Ankylosing spondylitis

Contributed by Dr Andrew Keat, consultant rheumatologist at the Arthritis Centre, Northwick Park Hospital, Harrow, Middlesex

1. Aetiology and epidemiology

Ankylosing spondylitis (AS) is an inflammatory disease of spinal joints and ligamentous attachments (entheses) which produces persistent pain, stiffness and restricted movement in the buttocks, back and neck. It starts in young adult life. In some people other joints and tissues are also affected and AS is more common in people with inflammatory bowel disease (IBD), psoriasis and iritis.

Many people with AS develop spinal fusion, need joint surgery, lead poor quality lives and cease working.


Best estimates indicate that around one in 500 people in the UK have AS. We do not know how common AS is in European populations because it has never been measured accurately. This is partly because many people have mild to moderate symptoms and do not seek medical advice while others have troublesome but undiagnosed disease.

AS is a member of the spondyloarthropathy (SpA) group, with enteropathic arthritis, psoriatic arthritis, reactive arthritis and undifferentiated SpA. Spondylitis may occur in these conditions so, overall, inflammatory spinal disease is more common. The disease is under-recognised in women, in whom it is not rare. The mean interval between onset of symptoms and diagnosis remains an unacceptable five to eight years.


The cause of AS is unknown, but several contributory factors are well recognised. First is the strong genetic predisposition associated with inheritance of the HLA-B27 gene. About 7 per cent of the healthy UK population have this gene but it occurs in more than 90 per cent of those with AS. Other genes must also contribute to susceptibility because B27 positive people with a family history of SpA are much more likely to develop AS than unselected HLA-B27 positive people.

The known function of the B27 surface protein and the unpredictable onset of AS have led to theories about the initiation of disease by bacterial or other environmental factors. It seems very likely that some environmental factors interacts with the B27 or related gene products to spark the process. However, despite careful and extensive consideration of candidate infective agents and provocative observations in HLA-B27 transgenic laboratory animals, no cogent understanding of the pathogenesis of AS has emerged.

2. Clinical features and diagnosis

The features of AS usually become apparent in late teenage or early adult life. Onset after 40 years of age is rare but the diagnosis may be made late in life, having been missed earlier.

Pain and stiffness

The key feature of AS is persistent inflammatory back pain. This is usually in the lumbar region and buttocks and is associated with stiffness which is aggravated by rest and improved by exercise.

Sacroiliac pain is usually felt in one or both buttocks and may alternate from side to side. It is very difficult to distinguish from mechanical back pain. The pain may disturb sleep.

With time, the pain and stiffness become continuous and may involve the thoracic and cervical segments of the spine. Thoracic involvement often leads to anterior rib and chest pain, raising concerns about heart disease.

Peripheral joint symptoms may precede, accompany or follow the onset of spinal pain. Knee swelling is characteristic and is often misattributed to an injury in a fit teenager or young adult. Pain and swelling at entheses is also characteristic of AS and the SpAs as a group. Pain at the heel, involving the Achilles’ tendon and/or plantar fascia attachments is typical and may be severe and disabling.

Many patients develop osteoporosis, particularly in the vertebrae, early on in the course of disease.

Associated conditions

AS is often accompanied by other SpA features.

Iritis is an episodic acute painful red eye and a history of such episodes is a useful pointer to diagnosis of AS. Iritis requires urgent treatment.

Between 2 and 18 per cent of people with established AS have Crohn’s disease or ulcerative colitis.

Psoriasis also occurs more frequently in people with AS and up to 20 per cent of those with psoriatic arthritis have sacroiliitis or full AS. In the presence of psoriasis, AS is often atypical with patchy spinal involvement by exuberant asymmetrical syndesmophytes.


Pointers to diagnosis are: young age, inflammatory character, history of knee swelling or iritis, family history suggestive of SpA, IBD and psoriasis.

Inflammatory back pain has a subtle or gradual onset, is worse with rest and improves with exercise and may be substantially improved by anti-inflammatory drugs.

In teenage years, AS often presents with knee swelling or heel pain, with the back symptoms coming on later.

Presentation later in life may also be problematic. The diagnosis may be made incidentally following an injury or incidental spinal imaging. In some individuals, however, it is the long-term diffuse discomfort and fatigue, sometimes associated with low mood, that precipitates a consultation.

Conventionally diagnosis is according to the modified New York criteria which requires both limited spinal movements and abnormal sacroiliac X-rays. This makes early diagnosis difficult because spinal restriction may be subtle and X-rays may not be clearly abnormal for several years. In practice, the presence of inflammatory spinal pain, with or without other diagnostic clues, should lead to sacroiliac imaging.

In men an X-ray may well be appropriate but, in women or men with persistent symptoms but normal X-rays, an MRI should be considered.

HLA-B27 testing may be useful when the diagnosis appears clinically likely, especially in teenagers or children in whom imaging may be non-contributary, but when sacroiliac imaging is negative or not interpretable with certainty.

Associated conditions





Aortic valve disease

Amyloid - rarely

3. Management

Early diagnosis is the essential basis of effective treatment. Deformities, restriction and social consequences are likely to be irreversible.

Regular exercise and NSAIDs are the fundamental elements of treatment. Daily stretching does limit stiffness and regular frequent spinal exercise, whether as a gym exercise or sport, helps to reduce ankylosis and prevent the familiar but preventable flexed posture. Motivation to continue regular frequent exercise throughout life is a problem.

Controlling symptoms

Long-acting NSAIDs or preparations are preferable, especially in suppressing symptoms over night. Diclofenac, as slow release tablets or as suppositories, and etoricoxib, especially when taken at the high dose of 120mg daily, provide a particularly good balance of efficacy and tolerability.

Continuous NSAID use provides better symptom control than intermittent dosing although for those with relatively mild symptoms, who are able to control symptoms by exercise, intermittent dosing may be preferable.

Peripheral lesions

Troublesome individual peripheral lesions, such as plantar fasciitis or knee synovitis may be effectively treated by local steroid injections. So too may unilateral sacroiliitis if the diagnosis is clear, although this should be carried out under imaging control. Peripheral arthritis and enthesitis may also respond to second-line drugs such as methotrexate and sulpha-salazine but these are not effective for spinal disease. No agents have been shown clearly to prevent ankylosis.

TNF blockade

As in rheumatoid arthritis, all three currently available TNF blocking drugs have been shown to be dramatically effective for symptom control in AS and are licensed for its treatment.

Reduced pain, stiffness and improved well-being is experienced by 60 to 70 per cent of patients who have been refractory to conventional treatment although it is not yet clear whether these agents prevent ankylosis. Peripheral arthritis and enthesitis are also helped and bone mineral density rises with treatment. TNF blockade treatment may also be effective for other conditions seen within the SpA spectrum, especially IBD and psoriasis.

Although infliximab, etanercept and adalimumab differ from each other in certain respects and in the manner and frequency of dosing, their clinical efficacy and potential toxicity appear similar. Long-term effects are not yet fully known so use of these drugs is limited by this as well as the risk of infection and their high cost. Their place in AS treatment is currently under consideration by NICE.

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