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 a higher prevalence in males and typically manifesting between the third and fifth decades of life. 1

Definition and Classification

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

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

The modified New York criteria for AS classification requires radiographic evidence of sacroiliitis, which may take years to develop. More recently, the Assessment of SpondyloArthritis international Society (ASAS) proposed classification criteria that include 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 Presentation

Key clinical features include:

• 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
• Enthesitis (inflammation at sites where tendons and ligaments insert into bone)
• Peripheral arthritis (particularly large joints)
• Extra-articular manifestations:
  • Uveitis (anterior uveitis/iritis)
  • Inflammatory bowel disease
  • Psoriasis
  • Cardiovascular involvement
  • Pulmonary complications
  • Renal involvement 3

Diagnostic Approach

Diagnosis requires a combination of imaging, laboratory tests, and clinical assessment:

• Imaging:

  • Conventional radiography is first-line for initial evaluation (showing erosions, sclerosis, joint space narrowing, and eventually ankylosis)
  • MRI is essential for identifying early inflammatory disease (bone marrow edema is the hallmark of active sacroiliitis)
  • CT demonstrates structural changes and is particularly useful for thoracic spine and facet joint evaluation 1

• Laboratory tests:

  • HLA-B27 testing has high sensitivity (90-95%) in AS patients
  • C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have limited sensitivity (around 50%) 1
  • Note: SpA should not be ruled out based solely on negative laboratory results 1

Disease Complications

Without proper treatment, AS can lead to:

• Spinal fusion and kyphosis
• Decreased mobility and function
• High risk of unstable spinal fractures from minor trauma, with associated neurologic injury 1, 4
• Reduced quality of life
• Work disability

Treatment Approach

The American College of Rheumatology recommends:

1. First-line therapy:

   • NSAIDs as initial treatment 2, 1
   • Physical therapy to maintain spinal flexibility and normal posture 2

2. For patients with persistent disease activity despite NSAIDs:

   • TNF inhibitors (adalimumab, infliximab, etanercept, golimumab, certolizumab) 2, 1, 5
   • No particular TNFi is preferred except in patients with:
     • Concomitant inflammatory bowel disease: use TNFi monoclonal antibodies (not etanercept)
     • Recurrent iritis: use TNFi monoclonal antibodies 2

3. For primary non-response to first TNFi:

   • Secukinumab or ixekizumab is recommended over a second TNFi 1

4. For advanced hip arthritis:

   • Hip arthroplasty 2

5. Not recommended:

   • Systemic glucocorticoids 2

Monitoring and Management

• Regular assessment of disease activity using validated tools like ASDAS-CRP 1
• Referral to a rheumatologist for diagnosis, treatment, and ongoing management 1
• Referral to orthopedic surgeon for patients with refractory pain or disability with radiographic evidence of structural damage 1
• Careful monitoring for complications, especially in patients with spinal ankylosis who are at high risk for fractures 4, 6

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 (average delay of 8-11 years from symptom onset to diagnosis)

Early diagnosis and treatment are crucial as newer therapies can contain the condition and potentially induce remission, preventing the progressive spinal fusion and disability that characterize advanced disease. 7