Spondyloarthritis (SpA) encompasses a group of rheumatic disorders that share clinical, genetic and radiographic features and includes psoriatic arthritis, reactive arthritis and arthritis of inflammatory bowel disease (IBD).
These disorders affect 2–3% of the population and are twice as common as rheumatoid arthritis.
The spectrum of spondyloarthritis (SpA) and overlap (cross-sectional and longitudinal) between different SpA forms. | IBD, inflammatory bowel disease. | Proft, F., & Poddubnyy, D. (2018). Ankylosing spondylitis and axial spondyloarthritis: recent insights and impact of new classification criteria. Therapeutic advances in musculoskeletal disease, 10(5-6), 129–139. doi:10.1177/1759720X18773726
Axial spondyloarthritis (axSpA): Umbrella term encompassing a number of inflammatory spine conditions, including:
Ankylosing spondylitis (AS) or radiographic axSpA Non-radiographic axial SpA (nr-axSpA) SpA-associated with inflammatory bowel disease (IBD) Undifferentiated SpA
Spectrum of axial spondyloarthritis: The figure presents the proposed grouping of axial spondyloarthritis, which normally starts with inflammation in the sacroiliac joints (non-radiographic stage; part a). Structural damage that is visible on X-ray scans (radiographic stage) develops later but not in all patients. Abnormalities in the spine also develop later and only in some patients. Some patients with non-radiographic disease show no abnormalities on MRI of the sacroiliac joints (part b). However, in most patients, inflammation of the sacroiliac joints is detectable by MRI before structural changes occur (part c). Structural changes that are visible on X-ray scans include sclerosis, erosion and new bone formation (part d). Syndesmophytes of the spine (that is, bone growth between vertebrae) are characteristic of spinal involvement in axial spondyloarthritis (part e). | ASAS, Assessment of Spondyloarthritis International | Sieper, J., Braun, J., Dougados, M., & Baeten, D. (2015). Axial spondyloarthritis. Nature Reviews Disease Primers, 1(1), 15013. https://doi.org/10.1038/nrdp.2015.13
Human leukocyte antigen (HLA)-B27 (5-6%)
Overview of hypotheses explaining role of HLA‐B27 in axial spondyloarthritis. A, Arthritogenic peptide hypothesis: Pathogen‐ or self‐ derived peptides bound to conventional HLA‐B27/beta‐2 microglobulin complexes are recognized by autoreactive CD8+ T cells through the T‐cell receptor (TCR). B, Cell surface HLA‐ B27 free heavy chain homodimer expression hypothesis: HLA‐B27 free heavy chains including dysfunctional HLA‐B27 homodimers are expressed at the cell surface and activate cells bearing killer immunoglobulin‐like receptors (KIR) and/or leucocyte immunoglobulin‐like receptors such as CD4+ cells or NK cells. C, Misfolded HLA‐B27 hypothesis: Misfolding of HLA‐B27 within the endoplasmic reticulum (ER) causes an unfolded protein response (UPR) or other form of cellular stress, or autophagy, which has downstream effects on cellular function (eg, excessive IL‐23 release) | de Koning, A., Schoones, J. W., van der Heijde, D., & van Gaalen, F. A. (2018). Pathophysiology of axial spondyloarthritis: Consensus and controversies. European Journal of Clinical Investigation, 48(5), e12913. https://doi.org/10.1111/eci.12913
Inflammatory back pain (IBP):
Alternating buttock pain Awakening only in the second half of the night with spinal pain/stiffness
Inflammatory Mechanical Age at symptom onset <40 years old Any age Onset Insidious, persists for >3 months Variable Activity Improves with exercise Improves with rest Morning stiffness Moderate, persists for >45 minutes Mild, short-lived Inflammatory markers Elevated in 50–70% Normal
Sacroiliitis (HALLMARK) Syndesmophytes → Spinal ankylosis (late-stage)
Asymmetric oligoarthritis (≤4 joints) (50%), often targeting the lower limb joints. Enthesitis (inflammation at insertions of tendons, ligaments and joint capsules into bone)
Intercostal enthesitis → chest wall pain Dactylitis “sausage digit”: Diffuse swelling of a finger/toe caused by tenosynovitis of the digital flexor tendon
Multiorgan involvement in spondyloarthritis shown on Leonardo da Vinci’s L’Uomo Vitruviano | de Koning, A., Schoones, J. W., van der Heijde, D., & van Gaalen, F. A. (2018). Pathophysiology of axial spondyloarthritis: Consensus and controversies. European Journal of Clinical Investigation, 48(5), e12913. https://doi.org/10.1111/eci.12913
Mucosal inflammation (60%) on colonoscopy (M/C extraarticular manifestation)
Symptomatic inflammatory bowel disease (IBD) (10%) Uniocular anterior uveitis (40%): Acute painful red eye, with blurred vision and photophobia.
℞: Corticosteroid and mydriatic eye drops Osteopenia and osteoporosis → ↑ risk of vertebral fracture Apical pulmonary fibrosis (15%) Aortic valve incompetence (10%) Psoriasis (10%)
Schematic of extra-skeletal manifestations of ankylosing spondylitis. | AS: Ankylosing spondylitis. | Ghasemi-Rad, M., Attaya, H., Lesha, E., Vegh, A., Maleki-Miandoab, T., Nosair, E., … Mohammadi, A. (2015). Ankylosing spondylitis: A state of the art factual backbone. World journal of radiology, 7(9), 236–252. doi:10.4329/wjr.v7.i9.236
Disease probabilities of the presence of axial spondyloarthritis (SpA) according to the presence of individual SpA parameters in individual patients: The prevalence (pretest probability) of having axial SpA among patients with chronic back pain is 5%. To calculate the disease probability for an individual patient, the likelihood ratios (LRs) of the parameters that are present in the patient are multiplied, resulting in an individual LR product. Thus, the resulting LR product depends on both the number of parameters present and the LR of the parameters present. If the LR product is 80, the disease probability will be 80%, and if the LR product is 200, the disease probability will be >90%. A disease probability of 90% or more is regarded by us as definite disease. | NSAIDs: nonsteroidal anti inflammatory drugs; MRI: magnetic resonance imaging; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; SpA: spondyloarthropathy | Rudwaleit, et al. Ann Rheum Dis 2004; 63:535–43, with permission.
Assessment of Spondyloarthritis International Society (ASAS) classification criteria:
ASAS classification criteria for axial spondyloarthritis. | IBD = inflammatory bowel disease, CRP = C-reactive protein, NSAID = non-steroidal antiinflammatory drug) | Golder, V., & Schachna, L. (2013). Ankylosing spondylitis An update. Australian Family Physician, 42, 780–784. Retrieved from http://www.racgp.org.au/afp/2013/november/ankylosing-spondylitis/
Reduced spinal mobility:
Modified Schober’s test: Serial measures to assess progression of spinal restriction
May be abnormal with disc disease and degenerative lumbar disease.
Lumbar side flexion (best measure of overall spinal restriction and disease activity) Occiput-to-wall distance: should be zero in normal people. Chest expansion (4th intercostal space): abnormal (<5 cm) in only a minority of patients during the first few years of disease
Modified Schober test for spinal mobility: (A) Patient standing erect. Mark an imaginary line connecting both posterior superior iliac spines (close to the dimples of Venus). (B) A mark is placed 10 cm above. (C) The patient bends forward maximally, measure the difference between the two marks. Report the increase (in cm to the nearest 0.1 cm). The best of two tries is recorded. | ASAS handbook, Ann Rheum Dis 2009; 68
Standardized plain radiographic grading scale exists for sacroiliitis:
Radiographic grading of sacroiliac joints. Grade 1: Suspicious changes, not definitive. Grade 2: Small localised areas of erosions or sclerosis; normal joint space width. Grade 3: Definite changes of erosions, sclerosis, narrowing or partial fusion. Grade 4: Complete fusion | Golder, V., & Schachna, L. (2013). Ankylosing spondylitis An update. Australian Family Physician, 42, 780–784. Retrieved from http://www.racgp.org.au/afp/2013/november/ankylosing-spondylitis/
Early findings: Squaring of vertebral bodies (early sign): Loss of normal concavity of the anterior and posterior borders of the vertebral body due to inflammation and bone deposition. Romanus lesions “shiny corner sign”: Small erosions and reactive sclerosis at the corners of the vertebral bodies Late-stage findings: Ankylosis (fusion) of the facet joints of the spine Syndesmophytes Calcification of anterior longitudinal ligament, supraspinous ligaments, and interspinous ligaments. Dagger sign represented as a single radiodense line running vertically down the spine on frontal radiographs. Bamboo spine sign: Vertebral body fusion by syndesmophytes This fusion predisposes to progressive back stiffness
Lumbar spine changes in AS. A) Shiny corners and erosions. B) Early syndesmophytes C) Spinal fusion or ankylosis | Golder, V., & Schachna, L. (2013). Ankylosing spondylitis An update. Australian Family Physician, 42, 780–784. Retrieved from http://www.racgp.org.au/afp/2013/november/ankylosing-spondylitis/
MRI of the spine in the sagittal plane using T2-STIR sequences that incorporate suppression of normal marrow fat signal. Abnormal increased signal on the STIR sequence represents increased concentration of “free water” otherwise referred to as “bone marrow edema.” This abnormal signal represents inflammation. Consecutive upper and lower anterior endplates of vertebrae are shown (arrows) at baseline and then after 12 and 54 weeks of treatment with Etanercept. Note the improvement of the inflammatory lesions seen at the endplates. | MRI: Magnetic resonance imaging. | Maksymowych WP, Lambert RGW, University of Alberta website (altarheum.com)
Treatment algorithm for axial spondyloarthritis (SpA) based on the Assessment in Spondyloarthritis International Society/European League Against Rheumatism and American College of Rheumatology/Spondylitis Association of America/SpA Research and Treatment Network recommendations. | bDMARDs, biologic disease-modifying antirheumatic drugs; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; IL-17A, interleukin-17A; NSAIDs, nonsteroidal anti-inflammatory drugs; TNF, tumour necrosis factor. | Proft, F., & Poddubnyy, D. (2018). Ankylosing spondylitis and axial spondyloarthritis: recent insights and impact of new classification criteria. Therapeutic advances in musculoskeletal disease, 10(5-6), 129–139. doi:10.1177/1759720X18773726
Sieper, J., Braun, J., Dougados, M., & Baeten, D. (2015). Axial spondyloarthritis. Nature Reviews Disease Primers, 1(1), 15013. https://doi.org/10.1038/nrdp.2015.13