Ankylosing Spondylitis

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

Who gets it. Prevalence is 0.1-0.5% in Caucasian populations. Men outnumber women 2-3:1, although the historically higher ratios reflect underdiagnosis in women. Onset peaks at 20-30 years and the disease rarely presents after the age of 45. First-degree relatives carry a 10-20 times increased risk.

Risk factors. HLA-B27 positivity is the major genetic risk factor, and there is strong familial aggregation. Male sex brings higher prevalence and more severe disease, and smoking is associated with worse outcomes and progression.

HLA-B27 in perspective. 90-95% of patients are positive, but the antigen is present in approximately 8% of the general Caucasian population and only 5-10% of HLA-B27 positive individuals develop AS. It is a risk factor, not a diagnostic test. A negative result does not exclude the disease, since approximately 5-10% of AS patients are HLA-B27 negative, and the diagnosis is made on clinical features plus imaging, sacroiliitis on MRI or radiograph.

The disease is an aberrant immune response at the entheses, which leads to inflammation and then to new bone formation. Understanding that sequence is what makes both the diagnosis and the management make sense.

HLA-B27. An MHC class I molecule expressed on cell surfaces. How it causes disease is not fully understood; the theories are arthritogenic peptide presentation, protein misfolding and cell-surface homodimer formation. There are over 100 HLA-B27 subtypes, of which B*27:05 and B*27:02 are the most associated with AS.

Non-HLA genes. The named ones are ERAP1, an aminopeptidase involved in peptide processing, and IL-23R, which points to the importance of the IL-23/IL-17 axis in pathogenesis; genome-wide association studies have identified multiple other loci.

Enthesitis. The primary site of inflammation is the enthesis, where tendon or ligament attaches to bone, and the entheses at the sacroiliac joints and spine are particularly affected. The inflammatory infiltrate carries TNF-alpha, IL-17 and IL-23.

From inflammation to bone. The paradox of the disease is that an erosive inflammatory process ends in ossification:

1. Erosive inflammation at the entheses
2. Bone marrow oedema, visible on MRI
3. TNF and IL-17 drive the inflammation
4. The repair response forms new bone, the syndesmophytes
5. Eventually, complete fusion

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Sacroiliac joints. The earliest site of involvement. Subchondral bone erosions appear, with sclerosis and widening of the joint initially, and then fusion.

Spine. Erosion at the vertebral body margins produces the Romanus lesion, a corner erosion. Repair produces the syndesmophyte, a vertical bony bridge between vertebrae. The vertebral bodies square, and complete fusion gives the bamboo spine.

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Inflammatory back pain is the cardinal feature, and its pattern is what separates it from mechanical back pain. The features are the five in NIGHT below; alternating buttock pain points to the sacroiliac joints.

Progressive restriction. As the spine stiffens, the lumbar lordosis is lost and the thoracic kyphosis increases, chest expansion falls, and cervical involvement leaves a fixed forward gaze. In severe cases the neck is fixed in flexion, the chin-on-chest deformity, and the global kyphosis produces the question mark posture.

The hips. Involved in 30-50% of patients, often bilaterally, and a major cause of disability. Hip involvement within the first 10 years of the disease carries a worse prognosis.

Other joints. Shoulder involvement is common; the knee and ankle are affected less often. The pattern is an asymmetric oligoarthritis.

Acute anterior uveitis is the most common extra-articular feature, in 25-40% of patients. It is unilateral and recurrent, presents as a painful red eye with photophobia, and is an ophthalmology emergency because it can cause vision loss.

Heart and lungs. The cardiovascular manifestations are aortitis, aortic root dilatation, aortic regurgitation in 1-10% and conduction defects. Apical pulmonary fibrosis is rare; restrictive lung disease follows fusion of the chest wall.

Examination. Inspect the posture first, then measure. The named tests:

• Schober test: mark L5 and a point 10 cm above; on forward flexion an increase of under 5 cm is abnormal
• Modified Schober: marks 5 cm below and 10 cm above the PSIS
• Chest expansion: under 2.5 cm at the nipple line is abnormal
• Occiput-to-wall distance: should be zero; any distance indicates cervical kyphosis
• Tragus-to-wall distance: an alternative measure of cervical mobility

Inflammatory markers. ESR and CRP are raised in 50-70%, so normal markers do not exclude AS. They are useful for monitoring disease activity.

HLA-B27 supports the clinical diagnosis rather than making it, and is most useful in early disease when imaging is inconclusive. Rheumatoid factor and anti-CCP are negative, which is what seronegative means, and helps distinguish AS from rheumatoid arthritis.

Radiographs. At the sacroiliac joints the picture is bilateral symmetric sacroiliitis: erosions, sclerosis, widening or narrowing of the joint space, and fusion, graded 0-4 by the modified New York criteria. In the spine look for squaring of the vertebral bodies, marginal vertical syndesmophytes, the Romanus lesion (the shiny corner sign), the Andersson lesion (discovertebral destruction) and, at the end, the bamboo spine of complete fusion.

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MRI. Bone marrow oedema at the sacroiliac joints is active sacroiliitis, and STIR or T2 fat-saturated sequences show it best. MRI can detect inflammation before any radiographic change and enables diagnosis 5-10 years earlier than radiographs.

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CT is the study for fracture in the AS spine. It is superior to radiographs for a fracture through fused segments, and when a fracture is suspected the entire spine is imaged; the fracture pathway is set out under Surgical Management.

The two highest-yield distinctions are AS versus DISH, both of which ankylose the spine and fracture as long bones, and inflammatory versus mechanical or degenerative back pain.

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Indications for spinal surgery. Four, of which spinal fracture is the most common:

1. Spinal fractures
2. Kyphosis correction, for a fixed forward gaze and inability to see the horizon
3. Spinal stenosis, rare, with cauda equina syndrome
4. Pseudarthrosis, an Andersson lesion causing instability

Fracture ManagementKyphosis CorrectionTHA in AS

ALL AS Spinal Fractures Are Unstable

The ankylosed spine functions as a long bone: fractures extend through all three columns, and even minor trauma can cause one. Neurological deficit is present on admission in 67.2% of AS patients in the largest systematic review (345 patients; PMID 18791749), and secondary neurological deterioration occurs frequently. Treat every fracture as unstable until proven otherwise.

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The fractures themselves. In the review most were cervical and followed low-energy impact; the mechanism is commonly hyperextension. Delayed diagnosis was common, from both patient and doctor factors.

Principles.

1. Assume unstable: all three columns are involved
2. Image the entire spine: non-contiguous fractures occur in 5-10%
3. CT is essential: radiographs miss 30% of fractures
4. MRI for the cord if there is a neurological deficit
5. Immobilise in the position of deformity: do not attempt correction

Surgery is usually preferred, and be honest about what it does and does not achieve. Early stabilisation permits mobilisation, nursing and pain control, and avoids the very real problems of external immobilisation in a rigid, deformed spine. The construct is long posterior instrumentation, three or more levels above and below, because the long lever arms of a fused spine load a short construct heavily; anterior support is considered where there is significant kyphosis, and cement augmentation for osteoporotic bone.

What stabilisation does not do. The systematic review's uncomfortable finding was that surgical and non-operative treatment "did not alter the neurological prospective for most patients" (PMID 18791749). Stabilisation is done to control the mechanics, not because it reliably reverses or prevents neurological injury, and that should not be overstated in a viva or to a family.

Conservative management is reserved for undisplaced, stable fractures without neurological deficit. A halo vest or Minerva cast is problematic because the rigid spine and its pre-existing deformity cannot be corrected into the orthosis.

Outcomes. In the 345 pooled AS patients (PMID 18791749), mortality was 17.7% within three months of injury, far higher than in the general trauma population and higher than the 5-15% often quoted, and the overall complication rate was 51.1%. The rate of epidural haematoma was high, and delayed union and pseudarthrosis are risks. For contrast, DISH patients in the same review fared better on neurology (40.0% deficit) and complications (32.7%) but similarly badly on mortality (20.0%).

Indications. A fixed forward gaze, unable to see the horizon, with severe functional limitation: difficulty with activities of daily living, eating and social interaction. Stable disease is preferred.

Smith-Petersen osteotomy (SPO, Ponte). Schwab grade 1-2. It takes the posterior column only and hinges on the anterior column, so it needs a mobile or at least openable anterior disc, which in a fully ossified AS spine is often the limiting factor. It gives about 10 degrees per level (commonly quoted as 5-10 degrees, up to about 15 in AS where the anterior column opens through an ossified disc), so multiple levels are usually needed and the correction sums across them. The risk is lower than a PSO, but the anterior opening lengthens the aorta and the anterior column, a recognised cause of vascular injury and delayed anterior column failure in the rigid AS spine.

Pedicle subtraction osteotomy (PSO). Schwab grade 3. All three columns: a closing wedge through the pedicle and vertebral body that closes posteriorly, so the anterior column is shortened rather than lengthened. It gives 30-40 degrees per level and is usually done in the lumbar spine (L2-L4; L3 is the workhorse), where the cauda equina rather than the cord is at risk. The price is higher neurological and vascular risk and greater blood loss.

Cervical osteotomy. For the chin-on-chest deformity, planned against the chin-brow vertical angle, and it can achieve 30-40 degrees of correction. C7-T1 is the preferred level, and the reason is vascular before it is neurological: the vertebral artery usually enters the transverse foramen at C6, so at C7 it lies outside the foramen and can be mobilised safely, which is the classic exam answer. The canal is also capacious at the cervicothoracic junction, and the C8 root is the one most readily tolerated if a root must be sacrificed to close the osteotomy. It is a high-risk procedure for an experienced team, historically performed awake under local anaesthesia in a halo precisely because the airway and the cord are both at risk.

Planning. Full-length standing radiographs, the sagittal vertical axis calculated, and the correction planned to restore horizontal gaze. Large corrections may be staged.

Who. THA is commonly required, given how often the hip is involved, and patients present for it at a younger age.

The stiff spine and the cup. A fixed spinal deformity affects cup orientation, and the stiff spine increases the mechanical demands on the hip. The standard acetabular position may not be appropriate, so spinopelvic mechanics are considered in planning.

Heterotopic ossification. The risk is higher in AS, up to 50% without prophylaxis, so prophylaxis is recommended: indomethacin 75 mg daily for 6 weeks, or a single dose of radiation (700-800 cGy) if NSAIDs are contraindicated.

Outcomes and positioning. Functional outcomes are generally good, with higher revision rates in some studies and higher HO rates, so counsel carefully about expectations. Position lateral or supine, accounting for the fixed spinal deformity; custom positioning may be needed, and forced positions are avoided.

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An Andersson lesion, named for Olof Andersson and frequently misspelt with a single "s", is a localised, lucent, destructive lesion of the discovertebral junction in the ankylosed spine. It is both a radiographic finding and, when it destabilises the spine, a surgical indication. Clinically it presents as new, focal pain in an otherwise stiff or fused back, and it has two recognised forms that are managed in opposite ways.

The mechanical type is the surgical one. It is effectively a non-union through the ankylosed spine, so when it causes instability or progressive deformity it is stabilised with long-segment fixation in the same way as an acute AS fracture.

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Of the disease. The spinal fracture after minor trauma, the fixed kyphosis and the hip are dealt with above; the rest of the list is what an examiner will expect alongside them.

• Cauda equina syndrome, a late complication of arachnoiditis
• Atlanto-axial subluxation, rare but serious
• Restrictive lung disease from costovertebral fusion
• Aortic regurgitation from aortitis
• Vision loss from untreated uveitis
• Secondary amyloidosis, rare and late

Of surgery. The list to have ready:

• Neurological injury, a high risk with fractures and with osteotomy
• Epidural haematoma, common with AS fractures
• Pseudarthrosis: healing is difficult, especially at osteotomy sites
• Implant failure in osteoporotic bone with long lever arms
• Dural tear, because ossified dura may be encountered
• Heterotopic ossification after hip surgery

Biologic eligibility and treat-to-target monitoring are expressed in indices, and the management and guideline sections quote them. Knowing what each one measures is high-yield.

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.

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, and the choice is comorbidity-driven rather than efficacy-driven: TNFi covers concomitant inflammatory bowel disease and uveitis better.

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, which affects 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 or 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 the use of multilevel SPO remain individualised.