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

HLA-B27 Testing in Ankylosing Spondylitis

HLA-B27 testing should be used as a screening parameter to increase diagnostic probability in patients with chronic inflammatory back pain, but never as a standalone diagnostic test—a negative result does not exclude ankylosing spondylitis, and a positive result does not confirm it. 1

Diagnostic Role and Limitations

• HLA-B27 is present in approximately 90% of ankylosing spondylitis patients, meaning about 10% of AS cases are HLA-B27 negative. 2

• Among patients with chronic back pain who test positive for HLA-B27, only 30-40% will ultimately receive an AS diagnosis, demonstrating the test's limited positive predictive value. 1

• The test should never be used to rule out spondyloarthritis based solely on a negative result, as HLA-B27 negative AS can be just as severe as HLA-B27 positive disease. 2, 1

• HLA-B27 testing only needs to be performed once in a patient's lifetime. 1

When to Order HLA-B27 Testing

Order HLA-B27 testing after establishing clinical suspicion based on inflammatory back pain characteristics, not as an initial screening test. 1

Clinical Features That Should Precede Testing:

• Chronic back pain lasting >3 months with onset before age 45 years 2, 1

• Inflammatory back pain characteristics: 2

  • Morning stiffness >30 minutes
  • Nocturnal or early morning pain
  • Improvement with exercise (not rest)
  • Improvement within 2 days of NSAID use 1

• Additional features that increase pre-test probability: 1

  • Back pain onset before age 35
  • Waking at night due to pain
  • Buttock pain
  • First-degree relative with spondyloarthritis
  • Current or previous arthritis, enthesitis, or psoriasis

Referral Algorithm to Rheumatology

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

• Referral should occur even in HLA-B27 negative patients if inflammatory back pain characteristics are present. 2, 1

• The presence of sacroiliitis on imaging (radiography or MRI) also mandates specialist referral regardless of HLA-B27 status. 2

Critical Pitfalls to Avoid

• Do not use HLA-B27 testing early in the diagnostic approach before establishing clinical suspicion—this leads to false reassurance from negative results and overinterpretation of positive results. 1

• Never rule out spondyloarthritis based on negative HLA-B27, normal CRP, or normal ESR, as inflammatory markers have limited sensitivity (≤50%). 2, 1

• Do not delay appropriate treatment in HLA-B27 negative patients, as disease severity is equivalent to HLA-B27 positive cases. 2

• Avoid using HLA-B27 as a screening test in asymptomatic populations or patients with non-inflammatory back pain—the test cannot confirm or exclude disease in isolation. 3, 4

Imaging Considerations

• MRI of the spine or pelvis should be obtained when disease activity is uncertain, as it can detect sacroiliitis before radiographic changes appear. 2

• If sacroiliitis on radiography meets modified New York criteria, the diagnosis can be confirmed regardless of HLA-B27 status. 1

• Systematic serial spine radiographs for monitoring are not recommended. 2