Ankylosing spondylitis

Source:
Clinical Knowledge Summaries - CKS
Publication date:
01 February 2013

Abstract

Ankylosing spondylitis Last revised in February 2013 Next planned review by December 2018 Summary Back to topAnkylosing spondylitis: Summary Ankylosing spondylitis is a chronic inflammatory rheumatic disease of unknown cause and varying clinical presentation. The principal features (not all of which are present at onset, or in all people) are:Inflammatory low back pain, (pain and stiffness worse at night and in the morning).Inflammation of the spinal joints and the junction (enthesis) of the intervertebral spinal ligaments and vertebrae, leading (after many years) to ankylosis (i.e. fusion from fibrosis and calcification).Inflammation of the sacroiliac joints (on X-ray or other radiological imaging such as MRI), which presents as alternating buttock pain.Enthesitis (inflammation of the sites where tendons and ligaments attach to bone), costochondritis (inflammation where cartilage joins the ribs), and epicondylitis (inflammation of an epicondyle of bone).Arthritis of peripheral joints, usually involving the large joints of the lower limbs, or asymmetric arthritis of peripheral joints.Insidious onset (over a period of at least 3 months, and often several years) usually beginning in late adolescence or early adulthood.Fatigue.Association with the human leukocyte antigen B27 (HLA-B27).Ankylosing spondylitis is not uncommon:About 2% of people in a general practice will present with back pain and up to 5% of these will show features of ankylosing spondylitis.It is about three times more common in men than women.It most commonly begins between 20 and 30 years of age, but also occurs in children and older adults.Common complications include:Progressive involvement of the lumbar, thoracic, and cervical spine, leading to a fixed and flexed posture.Damage to peripheral joints.Anterior uveitis (iritis).If ankylosing spondylitis is suspected:The presence of inflammation should be confirmed with erythrocyte sedimentation rate (ESR), and/or C-reactive protein (CRP), and full blood count (FBC) tests.Local referral protocols should be followed on imaging the sacroiliac joints and spine, or specialist advice sought on imaging before referral. In well-established cases, radiographs of the sacroiliac joints and spine are diagnostic. Magnetic resonance imaging can detect early changes in sacroiliac joints. Ultrasound scanning can confirm a clinical impression of enthesitis.Referral to a rheumatologist should be arranged.Treatment should be started with a nonsteroidal anti-inflammatory drug (NSAID).Treatments available from rheumatologists for ankylosing spondylitis include:For sacroiliitis: injection of corticosteroids.For enthesitis (inflammation where bone joins tendon or ligament): injection of corticosteroids.For uncontrolled disease in general: tumour necrosis factor (TNF)-alpha inhibitors such as etanercept and adalimumab or oral or intravenous bisphosphonates. Have I got the right topic? Back to topHave I got the right topic? From age 16 years onwards.This CKS topic covers the management of people with ankylosing spondylitis in primary care.This CKS topic does not cover the treatment of complications of ankylosing spondylitis such as uveitis, or give details of the use of disease-modifying anti-rheumatic drugs or the new 'biologic' drugs as these would usually be started and managed in secondary care.There are separate CKS topics on Back pain - low (without radiculopathy), Dyspepsia - proven peptic ulcer, Dyspepsia - unidentified cause, DMARDs, NSAIDs - prescribing issues, Sciatica (lumbar radiculopathy), and Uveitis.The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care. How up-to-date is this topic? Back to topHow up-to-date is this topic? Back to top Changes Changes February 2013 — reviewed. A literature search was conducted in December 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. Changes have been made to the sections on diagnosis and referral. Back to top Previous changes Previous changes February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.January 2012 — minor update. Information from the manufacturer's Summary of Product Characteristics about the possible interaction between pantoprazole and warfarin has been added to drug interactions. Information from the British National Formulary about the potentially serious interaction between proton pump inhibitors and protease inhibitors (atazanavir and saquinavir) has also been added. Issued in January 2012.May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic. Issued in June 2011.February 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.June 2010 — minor update. In people at risk of cardiovascular adverse events, ibuprofen up to 1200 mg per day or naproxen up to 1000 mg per day are recommended as first-line NSAIDs. Issued in July 2010.July 2009 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) has issued advice on the interaction between clopidogrel and proton pump inhibitors. Healthcare professionals are advised to avoid concomitant use of these drugs unless considered essential. Issued in July 2009.June 2009 — minor update. The intra-articular corticosteroid prescriptions have been updated. Issued in June 2009.March to July 2008 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.There are no major changes to the recommendations on managing ankylosing spondylitis. However, there are some changes in the recommendations on the use of nonsteroidal anti-inflammatory drugs (NSAIDs), with clearer advice on balancing the benefits and risks of treatment.October 2005 — minor technical update. Issued in November 2005.April 2005 — reviewed. Validated in June 2005 and issued in July 2005.June 2001 — reviewed. Validated in November 2001 and issued in April 2002.July 1999 — written. Validated in October 1999 and issued in January 2000. Back to top Update Update Back to top New evidence New evidence Evidence-based guidelinesNICE, (2017), Spondyloarthritis in over 16s: diagnosis and management. National Institute for Health and Clinical Excellence. www.nice.org.uk [Free Full-text]HTAs (Health Technology Assessments)No new technology appraisals since 1 December 2012.Economic appraisalsNo new economic appraisals since 1 December 2012.Systematic reviews and meta-analysesSystematic reviews published since the last revision of this topic:Machado, M.A., Barbosa, M.M., Almeida, A.M., et al. (2013) Treatment of ankylosing spondylitis with TNF blockers: a meta-analysis.Rheumatology International 33(9), 2199-2213. [Abstract]Wang, H., Zuo, D., Sun, M., et al. (2014) Randomized, placebo controlled and double-blind trials of efficacy and safety of adalimumab for treating ankylosing spondylitis: a meta-analysis.International Journal of Rheumatic Diseases 17(2), 142-148. [Abstract]Yang, Z., Zhao, W., Liu, W. et al. (2014) The efficacy evaluation of methotrexate in the treatment of ankylosing spondylitis using meta-analysis.International Journal of Clinical Pharmacology and Therapeutics epub ahead of print. [Abstract]Primary evidenceNo new randomized controlled trials published in the major journals since 1 December 2012. Back to top New policies New policies No new national policies or guidelines since 1 December 2012. Back to top New safety alerts New safety alerts No new safety alerts since 1 December 2012. Back to top Changes in product availability Changes in product availability No changes in product availability since 1 December 2012. Goals and outcome measures Back to topGoals and outcome measures Back to top Goals Goals To diagnose early in the course of the disease.To promptly implement effective management.To identify people in whom the disease is inadequately controlled, but who have not been offered referral for tumour necrosis factor (TNF)-alpha inhibitor treatment.To recognize and minimize the occurrence and effects of complications of the disease such as anterior uveitis (iritis) and osteoporosis, and of adverse effects of treatment such as hypertension and renal impairment.To recognize peripheral manifestations of ankylosing spondylitis such as enthesitis-related conditions.To help people remain in employment. Back to top Outcome measures Outcome measures No outcome measures were found during the review of this topic. Back to top Audit criteria Audit criteria No audit criteria were found during the review of this topic. Back to top QOF indicators QOF indicators No QOF indicators were found during the review of this topic. Back to top QIPP - Options for local implementation QIPP - Options for local implementation Non-steroidal anti-inflammatory drugs (NSAIDs)Review the appropriateness of NSAID prescribing widely and on a routine basis, especially in people who are at higher risk of both gastrointestinal (GI) and cardiovascular (CV) morbidity and mortality (e.g. older patients).If initiating an NSAID is obligatory, use ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).Review patients currently prescribed NSAIDs. If continued use is necessary, consider changing to ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).Review and, where appropriate, revise prescribing of etoricoxib to ensure it is in line with MHRA advice and the NICE clinical guideline on osteoarthritis [CSM, 2005; NICE, 2008].Co-prescribe a proton pump inhibitor (PPI) with NSAIDs for people with osteoarthritis, rheumatoid arthritis, or low back pain (for people over 45 years) in accordance with NICE guidance [NICE, 2008; NICE, 2009a; NICE, 2009b].Take account of drug interactions when co-prescribing NSAIDs with other medicines (see Summaries of Product Characteristics). For example, co-prescribing NSAIDs with ACE inhibitors or angiotensin receptor blockers (ARBs) may pose particular risks to renal function; this combination should be especially carefully considered and regularly monitored if continued.[NICE, 2015] Back to top NICE quality standards NICE quality standards No NICE quality standards were found during the review of this topic. Background information Back to topBackground information Back to top Definition What is it? Ankylosing spondylitis is a chronic inflammatory rheumatic disease of unknown cause and varying clinical presentation.The principal features (not all of which are present at onset, or in all people) are [Elyan and Khan, 2006; McVeigh and Cairns, 2006; Zochling et al, 2006a]:Inflammatory low back pain (pain and stiffness worse at night and in the morning).Inflammation of the spinal joints and the junction (enthesis) of the intervertebral spinal ligaments and vertebrae, leading (after many years) to ankylosis (i.e. fusion from fibrosis and calcification).Inflammation of the sacroiliac joints (on X-ray or other radiological imaging such as magnetic resonance imaging [MRI]), which presents as alternating buttock pain.Enthesitis (inflammation of the sites where tendons and ligaments attach to bone), costochondritis (inflammation where cartilage joins the ribs), and epicondylitis (inflammation of an epicondyle of bone).Arthritis of peripheral joints, usually involving the large joints of the lower limbs, or asymmetric arthritis of peripheral joints.Insidious onset (over a period of at least 3 months, and often several years) usually beginning in late adolescence or early adulthood.Fatigue.Association with the human leukocyte antigen B27 (HLA-B27).Axial spondyloarthritis is a term used to describe people with the symptoms of ankylosing spondylitis, but without the radiographic changes. Over a 10 year period, more than half of these people will progress to radiographic sacroiliitis and ankylosing spondylitis [Kain et al, 2008]. Back to top Causes What causes it? The cause of ankylosing spondylitis is not known.It is thought that ankylosing spondylitis is triggered by an environmental factor (or factors) in people who are genetically predisposed [Kim et al, 2005].There is a strong and complex association with the gene for human leukocyte antigen B27 (HLA-B27).The prevalence of HLA-B27 varies considerably between different populations [Mijiyawa et al, 2000; Bakland et al, 2005].In white western Europeans, the prevalence of HLA-B27 is about 90–95% in people with ankylosing spondylitis compared with about 8% in the general population.In sub-Saharan Africans, the prevalence of HLA-B27 is low and ankylosing spondylitis is rare (but more common in the presence of HIV infection).Non-HLA-B27 genes also play a role in susceptibility to ankylosing spondylitis [Wellcome Trust Case Control Consortium et al, 2007]. Back to top Prevalence How common is it? Ankylosing spondylitis is not uncommon:Incidence. It is estimated that each year about 2% of people in a general practice will present with back pain and up to 5% of these will show features of ankylosing spondylitis [Underwood and Dawes, 1995].Prevalence. Estimates of the prevalence of ankylosing spondylitis vary between 0.1% and 2% in different populations [Gran and Husby, 2003]. There are around 200,000 diagnosed cases in the UK [DH, 2006].Sex. It is about three times more common in men than women.Age. It most commonly begins between 20 and 30 years of age, with 90–95% of people aged less than 45 years at disease onset [Sieper, 2012].Familial association. It is more common in people with the HLA-B27 antigen, and in this group, the risk of ankylosing spondylitis or similar type of arthritis (i.e. spondyloarthropathy) is three times more common in first degree relatives [Khan, 2002]. Back to top Complications What are the complications? Common complicationsProgressive involvement of the lumbar, thoracic, and cervical spine can lead to a fixed and flexed posture. However, this seldom causes severe disability unless there is also severe arthritis of the hips.Damage to peripheral joints.Anterior uveitis (iritis).Less common complicationsFracture of spinal vertebrae:People with mild ankylosing spondylitis have a higher risk of fractures compared with the normal population and this increases with the duration of disease [Ralston et al, 1990; Cooper et al, 1994; Mitra et al, 2000].Cardiac complications:The risk of atherosclerotic cardiovascular events is increased in ankylosing spondylitis. It is therefore particularly important to identify and manage modifiable cardiovascular risk factors [Peters et al, 2004].Aortic regurgitation, mitral regurgitation, atrioventricular block, fibrosis.Apical fibrosis of the lung.Cauda equina syndrome: altered bladder and bowel function, saddle anaesthesia, widespread or progressive motor weakness in the legs or gait disturbance.Amyloidosis — in long term and severe disease.Secondary osteoarthritis.Secondary osteoporosis.Blindness from uveitis.[Elyan and Khan, 2006; McVeigh and Cairns, 2006] Back to top Prognosis What is the prognosis? Many people with ankylosing spondylitis do relatively well, although progression of the disease varies widely between different individuals, and a significant proportion are at risk of long term disability.After an initial period of inflammation, the disease tends to settle down, and 70–90% of those affected remain fully independent or minimally disabled in the long term. This is despite eventual severe restriction of spinal flexibility in 40% of those affected.However, if the spine becomes fixed with flexion, this can be significantly disabling. If spinal deformities do arise, they do so after at least 10 years. The mortality rate is increased only in people who have had severe disease for at least 20 years.Every attempt should be made to keep the person in employment until symptoms have been controlled. Once out of a job, people with ankylosing spondylitis rarely get back to work.The appropriate use of anti-TNF treatments for patients with severe persistent disease is likely to greatly reduce disability in this group in the shorter and longer term.Most people have mainly spinal symptoms, with occasional episodes of peripheral joint arthritis or anterior uveitis. A minority have spinal symptoms and recurrent extra-spinal problems (such as anterior uveitis).Rarely, fusion of the spine can lead to severe deformities and disability, especially if the hips are also involved. Replacements of affected hip joints will not only relieve pain in the hips and improve mobility, but will also allow flexion of the lower limb to compensate for restricted movement of the spine.Fusion of vertebral bodies and costovertebral joints may lead to a frozen thorax, which may cause respiratory impairment. This may be prevented by anti-TNF treatment.The risk of vertebral fractures is increased in people with ankylosing spondylitis. The spine is made brittle by rigidity and weak by osteoporosis, and fractures can occur with minimal force [Ralston et al, 1990; Cooper et al, 1994; Mitra et al, 2000].Factors that can affect outcomesGenderWomen tend to have milder spinal disease than men, but more symptoms in knees, wrists, ankles, hips, or pelvis.Men tend to have more severe disease than women, with involvement of the spine, pelvis, chest wall, hips, shoulders, or feet.Women are more likely to present with anterior uveitis.Age of onsetEarly onset of peripheral arthritis or intractable iritis is associated with more severe spinal restriction.Heredity and HLA-B27If the parent has ankylosing spondylitis and is HLA-B27-positive, the chance of a child developing ankylosing spondylitis is less than 2 in 10.If the parent has ankylosing spondylitis and is HLA-B27-negative, the chance of a child developing ankylosing spondylitis is less than 1 in 10.RadiotherapyRadiotherapy has not been used to treat ankylosing spondylitis for many years. However, those who have been irradiated are at increased risk of developing leukaemia in the early post-radiation stage, and carcinomas in the irradiation field at later stages.[Elyan and Khan, 2006; McVeigh and Cairns, 2006] Diagnosis Back to topDiagnosis of ankylosing spondylitis Back to top Diagnosis How do I make a working diagnosis of ankylosing spondylitis? Diagnosis is typically delayed by 5–7 years which has implications for disease progression. Making the diagnosis early is difficult because the onset of ankylosing spondylitis is insidious, with symptoms developing over several years, and there is no definitive diagnostic test. Early diagnosis therefore requires a high index of suspicion.Suspect ankylosing spondylitis in anyone with chronic or recurrent low back pain, fatigue and stiffness, especially if:They are a teenager, or adult aged less than 45 years.The back pain has been present for more than 3 months.Stiffness is inflammatory (rather than mechanical) and worse in the morning.They have current or previous:Buttock pain, sometimes on one side and sometimes on the other — distinguish from sciatica which usually radiates down one leg and is associated with neurological symptoms and signs.Arthritis predominately asymmetric and in the lower limbs.Enthesitis, costochondritis or epicondylitis.Anterior uveitis (iritis) — this presents as an acutely painful red eye with severe photophobia; if untreated, it can lead to loss of vision.Psoriasis or inflammatory bowel disease, or recent infective diarrhoea or sexually transmitted disease (especiallyChlamydia).Symptoms wake them in the night.Symptoms respond to a course of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours.Around three-quarters of people with ankylosing spondylitis have a good response to NSAIDs within 48 hours of treatment. In contrast, only around 15% of people with mechanical back pain will respond well.There is a family history of ankylosing spondylitis or spondyloarthropathy.Other conditions with similar presentations have been excluded, see Differential diagnosis.Refer to a rheumatologist for confirmation of the diagnosis as this can be difficult. There are a number of different classification criteria available to aid the diagnosis of ankylosing spondylitis. Certain investigations can be arranged from primary care prior to referral. Back to top Diagnostic criteria Diagnostic criteria These are examples of diagnostic criteria which may be used by rheumatologists to help to confirm a diagnosis of ankylosing spondylitis.For the 'modified New York criteria' for diagnosing ankylosing spondylitis, see Table 1.For the Assessment of Spondylitis international Society (ASAS) classification criteria for axial spondyloarthritis, see Table 2.Table 1. Modified New York criteria for diagnosing ankylosing spondylitis.Modified New York criteriaClinical criteria: Low back pain; present for more than 3 months; improved by exercise but not relieved by rest. Limitation of lumbar spine motion in both the sagittal and frontal planes. Limitation of chest expansion relative to normal values for age and sex.Radiological criterion: Sacroiliitis on X-ray.Diagnose: Definite ankylosing spondylitis if the radiological criterion is present plus at least one clinical criterion. Probable ankylosing spondylitis if three clinical criteria are present alone, or if the radiological criterion is present but no clinical criteria are present.Data from: [van der Linden, 1984]Table 2. ASAS classification criteria for axial spondyloarthritisASAS classification criteria (for people with back pain for 3 months or longer who were