What is ankylosing spondylitis (AS), a chronic inflammatory disease affecting the spine in younger adults?

What is Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease primarily affecting the axial skeleton, characterized by bilateral sacroiliitis, inflammatory back pain, progressive spinal fusion through entheseal ossification, and a strong genetic association with HLA-B27 (present in 90-95% of patients). 1

Disease Classification and Spectrum

AS represents the most severe and radiographically advanced form within the axial spondyloarthritis (axSpA) spectrum. 2 The broader axSpA category encompasses:

• Radiographic axial SpA (classic AS): Definite structural changes visible on plain radiographs 2
• Non-radiographic axial SpA: Inflammatory changes detectable only on MRI without radiographic sacroiliitis 2

AS is distinguished from other spondyloarthropathies by universal sacroiliac joint involvement and higher propensity for complete spinal ankylosis. 2

Epidemiology

• Prevalence: 0.1-0.5% of the general population, with estimates including early forms ranging from 0.2-1.4% 1, 2
• Age of onset: Typically before age 45, often presenting in late adolescence or early adulthood 2
• Genetic predisposition: HLA-B27 positivity in 74-95% of AS patients, though only 1% of HLA-B27 carriers develop the disease 2, 1

Cardinal Clinical Features

Inflammatory Back Pain

The hallmark symptom, present in 70-80% of patients, with distinct characteristics: 2

• Insidious onset over weeks to months
• Improves with exercise but not with rest
• Worsens at night, particularly in the second half
• Morning stiffness of prolonged duration (>30 minutes) 1
• Alternating buttock pain from sacroiliitis 2

Pathologic Process

The disease follows a characteristic anatomic progression: 2

1. Initial involvement: Bilateral sacroiliac joints (distinguishing AS from other spondyloarthropathies which may show unilateral involvement) 2
2. Spinal progression: Ascending involvement, most commonly affecting thoracic spine and thoracolumbar junction 2
3. Entheseal inflammation: Enthesitis, synovitis, and osteitis lead to bone erosion, sclerosis, and ultimately ossification 2
4. End-stage: Complete ankylosis ("bamboo spine") with loss of spinal mobility 1

Extra-Articular Manifestations

Approximately 30-50% of AS patients develop peripheral involvement: 2

• Peripheral arthritis: Typically asymmetric, lower extremity predominant
• Enthesitis: Achilles tendon and plantar fascia most common 2
• Anterior uveitis: Most frequent extra-articular manifestation 3, 4
• Inflammatory bowel disease: Associated in subset of patients 4
• Cardiovascular: Aortitis, conduction abnormalities 4
• Pulmonary: Apical fibrosis in advanced disease 4

Diagnostic Challenges

A critical diagnostic delay of 4.9-7 years persists between symptom onset and diagnosis, highlighting the difficulty in early recognition. 2, 1 This delay occurs because:

• Inflammatory back pain symptoms are present in 5-15% of the general population, creating diagnostic noise 2
• Radiographic changes evolve slowly over years, with structural damage lagging behind symptoms by 7+ years 2
• Early disease may only show inflammatory changes on MRI without radiographic findings 2

Diagnostic Criteria Evolution

Modified New York Criteria (Historical)

Required radiographic sacroiliitis plus clinical criteria, missing patients in early disease stages. 2

ASAS Classification Criteria (Current)

Designed for research purposes, incorporates MRI findings to capture non-radiographic disease, though these criteria are not intended for definitive clinical diagnosis. 2

Disease Impact and Prognosis

Untreated entheseal inflammation progresses inexorably to fibrosis and ossification at affected sites, leading to: 1

• Functional decline: Progressive loss of spinal mobility and normal posture 2
• Work disability: Substantial interference with employment and daily activities 1
• Quality of life: Chronic pain, stiffness, and psychological burden 2, 1
• Complications: Increased fracture risk from rigid, osteoporotic spine 3

Common Diagnostic Pitfalls

• Dismissing young adults with chronic back pain as having mechanical causes without screening for inflammatory features 2
• Waiting for radiographic changes before considering the diagnosis, missing the 7-year window for early intervention 2
• Failing to recognize that HLA-B27 negativity does not exclude AS (present in 5-26% of AS patients) 2
• Overlooking extra-articular manifestations (uveitis, IBD) that may precede or accompany axial symptoms 4