Pathophysiology and Clinical Features of Ankylosing Spondylitis

Core Pathological Process

Ankylosing spondylitis is an inflammatory arthropathy driven by enthesitis, synovitis, and osteitis of the axial skeleton, leading to a cascade of bone erosion, sclerosis, pathological new‑bone formation, and eventual ankylosis of affected sites. 1

The sacroiliac joints are typically the first sites involved, with bilateral sacroiliitis being characteristic of ankylosing spondylitis. 2
After sacroiliac involvement, the thoracic spine and thoracolumbar junction are the most common spinal regions affected. 2
A minority of patients may present with isolated spinal disease without prior sacroiliac involvement, reflecting disease heterogeneity. 2
Approximately 30 %–50 % of patients develop peripheral arthritis or enthesitis in addition to axial disease. 2

HLA‑B27 is present in 74 %–89 % of individuals with ankylosing spondylitis, representing the strongest genetic link, although it accounts for only about 20 % of the overall genetic risk. 3

The mechanosensor Piezo1 is up‑regulated in spinal tissues of patients with radiographic axial spondyloarthritis and at entheses where pathological new bone forms. 4
In animal models, pharmacologic inhibition of Piezo1 markedly suppresses pathological new‑bone formation, indicating that mechanical sensing contributes critically to disease progression. 4

Inflammatory back pain occurs in 70 %–80 % of patients, characterized by insidious onset, improvement with exercise, lack of improvement with rest, nocturnal pain, and onset before age 40. 2
Non‑specific elevations of inflammatory markers may be observed. 3
The average delay from symptom onset to formal diagnosis is about 4.9 years, highlighting challenges in early disease recognition. 2