Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the axial skeleton, leading to progressive spinal fusion. It is the prototypical seronegative spondyloarthropathy, characterized by sacroiliitis and enthesitis.

Epidemiology:

• Prevalence: 0.1-0.5% in Caucasian populations
• Male to female ratio: 2-3:1 (historically higher ratios due to underdiagnosis in women)
• Peak age of onset: 20-30 years (rarely presents after age 45)
• Strong HLA-B27 association: 90-95% of patients positive
• Family history: 10-20 times increased risk in first-degree relatives

Risk Factors:

• HLA-B27 positivity: Major genetic risk factor
• Family history: Strong familial aggregation
• Male sex: Higher prevalence and more severe disease
• Smoking: Associated with worse outcomes and progression

Understanding the pathophysiology of AS is essential for both diagnosis and management. The disease involves aberrant immune responses at entheses leading to inflammation and subsequent new bone formation.

Genetic Basis

HLA-B27 association:

• MHC Class I molecule expressed on cell surfaces
• Mechanism of disease association not fully understood
• Theories include: arthritogenic peptide presentation, protein misfolding, cell surface homodimer formation
• Over 100 HLA-B27 subtypes - B27:05 and B27:02 most associated with AS

Non-HLA genes:

• ERAP1 (aminopeptidase) - involved in peptide processing
• IL-23R - IL-23/IL-17 axis important in pathogenesis
• Multiple other loci identified by GWAS

Inflammation and New Bone Formation

Enthesitis:

• Primary site of inflammation - where tendons/ligaments attach to bone
• Entheses at sacroiliac joints and spine particularly affected
• Inflammatory infiltrate with TNF-alpha, IL-17, IL-23

Paradox of inflammation and ossification:

1. Initial erosive inflammation at entheses
2. Bone marrow edema visible on MRI
3. TNF and IL-17 drive inflammation
4. Repair response involves new bone formation (syndesmophytes)
5. Eventually leads to complete fusion

Pathological Features

Sacroiliac joints:

• Earliest site of involvement
• Subchondral bone erosions
• Sclerosis and widening initially, then fusion

Spine:

• Romanus lesion: Corner erosion at vertebral body margins
• Syndesmophytes: Vertical bony bridges between vertebrae
• Squaring of vertebral bodies
• Complete fusion: Bamboo spine appearance

Axial Symptoms

Inflammatory back pain (cardinal feature):

• Insidious onset over months
• Age of onset typically less than 40 years
• Morning stiffness greater than 30 minutes
• Improves with exercise, worse with rest
• Night pain - wakes in second half of night
• Alternating buttock pain (sacroiliitis)

Progressive spinal restriction:

• Loss of lumbar lordosis
• Thoracic kyphosis increases
• Reduced chest expansion (less than 2.5cm abnormal)
• Cervical involvement leads to fixed forward gaze

Peripheral Manifestations

Hip involvement:

• Present in 30-50% of patients
• Often bilateral
• Major cause of disability
• Early onset (less than 10 years disease duration) = worse prognosis

Other joints:

• Shoulder involvement common
• Knee, ankle less frequent
• Asymmetric oligoarthritis pattern

Extra-Articular Manifestations

Acute anterior uveitis:

• Most common extra-articular feature (25-40%)
• Unilateral, recurrent
• Presents with painful red eye, photophobia
• Ophthalmology emergency - can cause vision loss

Cardiovascular:

• Aortitis and aortic root dilatation
• Aortic regurgitation (1-10%)
• Conduction defects

Pulmonary:

• Apical pulmonary fibrosis (rare)
• Restrictive lung disease from chest wall fusion

Physical Examination

Inspection:

• Loss of lumbar lordosis
• Increased thoracic kyphosis
• Fixed cervical flexion (chin-on-chest deformity in severe cases)
• Question mark posture (global kyphosis)

Specific tests:

• Schober test: Mark L5 and 10cm above. On forward flexion, less than 5cm increase is abnormal
• Modified Schober: Mark 5cm below and 10cm above PSIS
• Chest expansion: Less than 2.5cm at nipple line is abnormal
• Occiput-to-wall distance: Should be zero - increased indicates cervical kyphosis
• Tragus-to-wall distance: Alternative cervical mobility measure

Laboratory Studies

Inflammatory markers:

• ESR and CRP elevated in 50-70%
• Normal inflammatory markers do not exclude AS
• Useful for monitoring disease activity

HLA-B27:

• Positive in 90-95% of AS patients
• Not diagnostic alone - supports clinical diagnosis
• Useful in early disease when imaging inconclusive

Rheumatoid factor and anti-CCP:

• Negative (seronegative spondyloarthropathy)
• Helps distinguish from RA

Imaging

Plain Radiographs:

Sacroiliac joints:

• Bilateral symmetric sacroiliitis
• Grading 0-4 (modified New York criteria)
• Erosions, sclerosis, joint space widening/narrowing, fusion

Spine:

• Squaring of vertebral bodies
• Syndesmophytes (marginal, vertical)
• Bamboo spine (complete fusion)
• Romanus lesion (shiny corner sign)
• Anderson lesion (discovertebral destruction)

View larger

MRI (Critical for early diagnosis):

• Bone marrow edema at SI joints - active sacroiliitis
• Can detect inflammation before radiographic changes
• STIR/T2 fat-sat sequences best for edema
• Enables diagnosis 5-10 years earlier than X-ray

CT:

• Best for fracture detection in AS spine
• Superior to X-ray for visualizing fractures through fused segments
• Image entire spine when fracture suspected

Indications for Spinal Surgery

1. Spinal fractures: Most common surgical indication
2. Kyphosis correction: For fixed forward gaze, inability to see horizon
3. Spinal stenosis: Rare, cauda equina syndrome
4. Pseudoarthrosis: Anderson lesion causing instability

Fracture ManagementKyphosis CorrectionTHA in AS

Spinal Fracture Management in AS

ALL AS Spinal Fractures Are Unstable

The ankylosed spine functions as a long bone. Fractures extend through all three columns. Even minor trauma can cause fractures. Neurological injury occurs in 50-70% of cases. Treat all fractures as unstable until proven otherwise.

View larger

View larger

Principles:

1. Assume unstable - all 3 columns involved
2. Image entire spine - non-contiguous fractures in 5-10%
3. CT is essential - X-rays miss 30% of fractures
4. MRI for cord assessment - if neurological deficit
5. Immobilize in position of deformity - do not attempt correction

Surgical Management (preferred):

• Early stabilization reduces complications
• Long posterior instrumentation (3+ levels above and below)
• Consider anterior support if significant kyphosis
• Cement augmentation for osteoporotic bone

Conservative management:

• Reserved for non-displaced, stable fractures without neurological deficit
• Halo vest or Minerva cast problematic due to rigid spine
• Higher complication rates than surgical treatment

Outcomes:

• Mortality 5-15% (higher than general population)
• Neurological injury in up to 70%
• High rate of epidural hematoma
• Delayed union and pseudoarthrosis risk

This section covers fracture management in AS.

Kyphosis Correction Osteotomy

Indications:

• Fixed forward gaze - cannot see horizon
• Severe functional limitation
• Difficulty with ADLs, eating, social interaction
• Stable disease preferred

Osteotomy types:

Smith-Petersen osteotomy (SPO):

• Posterior column only
• Limited correction per level (10-15 degrees)
• Multiple levels may be needed
• Lower risk than PSO

Pedicle subtraction osteotomy (PSO):

• All 3 columns through pedicle
• Greater correction per level (30-40 degrees)
• Usually at lumbar spine (L2-L4)
• Higher risk - neurological, vascular

Cervical osteotomy:

• For chin-on-chest deformity
• C7-T1 preferred level (lower cord risk)
• Can achieve 30-40 degrees correction
• High-risk procedure - requires experienced team

Surgical planning:

• Full-length standing X-rays
• Calculate sagittal vertical axis
• Plan correction to restore horizontal gaze
• Consider staged procedures for large corrections

This section covers osteotomy options.

Total Hip Arthroplasty in AS

View larger

Epidemiology:

• Hip involvement in 30-50% of AS patients
• Often bilateral
• Younger age at presentation for THA

Surgical considerations:

• Fixed spinal deformity affects cup orientation
• Stiff spine increases demands on hip
• Standard acetabular position may not be appropriate
• Consider spinopelvic mechanics

Heterotopic ossification:

• Higher risk in AS (up to 50% without prophylaxis)
• Prophylaxis recommended: NSAIDs or radiation
• Indomethacin 75mg daily for 6 weeks
• Single dose radiation (700-800cGy) if NSAID contraindicated

Outcomes:

• Generally good functional outcomes
• Higher revision rates in some studies
• Higher HO rates
• Careful preoperative counselling regarding expectations

Positioning:

• Lateral or supine - account for fixed spinal deformity
• May need custom positioning
• Avoid forced positions

This section covers THA considerations.

Disease Complications

• Spinal fractures: High risk with minor trauma
• Cauda equina syndrome: Late complication from arachnoiditis
• Atlanto-axial subluxation: Rare but serious
• Restrictive lung disease: Costovertebral fusion
• Aortic regurgitation: From aortitis
• Uveitis complications: Vision loss if untreated
• Amyloidosis: Rare, late complication

Surgical Complications

• Neurological injury: High risk with fractures, osteotomy
• Epidural hematoma: Common with AS fractures
• Pseudoarthrosis: Difficult healing, especially at osteotomy sites
• Implant failure: Osteoporotic bone, long lever arms
• Dural tear: Ossified dura may be encountered
• Heterotopic ossification: After hip surgery

The two highest-yield distinctions are AS versus DISH (both ankylose the spine and both fracture as long bones) and inflammatory versus mechanical/degenerative back pain.

• Do NSAIDs slow radiographic progression? Earlier data suggested continuous NSAIDs retard syndesmophyte formation, but the ENRADAS trial did not confirm a structural benefit of continuous over on-demand dosing. Continuous use is justified for symptom control, not proven disease modification.
• Do biologics prevent ankylosis? Anti-TNF and IL-17 agents control inflammation but the link to halting new bone formation is unresolved (the "TNF paradox"). Some long-term cohort and IL-17 data suggest reduced progression, but no agent reliably stops fusion.
• TNFi versus IL-17i first-line: Both are effective; IL-17 inhibitors are avoided in inflammatory bowel disease (may worsen it), while TNFi covers concomitant IBD and uveitis better - choice is comorbidity-driven rather than efficacy-driven.
• nr-axSpA as a disease entity: Whether non-radiographic axial SpA is early AS or a partly separate entity (with more women and a lower progression rate) remains debated, affecting how aggressively to treat.
• Spinopelvic targets for THA: With a stiff fused spine, optimal acetabular orientation is contested; "safe zone" cup targets derived from mobile-spine patients may not apply, and functional/spinopelvic planning is increasingly recommended.
• Osteotomy choice: Pedicle subtraction osteotomy gives more correction per level than Smith-Petersen but with higher neurovascular risk; the optimal trade-off and use of multilevel SPO remain individualised.

Global Epidemiology

• Pooled global prevalence of AS is approximately 0.2-0.5%, with the strongest determinant being background HLA-B27 frequency. AS is rare where HLA-B27 is rare (e.g. parts of sub-Saharan Africa, Japan has low prevalence) and more common where HLA-B27 is high (e.g. some Northern European and Indigenous Arctic/First Nations populations).
• Historic male predominance (2-3:1) is now recognised as partly artefact - women are diagnosed later and more often have non-radiographic axial SpA.
• Mean diagnostic delay remains 5-10 years globally, driven by attribution to mechanical back pain.

Side-by-Side Guidelines

Registry & Practice Variation

• Arthroplasty registries (NJR, AOANJRR, SHAR, NZJR) consistently show AS patients undergoing THA at a younger age than primary OA, with good implant survival but higher heterotopic ossification.
• High-resource settings: early MRI, rapid access to biologics (TNFi, IL-17i, JAK inhibitors), and treat-to-target monitoring with ASDAS.
• Limited-resource settings: diagnosis often at the bamboo-spine/fixed-deformity stage; NSAIDs and physiotherapy remain the mainstay where biologics are unaffordable, so fracture prevention, fall counselling and arthroplasty/osteotomy services carry greater burden.
• Across all settings, rheumatology-orthopaedic co-management is essential because spinal fractures and hip involvement are the principal orthopaedic endpoints of the disease.