Musculoskeletal · PANCE / PANRE

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 FeatureNotes
Onset <45 yearsInsidious onset
Duration >3 monthsChronic
Morning stiffness >30 minImproves with movement
Improves with exerciseNOT with rest
Pain at nightOften second half of night
Alternating buttock painSacroiliitis
HLA-B27Positive in 85-90%
MRI SI jointBone marrow edema = active sacroiliitis
Inflammatory vs mechanical back pain — the cardinal AS history. Use to decide whom to image with sacroiliac MRI.

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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