Key Facts

AxSpA represents a spectrum from non-radiographic (no X-ray sacroiliitis) to radiographic (ankylosing spondylitis). Early diagnosis and treatment prevent irreversible spinal fusion.

Epidemiology

• Prevalence: 0.1-0.5% of the UK population
• M:F 2-3:1 (being revised; women often present differently)
• Typical onset: 15-30 years; diagnosis often delayed by 8-10 years
• HLA-B27 positive in >90% of AS; only 5% of HLA-B27 carriers develop AS

Aetiology

• Strong genetic component: HLA-B27 (90%+), ERAP1, IL-23R polymorphisms
• Environmental triggers: gut microbiome, infections (reactive arthritis model)
• HLA-B27 misfolding hypothesis: accumulation of misfolded HLA-B27 → unfolded protein response → IL-23/IL-17 pathway activation

Pathophysiology

• Enthesitis (inflammation at tendon/ligament insertions into bone) is the primary pathological process
• Sacroiliac joints and spine most affected
• Inflammation → erosion → new bone formation (syndesmophytes) → ankylosis
• TNF-α and IL-17A are key cytokines driving inflammation and new bone formation
• Progressive fusion: sacroiliitis → ascending spinal involvement → bamboo spine

Inflammatory Back Pain (Key Feature)

• Insidious onset, age <40 years
• Duration >3 months
• Improves with exercise, worse with rest/inactivity
• Morning stiffness >30 minutes (often >1 hour)
• Wakes patient in second half of the night
• Alternating buttock pain (sacroiliac joint inflammation)
• Good response to NSAIDs

Spinal

• Reduced spinal mobility: Schober's test (<5cm increase; normal >5cm)
• Reduced chest expansion (<2.5cm in advanced disease)
• Loss of lumbar lordosis → thoracic kyphosis → fixed flexion deformity ("question mark posture")
• Tragus-to-wall distance increases as cervical spine fuses

Peripheral

• Peripheral arthritis (30-40%): large joint, asymmetric (hip, knee, shoulder)
• Enthesitis: Achilles tendinitis, plantar fasciitis
• Dactylitis: sausage digit (less common than psoriatic arthritis)

Extra-Articular Manifestations

• Anterior uveitis (25-40%): acute unilateral eye pain, photophobia, red eye
• Cardiovascular: aortitis, aortic regurgitation, conduction defects
• Pulmonary: apical fibrosis (rare)
• Renal: IgA nephropathy, amyloidosis (rare)
• IBD: Crohn's or UC in 5-10%
• Osteoporosis: paradoxically common despite new bone formation; increased fracture risk

Red Flags

• Acute anterior uveitis → urgent ophthalmology
• New neurological symptoms → spinal fracture (even minor trauma in fused spine)
• Cauda equina syndrome → rare late complication

Bloods

• HLA-B27: positive in >90% of AS; but NOT diagnostic alone (5-8% of general population are HLA-B27+)
• ESR/CRP: elevated in 50-70% (poor sensitivity; normal CRP does not exclude AS)
• FBC: normocytic anaemia of chronic disease may be present

Imaging

• MRI sacroiliac joints: first-line for early axSpA; bone marrow oedema on STIR sequences indicates active sacroiliitis
• X-ray pelvis (AP): sacroiliitis grading (0-IV); widening → erosions → sclerosis → ankylosis
• X-ray spine: squaring of vertebral bodies → syndesmophytes → bamboo spine; Romanus lesions (shiny corners)
• Modified New York criteria require radiographic sacroiliitis (grade ≥II bilateral or grade III-IV unilateral)

Clinical Assessment

• BASDAI (Bath AS Disease Activity Index): patient-reported; score 0-10 (≥4 = active disease)
• BASFI (Bath AS Functional Index): functional limitation
• BASMI (Bath AS Metrology Index): spinal mobility measurements
• Schober's test: mark at L5, measure 10cm above; flex forward; <5cm increase = reduced lumbar flexion
• Chest expansion: <2.5cm is abnormal

Non-pharmacological

• Regular exercise: most important intervention; supervised physiotherapy
• Hydrotherapy: warm water exercise; effective for pain and stiffness
• Posture advice: avoid prolonged flexion; firm mattress, sleep supine or prone
• NASS (National AS Society): patient education and support
• Smoking cessation: smokers have worse outcomes and poorer response to treatment

Pharmacological

First-line:

• NSAIDs (continuous): naproxen 500mg BD or etoricoxib 90mg OD
• UNIQUE in AS: regular NSAID use may slow radiographic progression (unlike other conditions)
• Try ≥2 different NSAIDs for ≥4 weeks each before declaring failure

Second-line (if NSAID failure + BASDAI ≥4):

• Anti-TNF: adalimumab 40mg SC alternate weeks, etanercept 50mg SC weekly, certolizumab, golimumab, infliximab (NICE TA383)
• IL-17A inhibitor: secukinumab 150mg SC monthly (NICE TA407), ixekizumab
• JAK inhibitors: tofacitinib, upadacitinib (emerging evidence)
• NO role for conventional DMARDs (methotrexate, sulfasalazine) for axial disease; sulfasalazine may help peripheral arthritis

Bridging:

• Local corticosteroid injection: for enthesitis, sacroiliac joint injection
• Oral prednisolone: NOT recommended for long-term use in AS (limited efficacy)

Surgical

• Hip replacement: for severe hip involvement (up to 30% require)
• Spinal osteotomy: for severe fixed kyphosis (rare, specialist centre)
• Spinal fracture fixation: fused spine is at high fracture risk (even minor trauma)

Monitoring

• BASDAI every 3-6 months
• CRP/ESR with disease activity assessments
• DEXA scan: osteoporosis screening (paradoxically common despite new bone formation)
• Cardiovascular risk: annual assessment

Referral Criteria

• Inflammatory back pain <45 years with ≥4 criteria → urgent rheumatology (NICE NG65)
• Inadequate response to ≥2 NSAIDs → biologic therapy assessment
• Acute anterior uveitis → ophthalmology (same day)

• Variable: many patients have mild disease with good functional outcomes
• Poor prognostic factors: hip involvement, high CRP, syndesmophytes at diagnosis, smoking, male sex, early onset
• Radiographic progression: ~30-50% develop significant spinal restriction; bamboo spine in ~10%
• Anti-TNF therapy: dramatically reduces disease activity and improves quality of life; may slow radiographic progression
• Life expectancy: slightly reduced (1.5-fold increased mortality, mainly cardiovascular)
• Work disability: 15-30% of patients unable to work after 20 years (improved with biologics)
• Spinal fracture risk: fused spine fractures easily (even with minor falls); often unstable → cord injury risk

Modified New York Criteria (1984)

Clinical criteria (≥1):

1. Inflammatory back pain
2. Limitation of lumbar motion (sagittal and frontal planes)
3. Reduced chest expansion (<2.5cm)

Radiological criterion:

• Sacroiliitis grade ≥II bilateral or grade III-IV unilateral

Definite AS: radiological criterion + ≥1 clinical criterion

ASAS Classification Criteria for axSpA

• Back pain ≥3 months, onset <45 years
• Imaging arm: sacroiliitis on MRI or X-ray + ≥1 SpA feature
• Clinical arm: HLA-B27 + ≥2 SpA features

SpA Features