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

Ankylosing spondylitis (AS) is a chronic, systemic inflammatory arthritis primarily affecting the axial skeleton — the sacroiliac joints and spine — and belonging to the spondyloarthropathy family. Progressive spinal inflammation leads to new bone formation (syndesmophytes) and eventual vertebral fusion (ankylosis), causing pain and structural rigidity. AS affects approximately 0.1–0.5% of the global adult population, with a 2:1 male predominance. Onset typically occurs in late adolescence to early adulthood (ages 17–35). The HLA-B27 gene is present in approximately 90% of AS patients but is not specific — only 2–5% of HLA-B27-positive individuals develop AS. AS is now classified under axial spondyloarthritis (axSpA), which includes non-radiographic (nr-axSpA) and radiographic (AS) forms. Early diagnosis — which is unfortunately often delayed by 7-10 years due to non-specific early symptoms — and prompt initiation of biological therapy when NSAIDs fail are the most critical factors in preventing long-term structural spinal damage and functional disability.

AS has a strong genetic component: HLA-B27 (chromosome 6p21) is the dominant genetic risk factor, though over 100 additional genetic loci contribute. The pathogenesis involves dysregulation of innate and adaptive immunity, with IL-17, IL-23, and TNF-alpha as key inflammatory cytokines driving enthesitis (inflammation at tendon and ligament insertions) and osteitis. Intestinal microbiome dysbiosis may trigger immune activation. Risk factors include HLA-B27 positivity (10-fold increased risk), family history of spondyloarthropathy, male sex (more severe axial disease), preceding gut inflammation (Crohn's disease, ulcerative colitis associated with AS in 5–10%), and psoriasis. Smoking worsens radiographic progression and reduces treatment response. Gut dysbiosis, particularly altered composition of intestinal microbiota including enrichment of Prevotella species, has been increasingly implicated in AS pathogenesis and may mechanistically link gut mucosal immunity to axial joint inflammation.

The hallmark symptom is inflammatory back pain — dull, insidious onset, worse at night and in the early morning (morning stiffness exceeding 45 minutes), and improves with exercise but not rest. This distinguishes it from mechanical back pain. Alternating buttock pain from sacroiliitis is characteristic. Peripheral arthritis (asymmetric, large joints — knees, hips, ankles) occurs in 25–35%. Enthesitis at the Achilles tendon insertion and plantar fascia insertion causes heel pain. Acute anterior uveitis (red, painful eye with photophobia) occurs in 25–40% — a common extra-articular feature. Other extra-articular features include psoriasis, inflammatory bowel disease, and aortitis with aortic regurgitation. Advanced AS causes kyphotic deformity (stooped posture) and reduced chest expansion.

AS is diagnosed using the modified New York criteria: radiographic sacroiliitis (grade 2 bilateral or grade 3–4 unilateral on X-ray) plus inflammatory back pain, limited lumbar motion, or reduced chest expansion. However, radiographic changes lag by 7–10 years from symptom onset. MRI of sacroiliac joints shows bone marrow oedema (active sacroiliitis) years before radiographic changes — essential for early diagnosis of nr-axSpA. HLA-B27 testing supports the diagnosis but is not sufficient alone. Elevated CRP and ESR indicate inflammatory activity in approximately 50% of patients — normal does not exclude AS. Assessment of Spondyloarthritis International Society (ASAS) criteria guide classification. Dual-energy X-ray absorptiometry (DEXA) assesses spinal osteoporosis risk.

NSAIDs (naproxen, indomethacin, diclofenac) are first-line treatment — they reduce pain and stiffness and may slow radiographic progression with continuous use. Two NSAIDs should fail before escalating. Biological disease-modifying antirheumatic drugs (bDMARDs) are indicated for BASDAI ≥4 with inadequate NSAID response. TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab) are highly effective, reducing BASDAI by 50%+ in 60–70% of patients. IL-17A inhibitors (secukinumab, ixekizumab) are alternatives — particularly preferred in patients with concomitant psoriasis or inflammatory bowel disease is not present. JAK inhibitors (upadacitinib, tofacitinib) are approved options for axSpA. Physiotherapy and supervised exercise programmes improve spinal mobility and posture — daily stretching is essential and complementary to medication. Sulfasalazine for peripheral arthritis. Hip replacement for severe hip involvement. Physical therapy programmes designed specifically for spondyloarthritis, such as the Royal National Hospital for Rheumatic Diseases (RNHRD) exercise protocol, should be continued lifelong alongside pharmacological management to preserve spinal mobility.

Untreated or poorly controlled AS leads to progressive spinal fusion — the characteristic 'bamboo spine' deformity where vertebrae fuse with bridging syndesmophytes, causing complete rigidity of the spine and loss of all axial movement. This is associated with severe hyperkyphosis (stooped, forward-bent posture), which impairs breathing by reducing chest expansion and can lead to restrictive lung disease. A rigidly fused spine is extremely vulnerable to fractures from minor trauma — even a simple fall can cause unstable spinal fractures, with high risk of spinal cord injury, paralysis, or death. Acute anterior uveitis affects 25-40% of AS patients and, if inadequately treated, can cause posterior synechiae, secondary glaucoma, cataract, and permanent vision loss. Aortitis and aortic regurgitation occur in a small percentage of longstanding AS and require cardiac surveillance. Secondary amyloidosis (AA amyloidosis) from chronic systemic inflammation may deposit in the kidneys causing renal failure. Psychological consequences of chronic pain and disability — depression and anxiety — affect over 40% of patients. Delayed diagnosis (average 7-10 years) is the greatest preventable harm, as biologic therapy initiated early prevents structural progression.

AS cannot be prevented, but disease progression and disability can be minimized. Daily physiotherapy and specific spinal exercises (ASAS exercise programmes) maintain mobility and posture — inactivity accelerates stiffness and deformity. Patients should sleep on a firm mattress without a pillow to reduce kyphosis. Swimming and yoga are particularly beneficial for spinal mobility. Smoking cessation is critical — smoking accelerates radiographic progression and reduces biologic treatment response. Annual eye examination by an ophthalmologist is recommended given uveitis risk. Patients on biologics require TB screening and avoid live vaccines. Osteoporosis prevention with vitamin D, calcium, and DEXA monitoring.

Seek urgent medical attention if you develop sudden, severe eye pain, redness, and photophobia — this suggests acute anterior uveitis requiring same-day ophthalmology assessment to prevent vision loss. Go to the emergency department if you experience a fall or minor trauma causing neck or back pain — spinal fractures in ankylosed spines can occur with minimal force and cause spinal cord injury without deformity. See a rheumatologist if: inflammatory back pain persists more than 3 months in an adult under 45; morning stiffness exceeds 45 minutes; alternating buttock pain is present; or pain improves with exercise but not rest. Earlier diagnosis and treatment significantly reduces the risk of spinal fusion and disability.