Clinical Guide to Axial Spondyloarthritis and Ankylosing Spondylitis

In this episode of Hospital Medicine Unplugged, we sprint through ankylosing spondylitis and axial spondyloarthritis—recognize inflammatory back pain early, understand the disease spectrum from non-radiographic to radiographic disease, and treat aggressively to prevent structural damage and disability. We begin with the modern concept of axial spondyloarthritis (axSpA), which represents a disease spectrum rather than a single condition. At one end is non-radiographic axial spondyloarthritis (nr-axSpA)—patients with typical symptoms but without definitive radiographic sacroiliitis. At the other end is radiographic axial spondyloarthritis (r-axSpA), historically known as ankylosing spondylitis, where structural changes in the sacroiliac joints are visible on X-ray. Globally, axial spondyloarthritis affects roughly 0.3% to 1.4% of the population, with about 1% prevalence in the United States. Disease onset typically occurs early in life—more than 80% of patients develop symptoms before age 30. Radiographic disease is more common in men, while non-radiographic disease occurs equally in men and women. A major challenge in this condition is diagnostic delay, which averages nearly seven years from symptom onset. This delay contributes to progressive inflammation, structural damage, and functional impairment before effective therapy is started. The pathogenesis of axial spondyloarthritis involves a combination of genetic susceptibility, immune dysregulation, and environmental triggers. The strongest genetic risk factor is HLA-B27, present in 80–90% of patients with ankylosing spondylitis. Several mechanisms have been proposed to explain how HLA-B27 contributes to disease: • Presentation of arthritogenic peptides to CD8+ T cells • Formation of HLA-B27 dimers, which activate innate immune receptors • Misfolding of HLA-B27 proteins, triggering an unfolded protein response and increased cytokine signaling At the center of the inflammatory cascade lies the IL-23 / IL-17 axis, which drives activation of Th17 cells and production of pro-inflammatory cytokines including IL-17 and TNF-α. Mechanical stress at the entheses—the sites where ligaments and tendons attach to bone—triggers inflammation, making enthesitis the hallmark pathological process. Chronic inflammation eventually stimulates pathologic new bone formation, producing syndesmophytes and spinal ankylosis. Clinically, the hallmark symptom is inflammatory back pain, present in more than 80% of patients. Key features include: • Onset before age 45 years • Gradual onset • Morning stiffness lasting more than 30 minutes • Improvement with exercise • No improvement with rest Extra-articular manifestations are common and often provide diagnostic clues. The most frequent is acute anterior uveitis, occurring in 25–30% of patients. Episodes typically present with sudden eye pain, redness, photophobia, and blurred vision. Other associated conditions include: • Inflammatory bowel disease (5–10%) • Psoriasis (about 10%) • Cardiovascular involvement, including aortic regurgitation and conduction abnormalities • Pulmonary restriction due to chest wall rigidity Because early disease may not show radiographic damage, classification relies on modern criteria. The Modified New York Criteria require definite radiographic sacroiliitis and therefore identify only advanced disease. In contrast, the ASAS classification criteria for axial spondyloarthritis allow earlier diagnosis. These criteria apply to patients with chronic back pain lasting ≥3 months with onset before age 45 and include two diagnostic pathways: • Imaging arm: sacroiliitis on MRI or radiograph plus ≥1 SpA feature • Clinical arm: HLA-B27 positivity plus ≥2 SpA features These criteria have approximately 83% sensitivity and 84% specificity, enabling detection of earlier disease stages. Monitoring disease activity is critical to guide treatment decisions. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is the preferred measure because it incorporates both patient-reported symptoms and inflammatory markers such as CRP. ASDAS categories include: • Inactive disease: <1.3 • Low activity: 1.3–2.1 • High activity: 2.1–3.5 • Very high activity: >3.5 Management begins with non-pharmacologic therapy, which remains foundational for all patients. This includes structured exercise programs, physical therapy, posture training, and smoking cessation, as smoking is associated with worse radiographic progression and poorer treatment response. First-line pharmacologic therapy is NSAIDs, which reduce pain and inflammation. Continuous therapy may be more effective than intermittent use, although fewer than one quarter of patients achieve complete symptom control with NSAIDs alone. For patients with persistent disease activity, biologic therapy is the next step. TNF inhibitors were the first biologics proven effective, producing ASAS20 response rates of roughly 60% ...