Can you have ankylosing spondylitis (AS) if you test negative for Human Leukocyte Antigen B27 (HLA-B27)?

Can You Have Ankylosing Spondylitis if You Test Negative for HLA-B27?

Yes, you can definitely have ankylosing spondylitis (AS) even if you test negative for HLA-B27. 1, 2 Spondyloarthritis should never be ruled out based solely on a negative HLA-B27 test result.

Prevalence and Significance of HLA-B27 Negativity in AS

• Approximately 10% of ankylosing spondylitis cases occur in HLA-B27 negative patients 2
• Axial spondyloarthritis occurs equally in men and women and can be found in persons who are negative for HLA-B27 1
• The disease can be just as severe in HLA-B27 negative patients as in those who are HLA-B27 positive 2

Diagnostic Approach for HLA-B27 Negative Patients

When evaluating patients with suspected AS despite negative HLA-B27:

• Focus on clinical features of inflammatory back pain, which are essential for diagnosis in HLA-B27 negative patients 2
• Look for key characteristics:
  • Back pain onset before age 45 years lasting more than 3 months 1, 2
  • Morning stiffness lasting more than 30 minutes 2
  • Nocturnal or early morning pain 2
  • Improvement with exercise or movement 2
  • Pain improved within 2 days of taking NSAIDs 1

Imaging Considerations

• Radiography should be discussed with patients who may have axial spondyloarthritis 1
• If sacroiliitis on radiography meets the modified New York criteria, AS diagnosis can be confirmed regardless of HLA-B27 status 1
• When radiographs are normal but clinical suspicion remains high, MRI of the spine or pelvis can help evaluate disease activity 2
• AS is possible even in persons without visible sacroiliitis on radiography 1

When to Refer to a Rheumatologist

Refer patients to a rheumatologist if they have:

• Back pain that started before age 45 and has lasted more than 3 months, plus at least 4 of these criteria: 1, 3

  • Back pain occurring before age 35
  • Waking at night due to pain
  • Buttock pain
  • Improved pain with movement or within 2 days of taking NSAIDs
  • First-degree relative with spondyloarthritis
  • Current or previous arthritis, enthesitis, or psoriasis

• Even if only 3 criteria are met, referral is still indicated if other inflammatory markers or imaging findings are present 1

Treatment Approach

• First-line treatment is NSAIDs at the lowest effective dose, regardless of HLA-B27 status 1, 3
• If the first NSAID is ineffective after 2-4 weeks, try another NSAID 1, 3
• All patients diagnosed with axial spondyloarthritis should be referred for a structured exercise program 1, 3
• For patients with active disease despite NSAIDs, tumor necrosis factor inhibitors (TNFi) are recommended as the first biologic agent 2, 3

Common Pitfalls to Avoid

• Relying solely on laboratory markers: Neither HLA-B27, C-reactive protein, nor erythrocyte sedimentation rate should be used to rule out spondyloarthritis 1
• Delaying appropriate treatment due to HLA-B27 negative status 2
• Overlooking AS in women: Women are more likely to manifest symptomatic disease without radiographic evidence of sacroiliitis 4
• Excessive invasive procedures: Patients with undiagnosed AS may undergo unnecessary spinal procedures before correct diagnosis 5

Monitoring

• Disease activity should be monitored using clinical signs, symptoms, and acute phase reactants 3
• Systematic radiographic monitoring with serial spine radiographs is not recommended 2
• Treatment should be guided by predefined therapeutic goals agreed upon between patient and rheumatologist 3