What does a positive HLA (Human Leukocyte Antigen) B27 result indicate and how is it managed?

HLA-B27 Positive: Clinical Significance and Management

A positive HLA-B27 test strongly indicates increased risk for axial spondyloarthritis (axSpA) and should prompt referral to a rheumatologist for patients with chronic back pain beginning before age 45, particularly when inflammatory characteristics are present. 1

Clinical Significance of HLA-B27 Positivity

• HLA-B27 has a high sensitivity (90%) for axial spondyloarthritis, making it an excellent screening parameter with good post-test probability (32%) - meaning approximately one in three HLA-B27 positive patients with chronic low back pain will have axSpA 1

• HLA-B27 positivity is associated with several conditions beyond axSpA, including:

  • Reactive arthritis
  • Psoriatic arthritis
  • Inflammatory bowel disease-associated arthritis
  • Acute anterior uveitis (most common form of non-infectious intraocular inflammation) 2, 1

• In inflammatory bowel disease (IBD), HLA-B27 is found in 25-75% of patients who develop ankylosing spondylitis, but only in 7-15% of patients with isolated sacroiliitis 1

Diagnostic Algorithm for HLA-B27 Positive Patients

1. For patients with chronic back pain (>3 months) with onset before age 45:

   • HLA-B27 positivity should trigger referral to a rheumatologist 1
   • Particularly important if patient has additional features such as:
     • Morning stiffness >30 minutes
     • Pain at night/early morning
     • Improvement with exercise
     • Buttock pain
     • Family history of spondyloarthritis 1

2. For patients with inflammatory eye conditions:

   • HLA-B27 positive anterior uveitis patients have a 40% chance of having an undiagnosed systemic disease, requiring thorough evaluation 2
   • Ophthalmologists play a major role in early detection of associated conditions 2

3. For patients with inflammatory bowel disease:

   • HLA-B27 testing may help identify those at higher risk for developing ankylosing spondylitis, though it has lower prevalence than in idiopathic AS, making it less reliable as a diagnostic test in IBD 1

Management Considerations

• Referral threshold: Patients with chronic back pain, HLA-B27 positivity, and at least three of the following should be referred to rheumatology:

  • Back pain onset before age 35
  • Waking at night due to pain
  • Buttock pain
  • Improvement with movement or NSAIDs
  • First-degree relative with spondyloarthritis
  • Current/previous arthritis, enthesitis, or psoriasis 1

• Imaging: Radiography of the sacroiliac joints should be considered in HLA-B27 positive patients with suspicious symptoms; if negative or inconclusive, MRI may identify early sacroiliitis 1

• Additional testing: Spondyloarthritis should not be ruled out based solely on negative laboratory results from HLA-B27, C-reactive protein, or erythrocyte sedimentation rate 1

Important Caveats and Pitfalls

• HLA-B27 positivity alone is not diagnostic of any condition - approximately 8% of the mid-European population carries this genetic marker without developing disease 3, 1

• Spondyloarthritis can occur in HLA-B27 negative individuals and in those without radiographic evidence of sacroiliitis 1, 3

• Using HLA-B27 for screening (rather than diagnosis) is appropriate, as it has high sensitivity (90%) and can identify patients needing further evaluation 1

• A 35-year follow-up study showed approximately 25% of HLA-B27 positive first-degree relatives of axSpA patients developed the condition, highlighting the importance of family history 1

• While HLA-B27 positive patients with axSpA may have increased disease severity, HLA-B27 positivity alone in the general population is not associated with increased mortality 1