What is ankylosing spondylitis?

What is Ankylosing Spondylitis?

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis characterized by sacroiliitis, enthesitis, and a marked propensity for sacroiliac joint and spinal fusion. 1

Disease Classification and Terminology

AS belongs to the spondyloarthritis (SpA) family of diseases, which share clinical, genetic, and immunologic features. 1 AS is distinguished within this family by:

• Universal involvement with sacroiliac joint inflammation or fusion 1
• More prevalent spinal ankylosis compared to other spondyloarthropathies 1
• Bilateral sacroiliitis as the typical pattern 1

The disease is now increasingly referred to under the broader umbrella term axial spondyloarthritis (axSpA), with AS specifically representing the radiographic form (r-axSpA). 1, 2 This terminology shift reflects recognition that the disease exists on a spectrum, with radiographic changes taking years to develop. 1, 3

Clinical Manifestations

Axial Features

• Inflammatory back pain - present in 70-80% of patients, characterized by insidious onset, improvement with exercise, no improvement with rest, occurring at night, and age of onset <40 years 1
• Chronic back pain and stiffness - the hallmark presenting symptom 1
• Progressive spinal fusion (ankylosis) - leading to loss of spinal flexibility and abnormal posture 1
• Sacroiliac joint involvement - universally present, typically bilateral 1

Spinal Involvement Pattern

• Thoracic spine and thoracolumbar junction are the most common sites of spinal involvement 1
• Inflammatory changes include enthesitis, synovitis, and osteitis resulting in bone erosion, sclerosis, bone formation, and potentially ankylosis 1

Extra-Axial Manifestations

• Peripheral arthritis or enthesitis - occurs in approximately 30-50% of patients 1
• Acute anterior uveitis (recurrent iritis) - common extra-articular manifestation 1
• Inflammatory bowel disease - associated comorbidity 1
• Psoriasis - can coexist with AS 1
• Aortitis - inflammation of the aorta 4

Epidemiology and Genetics

• Prevalence: 0.1-0.5% of the general population 1, with estimates of 0.9-1.4% in the United States adult population for the broader axSpA spectrum 1
• Age of onset: Typically begins in late adolescence and early adulthood, commonly before age 45 1
• Gender: Predominantly affects males, typically manifesting in their third decade 4
• HLA-B27 association: Strong genetic link, with 74-89% of AS patients being HLA-B27 positive 1, and overall 80-95% positivity reported 4
• Genetic risk: HLA-B27 accounts for approximately 20% of genetic risk, with over 100 genes connected to AS susceptibility 4, 5

Pathophysiology

The pathogenesis involves immune-mediated mechanisms with both autoinflammatory and autoimmune components:

• Innate immune system dominance - aberrant activity of innate and innate-like immune cells including γδ T cells, group 3 innate lymphoid cells, neutrophils, mucosal-associated invariant T cells, and mast cells 6
• Interleukin-23/17 axis - plays a crucial role in the disease cascade 4, 5
• Tumor necrosis factor alpha - key inflammatory cytokine involved in pathogenesis 5, 7
• Intestinal involvement - interaction between mucosal-associated immune cells and intestinal microbiota 6
• Biomechanical factors - entheseal micro-trauma may contribute to articular manifestations 6

Diagnostic Approach

Classification Criteria

• Modified New York criteria - requires radiographic sacroiliitis, but limited by excluding early disease 1, 3
• ASAS classification criteria - applies to both early and late disease under the term axial SpA, including non-radiographic forms 1, 3

Diagnostic Features

• Radiographic findings: Sacroiliitis and the "dagger sign" on radiographs are crucial for diagnosis 4
• MRI: Can detect early inflammatory changes before radiographic damage appears 1, 3
• HLA-B27 testing: Helps confirm diagnosis but is not diagnostic alone 4
• Inflammatory markers: Elevated C-reactive protein and erythrocyte sedimentation rate provide supporting but non-specific evidence 4

Diagnostic Delay

A mean delay of 4.9 years from symptom onset to diagnosis has been reported, highlighting the challenge of early recognition. 1

Disease Impact

AS imposes substantial burdens on patients:

• Physical limitations: Loss of spinal flexibility, abnormal posture, chronic pain 1
• Functional impairment: Reduced ability to perform daily activities 1
• Work disability: Loss of productivity and unemployment 7
• Quality of life: Significantly reduced 1, 7
• Healthcare utilization: Substantial use of healthcare resources 7
• Fatigue: Common debilitating symptom 4

Treatment Goals

The primary goals of AS management are to:

• Reduce symptoms (pain and stiffness) 1
• Maintain spinal flexibility and normal posture 1
• Reduce functional limitations 1
• Maintain work ability 1
• Decrease disease complications 1
• Forestall skeletal damage 1