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Putting the spotlight on ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton resulting in back pain and progressive spinal stiffness and deformity. AS characteristically affects young adults, with a peak age of onset in the second and third decade.

It is a spondyloarthropathy with a strong association with the human leukocyte antigen B27 (HLA-B27), most commonly manifesting as spinal disease, but can involve peripheral joints and there may be extra-articular features.

Epidemiology

The prevalence of AS reported in the literature may be underestimated, as it is a disease of insidious onset and diagnosis is often delayed.1 The figures quoted vary from 0 to 1.4 per cent depending on ethnic group, diagnostic criteria and the prevalence of HLA-B27 in the population studied.2

The prevalence reported for the Caucasian population in Europe and North America is between 0.05 and 0.23 per cent.2 The risk is increased to 1.3 per cent in those who are HLA-B27 positive. The male:female ratio is approximately 3:1.3

Clinical importance and significance of HLA-B27

HLA-B27 is a Class 1 HLA molecule found in 95 per cent of patients with AS, compared with a prevalence of 9 per cent in the normal population in the UK. The prevalence of AS parallels that of HLA-B27 and AS occurs with a greater prevalence in ethnic groups with a high population prevalence of B27, for example, the Haida Indians of North America.1

The pathogenetic role of B27 in AS is uncertain, but it may be associated with a number of genes that confer susceptibility to the disease.

Clinical features

Articular The principal feature of AS is inflammation of the junction of ligament to bone (enthesitis), with early involvement of the sacroiliac joints

leading to subsequent ankylosis of these joints. Squaring of the lower lumbar vertebral bodies and new bone formation in the outer layers of the annulus fibrosis of the intervertebral disks results in the formation of the characteristic syndesmophytes and progressive ankylosis of the spine.

Chronic, low-grade, low back pain is the first symptom in most patients. This is associated with morning stiffness and inactivity stiffness that improves with exercise. The back pain often wakes the patient in the early hours of the morning. These are the classical features of inflammatory back pain (see table 1,

page 25).

Involvement of the entheses leads to chest pain, epicondylitis, Achilles tendonitis and plantar fasciitis.

Synovitis occurs mainly in larger peripheral joints such as the knee and

the shoulder, with 20–40 per cent of patients having peripheral joint disease

at some stage. Hip disease occurs in 20 per cent of patients.

Ocular Anterior uveitis is the most common extra-articular complication of AS, occurring in 40 per cent of AS patients.4 The frequency of attacks of uveitis varies from one or two in a

lifetime to recurrent attacks that can lead to cataract formation and blindness.

Cardiovascular Aortic regurgitation is a well recognised although uncommon complication. Other cardiovascular complications reported include interventricular conduction defects, hypertension and an increased risk of cardiovascular events such as

myocardial infarction.

Respiratory A small proportion of

patients with AS develop apical pulmonary fibrosis, which is usually asymptomatic and associated with a

long disease duration. Many patients

also have restriction in chest expansion due to costovertebral joint involvement.

Renal Analgesic nephropathy, IgA nephropathy and secondary

amyloidosis are rarely associated with

AS. IgA nephropathy is uncommon, but should be suspected in patients with haematuria and proteinuria.

Gastrointestinal Crohn's disease and ulcerative colitis are found in 10–15 per cent of patients with AS.5 Endoscopic studies in patients with AS have

detected ileal and colonic mucosal

ulcers that have the histological features

of Crohn's disease but are usually asymptomatic.

Neurological A spondylodiscitis can

result in an unstable spinal segment leading to spinal cord compression, especially if there is spinal cord trauma. Cervical spine involvement may lead to atlanto-axial subluxation, but this is less common when compared with rheumatoid arthritis. More rarely, severe spinal ankylosis can be complicated by a cauda equina syndrome.

Enthesis-related arthropathy (ERA) in childhood characteristically presents predominantly in boys between the ages of 11 and 14 years and is associated with heel pain, dactylitis and knee effusions. The patients are seronegative, but the majority of the children are HLA-B27 positive. Acute anterior uveitis can occur at a very early age.

The overlapping clinical features between AS, psoriatic arthritis and enthesis-related arthropathy are shown in the Venn diagram above (figure 2).

Figure 3 (above) shows a patient with the typical question mark deformity of AS.

Imaging in diagnosis

The first radiographic changes in AS are usually of the sacroiliac (SI) joints. An antero-posterior pelvic X-ray with SI

views is therefore essential in any patient with suspected AS.

Interpreting X-rays of the SI joints is challenging because of the shape and oblique direction of the joint. In teenagers, X-rays of the SI joint are difficult to interpret since the epiphyses do not close until the age of 21 or 22 years.

A lateral plain X-ray of the vertebral bodies is also helpful as it may reveal squaring of the vertebral bodies – an early sign of the disease.

If plain X-rays do not demonstrate pathologic changes, but the clinical suspicion of AS is high from the history and examination, MRI of the SI joints and the lumbar spine should be performed. Typical MRI changes in early AS are an increased signal from the bone and bone marrow, characteristic of osteitis and oedema seen at the margins of the SI joints.6

Management

The treatment of AS aims to increase mobility and relieve pain and inflammation.7 Therapy should be individualised, with consideration given to functional impairment and concomitant medical and social problems.

Mild to moderate disease may respond to NSAIDs and aggressive physiotherapy, with patients being encouraged to undertake a home exercise programme.8

AS patients with peripheral joint disease and enthesitis have been shown to respond to sulfasalazine9 and occasionally methotrexate.10 Severe hip disease requires total joint replacement.

More recently, anti-TNFµ therapy has been shown to control symptoms and signs of inflammation in AS effectively.11 The anti-TNF drugs infliximab, etanercept

and adalimumab have all shown remarkable efficacy in AS.12

Prognosis

The disease activity in AS usually fluctuates. The majority of patients with mild disease are able to maintain a reasonable functional and employment capacity, but a significant minority of patients with severe disease develop progressive functional impairment.

One study identified seven variables that correlated with disease severity and hence poorer prognosis:13

• Hip arthritis

• Dactylitis

• Poor NSAID response

• High ESR (>30mm/h)

• Reduced range of lumbar spine movement

• Peripheral joint disease

• Disease onset age <16 years.

Only 1 per cent of patients enter

long-term remission (‘burn-out').14 Prognosis is adversely affected by smoking, recurrent extra-articular complications and peripheral joint disease.

Recent research suggests that AS patients are also at increased risk of cardiovascular complications because of their chronic, low-grade spinal inflammation.

References

1 Khan MA. HLA-B27 and its subtypes in world populations. Curr Opin Rheumatol 1995;7:263–9

2 Lawrence RC, Helmick CG, Arnett FC et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998;41(5):778–99

3 Ostensen M, Ostensen H. Ankylosing spondylitis – the female aspect. Rheumatol 1998;25(1):120–4

4 Maksymowych WP, Chou CT, Russell AS. Matching prevalence of peripheral arthritis and acute anterior uveitis in individuals with ankylosing spondylitis. Ann Rheum Dis 1995;54:128–30

5 Leirisalo-Repo M, Turunen U, Stenman S et al. High frequency of silent inflammatory bowel disease in spondyloarthropathy. Arthritis Rheum 1994;37:23–31

6 Van der Heijde D, Landewe R. Imaging in spondylitis. Curr Opin Rheumatol 2005;17(4):413–7

7 Zochling J, Braun J. Management and treatment of ankylosing spondylitis. Curr Opin Rheumatol 2005;17(4):418–25

8 Dagfinrud H, Kvein TK, Hagen KB. Physiotherapy interventions for ankylosing spondylitis. Cochrane Database Syst Rev 2004, Issue 4

9 Ferraz MB, Tugwell P, Goldsmith CH et al. Meta-analysis of sulfasalazine in ankylosing spondylitis.

J Rheumatol 1990;17:1482–6

10 Sampaia-Barros PD, Costallat LT, Bertolo MB et al. Methotrexate in the treatment of ankylosing spondylitis. Scand J Rheumatol 2000;29(3):160-2 (Abstract)

11 Wendling D, Toussirot E. Anti-TNF-alpha therapy in ankylosing spondylitis. Expert Opin Pharmacother 2004;5(7):1497–1507

12 Zochling J, Maxwell L, Beardmore J et al. TNF-alpha inhibitors for ankylosing spondylitis. (Protocol) Cochrane Database Syst Rev 2005;3

13 Amor B, Santos RS, Nahal R et al. Predictive factors for the long-term outcome of spondyloarthropathies.

J Rheumatol 1994;21:1883–7

14 Kennedy LG, Edmunds L, Calin A. The natural history of ankylosing spondylitis. Does it burn out?

J Rheumatol 1993;20(4):688–92

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