ankylosing spondylitis (AS)

Last edited 07/2021 and last reviewed 10/2023

Axial spondyloarthritis including ankylosing spondylitis (radiographic axial spondyloarthritis)

Ankylosing spondylitis is one of a group of inflammatory rheumatic diseases known as spondylarthropathies - these diseases are characterised by predominant involvement of axial and peripheral joints and entheses (areas where tendons, ligaments or joint capsules attach to bone).

• ankylosing spondylitis is a common seronegative spondylitis typically affecting the spine and sacroiliac joints
  • the prevalence amongst white males has been stated as about 0.5%
    • however NICE state that prevalence of 'clinically significant ankylosing spondylitis' is about 0.15%
      • annual incidence is 6.9 per 100,000 in the UK
  • male Caucasians are affected more severely and more often (3:1) than females. The mean age of onset is between 26 years of age
  • prevalence of ankylosing spondylitis in a population mirrors the frequency of the associated HLA-B27
    • aetiology of ankylosing spondylitis probably has a genetic component as 90% of Caucasians with the disease have the human leucocyte antigen HLA-B27, compared with around 10% of the general population of North and Central Europe
• the disease is highly debilitating and can reduce quality of life as a result of stiffness, pain, fatigue, poor sleep, anxiety or the unwanted effects of medication
• reported unemployment rates are three times higher among people with ankylosing spondylitis than in the general population
  • about a third of people with ankylosing spondylitis may be unable to work altogether, with a further 15% reporting some changes to their working lives (2)
• ankylosing spondylitis is associated with an increased risk of death: it is estimated that patients have a standardised mortality ratio of 1.5 or greater (2)
• therapeutic intervention aims to reduce inflammation and, therefore, pain and stiffness; to alleviate systemic symptoms such as fatigue; and to slow or stop the long-term progression of the disease, particularly the progressive loss of spinal mobility caused by ankylosis of the spine

Radiographic versus non-radiographic axial spondyloarthritis (4):

• previously, the diagnosis of ankylosing spondylitis required advanced changes on plain radiographs of the sacroiliac joints. Classification criteria released in 2009, however, identified a subset of patients, under the age of 45, with back pain for more than three months in the absence of radiographic sacroiliitis who were classified as axSpA based on a positive magnetic resonance imaging or HLAB27 positivity and specific clinical features. This subgroup was labeled non-radiographic axial spondyloarthritis
• many patients without radiographic findings manifest MRI findings of bone marrow edema (BME) adjacent to the SIJ, suggestive of osteitis
• progression from non-radiographic to radiographic SpA is 10-20% over the first year, depending on baseline features such as elevated C reactive protein or positive MRI and 20.3% over two to six years

Axial presentations of spondyloarthritis are often misdiagnosed as mechanical low back pain, leading to delays in access to effective treatments. Peripheral presentations are often seen as unrelated joint or tendon problems, and can be misdiagnosed because problems can move around between joints (3).

Referral for suspected axial spondyloarthritis (3):

• if a person has low back pain that started before the age of 45 years and has lasted for longer than 3 months, refer the person to a rheumatologist for a spondyloarthritis assessment if 4 or more of the following additional criteria are also present:
• low back pain that started before the age of 35 years (this further increases the likelihood that back pain is due to spondyloarthritis compared with low back pain that started between 35 and 44 years)
• waking during the second half of the night because of symptoms
• buttock pain
• improvement with movement
• improvement within 48 hours of taking non-steroidal anti-inflammatory drugs (NSAIDs)
• a first-degree relative with spondyloarthritis
• current or past arthritis
• current or past enthesitis
• current or past psoriasis.

If exactly 3 of the additional criteria are present, perform an HLA-B27 test. If the test is positive, refer the person to a rheumatologist for a spondyloarthritis assessment.

• if the person does not meet the criteria in recommendation above but clinical suspicion of axial spondyloarthritis remains, advise the person to seek repeat assessment if new signs, symptoms or risk factors listed in recommendation above develop
• may be especially appropriate if the person has current or past inflammatory bowel disease (Crohn's disease or ulcerative colitis), psoriasis or uveitis

Do not rule out a diagnosis of spondyloarthritis solely on the basis of a negative HLA-B27 result (3)

Do not rule out a diagnosis of spondyloarthritis if a person's C reactive protein and erythrocyte sedimentation rate are normal (3)

Reference:

• (1) Drug and Therapeutics Bulletin 2005; 43(3):19-22.
• (2) NICE (May 2008).Adalimumab, etanercept and infliximab for ankylosing spondylitis
• (3) NICE (2017). Spondyloarthritis in over 16s: diagnosis and management
• (4) Ritchlin C, E Adamopoulos IE. Axial spondyloarthritis: new advances in diagnosis and management. BMJ 2021;372:m4447