What are the management and treatment options for a patient with an HLA (Human Leukocyte Antigen) B27 abnormality, potentially indicating ankylosing spondylitis or other spondyloarthropathies?

Management of HLA-B27 Positive Patients

A positive HLA-B27 test in a patient with chronic back pain (>3 months) starting before age 45 warrants referral to a rheumatologist for evaluation of axial spondyloarthropathy, as only 3 HLA-B27 positive patients with chronic back pain need to be evaluated to diagnose one case of spondyloarthritis. 1

Understanding HLA-B27 as a Screening Tool

HLA-B27 is a screening parameter, not a diagnostic test. 2, 3 The key performance characteristics are:

• Sensitivity: 90% (only 10% of AS patients are HLA-B27 negative) 1
• Post-test probability: 32% in patients with chronic back pain 1
• Likelihood ratio: 9 1
• Prevalence in AS: 74-89% of patients 3

Approximately 30-40% of patients with chronic back pain and positive HLA-B27 will ultimately receive an AS diagnosis. 2, 3 This means HLA-B27 positivity increases disease likelihood substantially but does not confirm diagnosis. 1

When to Refer to Rheumatology

Refer immediately if the patient has:

• Chronic back pain >3 months 1, 2
• First symptoms before age 45 1
• AND inflammatory back pain characteristics (morning stiffness >30 minutes, pain at night/early morning, improvement with exercise) 1
• OR HLA-B27 positivity 1
• OR sacroiliitis on imaging (X-ray or MRI) 1

The American Academy of Family Physicians recommends referral when patients have chronic back pain with onset before age 45 AND at least four criteria including: back pain before age 35, waking at night due to pain, buttock pain, improvement with exercise or within two days of NSAID use, first-degree relative with spondyloarthritis, or current/previous arthritis, enthesitis, or psoriasis. 2

Management Approach for HLA-B27 Positive Patients

Non-Pharmacological Treatment (Mandatory from Diagnosis)

• Patient education and regular exercise form the cornerstone and must be implemented immediately 4
• Supervised exercise programs are superior to home exercises alone and should be preferred 4
• Physical therapy improves patient global assessment significantly (Level II evidence) 4

First-Line Pharmacological Treatment

• NSAIDs (including COX-2 inhibitors) are first-line drug treatment for pain and stiffness with Level Ib evidence for improving spinal pain, peripheral joint pain, and function 4
• Continuous NSAID treatment is preferred over on-demand use for persistently active, symptomatic disease 4
• Patients who respond well to NSAIDs but have axial SpA have worse prognosis and should be referred to specialists 1

Second-Line Options

• Analgesics (paracetamol, opioid-like drugs) may be considered for residual pain after NSAID failure, contraindication, or poor tolerance 4
• Corticosteroid injections directed to local sites of musculoskeletal inflammation may be considered 4
• Systemic glucocorticoids for axial disease are NOT supported by evidence 4

Biologic Therapy for Refractory Disease

• Anti-TNF treatment should be given to patients with persistently high disease activity despite conventional treatments (Level I evidence) 4
• TNF inhibitors, IL-17 inhibitors, and JAK inhibitors have demonstrated efficacy and good tolerability 4

Critical Pitfalls to Avoid

Do NOT rule out spondyloarthritis based on:

• Negative HLA-B27 test alone (10% of AS cases are HLA-B27 negative) 2, 3
• Normal C-reactive protein 2, 3
• Normal erythrocyte sedimentation rate 2, 3

ESR/CRP have only 50% sensitivity in AS patients and provide only 12% post-test probability when raised. 1 These markers should be monitored alongside validated AS disease activity measures but cannot exclude disease. 3

Avoid using HLA-B27 testing too early in the diagnostic approach before increasing pre-test probability with clinical parameters. 2 The test should be reserved for patients who already have clinical features suggestive of inflammatory back pain. 1

Imaging Considerations

• X-ray sacroiliitis (grade 2 bilaterally or grade 3+ unilaterally) has sensitivity and specificity of only ~80% 1
• MRI of sacroiliac joints has good sensitivity and specificity but is expensive and not recommended for primary screening 1
• If sacroiliitis is present on either X-ray or MRI in a young patient with chronic back pain, this supports referral to rheumatology 1

Monitoring Strategy

Regular monitoring should include patient history, clinical parameters, laboratory tests (CRP/ESR), imaging, and ASAS core set assessments, with frequency determined individually based on symptoms, severity, and drug treatment. 4

Treatment Goals

The primary goal is maximizing long-term health-related quality of life through control of symptoms and inflammation, prevention of structural damage, and preservation of function and social participation. 4