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

What a Positive HLA-B27 Result Indicates

A positive HLA-B27 test in a patient with chronic back pain (>3 months, onset <45 years) increases the probability of axial spondyloarthritis to approximately 30-40% and warrants referral to a rheumatologist for definitive diagnosis, particularly when accompanied by inflammatory back pain features. 1

Clinical Significance of HLA-B27 Positivity

HLA-B27 is a screening parameter, not a diagnostic test by itself. 1 The test has excellent performance characteristics for identifying patients who need specialist evaluation:

• Sensitivity: 90% (only 10% of axial SpA patients are HLA-B27 negative) 2
• Likelihood ratio: 9, yielding a post-test probability of 32% 2
• Practical implication: Only 3 HLA-B27 positive patients with chronic back pain need rheumatology evaluation to diagnose 1 case of axial spondyloarthritis 2

Approximately 60-90% of axial spondyloarthritis patients worldwide carry HLA-B27, though this varies by population. 3

When to Refer to Rheumatology

Refer immediately if the patient has:

• Chronic back pain >3 months with onset before age 45 years, AND 1
• HLA-B27 positivity, AND 2, 1
• At least one of the following inflammatory back pain features:
  • Morning stiffness >30 minutes 2, 4
  • Pain at night or early morning 2, 4
  • Improvement with exercise 2, 4
  • Good response to NSAIDs (improvement within 48 hours) 1

Also refer if imaging shows sacroiliitis:

• X-ray: Grade ≥2 bilaterally or grade ≥3 unilaterally 2
• MRI: Active sacroiliitis (if already obtained) 2, 1

Critical Pitfalls to Avoid

Do not dismiss spondyloarthritis based on:

• Normal inflammatory markers (ESR/CRP have only 50% sensitivity in axial SpA) 2, 4
• Absence of radiographic changes (early disease may be pre-radiographic) 2
• The fact that most HLA-B27 positive individuals never develop disease 5, 6

Do not order HLA-B27 indiscriminately:

• Only test patients with appropriate pre-test probability (chronic back pain with inflammatory features) 1
• Testing costs approximately €40 and only needs to be done once in a lifetime 2, 1

Prognostic Implications

HLA-B27 positivity indicates:

• Worse prognosis in patients with confirmed axial spondyloarthritis 2
• Increased risk in first-degree relatives: 25% of HLA-B27 positive first-degree relatives develop axial SpA versus only 3% of HLA-B27 negative relatives 2
• No increased mortality from HLA-B27 carriage alone in the general population (reassuring for those who test positive but don't develop disease) 2

What HLA-B27 Does NOT Mean

Reassure patients that:

• HLA-B27 positivity alone does not cause disease—most carriers remain healthy 5, 6
• The prevalence in mid-European populations is approximately 8% 3
• HLA-B27 carriage without spondyloarthritis does not adversely impact survival or cardiovascular mortality 2

Next Steps After Positive Result

The rheumatologist will:

• Confirm diagnosis using clinical criteria plus imaging (X-ray or MRI of sacroiliac joints) 2, 1
• Initiate treatment with NSAIDs as first-line therapy 4
• Consider biologics (TNF inhibitors, IL-17 inhibitors) if NSAIDs fail 4
• Monitor for extra-articular manifestations (uveitis, which occurs more frequently in HLA-B27 positive patients and may predict axial SpA development) 2