Spondyloarthritis Axial, Peripheral, Radiographic and Non-radiographic

Authored by , Reviewed by Dr Laurence Knott | Last edited

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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.

Spondyloarthritis is a term given to a range of inflammatory arthritis which can predominantly affect the spine (known as axial spondyloarthritis) or the peripheral joints (known as peripheral spondyloarthritis). The most common symptoms are inflammatory back pain, stiffness, swelling and tenderness of joints.

Spondyloarthritis can be associated with other inflammatory conditions such as psoriasis, uveitis, and inflammatory bowel disease (Crohn’s disease or ulcerative colitis).

Spondyloarthritis may be classified as[1] :

People with predominantly axial spondyloarthritis may have additional peripheral spondyloarthritis symptoms, and vice versa[2] .

Progression of patients with non-radiographic axial spondyloarthritis to radiographic axial spondyloarthritis is slow, with estimates of 5.1% in 5 years and 19% in 10 years[3] .

A UK cross-sectional cohort study found a prevalence of axial spondyloarthritis of 0.66% (using modified New York criteria) in an adult primary care population with low back pain, and 0.15% in the general adult primary care population[4] .

Axial spondyloarthritis is associated with the HLA-B27 antigen, but can occur in people without HLA-B27. Over 90% of patients with axial spondyloarthritis are HLA-B27 positive.

The initial presentation may be musculoskeletal - eg, back pain, enthesitis (inflammation of the sites where ligaments or tendons attach to bone) or dactylitis (swelling of a finger or toe), or extra-articular - eg, uveitis or psoriasis.

Half of the patients classified as having axial spondyloarthritis also have peripheral disease manifestations such as arthritis, enthesitis and/or dactylitis. These peripheral disease manifestations contribute significantly to overall disease activity[5] .

Spondyloarthritis can have diverse symptoms and be difficult to identify, which can lead to delayed or missed diagnoses. A delay of several years between symptom onset and diagnosis is common[6] .

Several factors are independently associated with a long diagnostic delay, including female sex, HLA-B27 negativity, presence of psoriasis and young age of symptom onset[7] .

Spondyloarthritis[4] cannot be reliably diagnosed or ruled out by a single test.

  • Blood tests for ESR, and/or CRP. The diagnosis of spondyloarthritis should not be ruled out if CRP and ESR are normal.
  • X-rays:
    • Radiographic axial spondyloarthritis is suggested by X-ray changes of the sacroiliac joints and spine, including sacroiliitis, sclerosis (thickening of bone), erosions, and partial or total ankylosis (fusion of joints).
    • Axial spondyloarthritis may be present despite no evidence of sacroiliitis on a plain film X-ray.
  • MRI:
    • Inflammation of the sacroiliac joints can be detected on MRI despite an absence of changes on X-ray.
    • The use of MRI has enabled an increase in detection of sacroiliitis and inflammatory back pain, and the diagnosis of non-radiographic axial spondyloarthritis.
    • Refer for MRI if the plain film X-ray does not show sacroiliitis or an X-ray is not appropriate because the person's skeleton is not fully mature.
  • HLA-B27: only perform an HLA-B27 test in primary care if a person has exactly three referral criteria, to help determine whether referral to a rheumatologist is necessary (see below).

Axial spondyloarthritis presentations of spondyloarthritis are often misdiagnosed as mechanical low back pain, leading to delays in access to effective treatments.

Peripheral spondyloarthritis presentations are often seen as unrelated joint or tendon problems, and can be misdiagnosed because problems can move around between joints.

The differential diagnoses of axial spondyloarthritis include[1] :

  • Degenerative or mechanical problems - eg, degenerative disc disease, spondylosis, congenital vertebral anomalies, degenerative changes in the intevertebral (facet) joints, osteoarthritis of sacroiliac joints.
  • Fractures.
  • Infectious sacroiliitis.
  • Bone metastasis.
  • Primary bone tumours.
  • Spinal stenosis.
  • Hypermobility.

For a person presenting with low back pain that started before the age of 45 years and which has lasted for longer than three months, the National Institute for Health and Care Excellence (NICE) recommends referral to a rheumatologist for a spondyloarthritis assessment if four 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 three 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 these criteria but clinical suspicion of axial spondyloarthritis remains, advise the person to seek repeat assessment if new signs, symptoms or risk factors develop. This may be especially appropriate if the person has current or past inflammatory bowel disease (Crohn's disease or ulcerative colitis), psoriasis or uveitis.

Urgently refer people with suspected new-onset inflammatory arthritis to a rheumatologist for a spondyloarthritis assessment, unless rheumatoid arthritis, gout or acute calcium pyrophosphate (CPP) arthritis ('pseudogout') is suspected.

Refer people with dactylitis to a rheumatologist for a spondyloarthritis assessment.

Refer people with enthesitis without apparent mechanical cause to a rheumatologist for a spondyloarthritis assessment if it is persistent, or it is in multiple sites, or if any of the following are also present:

  • Back pain without apparent mechanical cause.
  • Current or past uveitis. Refer people for an immediate (same-day) ophthalmological assessment if they have symptoms of acute anterior uveitis (for example, eye pain, eye redness, sensitivity to light or blurred vision).
  • Current or past psoriasis.
  • Gastrointestinal or genitourinary infection.
  • Inflammatory bowel disease (Crohn's disease or ulcerative colitis).
  • A first-degree relative with spondyloarthritis or psoriasis.

Early treatment is very important to prevent long-term complications and joint damage.

Self-care advice

  • Regular physical activity is very important and helps to reduce stiffness and increase range of movements.
  • Maintaining good posture can help ease pain and stiffness.
  • Stretching exercises also help to relieve pain and stiffness.

Discuss risk factors for cardiovascular disease with all people with spondyloarthritis, in view of the increased risk of cardiovascular disease.

Physical therapies

  • Specialist physiotherapist: individualised, structured exercise programme which should include: stretching, strengthening and postural exercises, deep breathing, spinal extension, range of motion exercises for the lumbar, thoracic and cervical sections of the spine, and aerobic exercise.
  • Hydrotherapy as an adjunctive therapy to manage pain and maintain or improve function for people with axial spondyloarthritis.
  • Consider a referral to a specialist therapist (such as a physiotherapist, occupational therapist, hand therapist, orthotist or podiatrist) for people with spondyloarthritis who have difficulties with any of their everyday activities.

Medication

Non-steroidal anti-inflammatory drugs

  • Both traditional and COX-2 NSAIDs are effective for treating axial spondyloarthritis. Various NSAIDs are equally effective[8] .
  • Offer NSAIDs at the lowest effective dose to people with pain associated with axial spondyloarthritis, and think about appropriate clinical assessment, ongoing monitoring of risk factors, and the use of gastroprotective treatment.
  • If an NSAID taken at the maximum tolerated dose for 2-4 weeks does not provide adequate pain relief, consider switching to another NSAID.

Biological disease modifying antirheumatic drugs

  • Adalimumab, certolizumab pegol, etanercept, golimumab and infliximab[9] :
    • Are recommended as options for treating severe active radiographic axial spondyloarthritis or non-radiographic axial spondyloarthritis in adults whose disease has responded inadequately to, or who cannot tolerate, NSAIDs.
    • The response to adalimumab, certolizumab pegol, etanercept, golimumab or infliximab treatment should be assessed 12 weeks after the start of treatment. Treatment should only be continued if there is clear evidence of response.
    • Treatment with another tumour necrosis factor (TNF)-alpha inhibitor is recommended for people who cannot tolerate, or whose disease has not responded to, treatment with the first TNF-alpha inhibitor, or whose disease has stopped responding after an initial response.
  • Secukinumab[10] :
    • Is recommended as an option for treating active non-radiographic axial spondyloarthritis with objective signs of inflammation (shown by elevated C-reactive protein or MRI) that is not controlled well enough with non-steroidal anti-inflammatory drugs in adults.
    • It is recommended only if TNF-alpha inhibitors are not suitable or do not control the condition well enough.
    • Response to secukinumab should be assessed after 16 weeks of treatment, and treatment continued only if there is clear evidence of response.
  • Ixekizumab[11] :
    • Is recommended as an option for treating active radiographic axial spondylitis that is not controlled well enough with conventional therapy, or active non-radiographic axial spondyloarthritis with objective signs of inflammation (shown by elevated C-reactive protein or MRI) that is not controlled well enough NSAIDs, in adults.
    • It is recommended only if TNF-alpha inhibitors are not suitable or do not control the condition well enough.
    • Response to ixekizumab should be assessed after 16-20 weeks of treatment, and treatment continued only if there is clear evidence of response.

Surgery for spondyloarthritis

Most people with axial spondyloarthritis will not need surgery. However:

  • Joint replacement may be needed for people with severe pain or joint damage.
  • Corrective surgery may also be required for severe scoliosis or kyphosis.

Do not refer people with axial spondyloarthritis to a complex spinal surgery service to be assessed for spinal deformity correction unless the spinal deformity is: significantly affecting their quality of life, and severe or progressing despite optimal non-surgical management (including physiotherapy).

If a person with axial spondyloarthritis presents with a suspected spinal fracture, refer them to a specialist to confirm the spinal fracture and carry out a stability assessment. After the stability assessment, the specialist should refer people with a potentially unstable spinal fracture to a spinal surgeon.

Managing flares

When managing flares in primary care, seek advice from specialist care as needed, particularly for people who: have recurrent or persistent flares, are taking biological disease-modifying antirheumatic drugs (DMARDs), and have comorbidities that may affect treatment or management of flares.

Uveitis can occur during flare episodes.

  • Osteoporosis: consider regular osteoporosis assessments (every two years). Bone mineral density measures may be elevated on spinal dual-energy X-ray absorptiometry (DXA) due to the presence of syndesmophytes and ligamentous calcification, whereas hip measurements may be more reliable.
  • Increased risk of fractures.
  • Kyphosis and scoliosis.
  • Increased risk of cardiovascular disease. It is therefore particularly important to identify and manage modifiable cardiovascular risk factors.
  • Aortic and non-aortic valvular heart disease.
  • Congestive heart failure.
  • Cardiac arrhythmias - eg, ventricular and supraventricular extrasystoles.
  • Lung involvement such as restrictive pulmonary disease and apical fibrosis. Dyspnoea may also occur as a result of costovertebral involvement decreasing vital capacity.
  • Neurological involvement: vertebral fracture, dislocation, or cauda equina syndrome.
  • Adverse effects from drugs used for treatment, including NSAIDs (eg, gastritis, peptic ulcers, adverse renal effects), biological DMARDs (eg, infection, immunosuppression, malignancy).
  • Decreased quality of life and work productivity due to pain, stiffness, fatigue, reduction in spinal mobility and physical function, and sleep problems.

Please see the NICE CKS reference guidance as well[4] .

Axial spondyloarthritis is often characterised by persistent or fluctuating axial inflammation (on MRI) and structural progression (on X-ray). Both the inflammation and new bone formation (if inflammation is ongoing) affect quality of life due to pain, reduction in mobility and function[4] .

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Further reading and references

  • Carron P, De Craemer AS, Van den Bosch F; Peripheral spondyloarthritis: a neglected entity-state of the art. RMD Open. 2020 May6(1). pii: rmdopen-2019-001136. doi: 10.1136/rmdopen-2019-001136.

  • Ward MM, Deodhar A, Gensler LS, et al; 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Care Res (Hoboken). 2019 Oct71(10):1285-1299. doi: 10.1002/acr.24025. Epub 2019 Aug 21.

  • van der Heijde D, Ramiro S, Landewe R, et al; 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017 Jun76(6):978-991. doi: 10.1136/annrheumdis-2016-210770. Epub 2017 Jan 13.

  1. Spondyloarthritis in over 16s: diagnosis and management; NICE Guidance (Feb 2017)

  2. Lopez-Medina C, Molto A, Sieper J, et al; Prevalence and distribution of peripheral musculoskeletal manifestations in spondyloarthritis including psoriatic arthritis: results of the worldwide, cross-sectional ASAS-PerSpA study. RMD Open. 2021 Jan7(1). pii: rmdopen-2020-001450. doi: 10.1136/rmdopen-2020-001450.

  3. Wang R, Ward MM; Epidemiology of axial spondyloarthritis: an update. Curr Opin Rheumatol. 2018 Mar30(2):137-143. doi: 10.1097/BOR.0000000000000475.

  4. Ankylosing spondylitis; NICE CKS, May 2019 (UK access only)

  5. de Winter JJ, Paramarta JE, de Jong HM, et al; Peripheral disease contributes significantly to the level of disease activity in axial spondyloarthritis. RMD Open. 2019 Jan 115(1):e000802. doi: 10.1136/rmdopen-2018-000802. eCollection 2019.

  6. Magrey MN, Danve AS, Ermann J, et al; Recognizing Axial Spondyloarthritis: A Guide for Primary Care. Mayo Clin Proc. 2020 Nov95(11):2499-2508. doi: 10.1016/j.mayocp.2020.02.007. Epub 2020 Jul 29.

  7. Barnett R, Ingram T, Sengupta R; Axial spondyloarthritis 10 years on: still looking for the lost tribe. Rheumatology (Oxford). 2020 Oct 159(Suppl4):iv25-iv37. doi: 10.1093/rheumatology/keaa472.

  8. Kroon FP, van der Burg LR, Ramiro S, et al; Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis). Cochrane Database Syst Rev. 2015 Jul 17(7):CD010952. doi: 10.1002/14651858.CD010952.pub2.

  9. TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis; NICE Technology Appraisal Guidance, February 2016

  10. Secukinumab for treating non-radiographic axial spondyloarthritis; NICE Technology appraisal guidance, July 2021

  11. Ixekizumab for treating axial spondyloarthritis; NICE Technology appraisal guidance, July 2021

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