiographic axSpA, and is present in 70–80% of patients
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HLA-B27 is the key laboratory marker of axSpA, present in 70–95% of patients
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Referral programs have focused on patients with chronic back pain, age at onset ≤45 years and presence of at least one further spondyloarthritis parameter, including IBP and/or HLA-B27
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In all referral programs, a diagnosis of axSpA was made in 33–45% of referred patients
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Easy-to-apply referral parameters for primary care physicians will contribute to shortening the diagnostic delay in axSpA
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References
Sieper, J., Braun, J., Rudwaleit, M., Boonen, A. & Zink, A. Ankylosing spondylitis: an overview. Ann. Rheum. Dis. 61 (Suppl. 3), iii8–iii18 (2002).
Braun, J. & Sieper, J. Ankylosing spondylitis. Lancet 369, 1379–1390 (2007).
van der Linden, S. M., Valkenburg, H. A., de Jongh, B. M. & 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. 27, 241–249 (1984).
Rudwaleit, M., Khan, M. A. & Sieper, J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum. 52, 1000–1008 (2005).
Underwood, M. R. & Dawes, P. Inflammatory back pain in primary care. Br. J. Rheumatol. 34, 1074–1077 (1995).
Chou, R. et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann. Intern. Med. 147, 478–491 (2007).
Muche, B. et al. Anatomic structures involved in early and late-stage sacroiliitis in spondylarthritis: a detailed analysis by contrast-enhanced magnetic resonance imaging. Arthritis Rheum. 48, 1374–1384 (2003).
Rudwaleit, M. et al. Defining active sacroiliitis on magnetic resonance imaging (MRI) for classification of axial spondyloarthritis—a consensual approach by the ASAS/OMERACT MRI Group. Ann. Rheum. Dis. 68, 1520–1527 (2009).
Rudwaleit, M., van der Heijde, D., Khan, M. A., Braun, J. & Sieper, J. How to diagnose axial spondyloarthritis early. Ann. Rheum. Dis. 63, 535–543 (2004).
Rudwaleit, M., Feldtkeller, E. & Sieper, J. Easy assessment of axial spondyloarthritis (early ankylosing spondylitis) at the bedside. Ann. Rheum. Dis. 65, 1251–1252 (2006).
Rudwaleit, M. et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann. Rheum. Dis. 68, 770–776 (2009).
Rudwaleit, M. et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann. Rheum. Dis. 68, 777–783 (2009).
Poddubnyy, D. et al. Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann. Rheum. Dis. 70, 1369–1374 (2011).
Sampaio-Barros, P. D. et al. Undifferentiated spondyloarthritis: a long-term follow-up. J. Rheumatol. 37, 1195–1199 (2010).
Bennett, A. N. et al. Severity of baseline magnetic resonance imaging-evident sacroiliitis and HLA-B27 status in early inflammatory back pain predict radiographically evident ankylosing spondylitis at eight years. Arthritis Rheum. 58, 3413–3418 (2008).
Mau, W. et al. Clinical features and prognosis of patients with possible ankylosing spondylitis. Results of a 10-year follow-up. J. Rheumatol. 15, 1109–1114 (1988).
Oostveen, J. et al. Early detection of sacroiliitis on magnetic resonance imaging and subsequent development of sacroiliitis on plain radiography. A prospective, longitudinal study. J. Rheumatol. 26, 1953–1958 (1999).
Rudwaleit, M. et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum. 60, 717–727 (2009).
Poddubnyy, D. et al. Baseline radiographic damage, elevated acute phase reactants and cigarette smoking status predict radiographic progression in the spine in early axial spondyloarthritis. Arthritis Rheum. http://dx.doi.org/10.1002/art.33465.
van Tubergen, A. et al. Development of new syndesmophytes and bridges in ankylosing spondylitis and their predictors: a longitudinal study. Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis-2011-200411.
Braun, J. et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann. Rheum. Dis. 70, 896–904 (2011).
van der Heijde, D. et al. 2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann. Rheum. Dis. 70, 905–908 (2011).
Haibel, H. et al. Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Arthritis Rheum. 58, 1981–1991 (2008).
Barkham, N. et al. Clinical and imaging efficacy of infliximab in HLA-B27-positive patients with magnetic resonance imaging-determined early sacroiliitis. Arthritis Rheum. 60, 946–954 (2009).
Song, I. H. et al. Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial. Ann. Rheum. Dis. 70, 590–596 (2011).
Rudwaleit, M., Listing, J., Brandt, J., Braun, J. & Sieper, J. Prediction of a major clinical response (BASDAI 50) to TNF-alpha blockers in ankylosing spondylitis. Ann. Rheum. Dis. 63, 665–670 (2004).
Rudwaleit, M. et al. Effectiveness, safety, and predictors of good clinical response in 1,250 patients treated with adalimumab for active ankylosing spondylitis. J. Rheumatol. 36, 801–808 (2009).
Vastesaeger, N. et al. Predicting the outcome of ankylosing spondylitis therapy. Ann. Rheum. Dis. 70, 973–981 (2011).
Bakland, G., Nossent, H. C. & Gran, J. T. Incidence and prevalence of ankylosing spondylitis in Northern Norway. Arthritis Care Res. 53, 850–855 (2005).
Gran, J. T., Husby, G. & Hordvik, M. Prevalence of ankylosing spondylitis in males and females in a young middle-aged population of Tromsø, northern Norway. Ann. Rheum. Dis. 44, 359–367 (1985).
Liao, Z. T. et al. An epidemiological survey of low back pain and axial spondyloarthritis in a Chinese Han population. Scand. J. Rheumatol. 38, 455–459 (2009).
Braun, J. et al. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum. 41, 58–67 (1998).
Akkoc, N. & Khan, M. A. Overestimation of the prevalence of ankylosing spondylitis in the Berlin study: comment on the article by Braun, et al. Arthritis Rheum. 52, 4048–4049 (2005).
Gabriel, S. E. & Michaud, K. Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res. Ther. 11, 229 (2009).
Helmick, C. G. et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 58, 15–25 (2008).
Adomaviciute, D. et al. Prevalence survey of rheumatoid arthritis and spondyloarthropathy in Lithuania. Scand. J. Rheumatol. 37, 113–119 (2008).
Brandt, H. C. et al. Performance of referral recommendations in patients with chronic back pain and suspected axial spondyloarthritis. Ann. Rheum. Dis. 66, 1479–1484 (2007).
Poddubnyy, D. et al. Evaluation of 2 screening strategies for early identification of patients with axial spondyloarthritis in primary care. J. Rheumatol. 38, 2452–2460 (2011).
Feldtkeller, E., Khan, M. A., van der Heijde, D., van der Linden, S. & Braun, J. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol. Int. 23, 61–66 (2003).
Sieper, J. & Rudwaleit, M. Early referral recommendations for ankylosing spondylitis (including pre-radiographic and radiographic forms) in primary care. Ann. Rheum. Dis. 64, 659–663 (2005).
Amor, B., Dougados, M. & Mijiyawa, M. Critères de classification des spondylarthropathies [French]. Rev. Rhum. 57, 85–89 (1990).
Calin, A. et al. Clinical history as a screening test for ankylosing spondylitis. JAMA 237, 2613–2614 (1977).
Rudwaleit, M., Metter, A., Listing, J., Sieper, J. & Braun, J. Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria. Arthritis Rheum. 54, 569–578 (2006).
Sieper, J. et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann. Rheum. Dis. 68, 784–788 (2009).
Hermann, J., Giessauf, H., Schaffler, G., Ofner, P. & Graninger, W. Early spondyloarthritis: usefulness of clinical screening. Rheumatology (Oxford) 48, 812–816 (2009).
Braun, A., Saracbasi, E., Grifka, J., Schnitker, J. & Braun, J. Identifying patients with axial spondyloarthritis in primary care: how useful are items indicative of inflammatory back pain? Ann. Rheum. Dis. 70, 1782–1787 (2011).
Sieper, J. et al. Comparing 2 referral strategies to diagnose axial Spondyloarthritis: RADAR. Ann. Rheum. Dis. 70 (Suppl. 3), 81 (2011).
Jois, R. N., Macgregor, A. J. & Gaffney, K. Recognition of inflammatory back pain and ankylosing spondylitis in primary care. Rheumatology (Oxford) 47, 1364–1366 (2008).
Weisman, M. H. et al. Development and validation of a case ascertainment tool for ankylosing spondylitis. Arthritis Care Res. (Hoboken) 62, 19–27 (2010).
Schett, G. & Rudwaleit, M. Can we stop progression of ankylosing spondylitis? Best Pract. Res. Clin. Rheumatol. 24, 363–371 (2010).
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M. Rudwaleit and J. Sieper researched data for the article and substantially contributed to the discussion of content. M. Rudwaleit also wrote the article and edited the manuscript prior to submission.
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M. Rudwaleit has been a member of a speakers bureau, or has served as a scientific advisor for Abbott, Chugai Pharmaceutical Co. (a subsidiary of Roche), MSD, Pfizer and UCB. In addition, he receives grants/research support from Abbott, MSD and Pfizer. J. Sieper has worked as a consultant for Abbott, Merck, Pfizer, Roche and UCB, has been a member of a speakers bureau for Abbott, Merck, Pfizer and UCB, and has received grant or research support from Abbott, Bristol-Myers Squibb, Merck, Pfizer and Roche.
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Comparison of clinical and laboratory SpA features relevant for axial SpA (DOC 95 kb)
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Rudwaleit, M., Sieper, J. Referral strategies for early diagnosis of axial spondyloarthritis. Nat Rev Rheumatol 8, 262–268 (2012). https://doi.org/10.1038/nrrheum.2012.39
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DOI: https://doi.org/10.1038/nrrheum.2012.39
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