Ankylosing spondylitis and axial spondyloarthritis

At a glance

• Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the sacroiliac joints and spine. Ankylosing spondylitis (radiographic axSpA) has definite sacroiliitis on X-ray. Non-radiographic axSpA has inflammation on MRI without X-ray change; about 10% progress to radiographic disease within 2 years and about a quarter by 15 years (Wang 2016: 17% at 10 years, 26% at 15).
• Onset is usually in the 20s and almost always before 45. AS is two to three times more common in men; nr-axSpA affects men and women about equally.
• The average delay to diagnosis is around 7 years. Recognise inflammatory back pain and image the sacroiliac joints, not the lumbar spine. The approach to back pain is in Acute low back pain.
• NSAIDs and exercise first. Then a TNF or IL-17 inhibitor, equal first choices in the 2026 ACR/SAA/SPARTAN update, with JAK inhibitors after that.
• Oral glucocorticoids and conventional DMARDs don't help spinal disease.

Pathophysiology

• HLA-B27 is the strongest genetic risk. Theories include misfolding with an unfolded protein response, arthritogenic peptide presentation and free heavy chains. ERAP1, IL23R and other genes add risk.
• Inflammation starts at the enthesis, where tendon and ligament insert into bone. The IL-23/IL-17 axis and TNF drive it.
• Osteitis is followed by erosion, then new bone: syndesmophytes bridge vertebrae and the sacroiliac joints fuse. Bone loss happens at the same time, so the fused spine is also osteoporotic.
• Subclinical gut inflammation is found in up to 60% at colonoscopy, which links axSpA to IBD (see Enteropathic arthritis).

Recognition

Inflammatory back pain (ASAS)

Four of five: onset before 40, insidious onset, improves with exercise, no improvement with rest, night pain that eases on getting up. Morning stiffness over 30 minutes and alternating buttock pain add weight.

SpA features

Feature	Notes
Acute anterior uveitis	About 30%; unilateral, recurrent, alternating. See Acute red eye
Enthesitis	Achilles and plantar fascia insertions, heel pain
Peripheral arthritis	Asymmetric, lower limb, large joints; hip disease predicts worse function
Dactylitis	Whole-digit swelling
Psoriasis	About 10%
IBD	5 to 10% with clinical Crohn disease or UC
Family history, good NSAID response, raised CRP, HLA-B27	Count as SpA features in ASAS criteria

Examination

• Loss of lumbar lordosis, thoracic kyphosis, and in late disease the "question mark" posture.
• Modified Schober test: mark 10 cm above and 5 cm below the lumbosacral junction (dimples of Venus). Less than 5 cm increase on forward flexion is reduced.
• Occiput-to-wall distance (any gap is abnormal) and chest expansion under 2.5 cm (a modified New York clinical criterion).
• BASMI has five parts: tragus-to-wall distance, modified Schober, cervical rotation, lumbar side flexion and intermalleolar distance.
• Sacroiliac joint tenderness, entheses, peripheral joints, skin, nails, eyes, and a murmur of aortic regurgitation.

Extra-articular and late complications

• Cardiac: aortitis with aortic regurgitation, AV conduction block.
• Lung: restrictive defect from a rigid chest wall, upper lobe fibrosis.
• Bone: osteoporosis and vertebral fractures. An ankylosed spine snaps like a long bone: minor trauma can cause an unstable fracture, often cervical, missed on plain films.
• Neurological: cauda equina syndrome from dural ectasia (rare), atlantoaxial subluxation.
• Renal: IgA nephropathy, secondary AA amyloidosis (now rare), NSAID kidney injury.

Classification

ASAS 2009 (back pain for 3 months or more, onset before 45)

• Imaging arm: sacroiliitis on MRI (active inflammation) or definite X-ray sacroiliitis, plus at least one SpA feature.
• Clinical arm: HLA-B27 plus at least two other SpA features.

The modified New York criteria define AS: X-ray sacroiliitis of bilateral grade 2 or more, or unilateral grade 3 or 4, plus a clinical criterion. Revised ASAS-SPARTAN criteria from the CLASSIC cohort, presented in October 2025, put imaging at the centre and are more specific. Exams and PBS criteria still use the 2009 and modified New York definitions as of November 2026.

Investigations

• CRP and ESR: raised in only about half. A normal CRP doesn't exclude axSpA. A raised CRP predicts progression and response to biologics.
• HLA-B27: useful when the pre-test probability is moderate. A negative result lowers it sharply in people of European descent.
• X-ray of the pelvis (sacroiliac joints): the 2026 ACR guideline's preferred first test. Look for erosions, sclerosis, joint widening then fusion.
• MRI of the sacroiliac joints (STIR) if X-ray is normal or equivocal: bone marrow oedema shows active disease; erosions and fat metaplasia show structural damage.
• Spine X-ray: squaring of vertebrae, Romanus lesions (corner erosions, healing as sclerotic shiny corners), syndesmophytes, and the bamboo spine of late disease.
• Baseline before biologics: hepatitis B and C, HIV, latent TB screening (IGRA, chest X-ray), vaccination review.

Pitfall: bone marrow oedema at the sacroiliac joints occurs in up to a quarter of healthy people, and more often in postpartum women, runners and military recruits. MRI changes without the clinical picture don't make axSpA.

Activity measures

Measure	Use
BASDAI (0 to 10)	Patient-reported; 4 or more is active, the PBS threshold
ASDAS-CRP	Inactive under 1.3, low under 2.1, high 2.1 to 3.5, very high over 3.5. A fall of 1.1 or more is clinically important
BASFI, BASMI	Function and spinal mobility

Management

Non-drug

• Daily exercise and physiotherapy (supervised group or hydrotherapy is better than home alone), posture work and education.
• Stop smoking. Smoking speeds radiographic progression and worsens activity.
• Avoid systemic glucocorticoids and opioids for axial disease (2026 ACR guideline).

NSAIDs

• First-line drug treatment. Use the full dose; try at least two NSAIDs over a total of 4 weeks before calling them a failure.
• Continuous use for symptoms is fine when needed. Weigh GI, renal and cardiovascular risk; a COX-2 inhibitor with fewer GI effects is an option.

Conventional DMARDs and steroids

• Sulfasalazine (or methotrexate) only for peripheral arthritis. They do nothing for the spine.
• Local glucocorticoid injections for a sacroiliac joint, enthesis or peripheral joint.

Biologic and targeted synthetic DMARDs

Start after NSAID failure with high activity (ASDAS 2.1 or more, or BASDAI 4 or more) and a raised CRP, MRI sacroiliitis or definite X-ray sacroiliitis (ASAS-EULAR 2022).

Class	Drugs	Choose when	Avoid when
TNF inhibitor	Adalimumab, etanercept, infliximab, golimumab, certolizumab	Recurrent uveitis or IBD (monoclonal antibodies); pregnancy (certolizumab crosses the placenta least)	Etanercept for IBD or uveitis; untreated latent TB; demyelination; severe heart failure
IL-17 inhibitor	Secukinumab, ixekizumab, bimekizumab	Significant psoriasis	IBD (can trigger or worsen it); candidiasis is common with bimekizumab
JAK inhibitor	Upadacitinib, tofacitinib	After a biologic, or when an oral drug is preferred	Age 65 or over, smoking, cardiovascular or VTE risk, cancer (ORAL Surveillance), unless no alternative
IL-23 or IL-12/23	Ustekinumab, guselkumab, risankizumab	Not used	Ineffective for axial disease

• 2026 ACR/SAA/SPARTAN update: TNF and IL-17 inhibitors are equal first choices. JAK inhibitors are recommended but not first. If the first drug fails, switch mechanism. For sustained remission, consider tapering the dose rather than stopping, as stopping brings flares in most.
• PBS (as of November 2026): a rheumatologist or clinical immunologist applies after at least 3 months of exercise and NSAIDs. For AS: X-ray sacroiliitis meeting modified New York criteria, BASDAI of 4 or more, and a raised ESR (over 25 mm/h) or CRP (over 10 mg/L). For nr-axSpA: MRI inflammation of the sacroiliac joints, BASDAI of 4 or more and CRP over 10 mg/L. Continuing (AS) needs a BASDAI of 2 or less or a fall of 2 or more, plus ESR 25 mm/h or less or CRP 10 mg/L or less, or a 20% fall in either from baseline. Continuing (nr-axSpA) needs a BASDAI fall of 2 or more plus CRP 10 mg/L or less or a 20% fall from baseline. Only one biologic is subsidised at a time.

Surgery

• Total hip replacement for destructive hip disease. Corrective spinal osteotomy for severe fixed kyphosis is rare and high risk.

Special situations

• Pregnancy: disease activity often doesn't ease, unlike RA. Avoid NSAIDs from 20 weeks (oligohydramnios, ductal closure). TNF inhibitors can continue; certolizumab has minimal placental transfer.
• Older people: new inflammatory back pain after 45 is not axSpA until infection, malignancy and diffuse idiopathic skeletal hyperostosis (DISH) are excluded. DISH spares the sacroiliac joints and has flowing anterior ossification along four or more vertebrae with normal CRP.
• Uveitis: every patient should know to seek same-day eye review for a painful red eye with photophobia.

Pitfalls

• Imaging the lumbar spine for inflammatory back pain, or reassuring because the lumbar X-ray is normal.
• Ruling out axSpA because the CRP is normal or HLA-B27 is negative.
• Diagnosing axSpA on MRI bone marrow oedema alone in a postpartum woman or a runner.
• Starting an IL-17 inhibitor in someone with gut symptoms or known IBD.
• Prescribing methotrexate or oral prednisolone for spinal disease.
• Missing a cervical fracture after a minor fall in a patient with a fused spine.
• Forgetting fibromyalgia, which coexists in about 1 in 5 and inflates BASDAI without raising CRP.