Ankylosing Spondylitis — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease belonging to the spondyloarthropathy (SpA) group — a family of related seronegative (rheumatoid-factor negative) inflammatory arthritides sharing HLA-B27 genetic association and predilection for the axial skeleton and entheses (ligament-bone insertion sites). AS primarily affects the sacroiliac joints and spine — causing progressive pain, stiffness, and syndesmophyte formation (bony bridges between vertebrae) that in severe disease results in complete vertebral fusion ('bamboo spine' — ankylosis). Beyond the axial skeleton, AS can cause: peripheral joint arthritis (affecting shoulders, hips, knees — in up to 30-50% of patients); enthesitis (Achilles tendon insertion, plantar fascia, costochondral junctions); and extra-articular manifestations — acute anterior uveitis (25-40% lifetime risk), psoriasis (10%), inflammatory bowel disease (6-14%), and cardiac conduction abnormalities (aortitis, first-degree heart block). AS predominantly affects young men (male:female ratio approximately 2-3:1 in radiographic AS, though non-radiographic axSpA has roughly equal sex distribution) and typically begins insidiously between ages 17-45 years — with an average diagnostic delay of 7-10 years due to initial misattribution of symptoms to mechanical causes. Globally, AS affects approximately 0.1-0.5% of the general population, with prevalence tracking HLA-B27 frequency across populations (higher in Scandinavian and indigenous North American populations; lower in sub-Saharan African populations). Under the modern ASAS (Assessment of SpondyloArthritis International Society) framework, AS is classified as the radiographic form of axial spondyloarthritis (axSpA), recognising a spectrum from early non-radiographic axSpA to established radiographic AS.

AS has the strongest genetic association of any common rheumatic disease — approximately 90-95% of White patients with AS carry the HLA-B27 allele (compared to 8-10% of the general White population), conferring an approximate 10-20-fold increased risk for developing AS in HLA-B27 positive individuals. However, only 1-5% of HLA-B27 positive individuals develop AS, demonstrating that additional genetic and environmental factors are required — the heritability of AS is estimated at 90%+, among the highest of any autoimmune disease. Non-HLA genetic contributors identified in GWAS include: ERAP1 (endoplasmic reticulum aminopeptidase — processes peptides for HLA-B27 presentation), ERAP2, IL23R (IL-23 receptor — key pathway for IL-17 induction), IL1R2, CARD9, and genes of the IL-17 and TNF pathways. Pathological mechanisms: the proposed 'misfolding hypothesis' suggests HLA-B27 misfolded heavy chains activate UPR (unfolded protein response) and inflammatory cytokine cascades; the 'arthritogenic peptide hypothesis' proposes that HLA-B27 presents self-peptides mimicking microbial antigens (molecular mimicry) — both HLA-B27 and gut microbiome interaction are likely important. Gut microbiome dysbiosis (reduced Faecalibacterium prausnitzii, altered Bacteroides and Ruminococcus) is strongly implicated in triggering immune activation in genetically susceptible individuals — evidenced by shared genetics with Crohn's disease and the 6-14% IBD comorbidity. Risk factors: HLA-B27 positivity (essential genetic factor in most populations), first-degree family history (risk 15-20% in HLA-B27 positive first-degree relatives), male sex, age of onset under 45, and underlying inflammatory bowel disease (Crohn's disease or ulcerative colitis).

The hallmark presenting symptom is chronic inflammatory back pain — characterised by five key features distinguishing it from common mechanical back pain: (1) insidious onset before age 40; (2) symptom duration exceeding 3 months; (3) morning stiffness lasting more than 30 minutes; (4) improvement with physical exercise and movement (not rest or lying down); and (5) awakening from sleep in the second half of the night due to back pain (night awakening). Sacroiliac joint pain: deep gluteal or buttock pain that alternates sides ('alternating buttock pain' — characteristic of sacroiliitis), occasionally radiating to the posterior thigh. Spinal involvement: progressive loss of lumbar lordosis, reduced thoracic and lumbar flexion and extension, reduced cervical rotation, and diminished chest expansion (below 2.5 cm in Schober's test). Enthesitis: Achilles tendon pain and swelling (at the calcaneal insertion), plantar fasciitis (calcaneal plantar insertion), patellar and quadriceps tendon enthesitis, and costochondral junction pain (causing pleuritic chest pain and reduced chest expansion). Peripheral arthritis: shoulder and hip joint involvement (in up to 30-50%) is particularly functionally significant; knee and ankle less commonly. Extra-articular features: acute anterior uveitis — the most common extra-articular manifestation — presents as sudden-onset unilateral painful red eye, photophobia, blurred vision, and circumcorneal injection; attacks typically resolve in weeks but recur in 50% and require urgent ophthalmological treatment (topical steroids, cycloplegics) to prevent posterior synechiae. Psoriasis (10% prevalence) and inflammatory bowel disease (6-14%). Severe long-standing AS: complete vertebral column fusion ('bamboo spine'), fixed flexion deformity (kyphosis), significant impairment of respiratory mechanics from rib cage involvement, and markedly restricted neck rotation with profound disability.

Diagnosis uses two complementary classification frameworks: (1) The modified New York Criteria (1984) — for established radiographic AS — requires radiographic sacroiliitis (grade 2 bilateral or grade 3-4 unilateral on plain X-ray) plus at least one clinical criterion (inflammatory back pain, limited lumbar movement, or reduced chest expansion); sensitivity is high for established disease but misses early inflammatory stages. (2) The ASAS (Assessment of SpondyloArthritis International Society) criteria for axial spondyloarthritis (2009) — more sensitive for early disease — classify axSpA based on either: imaging arm (sacroiliitis on X-ray or MRI) plus one SpA feature (inflammatory back pain, HLA-B27, good NSAID response, elevated CRP, family history of AS, uveitis, arthritis, enthesitis, psoriasis, IBD, dactylitis); or clinical arm (HLA-B27 positive) plus two or more SpA features. MRI of the sacroiliac joints (short-tau inversion recovery/STIR sequences): highly sensitive for detecting active bone marrow oedema (periarticular sacroiliac joint oedema — 'bone marrow oedema lesion') in non-radiographic early disease, years before X-ray changes appear — the cornerstone of early diagnosis. HLA-B27 testing: a positive result in a patient with characteristic inflammatory back pain increases the probability of AS substantially — present in 90-95% of AS patients; however, HLA-B27 is neither necessary nor sufficient for diagnosis. Inflammatory markers: CRP and ESR are elevated in approximately 50-70% of active AS; normal CRP does not exclude active disease. Disease activity assessment: BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) 0-10 (score above 4 indicates high disease activity warranting biologic therapy); ASDAS (Ankylosing Spondylitis Disease Activity Score) for more precise monitoring including CRP. Chest expansion (normal above 5 cm at the 4th intercostal space); modified Schober's test (lumbosacral flexion — normal above 4 cm increase from 15 cm above S1); lateral lumbar flexion.

Non-pharmacological: structured daily physiotherapy and active exercise are the cornerstone of AS management — specific spinal extension and rotation exercises, swimming, hydrotherapy, and breathing exercises maintain flexibility, posture, and lung function; ASAS/EULAR guidelines strongly recommend exercise over rest; group physiotherapy and supervised exercise programmes improve both physical and psychological outcomes. NSAIDs (first-line pharmacological): indomethacin 25-50 mg three times daily, naproxen 500 mg twice daily, diclofenac 75 mg twice daily, or celecoxib 200 mg twice daily — NSAIDs provide rapid pain and stiffness relief in 70-85% of AS patients; continuous daily NSAID use (versus on-demand) appears to slow radiographic progression (syndesmophyte formation) in high-disease-activity patients; regular GI protection (PPI) recommended with long-term NSAID use; contraindicated in IBD-associated spondylitis (worsen bowel disease). Intra-articular corticosteroids: useful for peripheral joint injections (hip, knee) or direct sacroiliac joint injection under image guidance — but systemic corticosteroids are not effective for axial AS. Biologic DMARD therapy — indicated when BASDAI above 4 despite two different NSAIDs used at full dose for at least 2 weeks each: TNF-alpha inhibitors (first-choice biologics): adalimumab 40 mg SC every 2 weeks, etanercept 50 mg SC weekly, infliximab 5 mg/kg IV every 8 weeks, certolizumab pegol 200 mg SC every 2 weeks, golimumab 50 mg SC monthly — all are highly effective at reducing BASDAI, ASDAS, CRP, and improving mobility; 40-60% achieve ASAS20 response (20% improvement) and 20-30% achieve clinical remission (ASDAS below 1.3). IL-17A inhibitors (effective alternative, particularly with coexistent psoriasis): secukinumab 150-300 mg SC (after monthly loading doses), ixekizumab 80 mg SC every 4 weeks — comparable efficacy to TNF inhibitors in axial disease; do not use in active IBD. JAK inhibitors (oral targeted therapy): tofacitinib 5 mg BD, upadacitinib 15 mg OD — evidence for AS, used in TNF/IL-17 failure; monitor for VTE, cardiovascular events, and infections. All patients on biologic therapy require TB screening (Mantoux/QuantiFERON), hepatitis B/C serology, and live vaccine avoidance.

Progressive untreated AS leads to spinal syndesmophyte formation and eventual complete fusion (bamboo spine — classic radiographic sign showing flowing calcification of the anterior longitudinal ligament and annulus fibrosus), causing severe fixed hyperkyphotic deformity (chin-on-chest posture), cervical rigidity, and permanent functional disability with inability to look forward or lie flat. Spinal fractures in a fused, rigid, osteoporotic spine from seemingly trivial trauma can cause unstable fractures at the disc level or through ossified segments, with high risk of spinal cord injury and death — particularly in the cervical spine. Osteoporosis affects up to 50% of AS patients from chronic inflammation, reduced mobility, and corticosteroid use, independent of bone formation at entheses. Extra-articular complications: recurring acute anterior uveitis (25-40% of AS patients — treated as an ophthalmological emergency with topical steroids and cycloplegics to prevent synechiae and vision loss); aortitis causing aortic regurgitation and cardiac conduction defects (complete heart block — requiring pacemaker); restrictive lung disease from progressive rib cage and costovertebral joint involvement reduces inspiratory vital capacity; secondary AA amyloidosis in long-standing uncontrolled disease causing renal failure; IgA nephropathy. Depression and anxiety affect 30-40% of AS patients from chronic pain and disability.

Regular daily exercise is the most important lifestyle intervention — swimming, yoga, Pilates, and specific spinal extension exercises maintain mobility and delay fusion. Maintain good posture throughout the day: sleep on a firm flat mattress without a pillow (if tolerated), keep the neck and spine in a neutral position at work. Never smoke — smoking accelerates radiographic progression in AS. Regular ophthalmology check-ups detect silent uveitis. Early biologic treatment in patients with high disease activity prevents long-term structural damage and disability.

See a GP if you have inflammatory back pain — onset before age 40, insidious onset over 3+ months, worse in the mornings with stiffness lasting over 30 minutes, improving with exercise but not with rest — particularly with associated sacroiliac or buttock pain alternating between sides. Also seek review for: sudden painful red eye (acute anterior uveitis — requires same-day ophthalmology referral); persistent heel or Achilles tendon pain (enthesitis); and peripheral joint swelling. Request rheumatology referral if AS is suspected — diagnosis averages 7-10 years without specialist review; early biologic treatment prevents spinal fusion. Seek immediate emergency care for any acute spinal pain following trauma in an established AS patient — spinal fractures on ankylosed spines require urgent CT or MRI, as X-rays are unreliable.