What is the role of HLA (Human Leukocyte Antigen)-B27 testing in the diagnosis and treatment of ankylosing spondylitis?

Role of HLA-B27 Testing in Ankylosing Spondylitis

HLA-B27 testing is a valuable screening tool for ankylosing spondylitis (AS) in patients with chronic back pain starting before age 45, with a sensitivity of 90% and specificity of 90%, but should not be used alone for diagnosis as approximately 10% of AS cases are HLA-B27 negative. 1, 2

Diagnostic Value of HLA-B27

• HLA-B27 testing should be used as a screening parameter rather than a definitive diagnostic test, with approximately 30-40% of patients with chronic back pain and positive HLA-B27 ultimately receiving an AS diagnosis 1
• The test should not be used to screen asymptomatic populations but is most valuable when the pre-test probability has been increased by clinical features 3
• HLA-B27 positivity increases the likelihood of peripheral spondyloarthritis, but a negative result should not rule out spondyloarthritis 1
• About 60-90% of axial spondyloarthritis patients worldwide carry HLA-B27, with prevalence varying by population 4

Referral Algorithm Using HLA-B27

For patients with suspected axial spondyloarthritis:

• Refer to a rheumatologist if the patient has chronic back pain (>3 months) with onset before age 45 AND at least four of the following criteria 1:

  • Back pain occurring before age 35
  • Waking at night due to pain
  • Buttock pain
  • Improvement with exercise or within two days of NSAID use
  • First-degree relative with spondyloarthritis
  • Current or previous arthritis, enthesitis, or psoriasis

• If only three of these criteria are met but HLA-B27 is positive, referral is still recommended 1

Diagnostic Approach

• Inflammatory back pain characteristics are essential for diagnosis, especially in HLA-B27 negative patients 2
• Radiography should be discussed with patients who may have axial spondyloarthritis (with mature skeleton) 1
• If sacroiliitis on radiography meets modified New York criteria, diagnosis can be confirmed 1
• If criteria are not met or radiography cannot be performed, MRI can be used 1
• A follow-up MRI is an option when diagnosis remains uncertain 1

Common Pitfalls to Avoid

• Do not rule out spondyloarthritis based solely on a negative HLA-B27 test, normal C-reactive protein, or normal erythrocyte sedimentation rate 1
• Avoid using HLA-B27 early in the diagnostic approach before increasing pre-test probability with clinical parameters 1
• Do not delay appropriate treatment for HLA-B27 negative patients, as disease can be just as severe as in HLA-B27 positive patients 2
• Inflammatory markers (ESR/CRP) have limited sensitivity (≤50%) and are not suitable as isolated screening parameters 2
• Do not use scintigraphy for diagnosis 1

Cost Considerations

• HLA-B27 testing costs approximately €40 (in Germany, equivalent to a chest or pelvis X-ray) 1
• Testing only needs to be performed once in a patient's lifetime 1
• When used appropriately in patients with chronic back pain starting before age 45, HLA-B27 testing is considered cost-effective 1