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Axial Spondyloarthritis (AS,nr-axSpA) 3D Explorer

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AS/r-axSpA

nr-axSpA

nr-axSpA

Patient symptoms

First nr-axSpA case is a 35-year-old female patient who presented with:

  • Chronic, dull, moderate-to-severe back pain for 7 years, which worsens when reclining and improves with walking3,14

  • Fatigue3,15,18

  • Three hours of morning stiffness15,16

  • Neck pain3

She was initially treated with NSAIDs for “lumbago due to poor posture” and was referred to several different specialists, including chiropractors, physiatrists, and neurologists. She also completed several physical therapy treatments

She previously presented with “red eye”, which was diagnosed by an ophthalmologist as immune uveitis3

Inflammation with minor erosion and joint space irregularities in the SIJs along with inflammation in the spine

Models for illustrative purposes only. Not representative of all cases.


Skeletal changes in the SIJs depicting inflammation, minor erosion, and joint space irregularities for nr-axSpA

Models for illustrative purposes only. Not representative of all cases.

SIJ Skeletal Changes

Sacroiliitis is not evident from X-rays; however, MRI can reveal inflammation of the sacroiliac joints16,17

Imaging Arm | SIJ X-ray

An X-ray of SIJ showing unilateral joint space narrowing
An X-ray of SIJ showing unilateral joint space narrowing
An X-ray of SIJ showing unilateral joint space narrowing
Unilateral joint space narrowing consistent with Grade 1 sacroiliitis, and is thus nondiagnostic per mNY criteria3

  1. Unilateral joint space narrowing

Imaging Arm | SIJ MRI

An MRI of SIJ showing bone marrow edema suggestive of unilateral sacroiliitis on the left
An MRI of SIJ showing bone marrow edema suggestive of unilateral sacroiliitis on the left
An MRI of SIJ showing bone marrow edema suggestive of unilateral sacroiliitis on the left
Asymmetric bone marrow edema suggestive of unilateral inflammation of the sacroiliac joints3

  1. Bone marrow edema suggestive of unilateral sacroiliitis of the left side

Images courtesy of Dr. R. Inman (2019) with permission to use in the AS/r-axSpA 3D Explorer Tool for educating HCPs globally.


Skeletal changes in the spine depicting inflammation for nr-axSpA

Models for illustrative purposes only. Not representative of all cases.

Spine Skeletal Changes

While X-rays of the cervical and lumbar spine are performed to look for changes, typically no major structural changes in the spine are visible in images of patients with nr-axSpA3


Imaging Arm | Spine X-ray

An X-ray of the lumbar spine
An X-ray of the lumbar spine
An X-ray of the lumbar spine
Lumbar spine, nondiagnostic
An X-ray of the cervical spine
An X-ray of the cervical spine
An X-ray of the cervical spine
Cervical spine, nondiagnostic

Images courtesy of Dr. R. Inman (2021) with permission to use in the AS/r-axSpA nr-axSpA 3D Explorer Tool for educating HCPs globally.


Important Clinical Features

  • Inflammatory back pain3,14

  • HLA-B27 negative, consistent with clinical cohorts that have shown that patients with nr-axSpA and are HLA-B27negative are more likely to be female18

  • Slightly elevated CRP levels (8mg/L) in comparison to normal (5mg/L), consistent with what clinical cohorts have shown; CRP levels tend not to be as elevated as in AS18,19,21

  • X-rays showing unilateral sacroilitis grade 1 which does not meet the definition requirements for AS as per mNY criteria16,18

  • Some arthritis of C-5 visible on X-ray and MRI images of the neck. X-rays of other areas of the spine usually show minimal to no changes and therefore are nondiagnostic3
Skeletal changes in nr-axSpA

Models for illustrative purposes only. Not representative of all cases.

Patient symptoms

Second nr-axSpA case is with a 30-year-old male patient who presented with:

  • Chronic back pain for 8 years which worsens when resting and improves with walking3,14,20

  • Gradual onset of symptoms accompanied by 2 hours of morning stiffness and fatigue3

  • Worsening pain at night, with patient getting up to walk “to stretch his back as that seems to help”20

  • Patient is HLA-B27 positive18,22

  • Pain in the interscapular area3

  • Elevated CRP levels in comparison to normal18,19,21

He was diagnosed with nr-axSpA by a rheumatologist who started him on NSAIDs3

Skeletal depiction of the nr-axSpA

Models for illustrative purposes only. Not representative of all cases.


Skeletal changes in the SIJs for nr-axSpA

Models for illustrative purposes only. Not representative of all cases.

SIJ Skeletal Changes

Sacroiliitis may not be evident from X-rays or MRIs20

Clinical Arm | SIJ X-ray

A normal X-ray of the SIJs
A normal X-ray of the SIJs
A normal X-ray of the SIJs
Nondiagnostic per mNY criteria3

Clinical Arm | SIJ MRI

A normal MRI of the SIJs
A normal MRI of the SIJs
A normal MRI of the SIJs
Nondiagnostic per ASAS classification criteria3

Images courtesy of Dr. R. Inman (2019) with permission to use in the AS/r-axSpA 3D Explorer Tool for educating HCPs globally.


Skeletal changes in the spine for nr-axSpA

Models for illustrative purposes only. Not representative of all cases.

Spine Skeletal Changes

While X-rays of the cervical and lumbar spine are performed to look for changes, typically no major structural changes in the spine are visible in images of patients with nr-axSpA3


Clinical Arm | Spine X-ray

An X-ray of the cervical spine
An X-ray of the lumbar spine
An X-ray of the cervical spine
An X-ray of the lumbar spine
Lumbar spine, nondiagnostic

Clinical Arm | Spine MRI

An MRI of the thoracic spine with bone marrow edema
An MRI of the thoracic spine with bone marrow edema
An MRI of the thoracic spine with bone marrow edema
Thoracic spine MRI showing bone marrow edema of two thoracic vertebrae

Images courtesy of Dr. R. Inman (2019) with permission to use in the AS/r-axSpA 3D Explorer Tool for educating HCPs globally.


Important Clinical Features

  • Inflammatory back pain3,14,20

  • HLA-B27 positive, which is a mandatory SpA feature for the clinical arm of the ASAS classification criteria3

  • Consistent with findings that males are more likely to be HLA-B27 positive18,22

  • Elevated CRP levels in comparison to normal18,19,21

  • Enthesitis on left heel (1 year ago) which improved with corticosteroid injection under ultrasound guidance3,20

  • No evidence of sacroiliitis or significant changes in the spine/pelvis on X-ray and MRI images3,16,20

  • Clinical arm of the ASAS classification criteria: HLA-B27 positive + ≥2 SpA features; in this particular case, SpA features include inflammatory back pain, enthesitis, and elevated CRP3
Skeletal changes in nr-axSpA

Models for illustrative purposes only. Not representative of all cases.

References

  1. Van Mechelen M, Gulino GR, de Valm K, Lories R. Bone disease in axial spondyloarthritis. Calcif Tissue Int. 2018;102(5):547-558.
  2. 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(5):703-709.
  3. Sieper J, Rudwaleit M, Baraliakos X, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis. 2009;68(Suppl 2):ii1-ii44.
  4. Østergaard M, Lambert RGW. Imaging in ankylosing spondylitis. Ther Adv Musculoskel Dis. 2012;4(4):301-311.
  5. Jurik, A. Spondylarthropathy Imaging. www.spa-imaging.org. Accessed July 26, 2023.
  6. Neerinckx B, Lories RJ. Structural disease progression in axial spondyloarthritis: still a cause for concern? Curr Rheumatol Rep. 2017;19:14.
  7. Maksymowych WP, Inman RD, Salonen D, et al. Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of spinal inflammation in ankylosing spondylitis. Arthritis Rheum. 2005;53(4):502-509
  8. Raychaudhuri SK, Saxena A, Raychaudhuri SP. Role of IL-17 in the pathogenesis of psoriatic arthritis and axial spondyloarthritis. Clin Rheumatol. 2015;34(6):1019-1023.
  9. Watad A, Bridgewood C, Russell T, et al. The early phases of ankylosing spondylitis: emerging insights from clinical and basic science. Front Immunol. 2018;9:2668.
  10. Pialat JB, Di Marco L, Feydy A, et al. Sacroiliac joints imaging in axial spondyloarthritis. Diagn Interv Imaging. 2016;97(7-8):697-708.
  11. Braun J, van der Heijde D, Dougados M, et al. Staging of patients with ankylosing spondylitis: a preliminary proposal. Ann Rheum Dis. 2002;61(Suppl III):iii19-iii23.
  12. Poddubnyy D, Sieper J. Mechanism of new bone formation in axial spondyloarthritis. Curr Rheumatol Rep. 2017;19(9):55.
  13. Osta B, Benedetti G, Miossec P. Classical and paradoxical effects of TNF-α on bone homeostasis. Front Immunol. 2014;5:48.
  14. Baraliakos X, Braun J. Non-radiographic axial spondyloarthritis and ankylosing spondylitis: what are the similarities and differences? RMD Open. 2015;1(Suppl 1):e000053.
  15. Kiltz U, Baraliakos X, Regel A, et al. Causes of pain in patients with axial spondyloarthritis. Clin Exp Rheumatol. 2017;35(Suppl 107):S102-107.
  16. Deodhar A, Reveille JD, van den Bosch F, et al. The concept of axial spondyloarthritis: joint statement of the spondyloarthritis research and treatment network and the Assessment of SpondyloArthritis international Society in response to the US Food and Drug Administration's comments and concerns. Arthritis & Rheumatol. 2014;66(10):2649-2656.
  17. Bubová K, Forejtová Š, Zegzulková K, et al. Cross-sectional study of patients with axial spondyloarthritis fulfilling imaging arm of ASAS classification criteria: baseline clinical characteristics and subset differences in a single-centre cohort. BMJ Open. 2019;9:e024713.
  18. Ghosh N, Ruderman EM. Nonradiographic axial spondyloarthritis: clinical and therapeutic relevance. Arthritis Res Ther. 2017;19(1):286.
  19. Deodhar A, van der Heijde D, Gensler LS, et al. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet. 2020;395(10217):53-64.
  20. Rudwaleit M, Landewé R, van der Heijde D, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part 1): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis. 2009;68(6):770-776.
  21. Poddubnyy D, Rudwaleit M, Haibel H, et al. Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann Rheum Dis. 2011;70(8):1369-1374.
  22. Zhang S, Wang Y, Peng L, et al. Comparison of clinical features in HLA-B27 positive and negative patients with axial spondyloarthritis: results from a cohort of 4,131 patients. Front Med (Lausanne). 2020;7:609562.
  23. Barhum, L. Verywell Health. www.verywellhealth.com/axial-spondyloarthritis-progression-6890574. Accessed July 26, 2023.
  24. Danve, A., Deodhar, A. Treatment of axial spondyloarthritis: an update. Nat Rev Rheumatol 18, 205–216 (2022). https://doi.org/10.1038/s41584-022-00761-z
  25. Schwartzman, S., Ruderman, EMR. A Road Map of the Axial Spondyloarthritis Continuum. Mayo Clin Proc. 2022;97(1):134-145

Abbreviations

AS: ankylosing spondylitis; ASAS: Assessment of SpondyloArthritis international Society; CRP: C-reactive protein; HCP: health care practitioner; HLA-B27: human leukocyte antigen B27; mNY: modified New York; MRI: magnetic resonance imaging; nr-axSpA: nonradiographic axial spondyloarthritis; NSAID: nonsteroidal anti-inflammatory drug; r-axSpA: radiographic axial spondyloarthritis; SIJ: sacroiliac joint; SpA: spondyloarthritis; STIR: short tau inversion recovery


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