Ankylosing Spondylitis

Ankylosing spondylitis (radiographic axial spondyloarthritis) is a chronic inflammatory disease of the axial skeleton that begins in the sacroiliac joints and spine, causes inflammatory back pain, stiffness and in time bony fusion (syndesmophytes and ankylosis), with extra-articular features in the eyes, gut, heart and skin.

The prevalence is about 0.1 to 1.4% depending on the population and HLA-B27 frequency. Onset is usually before 45 years, with a peak in the late teens and twenties, and radiographic disease is 2 to 3 times more common in men than women. HLA-B27 is present in about 90% of white patients with the disease, and the risk is raised in first degree relatives.

Associated conditions are acute anterior uveitis (25 to 40%), psoriasis, inflammatory bowel disease (5 to 10%), enthesitis, peripheral arthritis, aortic regurgitation and conduction defects, osteoporosis and vertebral fracture, and, rarely, amyloidosis and cauda equina syndrome.

The course is variable. Progression to fusion is influenced by smoking, male sex, early hip involvement, raised CRP and baseline syndesmophytes. Complications are chronic pain, loss of spinal mobility and thoracic kyphosis, restricted chest expansion, spinal fracture after minor trauma, hip destruction, and reduced work capacity.

Pathophysiology.

Immune mediated inflammation (the interleukin-23 and interleukin-17 axis, and tumour necrosis factor) targets the entheses, with inflammatory osteitis followed by new bone formation at the vertebral margins. Misfolded HLA-B27, endoplasmic reticulum stress, gut microbial factors and mechanical stress contribute. Fusion of the vertebrae produces a rigid "bamboo" spine, which is brittle and breaks with low energy.

Inflammatory back pain: insidious onset before 45 years, lasting over 3 months, worse at night and in the early morning, morning stiffness over 30 minutes, improving with exercise and not with rest. Buttock pain alternating between sides, heel pain (enthesitis), hip and shoulder pain, chest wall pain, and fatigue are common. Eye pain and redness suggest uveitis.

Examine posture (loss of lumbar lordosis, thoracic kyphosis, forward head), lumbar flexion (modified Schober test under 5 cm), lateral flexion, chest expansion (under 2.5 cm), occiput-to-wall distance, sacroiliac joint tenderness and stress tests, hips, entheses, eyes, skin, and the heart.

• Radiographs of the pelvis (sacroiliitis: erosions, sclerosis, joint space loss, fusion) and spine (squaring of vertebrae, syndesmophytes, bamboo spine); radiographic change takes years to appear.
• MRI of the sacroiliac joints (STIR sequences) for early disease: bone marrow oedema, erosions, fat metaplasia; MRI of the spine when needed.
• Blood tests: CRP and ESR (normal in up to 40%), HLA-B27, full blood count, and the disease activity index (BASDAI) and functional index (BASFI).
• Before biologic therapy: tuberculosis screening (interferon gamma release assay and chest radiograph), hepatitis B and C and HIV serology, pregnancy test, and vaccination review.
• Bone density measurement and vertebral imaging when there is back pain after minor trauma.

Differential diagnosis.

• Mechanical low back pain and degenerative disc disease.
• Psoriatic arthritis, reactive arthritis and enteropathic arthritis.
• Diffuse idiopathic skeletal hyperostosis and osteitis condensans ilii.
• Infection (sacroiliac joint, tuberculosis, brucellosis), fibromyalgia and osteoporotic fracture.

The aims are to control inflammation and pain, preserve mobility and posture, and prevent complications.

Non-drug care. Education, daily exercise and stretching programme, supervised physiotherapy (spinal extension, chest expansion, hip mobility), hydrotherapy, smoking cessation, sleep posture advice (firm mattress, no thick pillow), and weight control.

Non-steroidal anti-inflammatory drugs (first line, continuous if effective).

• Naproxen 500 mg orally twice daily with food (maximum 1000 mg daily). Or ibuprofen 600 mg orally three times daily with food (maximum 2400 mg daily). Or celecoxib 200 mg orally once or twice daily (maximum 400 mg daily). Or etoricoxib 60 to 90 mg orally once daily (maximum 90 mg daily). Test one drug for 2 to 4 weeks at full dose before switching; two failures define inadequate response.
• Add omeprazole 20 mg orally once daily in patients over 65 or with ulcer risk. Avoid with eGFR under 30 mL/min/1.73 m2, peptic ulcer, heart failure, uncontrolled hypertension, ischaemic heart disease (especially coxibs), and anticoagulant use. Monitor blood pressure, creatinine and haemoglobin.

Biologic and targeted therapy (active disease despite two NSAIDs over 4 weeks, with objective evidence).

• Tumour necrosis factor inhibitors: adalimumab 40 mg subcutaneously every 2 weeks; etanercept 50 mg subcutaneously once weekly; golimumab 50 mg subcutaneously once monthly.
• Certolizumab pegol 400 mg subcutaneously at weeks 0, 2 and 4, then 200 mg every 2 weeks or 400 mg every 4 weeks; infliximab 5 mg/kg intravenously at weeks 0, 2 and 6, then every 6 to 8 weeks.
• Infliximab, adalimumab, golimumab and certolizumab also treat uveitis and bowel disease (etanercept does not). Avoid with active infection, untreated latent tuberculosis, demyelinating disease, and severe heart failure; monitor for infection, lupus like syndromes and malignancy.
• Interleukin-17 inhibitors: secukinumab 150 mg subcutaneously weekly for 5 weeks then every 4 weeks (300 mg if the response is inadequate), or ixekizumab 160 mg then 80 mg every 4 weeks; avoid with active inflammatory bowel disease, and monitor for candidiasis and neutropenia.
• Janus kinase inhibitors (after a failed biologic or when biologics are not suitable): tofacitinib 5 mg orally twice daily, or upadacitinib 15 mg orally once daily. Avoid with age over 65, current or past smoking, cardiovascular disease, venous thromboembolism risk, or malignancy unless no alternative. Check lipids, liver enzymes and blood count.
• Before and during biologics: no live vaccines; inactivated influenza, pneumococcal and COVID-19 vaccination; screen for tuberculosis yearly in high risk patients.
• Review response at 12 weeks (a fall of BASDAI by 2 units or 50%); consider dose tapering only after sustained remission.

Other drugs.

• Sulfasalazine 500 mg orally daily, increased by 500 mg weekly to 1.5 to 3 g daily in divided doses, for peripheral arthritis only (no benefit for axial disease); monitor blood count and liver function; avoid with sulphonamide allergy.
• Local corticosteroid injection into the sacroiliac joint, entheses or peripheral joints (methylprednisolone acetate 40 mg). Systemic corticosteroids are not used for axial disease.
• Opioids and neuropathic agents only for refractory pain, with the doses used for other chronic pain; paracetamol 1 g every 6 hours as an adjunct.
• Uveitis: topical corticosteroid (prednisolone acetate 1% eye drops hourly then tapered) and mydriatic, with urgent ophthalmology review.

Surgery. Hip arthroplasty for hip destruction; corrective spinal osteotomy for fixed severe kyphosis with inability to look forward; stabilisation (long segment) for spinal fracture.

Perioperative care:

• cefazolin 2 g intravenously within 60 minutes before incision
• enoxaparin 40 mg subcutaneously once daily started 6 to 12 hours after surgery for hip arthroplasty and continued for 28 to 35 days (20 mg at creatinine clearance under 30 mL/min)
• time the last biologic dose to the drug half life before surgery
• difficult intubation planning because of cervical fusion

Bone health. Calcium intake 1000 to 1200 mg daily, vitamin D 800 to 2000 units daily, weight bearing exercise, and bisphosphonate (alendronate 70 mg orally once weekly) when osteoporosis or fracture is present.

Monitoring. Review every 3 to 6 months: BASDAI, CRP, spinal mobility and posture, chest expansion; blood tests every 3 months on biologics or sulfasalazine; radiographs of the spine every 2 years; echocardiogram if murmur or conduction defect; bone density every 2 to 5 years.

Referral and escalation. Refer adults with chronic back pain starting before 45 years and features of inflammatory back pain to rheumatology. Emergency referral for any new spinal pain after even minor trauma (suspect fracture, which may be unstable and silent), neurological deficit, painful red eye, or severe infection on biologics.

Special groups.

• Pregnancy and conception: continue NSAIDs only until conception or the first trimester; certolizumab is compatible throughout pregnancy and breastfeeding; stop JAK inhibitors; avoid sulfasalazine without folic acid 5 mg daily.
• Older adults: lower NSAID doses, bone health, falls risk, and cardiovascular review.
• Women: often present later with non-radiographic disease and more peripheral and neck pain.
• Fracture: any fracture in an ankylosed spine is unstable until proven otherwise; keep the neck and trunk in their usual alignment and avoid forcing the spine flat.