HLA-B27 Testing for Joint Pain
For a patient with joint pain suspected of having ankylosing spondylitis or other spondyloarthropathies, order HLA-B27 testing. This is the relevant HLA test to draw, as HLA-B27 is present in 74-89% of patients with axial spondyloarthritis and provides important diagnostic information when combined with clinical features and imaging 1, 2.
When to Order HLA-B27
Order HLA-B27 testing when the patient presents with:
- Inflammatory back pain (insidious onset before age 45, morning stiffness, improvement with exercise but not rest, pain at night in the second half, alternating buttock pain) 1
- Chronic back pain lasting ≥3 months with inflammatory characteristics 3, 1
- Peripheral joint involvement in an oligoarticular, asymmetric pattern affecting large joints (especially knees) 1
- Extra-articular manifestations such as uveitis, psoriasis, or inflammatory bowel disease 1
Diagnostic Value and Interpretation
HLA-B27 has 90% sensitivity and specificity for axial spondyloarthritis, yielding a 32% post-test probability 4. However, critical caveats exist:
- Do not rule out spondyloarthritis based solely on a negative HLA-B27 test 3. The disease can occur in HLA-B27 negative individuals, and 10-26% of axial spondyloarthritis patients are HLA-B27 negative 1, 2
- HLA-B27 positivity alone is not diagnostic 5. Approximately 8% of the general mid-European population carries HLA-B27, but only 1.3% of HLA-B27 positive individuals in the general population develop ankylosing spondylitis 6, 2
- The risk increases dramatically with family history: HLA-B27 positive first-degree relatives of AS patients have a 21% risk of developing AS (16 times higher than HLA-B27 positive individuals in the general population) 6
Diagnostic Algorithm
Clinical assessment first: Determine if inflammatory back pain criteria are met (morning stiffness, improvement with exercise, night pain, alternating buttock pain) 4
Order HLA-B27 testing when clinical suspicion exists, particularly if the patient meets referral criteria: back pain since before age 45 lasting >3 months plus at least 4 of the following: onset before age 35, waking at night, buttock pain, improvement with movement or NSAIDs within 2 days, first-degree relative with spondyloarthritis, or current/previous arthritis/enthesitis/psoriasis 3
Refer to rheumatology if only 3 criteria are met but HLA-B27 is positive 3
Combine with imaging: Order plain radiographs of sacroiliac joints as initial imaging (rated 9/9 appropriateness) 3, 7. If radiographs are negative or equivocal but clinical suspicion remains high, proceed to MRI of sacroiliac joints without contrast (79-82% sensitivity, 89-97% specificity) 4, 7
Common Pitfalls to Avoid
- Do not use HLA-B27 as a screening test in patients without inflammatory symptoms, as the low specificity in the general population leads to false positives 5
- Do not rely on inflammatory markers alone: C-reactive protein and ESR have low sensitivity and specificity for spondyloarthritis and should not be used to rule out disease 3, 5
- Recognize diagnostic delay: The average delay from symptom onset to diagnosis is 4.9-8 years, so maintain high clinical suspicion even with initially negative tests 1
Specific HLA-B27 Subtype
HLA-B*2705 is the most common disease-associated subtype, conferring a relative risk of 126 for ankylosing spondylitis 8. However, routine subtyping is not necessary for clinical diagnosis, as approximately 200 HLA-B27 subtypes exist with only two that are not disease-associated 2. Standard HLA-B27 testing without subtyping is sufficient for clinical decision-making 2, 9.