Ankylosing Spondylitis

Ankylosing spondylitis is a chronic seronegative spondyloarthropathy which primarily involves the axial skeleton (e.g. sacroiliitis and spondylitis). The aetiology is unknown but involves the interaction of genetic and environmental factors. The diagnosis is made by combining clinical criteria of inflammatory back pain and enthesitis (inflammation at the site of bone insertion of ligaments and tendons) or arthritis with radiological findings.¹

• Prevalence is 0.1-2% of the general population, with the highest prevalence in northern European countries and the lowest in Afro-Caribbeans. Peak onset 15-25 years of age.¹
• Male:female ration is 5:1. Women tend to have milder or sub-clinical disease.

• There is a strong familial tendency.
• Strong association with HLA-B27² (92% of patients compared with 6% of the general population). Approximately 1-2% of all people who are positive for HLA-B27 develop ankylosing spondylitis. This increases to 15-20% if they also have an affected first-degree relative.
• Other associated genetic factors include HLA-B60 and HLA-B39 (in HLA-B27-negative patients).
• Many patients with mild disease may remain undiagnosed.³

• Symptoms may be subtle in early stages or mild disease.
• Usually presents before the age of 30 years.
• Most patients have mild chronic disease or intermittent flares with periods of remission.
• Systemic features are common. Fever and weight loss may occur during periods of active disease.
• Morning stiffness is characteristic, and fatigue is common.
• Inflammatory back pain:
  • Insidious onset occurring over months or years.
  • Often improves with moderate physical activity, and associated with diffuse non-specific radiation of pain into both buttocks.
  • Unlike mechanical back pain, patients often experience stiffness and pain that awakens them in the early morning hours.
  • The spinal disease starts in the sacroiliac joints (bilateral lumbosacral region) and progresses proximally, with ossification of the annulus fibrosus that results in fusion of the spine (bamboo spine).
  • On examination there is often tenderness of the sacroiliac joints or a limited range of spine motion. May have loss of lumbar lordosis and accentuated thoracic kyphosis.
  • Stiffness and kyphosis resulting in a stooped posture are characteristic in the advanced stages.
  
• Peripheral enthesitis:
  • Occurs in approximately 33% of patients and often involves the Achilles tendon insertion, the insertion of the plantar fascia on the calcaneus or the metatarsal heads, the base of the fifth metatarsal head, the tibial tuberosity, the superior and inferior poles of the patella and the iliac crest.
  • Lesions tend to be painful, especially in the morning. There may be associated swelling of the tendon or ligament insertion.
• Peripheral arthritis:
  • Occurs in 33% of patients.
  • Joint involvement tends to occur most often in the hips (often bilateral), shoulder girdle (glenohumeral, acromioclavicular, sternoclavicular joints), and joints of the chest wall (costovertebral joints, costosternal junctions) and symphysis pubis.
  • Other peripheral joints are less often and less severely affected, usually as asymmetrical oligoarthritis.
  • Temporomandibular joints are occasionally involved.

Examination

• Measure chest expansion, lateral lumbar flexion and forward lumbar flexion.
• Schober's test - see separate article Back Examination (Thoraco-lumbar).
• Palpate and stress the sacroiliac joints.
• Examine peripheral joints for synovitis or enthesitis.
• Always look for extra-articular manifestations of ankylosing spondylitis (up to 40% of patients); eg aortic regurgitation, conduction disorders or lung fibrosis).

The British Society for Rheumatology recommends that the Modified New York criteria be used to diagnose ankylosing spondylitis:⁴

• Clinical criteria
  • Low back pain, for more than 3 months; improved by exercise, not relieved by rest
  • Limitation of lumbar spine motion in both the sagittal and the frontal planes
  • Limitation of chest expansion relative to normal values for age and sex
• Radiological criterion: sacroiliitis

Definite ankylosing spondylitis is diagnosed if the radiological criterion is present plus at least 1 clinical criterion. Probable AS if 3 clinical criteria are present, or if the radiological criterion is present, but no clinical criteria are present.

Ankylosing spondylitis may overlap with other spondyloarthropathies, e.g. psoriatic arthritis, reactive arthritis, or enteropathic arthropathy.¹

• Mechanical back pain
• Inflammatory conditions, e.g. rheumatoid arthritis, psoriatic arthritis, reactive arthritis, Reiter syndrome
• Degenerative, e.g. osteoarthritis
• Infection, e.g. tuberculosis
• Neoplastic; primary or secondary
• Referred pain

• Blood tests:
  • No laboratory tests are specific. May be normochromic normocytic anaemia of chronic disease. The ESR or CRP level may correlate with disease activity (less useful for monitoring activity than in other inflammatory arthritis such as rheumatoid arthritis). Alkaline phosphatase is often elevated.
  • HLA-B27 positivity is present in 92% of whites with ankylosing spondylitis and is present less commonly in patients of other ethnicities. Determining HLA-B27 status may help support the diagnosis but is not a necessary part of the clinical evaluation.
• Imaging:
  • X-rays:
    • Are most helpful in establishing a diagnosis (although may be normal in early disease).
    • Look for sacroiliitis or enthesitis (particularly of the annulus fibrosus). Sacroiliitis initially shows as blurring in the lower part of the joint, then bony erosions or sclerosis occurs, and widening or eventual fusion of the joint.
    • The vertebral bodies may become "squared". In later stages bony bridges (syndesmophytes) form between adjacent vertebrae, there is ossification of spinal ligaments, and in late disease there may be complete fusion of the vertebral column (bamboo spine).
    • Spinal osteopenia is common.¹
  • MRI may be useful in identifying early Sacroiliitis. MRI of the sacroiliac joints is more sensitive than either plain X-ray or CT in demonstrating sacroiliitis.⁵ Consider in HLA-B27 positive patients with appropriate history of back pain.
  • MRI and CT scans: may be useful in making the diagnosis of a spinal fracture in patients with late-stage spinal disease (i.e. you should have a higher index of suspicion for fracture in patients with Ankylosing spondylitis).
  • Dual energy x-ray absorptiometry tends to under-estimate fracture risk in ankylosing spondylitis because of new bone formation in the spine.⁵
  • Musculoskeletal ultrasound scanning can help in diagnosing enthesitis.⁶

Treatment is essentially symptomatic with control of symptoms, maintainance of function and early diagnosis and management of complications.

• Physiotherapy, including an exercise program and postural training, is important to maintain function.⁵ A Cochrane review found that an individual home-based or supervised exercise program is better than no intervention; that supervised group physiotherapy is better than home exercises; and that combined inpatient spa-exercise therapy followed by group physiotherapy is better than group physiotherapy alone.⁷
• Spinal extension and deep-breathing exercises help maintain spinal mobility, encourage erect posture, and promote chest expansion.
• Maintaining an erect posture during daily activities and sleeping on a firm mattress with a thin pillow also tend to reduce the tendency towards thoracic kyphosis.
• Hydrotherapy and swimming are excellent activities to maintain mobility and fitness.
• Extra-articular manifestations are treated dependent on the clinical setting.

Drugs

• No drugs modify the course of the disease.
• NSAIDs improve the symptoms of the disease.¹
• Sulphasalazine may be helpful for peripheral joint involvement although evidence is inconclusive.^1,8
• Anecdotal reports suggest that other medications are helpful in treatment, including methotrexate,⁹ azathioprine, cyclophosphamide and ciclosporin (no conclusive evidence for routine use of any of these).
• Oral corticosteroids are occasionally beneficial in short-term use for controlling symptoms. They do not alter disease outcome and increase the risk of spinal osteoporosis.
• Local corticosteroid injections are useful for symptomatic sacroiliitis, peripheral enthesitis, and arthritis.
• Bisphosphonates are often used to reduce risk of fracture in ankylosing spondylitis.⁵
• Cytokine modulators:
  • The tumour necrosis factor-alpha (TNF-alpha) inhibitors, infliximab and etanercept, have been shown to be effective and are indicated in patients with severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy.^10,11
  • Adalimumab, etanercept and infliximab are licensed for the treatment of severe active ankylosing spondylitis that have not responded adequately to other disease-modifying antirheumatic drugs.
  • The British Society for Rheumatology have recommended the use of etanercept and infliximab for patients with active disease for whom conventional treatment with NSAIDs has failed (at least two NSAIDs taken separately for at least 4 weeks at maximum tolerated/recommended doses) and no contraindications present (e.g. pregnancy, breastfeeding, significant infection, severe heart failure, demyelinating disease).^11,12

Surgical

• Surgery is occasionally useful to correct spinal deformities or repair damaged peripheral joints. Vertebral osteotomy may be performed to correct spinal deformities, but may cause significant neurological complications
• Patients may need total hip replacement and, occasionally, total shoulder replacement.
• Heterotopic bone formation may occur after total joint replacement, especially around the hip. This can be reduced by using postoperative NSAIDs.

• A small minority of patients develop spinal fusion, which may result in severe kyphosis and limited motion of the spine, including the cervical region. The fused spine is more susceptible to fracture, even with relatively minor trauma. The Kyphosis may also cause respiratory problems, by restricting lung expansion.
• Patients with severe long-standing AS rarely may develop significant extra-articular manifestations such as recurrent uveitis, cardiovascular disease, including cardiac conduction defects and aortic regurgitation; pulmonary fibrosis; neurological sequelae (e.g. cauda equina syndrome) or amyloidosis. Extra-articular manifestations rarely result in significant morbidity or mortality.⁴
• Patients with ankylosing spondylitis have increased rates of cardiovascular morbidity and mortality.¹

• Prognosis is generally good. Many patients have few, if any, symptoms.
• A small minority of patients with chronic progressive disease develop disability due to spinal fusion, often with thoracic kyphosis or erosive disease involving peripheral joints, especially the hips and shoulders. Most functional loss occurs during the first 10 years of illness.¹³
• Patients often require long-term anti-inflammatory therapy. Morbidity can occur related to spinal and peripheral joint involvement or, rarely, extra-articular manifestations.
• Poor prognostic indicators include peripheral joint involvement, young age of onset, elevated ESR, and poor response to NSAIDs.
• Mortality is increased in patients who have severe long-standing disease and significant extra-articular manifestations.