Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Ankylosing Spondylitis article more useful, or one of our other health articles.
Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Synonyms: rheumatoid spondylitis, Marie-Strümpell disease, von Bechterew's disease
Ankylosing spondylitis (AS) is a chronic seronegative spondyloarthropathy which primarily involves the axial skeleton (ie 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.
- Prevalence is 0.1-2% of the general population, with the highest prevalence in northern European countries and the lowest in people of Afro-Caribbean descent.
- Peak onset is between 20-30 years of age.
- Male:female ratio is 3:1. Women tend to have milder or subclinical disease.
- Many patients with mild disease may remain undiagnosed.
- There is a strong familial tendency with >90% of the risk of disease determined genetically.
- A strong association with HLA-B27 exists, particularly in white western European populations. Approximately 1-2% of all people who are positive for HLA-B27 develop AS. This increases to 15-20% if they also have an affected first-degree relative. However, despite much study, it is not clear how the association with HLA-B27 determines disease susceptibility.
- In AS, the major histocompatibility complex (MHC) - a cell surface molecule encoded by a large gene family which mediates the actions of leukocytes - accounts for nearly half of the disease susceptibility.
- Other associated genetic factors include HLA-B60 and HLA-B39 (in HLA-B27-negative patients).
- Symptoms may be subtle in early stages or mild disease, with an insidious onset over several months to years.
- AS 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. Fatigue is also prominent.
- Morning stiffness is characteristic.
- Inflammatory back pain:
- Often improves with moderate physical activity.
- Unlike mechanical back pain, patients often experience stiffness and pain which awaken them in the early morning hours.
- The spinal disease starts in the sacroiliac joints (bilateral lumbosacral region) and may be felt as diffuse nonspecific buttock pain.
- On examination there is often tenderness of the sacroiliac joints or a limited range of spinal motion.
- In the advanced stages, patients develop loss of lumbar lordosis, buttock atrophy, and an exaggerated thoracic kyphosis with a stooped forward neck sometimes referred to as a 'question mark posture'.
- Peripheral enthesitis:
- Occurs in approximately a third of patients.
- Common sites - behind the heel (Achilles tendonitis), the heel pad (plantar fasciitis) and the tibial tuberosity.
- Lesions tend to be painful, especially in the morning. There may be associated swelling of the tendon or ligament insertion.
- Peripheral arthritis:
- Also occurs in about a third of patients.
- Joint involvement is usually asymmetric, involving the hips, shoulder girdle (glenohumeral, acromioclavicular, and sternoclavicular joints), 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.
- In children, AS tends to commence with arthritis prior to spinal disease developing.
- Temporomandibular joints are occasionally involved.
- Measure chest expansion, lateral lumbar flexion and forward lumbar flexion.
- Schober's test - see separate article Examination of the Spine, which deals with thoracolumbar back examination.
- Palpate and stress the sacroiliac joints.
- Examine peripheral joints for synovitis or enthesitis.
- Always look for extra-articular manifestations of AS, as these occur in up to 40% of patients.
- Acute anterior uveitis occurs in 20-30% of patients. Of all patients presenting with acute anterior uveitis, a third to a half have or will go on to develop AS.
- Acute anterior uveitis presents with an acutely painful red eye and severe photophobia and requires emergency treatment to prevent visual loss.
- This occurs in <10% of patients, usually in those with severe long-standing disease.
- Aortitis of the ascending aorta may lead to distortion of the aortic ring, causing aortic regurgitation.
- Fibrosis of the conduction system may result in various degrees of atrioventricular block, including complete heart block.
- Restrictive lung disease may occur in patients in later stages, with costovertebral and costosternal involvement limiting chest expansion.
- Pulmonary fibrosis of the upper lobes.
- Amyloidosis is a very rare complication in patients with severe, active and long-standing disease and may cause renal dysfunction with proteinuria and renal insufficiency or chronic kidney disease.
- Immunoglobulin A (IgA) nephropathy is another association.
- This usually occurs secondary to fractures of a fused spine.
- Also, patients with AS are prone to atlanto-axial subluxation, which may lead to cervical myelopathy.
- Cauda equina syndrome may occur in patients with severe long-standing disease.
Metabolic bone disease
- Osteopenia and osteoporosis may occur in patients with long-standing spondylitis, further increasing risk of fracture.
The British Society for Rheumatology recommends that the modified New York criteria be used to diagnose AS.
- Clinical criteria:
- Low back pain, for more than three 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 on X-ray.
Definite AS is diagnosed if the radiological criterion is present plus at least one clinical criterion and probable AS if three clinical criteria are present, or if the radiological criterion is present but no clinical criteria are present.
- They are a teenager or young adult.
- They have inflammatory back pain and stiffness that improves with exercise but not with rest, wake from sleep during the second half of the night and have morning stiffness lasting >30 minutes.
- They have current or previous buttock pain (felt on alternating sides), arthritis, enthesitis, costochondritis, epicondylitis, anterior uveitis, psoriasis or inflammatory bowel disease, or recent infective diarrhoea or sexually transmitted disease.
The differential diagnosis for AS includes:
- Mechanical back pain.
- Inflammatory conditions - eg, rheumatoid arthritis, psoriatic arthritis, reactive arthritis.
- Degenerative conditions - eg, osteoarthritis.
- Infection - eg, tuberculosis.
- Neoplasms, primary or secondary.
- Referred pain.
- Congenital spinal deformity.
- No laboratory tests are specific and are often more helpful to exclude other diagnoses rather than confirming AS.
- Guidance suggests that only FBC and inflammatory markers should be taken prior to referral. Rheumatoid factor, antinuclear antibodies (ANAs) and HLA testing are not thought to improve diagnosis in primary care.
- There may be normochromic normocytic anaemia of chronic disease. ESR or CRP level may correlate with disease activity but these are less useful for monitoring activity than in other inflammatory arthritis such as rheumatoid arthritis. Alkaline phosphatase is often elevated.
Advice is to follow local referral protocols on imaging the sacroiliac joints and spine, or to seek specialist advice on imaging ahead of referral.
- X-rays are the most helpful imaging modality in established disease, although they 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 occur 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.
- MRI scanning may be useful in identifying early sacroiliitis. MRI of the sacroiliac joints is more sensitive than either plain X-ray or CT scan in demonstrating sacroiliitis. It has a growing role in diagnosis, prognostication and selection of patients for biological treatment.
- MRI/CT scans - useful in making the diagnosis of a spinal fracture in patients with late-stage spinal disease.
- Dual-energy X-ray absorptiometry (DEXA) scans are used to assess for osteoporosis but may underestimate the fracture risk in AS, due to new bone formation in the spine.
- Musculoskeletal ultrasound scanning can help in diagnosing enthesitis.
By Stevenfruitsmaak via Wikimedia Commons
- AS is a chronic condition for which there is currently no cure. There are wide individual differences in the impact of AS and the aim of treatment is essentially symptomatic with good control of symptoms, maintenance of function (facilitated by early diagnosis) and management of complications.
- Refer all new or suspected cases of AS to a rheumatologist. This is for confirmation of the diagnosis, review of current treatment, access to specialist physiotherapy and occupational therapy and the arrangement of follow-up (often as part of a shared care arrangement with primary care).
- Treatment of extra-articular manifestations may require the involvement of other specialist teams.
Physiotherapy and rehabilitation
- Physiotherapy, including an exercise programme and postural training, is important to maintain function and, in some severe cases, a period of inpatient intensive rehabilitation may be warranted.
- A Cochrane review found that an individual home-based or supervised exercise programme 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 are better than group physiotherapy alone.
- Spinal extension and deep-breathing exercises help to 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.
No drugs have been shown to modify the course of the disease and there is no evidence to support the use of disease-modifying antirheumatic drugs such as methotrexate or sulfasalazine.
- Non-steroidal anti-inflammatory drugs (NSAIDs) improve the symptoms of the disease and form the cornerstone of treatment. Commence treatment with an NSAID unless contra-indicated and, in those at increased risk of gastrointestinal side-effects, consider the combination of an NSAID and proton pump inhibitor (PPI) or cyclo-oxygenase-2 (COX-2) inhibitor and PPI. Where contra-indicated or poorly tolerated, a standard analgesic such as paracetamol +/- codeine should be substituted[1, 1].
- Where NSAIDs do not control symptoms sufficiently:
- Consider a slow-release preparation if morning stiffness is a particular issue.
- Add additional pain relief (eg, simple analgesics, amitriptyline) where there is poor sleep due to pain.
- Local corticosteroid injections are useful for symptomatic sacroiliitis, peripheral enthesitis and arthritis.
- Oral corticosteroids are occasionally beneficial in short-term use for controlling symptoms. They do not alter disease outcome and they increase the risk of spinal osteoporosis.
- Refer to a rheumatologist for consideration of additional therapy.
- TNF-alpha inhibitors are effective in AS that is poorly controlled with NSAIDs. They should only be used under the care of a rheumatologist.
- National Institute for Health and Care Excellence (NICE) guidance suggests that etanercept and adalimumab be used in patients with severe AS where:
- The modified New York criteria (see 'Diagnosis', above) for diagnosis of AS are satisfied.
- There is confirmed, sustained active spinal disease over at least 12 weeks.
- Maximal, conventional treatment with two or more NSAIDs has failed.
- There are no contra-indications present (eg, pregnancy, breast-feeding, significant infection, severe heart failure, demyelinating disease).
- Golimumab has recently been recommended by NICE on a similar basis.
- Infliximab is not recommended.
- The NICE recommendations concerning etanercept and adalimumab were published in 2008. Since then, several studies suggest that whilst anti-TNF therapies are useful in advanced disease they are of their greatest benefit when given early in the condition and this approach is supported by the joint Assessments in Ankylosing Spondylitis International Society (ASAS) and the European League Against Rheumatism (EULAR), so the NICE guidance may have to be reviewed in due course.
- The use of TNF-alpha inhibitors is known to increase the risk of serious infections in other diseases such as rheumatoid arthritis but the association did not reach significance in a small study in patients with AS.
- Surgery is occasionally useful to correct spinal deformities or to 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.
- Cardiovascular disease (CVD):
- AS carries an increased risk of CVD; studies suggest lipid regulation abnormalities and microvascular changes.
- It is important to manage modifiable cardiovascular risk factors where present (eg, smoking, raised body mass index (BMI), cholesterol, sedentary lifestyle, comorbidities).
- Osteoporosis: bisphosphonates are often used to treat osteoporosis and reduce the risk of fracture in AS.
- A small minority of patients will develop spinal fusion, which may result in severe kyphosis and a 'frozen thorax' with limited motion of the spine. The fused spine is more susceptible to fracture, even with relatively minor trauma. The kyphosis may also cause respiratory problems, by restricting lung expansion.
- Extra-articular manifestations of the disease may cause complications - eg, blindness from recurrent uveitis.
- Prognosis is variable, and the pattern of symptoms within the first 10 years of disease often correlates well with the likely long-term degree of disability. In one study, 74% of patients with mild spinal restriction after 10 years did not progress to severe spinal involvement. By contrast, among patients who developed long-term severe spinal involvement, 81% had severe spinal restriction within 10 years.
- A minority of patients with chronic progressive disease develop significant disability due to spinal fusion, often with thoracic kyphosis or erosive disease involving peripheral joints, especially the hips and shoulders.
- 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 male sex, peripheral joint involvement or intractable iritis, young age of onset, elevated ESR and poor response to NSAIDs.
- Mortality is increased compared with the general population. A recent meta analysis found that patients with AS had an increased risk of myocardial infarction and stroke. Another study found that circulatory diseases, malignancy and infection were the three leading causes of deathPsychological health should not be neglected in AS patients.
Further reading and references
BSR and BHPR guideline for the treatment of axial spondyloarthritis (including ankylosing spondylitis) with biologics; British Society for Rheumatology (2016)
Thomas GP, Brown MA; Genomics of ankylosing spondylitis. Discov Med. 2010 Sep10(52):263-71.
Slaus M, Novak M, Cavka M; Four cases of ankylosing spondylitis in medieval skeletal series from Croatia. Rheumatol Int. 2011 Dec 31.
TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis; NICE Technology Appraisal Guidance, February 2016
Ankylosing spondylitis; NICE CKS, February 2013 (UK access only)
Brown MA; Genetics of ankylosing spondylitis. Curr Opin Rheumatol. 2010 Mar22(2):126-32.
Reveille JD; The genetic basis of spondyloarthritis. Ann Rheum Dis. 2011 Mar70 Suppl 1:i44-50.
Reveille JD; The genetic basis of ankylosing spondylitis. Curr Opin Rheumatol. 2006 Jul18(4):332-41.
El Maghraoui A; Extra-articular manifestations of ankylosing spondylitis: prevalence, Eur J Intern Med. 2011 Dec22(6):554-60. Epub 2011 Jul 13.
Hamdi W, Chelli-Bouaziz M, Ahmed MS, et al; Correlations among clinical, radiographic, and sonographic scores for enthesitis Joint Bone Spine. 2011 May78(3):270-4. Epub 2010 Oct 30.
Braun J, van den Berg R, Baraliakos X, et al; 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011 Jun70(6):896-904.
Dagfinrud H, Kvien TK, Hagen KB; Physiotherapy interventions for ankylosing spondylitis. Cochrane Database Syst Rev. 2008 Jan 23(1):CD002822.
Sidiropoulos PI, Hatemi G, Song IH, et al; Evidence-based recommendations for the management of ankylosing spondylitis: systematic literature search of the 3E Initiative in Rheumatology involving a broad panel of experts and practising rheumatologists. Rheumatology (Oxford). 2008 Mar47(3):355-61.
McVeigh CM, Cairns AP; Diagnosis and management of ankylosing spondylitis. BMJ. 2006 Sep 16333(7568):581-5.
Zochling J, van der Heijde D, Dougados M, et al; Current evidence for the management of ankylosing spondylitis: a systematic Ann Rheum Dis. 2006 Apr65(4):423-32. Epub 2005 Aug 26.
Ankylosing spondylitis - adalimumab, etanercept and infliximab; NICE Technology Appraisal Guidance, May 2008
Golimumab for the treatment of ankylosing spondylitis; NICE Technology Appraisal, August 2011
Fouque-Aubert A, Jette-Paulin L, Combescure C, et al; Serious infections in patients with ankylosing spondylitis with and without TNF Ann Rheum Dis. 2010 Aug 10.
Albert GW, Menezes AH; Ankylosing spondylitis of the craniovertebral junction: a single surgeon's J Neurosurg Spine. 2011 Apr14(4):429-36. Epub 2011 Feb 4.
Baraliakos X, Braun J; Hip involvement in ankylosing spondylitis: what is the verdict? Rheumatology (Oxford). 2010 Jan49(1):3-4. Epub 2009 Sep 15.
Magrey M, Khan MA; Osteoporosis in ankylosing spondylitis. Curr Rheumatol Rep. 2010 Oct12(5):332-6.
Pradeep DJ, Keat A, Gaffney K; Predicting outcome in ankylosing spondylitis, Rheumatology - Oxford University Press, 2008
Mathieu S, Pereira B, Soubrier M; Cardiovascular events in ankylosing spondylitis: An updated meta-analysis. Semin Arthritis Rheum. 2014 Oct 18. pii: S0049-0172(14)00248-0. doi: 10.1016/j.semarthrit.2014.10.007.
Bakland G, Gran JT, Nossent JC; Increased mortality in ankylosing spondylitis is related to disease activity. Ann Rheum Dis. 2011 Nov70(11):1921-5. Epub 2011 Jul 21.