Epidemiology

Etiology

• Genetic predisposition: 90–95% of patients are HLA-B27 positive.

Pathophysiology

• AS is distinct from rheumatoid arthritis:
  • AS → simultaneous bone erosion AND new bone formation.
  • Rheumatoid arthritis → primarily only erosions.
• Initial Pathogenesis (Inflammatory Phase):
  • Driven partly by inflammatory cytokines (e.g., tumor necrosis factor (TNF), IL-17) → activation of osteoclast precursor cells → bony erosions.
  • Bony erosions occur primarily in vertebral bodies → destruction of the trabecular microarchitecture → increased risk for secondary osteoporosis and compression fractures.
• Reparative Process (Post-Inflammation):
  • Inflammation subsides → reparative process begins → excessive new bone formation.
  • New bone formation occurs especially where fat metaplasia fills previously eroded sites.
  • In contrast to erosion, bone formation occurs primarily at the periosteum-cartilage junction → manifests as bridging syndesmophytes in the vertebral column.
  • Bridging syndesmophytes → spinal rigidity → postural alterations → increased risk of fracture.
• Initiation of innate immune response
• Release of cytokines (TGF-beta and TNF-α) and interleukins (IL-17 and IL-23)
• Infiltration of paravertebral and sacroiliac entheses with macrophages, CD4 T cells, and CD8 T cells
• Enthesitis: an inflammation of the enthesis (the point at which a tendon attaches to bone). Typically seen in patients with ankylosing spondylitis, psoriatic arthritis, enthesitis-associated juvenile idiopathic arthritis, or reactive arthritis. Commonly affected sites include the spine, Achilles tendon, plantar fascia, and supraspinatus tendon.
• Chronic enthesitis leads to:
  1. Erosion of the iliac part of the sacroiliac joints
  2. Vertical formation of syndesmophytes along the spinal ligament or around the annulus fibrosus of the intervertebral discs
  3. Fusion of syndesmophytes → ankylosis of intervertebral discs and vertebral bodies

Clinical features

• Inflammatory back pain (sacroiliitis)
  • Insidious onset at age <40
  • Morning stiffness > 30 minutes that improves with activity
  • Pain is independent of positioning
  • Relieved with exercise, worse with rest (overnight & in the morning)
  • Relieved with activity & warm showers
  • Nocturnal pain
• Reduced chest expansion & spinal mobility
• Stiff or stooped posture
• Tenderness at spine, sacroiliac joints & peripheral tendon insertions (eg, Achilles)
• Enthesitis (tenderness at tendon insertion sites)
• Dactylitis (swelling of fingers & toes)
• Uveitis

Diagnostics

AS is a seronegative spondyloarthropathy, and there are no serologic tests to confirm the diagnosis.

Laboratory findings

• Elevated ESR & CRP
• HLA-B27: Positive in 90–95% of patients with axial spondyloarthritis
• Autoantibodies (e.g., rheumatoid factor, antinuclear antibodies) are negative

X-ray

• Sacroiliitis: bone erosions, subchondral sclerosis, eventual bony fusion (ankylosis)
• Bridging syndesmophytes: ossification at vertebral body margins (bamboo spine)

Treatment