Ankylosing Spondylitis (Axial Spondyloarthritis)
Chronic inflammatory arthritis of the spine and sacroiliac joints; HLA-B27-associated; presents with inflammatory back pain in young adults.
Also known as: AS, ankylosing spondylitis, axial spondyloarthritis, axSpA, Bechterew disease
Overview
Chronic inflammatory disease of the axial skeleton — sacroiliac joints, spine, and hips — leading to enthesitis, syndesmophyte formation, and eventually bony ankylosis. The prototypical seronegative spondyloarthropathy.
Epidemiology
Onset typically 15-40; rarely begins after age 45. Male-to-female ratio ~2-3:1, though women often have milder, less radiographic disease and are underdiagnosed. Prevalence parallels HLA-B27 prevalence in the population (0.1-1%).
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Risk factors
- HLA-B27 positivity (present in 85-90% of AS patients; only ~5% of HLA-B27 carriers develop AS)
- Family history of spondyloarthritis
- Male sex
- IBD, psoriasis, recurrent uveitis (related spondyloarthritis spectrum)
Pathophysiology
Enthesitis — inflammation at insertions of tendons, ligaments, and joint capsules — is the unifying lesion. Driven by IL-17/IL-23 axis and TNF-alpha. Inflammation is followed by reactive new bone formation, producing syndesmophytes that bridge vertebral bodies and ultimately fuse the spine ('bamboo spine').
Clinical presentation
Symptoms
- Inflammatory back pain — insidious onset before age 45, duration >3 months
- Morning stiffness >30 minutes
- Pain improves with exercise, worsens with rest
- Night pain, especially second half of night
- Alternating buttock pain (sacroiliitis)
- Peripheral enthesitis — Achilles tendon, plantar fascia
- Dactylitis (sausage digit)
- Anterior uveitis (acute, unilateral, recurrent — ~25% lifetime risk)
Signs / physical exam
- Reduced lumbar flexion (Schober test: <5 cm increase in 10 cm marked segment with forward flexion)
- Reduced chest expansion (<2.5 cm at 4th intercostal space) — costovertebral involvement
- Tenderness over sacroiliac joints (FABER/Patrick test)
- Loss of lumbar lordosis, increased thoracic kyphosis, occiput-to-wall distance increased (advanced disease)
- Aortic regurgitation murmur (rare, late)
Differential diagnosis
- Mechanical low back pain — Worse with activity, better with rest; no morning stiffness; normal inflammatory markers
- Lumbar disc disease / radiculopathy — Radicular leg pain, positive straight-leg raise, MRI findings
- Psoriatic arthritis / IBD-associated arthritis / reactive arthritis — Other spondyloarthritis subtypes — extra-articular features distinguish
- Diffuse idiopathic skeletal hyperostosis (DISH) — Older patients, flowing anterior osteophytes ≥4 levels, preserved SI joints, normal CRP
- Osteoarthritis of spine — Older patients, mechanical pattern, marginal osteophytes
- Fibromyalgia — Widespread pain, normal imaging, normal CRP
- Infection (vertebral osteomyelitis) — Fever, focal severe pain, elevated WBC; MRI and biopsy diagnostic
Diagnostic workup
Diagnostic criteria
ASAS axial spondyloarthritis criteria (patients with ≥3 months back pain, age <45): sacroiliitis on imaging plus ≥1 SpA feature, OR HLA-B27 plus ≥2 SpA features.
Labs
- HLA-B27 — strongly supportive when positive in the right clinical context
- CRP, ESR — elevated in active disease but normal in many patients
- CBC — anemia of chronic disease in active disease
- RF, anti-CCP — negative (seronegative)
Imaging
- Pelvic radiograph — sacroiliitis (sclerosis, erosions, joint space narrowing or fusion). Grade ≥2 bilateral or ≥3 unilateral required for modified New York criteria
- MRI of sacroiliac joints — detects bone marrow edema (active sacroiliitis) years before radiographic changes; essential for non-radiographic axial spondyloarthritis
- Spine radiographs — syndesmophytes, squaring of vertebral bodies, shiny corners (Romanus lesions), eventual 'bamboo spine'
- Lateral cervical spine radiograph before intubation or surgery to assess for fusion and fracture risk
Diagnostic algorithm
| Inflammatory Back Pain Feature | Notes |
|---|---|
| Onset <45 years | Insidious onset |
| Duration >3 months | Chronic |
| Morning stiffness >30 min | Improves with movement |
| Improves with exercise | NOT with rest |
| Pain at night | Often second half of night |
| Alternating buttock pain | Sacroiliitis |
| HLA-B27 | Positive in 85-90% |
| MRI SI joint | Bone marrow edema = active sacroiliitis |
Treatment
First-line
- Patient education and exercise — daily stretching, posture training, swimming or pilates
- NSAIDs — naproxen, ibuprofen, indomethacin, meloxicam — full anti-inflammatory dose for 2-4 weeks, then maintenance; continuous use may slow radiographic progression in active disease
- Smoking cessation — smoking accelerates radiographic progression
Second-line / adjunct
- TNF inhibitors — etanercept, adalimumab, infliximab, golimumab, certolizumab — first-line biologic when NSAIDs fail
- IL-17 inhibitors — secukinumab, ixekizumab — alternative when TNFi contraindicated or ineffective (avoid in IBD — may worsen)
- JAK inhibitors — tofacitinib, upadacitinib — newer option
- Sulfasalazine — useful for peripheral arthritis but ineffective for axial disease
- Methotrexate — limited efficacy for axial disease; reserved for peripheral joints
- Intra-articular corticosteroid injections for SI joints or enthesitis; systemic steroids generally avoided
Complications
- Spinal fusion ('bamboo spine') with rigid posture
- Vertebral fracture — fused spine is brittle; even minor trauma can cause unstable fractures; high suspicion required
- Atlantoaxial subluxation
- Anterior uveitis (recurrent)
- Aortic regurgitation, conduction defects
- Apical pulmonary fibrosis (rare)
- Restrictive lung disease from fused thoracic cage
- Osteoporosis paradoxically despite syndesmophytes
- Cauda equina syndrome (rare, late)
PANCE pearls
- Inflammatory back pain in a young adult that improves with activity is the cardinal history — opposite of mechanical pain.
- MRI of SI joints with bone marrow edema diagnoses non-radiographic axSpA years before plain films change.
- A fused spine fractures easily — image the entire spine, not just the symptomatic area, after any trauma.
- IL-17 inhibitors can worsen IBD — choose TNFi if both AS and IBD coexist.
- Acute anterior uveitis in a young person is HLA-B27 spondyloarthritis until proven otherwise — refer to ophthalmology urgently.
References
- ACR/SAA/SPARTAN 2019 — 2019 Update of the ACR/SAA/SPARTAN Treatment Recommendations for Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis (Ward et al., Arthritis Rheumatol 2019)
- ASAS-EULAR 2022 — ASAS-EULAR Recommendations for the Management of Axial Spondyloarthritis (Ramiro et al., Ann Rheum Dis 2023)
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