What is Ankylosing Spondylitis?

Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by sacroiliitis, enthesitis, and progressive spinal fusion, affecting 0.1-0.5% of the population, with universal involvement of sacroiliac joint inflammation and a marked propensity for spinal ankylosis. 1

Definition and Classification

Ankylosing spondylitis belongs to the spondyloarthritis (SpA) family of diseases that share clinical, genetic, and immunologic features. It is distinguished within this family by:

• Universal involvement of sacroiliac joint inflammation or fusion
• More prevalent spinal ankylosis 2
• Classification as a form of axial spondyloarthritis (axSpA), with an estimated prevalence of 0.9% to 1.4% in the US adult population 1

The modified New York criteria for AS classification requires advanced sacroiliac changes, which may take years to develop. More recently, the Assessment of SpondyloArthritis international Society (ASAS) proposed classification criteria that apply to both early and later stages of the disease under the umbrella term "axial SpA," with "nonradiographic axial SpA" encompassing patients with chronic back pain and SpA features who don't yet meet AS classification criteria. 2

Clinical Features

Key Symptoms

• Inflammatory back pain characterized by:
  • Insidious onset before age 45
  • Symptoms lasting >3 months
  • Morning stiffness >30 minutes
  • Pain at night/early morning
  • Improvement with exercise but not with rest
  • Alternating buttock pain 1

Disease Manifestations

• Primary site of inflammation: entheses (sites of insertion of tendons and ligaments into bone)
• If inflammation remains untreated: progression to fibrosis and ossification at entheseal sites 3
• Common extra-articular manifestations include:
  • Uveitis (eye inflammation)
  • Inflammatory bowel disease
  • Cardiac, pulmonary, skin, bone, and kidney involvement 4

Diagnostic Approach

Imaging

• Conventional radiography: first-line for initial evaluation
  • Shows sacroiliitis as erosions, sclerosis, joint space narrowing, and eventually ankylosis
  • Should not be repeated more frequently than every 2 years for monitoring 1
• MRI: essential for identifying early inflammatory disease
  • Bone marrow edema is the hallmark of active sacroiliitis 1
• CT: demonstrates structural changes not apparent on radiographs
  • Particularly useful for thoracic spine and facet joints
  • Necessary for fracture exclusion in patients with ankylosis after trauma 1

Laboratory Testing

• HLA-B27: high sensitivity (90-95%) in AS patients
  • 90-95% of AS patients are HLA-B27 positive 3
  • Most useful when pre-test probability is high 1
• C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
  • Limited sensitivity (around 50%) in AS patients
  • Spondyloarthritis should not be ruled out based solely on negative laboratory results 1

Treatment

First-Line Therapy

• NSAIDs are strongly recommended as first-line treatment for active AS 2, 1
• Physical therapy is strongly recommended 2

Biologic Therapy

• TNF inhibitors (TNFi) are strongly recommended when disease activity persists despite NSAID treatment 2
• No particular TNFi is preferred except in patients with:
  • Concomitant inflammatory bowel disease: use TNFi monoclonal antibodies
  • Recurrent uveitis: use TNFi monoclonal antibodies 2
• Secukinumab or ixekizumab is recommended over a second TNFi in patients with primary non-response to the first TNFi 1

Surgical Management

• Hip arthroplasty is strongly recommended for patients with advanced hip arthritis 2
• Patients with ankylosis of the spine have high incidence of unstable fractures from minor trauma, with high associated rate of neurologic injury 1, 5
• Spinal fractures in AS should be considered unstable unless proven otherwise 5

Disease Monitoring and Complications

Disease Assessment

• Regular assessment using validated tools is recommended
• ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) is recommended for monitoring disease activity 1

Complications

• Spinal ankylosis and deformity
• Increased risk of spinal fractures due to osteoporosis and spinal rigidity
• Spinal cord injury risk is elevated due to unstable nature of vertebral column fractures 6
• Missed fractures and spinal epidural hematomas can worsen severity of spinal cord injury 6

Referral Considerations

• Patients should be referred to a rheumatologist for diagnosis, treatment, and ongoing management 1
• Patients with refractory pain or disability with radiographic evidence of structural damage may require referral to an orthopedic surgeon 1

Common Pitfalls in Diagnosis

• Over-reliance on radiographs (may miss early disease)
• Ignoring inflammatory back pain patterns
• Neglecting extra-articular manifestations
• Misinterpreting normal inflammatory markers 1
• Delayed diagnosis (common) due to failure to recognize early symptoms 3