Axial spondyloarthritis: concept, construct, classification and implications for therapy

Axial spondyloarthritis: concept, construct, classification and implications for therapy

Axial spondyloarthritis: concept, construct, classification and implications for therapy
Nature Reviews Rheumatology volume 17, pages 109–118 (2021) Cite this article
2452 Accesses
Spondyloarthritis
Abstract
The axial spondyloarthritis (axSpA) disease concept has undergone substantial change from when the entity ankylosing spondylitis was defined by the modified New York criteria in 1984. Developments in imaging, therapy and genetics have all contributed to changing the concept of axSpA from one of erosions in the sacroiliac joints to a spectrum of disease with and without changes evident on plain radiographs. Changes to the previously held concept and construct of the disease have also necessitated new classification criteria. The use of MRI, primarily of the sacroiliac joints, has substantially altered the diagnosis and differential diagnosis of axSpA. Many in the axSpA community believe that the current classification criteria lack specificity, and the CLASSIC study is underway to examine this area. Although much about the evolving axSpA disease concept is universally agreed, there remains disagreement about operationalizing aspects of it, such as the requirement for the objective demonstration of axial inflammation for the classification of axSpA. New imaging technologies, biomarkers and genetics data will probably necessitate ongoing revision of axSpA classification criteria. Advances in our knowledge of the biology of axSpA will settle some differences in opinion as to how the disease concept is applied to the classification and diagnosis of patients.
Key points
The concept of axial spondyloarthritis (axSpA) has expanded from ankylosing spondylitis with evidence of erosions to a spectrum of disease encompassing non-radiographic axSpA and radiographic axSpA.
The current classification criteria capture the entire spectrum of axSpA, but many in the field believe they lack specificity; the CLASSIC study is underway to further assess this issue.
The concept of axSpA is largely agreed upon in the research community, but opinion still diverges about some aspects, for example, the demonstration of objective axial inflammation for axSpA classification.
The current definition of a positive sacroiliac joint MRI scan lacks specificity for axSpA, as demonstrated in imaging studies of individuals with and without back pain and post-partum women.
Concepts such as the theory of natural kinds and latent class analysis enable us to further examine the crucial features of the axSpA concept, with sacroiliitis being the core feature.
Advances in our understanding of the biology of axSpA via novel imaging, genetic and biomarker studies will probably enable the resolution of many current issues in axSpA diagnosis and classification.
Access options
Get full journal access for 1 year
$59.00
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
from$8.99
All prices are NET prices.
Additional access options:
Fig. 1: The spectrum of axial spondyloarthritis.
Fig. 2: Clinical features of axial spondyloarthritis in addition to axial disease.
Fig. 3: The concept of axial spondyloarthritis.
Fig. 4: Classification criteria for axSpA.
References
1.
van der Linden, S., Valkenburg, H. A. & Cats, A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 27, 361–368 (1984).
PubMed   Google Scholar  
2.
de Winter, J. J. et al. Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: a meta-analysis. Arthritis Res. Ther. 18, 196 (2016).
PubMed   PubMed Central   Google Scholar  
3.
Panush, R. S., Paraschiv, D. & Dorff, R. E. The tainted legacy of Hans Reiter. Semin. Arthritis Rheum. 32, 231–236 (2003).
PubMed   Google Scholar  
4.
Dougados, M. et al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum. 34, 1218–1227 (1991).
CAS   PubMed   Google Scholar  
5.
Zochling, J., Brandt, J. & Braun, J. The current concept of spondyloarthritis with special emphasis on undifferentiated spondyloarthritis. Rheumatology 44, 1483–1491 (2005).
CAS   PubMed   Google Scholar  
6.
Moll, J. M. et al. Associations between ankylosing spondylitis, psoriatic arthritis, Reiter’s disease, the intestinal arthropathies, and Behcet’s syndrome. Medicine 53, 343–364 (1974).
CAS   PubMed   Google Scholar  
7.
Kirino, Y. et al. Genome-wide association analysis identifies new susceptibility loci for Behcet’s disease and epistasis between HLA-B*51 and ERAP1. Nat. Genet. 45, 202–207 (2013).
CAS   PubMed   PubMed Central   Google Scholar  
8.
International Genetics of Ankylosing Spondylitis Consortium (IGAS). et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat. Genet. 45, 730–738 (2013).
9.
Wright, V. & Moll, J. The Meaning of Seronegativity and Seropositivity, in Seronegative Polyarthritis. (Elsevier/North-Holland Biomedical Press, 1976).
10.
Nash, P. et al. Seronegative spondyloarthropathies: to lump or split? Ann. Rheum. Dis. 64, ii9–ii13 (2005).
PubMed   PubMed Central   Google Scholar  
11.
Taylor, W. J. & Robinson, P. C. Classification criteria: peripheral spondyloarthropathy and psoriatic arthritis. Curr. Rheumatol. Rep. 15, 317 (2013).
PubMed   Google Scholar  
15.
Toussirot, E. Late-onset ankylosing spondylitis and spondylarthritis: an update on clinical manifestations, differential diagnosis and pharmacological therapies. Drugs Aging 27, 523–531 (2010).
CAS   PubMed   Google Scholar  
16.
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).
CAS   PubMed   Google Scholar  
17.
Poddubnyy, D. et al. Diagnostic accuracy of inflammatory back pain for axial spondyloarthritis in rheumatological care. RMD Open 4, e000825 (2018).
PubMed   PubMed Central   Google Scholar  
18.
Hermann, K. G. et al. Magnetic resonance imaging of inflammatory lesions in the spine in ankylosing spondylitis clinical trials: is paramagnetic contrast medium necessary? J. Rheumatol. 32, 2056–2060 (2005).
PubMed   Google Scholar  
19.
de Hooge, M. et al. Magnetic resonance imaging of the sacroiliac joints in the early detection of spondyloarthritis: no added value of gadolinium compared with short tau inversion recovery sequence. Rheumatology 52, 1220–1224 (2013).
PubMed   Google Scholar  
20.
Maksymowych, W. P. et al. MRI lesions in the sacroiliac joints of patients with spondyloarthritis: an update of definitions and validation by the ASAS MRI working group. Ann. Rheum. Dis. 78, 1550–1558 (2019).
PubMed   Google Scholar  
21.
Gong, Y. et al. Ten years’ experience with needle biopsy in the early diagnosis of sacroiliitis. Arthritis Rheum. 64, 1399–1406 (2012).
PubMed   Google Scholar  
22.
Bakker, P. A. et al. Is it useful to repeat MRI of the sacroiliac joints after three months or one year in the diagnostic process of patients with chronic back pain suspected of axial spondyloarthritis? Arthritis Rheumatol. 71, 382–391 (2019).
CAS   PubMed   PubMed Central   Google Scholar  
23.
Sengupta, R. et al. Short-term repeat magnetic resonance imaging scans in suspected early axial spondyloarthritis are clinically relevant only in HLA-B27-positive male subjects. J. Rheumatol. 45, 202–205 (2018).
PubMed   Google Scholar  
24.
Rusman, T. et al. Presence of active MRI lesions in patients suspected of non-radiographic axial spondyloarthritis with high disease activity and chance at conversion after a 6-month follow-up period. Clin. Rheumatol. 39, 1521–1529 (2020).
PubMed   Google Scholar  
25.
van Onna, M. et al. HLA-B27 and gender independently determine the likelihood of a positive MRI of the sacroiliac joints in patients with early inflammatory back pain: a 2-year MRI follow-up study. Ann. Rheum. Dis. 70, 1981–1985 (2011).
PubMed   Google Scholar  
26.
Landewe, R. et al. A single determination of C-reactive protein does not suffice to declare a patient with a diagnosis of axial spondyloarthritis ‘CRP-negative’. Arthritis Res. Ther. 20, 209 (2018).
PubMed   PubMed Central   Google Scholar  
27.
Visser, M. et al. Elevated C-reactive protein levels in overweight and obese adults. JAMA 282, 2131–2135 (1999).
28.
Aggarwal, R. et al. Distinctions between diagnostic and classification criteria? Arthritis Care Res. 67, 891–897 (2015).
Google Scholar  
29.
Khan, M. A. & van der Linden, S. Axial spondyloarthritis: a better name for an old disease: a step toward uniform reporting. ACR Open Rheumatol. 1, 336–339 (2019).
PubMed   PubMed Central   Google Scholar  
30.
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).
PubMed   Google Scholar  
31.
Maksymowych, W. P. The role of imaging in the diagnosis and management of axial spondyloarthritis. Nat. Rev. Rheumatol. 15, 657–672 (2019).
CAS   PubMed   Google Scholar  
32.
Feldtkeller, E. et al. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol. Int. 23, 61–66 (2003).
PubMed   Google Scholar  
33.
Seven, S. et al. Magnetic resonance imaging of lesions in the sacroiliac joints for differentiation of patients with axial spondyloarthritis from control subjects with or without pelvic or buttock pain: a prospective, cross-sectional study of 204 participants. Arthritis Rheumatol. 71, 2034–2046 (2019).
PubMed   Google Scholar  
34.
de Winter, J. et al. Magnetic resonance imaging of the sacroiliac joints indicating sacroiliitis according to the Assessment of Spondyloarthritis International Society definition in healthy individuals, runners, and women with postpartum back pain. Arthritis Rheumatol. 70, 1042–1048 (2018).
PubMed   PubMed Central   Google Scholar  
35.
Baraliakos, X. et al. Frequency of MRI changes suggestive of axial spondyloarthritis in the axial skeleton in a large population-based cohort of individuals aged

Images Powered by Shutterstock