Ankylosing Spondylitis

Chronic seronegative spondyloarthropathy which primarily involves the axial skeleton.

Background/Epidemiology

• AS results in inflammation of the joints of the spine and is one of a group of spondyloarthropathies which includes Reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease and undifferentiated spondyloarthropathy
• Prevalence of 0.1-2.0% of the population
• Peak onset is in late adolescence/early adulthood (15-25)
• More common in males (3:1)

Aetiology/Pathophysiology

• HLA-B27
  • HLA-B27 allele confers around a 5-fold increase in risk- 2% of people with HLA-B27 have AS, but 92% of patients with AS have HLA-B27)
• It is proposed that HLA-B27 heavy chains could undergo transformation such that residues of the HLA chain is occupying its own binding site
• Another explanation is that incorrect folding of HLA-B27 molecules causes abnormal trimerisation and dimerisation.  Surface expression of these grouped molecules can initiate an immune response
• Unlike other autoimmune conditions, inflammation in AS is partially mediated by CD8+ (cytotoxic) T cells as well as CD4+ (helper) T cells
• The classic pathological features include subchondral granulation tissue that erodes the joint and is slowly replaced by fibrocartilage and then ossification.  This occurs at sites of attachment of ligaments/capsules to bone (enthesitis)
  • When this occurs between the discs (at the annular fibrosus insertion), you get fusion of the vertebrae via syndesmophytes and classic ‘bamboo’ spine appearance

Presentation

• Insidious onset
• Constitutional symptoms are fairly common, particularly during flares e.g. fever, weight loss, fatigue

Back symptoms

• Morning stiffness which will characteristically last >30 mins (not always)
• Back pain
  • Improves with physical activity
  • Can often waken sleep/ worse at night
  • May be felt as non-specific buttock pain, particularly in early disease
    • Alternating buttock pain is classical of sacroiliitis
• Tenderness of the spine (sacroiliac) and reduced range of movement (lumber flexion)
  • In advanced disease, there may be loss of lumbar lordosis, buttock atrophy and an exaggerated thoracic kyphosis (question mark posture)
  • Reduced Schober test (<5cm)

Other joint symptoms

• Enthesitis of the heel (Achilles’ tendonitis and plantar fasciitis) and the tibial tuberosity
  • Can be swollen, painful- particularly in morning
• Peripheral arthritis
  • Commonly asymmetrical and in hips, shoulder girdle, joints of the chest wall, pelvis and TMJ (cf rheumatoid)
  • Common presentation in children; also symptoms are usually milder than those of the back or than those seen in RA.

Extra-articular symptoms

• Anterior uveitis– occurs in 20-30% of patients with ank spon.
  • NB Around a third-half of patients who develop anterior uveitis will go on the develop AS

Investigations

• There are no routine blood tests that will aid a diagnosis
  • FBC may show anaemia of chronic disease
  • Inflammatory markers may be raised and may correlate with disease activity but are non-specific
  • Rheumatoid factor may exclude rheumatoid disease (if negative), as may other antibodies
  • Genetic testing for HLA-B27 may be used (not routine)
• Spinal imaging
  • MRI is most useful for early disease as osteophytic change may be a late feature- enthesitis/sacroiliitis will not usually be seen on an X-ray in early disease
  • X-rays may show features of sacroiliitis (blurring/fusion of the joint line)- more common in established disease
    • Can be normal early on
    • Later features include
      • Sacroiliitis (subchondral erosions/sclerosis)
      • squaring of the lumbar vertebrae
      • rarely, late/severe AS causes ‘bamboo spine’
      • syndesmophytes
• CXR may show apical fibrosis (fibrotic lung disease is not uncommon in AS)

Diagnostic criteria (New York criteria)

Management

• NSAIDs or COX2 inhibitorys are the first-line drug offered to patients
  • Past evidence has suggested DMARDs (e.g. MTX/sulfasalazine) are not effective in relieving back symptoms, however, they may be helpful in patients with peripheral arthropathy.  More recent evidence is suggesting they might be beneficial in AS.
  • Other pain killers may be required
  • Corticosteroids (either oral or intraarticular injection) may be beneficial in a patient with recurrently painful arthritis affecting minimal joints
• Biological agents (adalimumab; etanercept; infliximab- all TNF)
  • Can be used in patients with
    • confirmed (New York) Diagnosis
    • a score of >=4 on the Bath AS disease activity index
    • at least 4cm on the 0-10cm spinal pain visual analogue scale
• Physiotherapy is VERY important as it can often prevent the fusion of the spinal joints and greatly limit morbidity
• Surgery is a last resort to correct deformities and manage associated arthropathy
• Lifestyle advice is important due to the complications of AS

Complications

• Progression can lead to fixed and flexed posture (bamboo spine)
• Cricoarytenoid arthritis may also occur, as can pleural disease, necrobiotic nodules, Caplan’s syndrome (usually associated with pneumoconiosis), fibrosing alveolitis and other idiopathic interstitial lung disease
• Cardiovascular
  • Atherosclerosis
    • Treat cardiovascular risk factors e.g. hyperlipidaemia, hypertension etc
  • Aortic regurgitation, mitral regurgitation, AV block, fibrosis
• Apical lung fibrosis
• Secondary osteoarthritis/osteoporosis
• Eye problems (recurrent/severe uveitis)
• Amyloidosis (may cause renal dysfunction)
• Cauda equina syndrome