Which specific blood tests are recommended to evaluate a patient with suspected rheumatoid arthritis?

Specific Blood Tests for Rheumatoid Arthritis

Order rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA/anti-CCP), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) as the core serologic panel for any patient with suspected rheumatoid arthritis. 1, 2, 3

Essential First-Line Serologic Tests

Autoantibody Testing

• Anti-CCP antibodies have approximately 90% specificity and 60% sensitivity for rheumatoid arthritis, making them more specific than rheumatoid factor for diagnosis 1, 3, 4
• Rheumatoid factor (RF) has approximately 70% specificity and 62% sensitivity; it is less specific than anti-CCP but remains essential for diagnosis and prognosis 1, 3, 5
• Both RF and anti-CCP should be ordered simultaneously at initial presentation, as they provide complementary diagnostic and prognostic information 1, 2
• When both antibodies are used together, specificity reaches 99.6%, substantially improving diagnostic accuracy 4
• High-positive RF or ACPA carries 3 points in the 2010 ACR/EULAR classification criteria, while low-positive results carry 2 points 1, 2

Inflammatory Markers

• C-reactive protein (CRP) is preferred over ESR because it is more reliable, not age-dependent, and provides a simple, validated, reproducible measure of inflammation 1, 3
• ESR should also be measured at baseline for diagnostic and prognostic purposes, as it contributes to the 2010 ACR/EULAR classification criteria 6, 1, 2
• Abnormal CRP or ESR contributes 1 point to the classification score 1

Additional Baseline Laboratory Tests

Pre-Treatment Safety Panel

• Complete blood count with differential to assess for cytopenias before starting disease-modifying antirheumatic drugs (DMARDs) 6, 1
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and urate levels is required before initiating methotrexate 6, 1, 3
• Urinalysis as part of the standard initial workup 6, 1

Screening Before Biologic Therapy

• Hepatitis B, hepatitis C, and tuberculosis screening must be completed before starting any biologic agent 1, 5

Conditional Testing Based on Clinical Context

When Diagnosis Remains Uncertain

• Antinuclear antibodies (ANA) can be ordered to screen for other connective tissue diseases like systemic lupus erythematosus if the diagnosis is uncertain 6, 1
• If ANA is positive, order anti-dsDNA and extractable nuclear antigen (ENA) panels to exclude SLE 1

When Spondyloarthropathy Is Considered

• HLA-B27 typing should be considered if symptoms suggest axial involvement, entheseal involvement, or reactive arthritis 6, 1

Critical Clinical Pearls and Pitfalls

Understanding Seronegative Disease

• Seronegative rheumatoid arthritis accounts for 20-30% of cases, so negative RF does not exclude the diagnosis 1, 3, 7
• More than 30-40% of patients with rheumatoid arthritis have negative tests for RF or anti-CCP antibodies 7
• Do not delay treatment waiting for positive serology—seronegative disease has a similar prognosis and requires equally aggressive management 1, 3

Interpreting Normal Inflammatory Markers

• 40% of patients with active rheumatoid arthritis have normal ESR or CRP, so normal acute-phase reactants do not exclude the diagnosis 1, 3, 7
• Do not dismiss the diagnosis based on normal inflammatory markers—acute-phase reactants are poor predictors and can be normal even in active disease 1, 3

Monitoring Disease Activity

• Repeat CRP and ESR every 4-6 weeks after treatment initiation to monitor disease activity and treatment response 1, 2
• Serial inflammatory markers are useful for longitudinal disease monitoring but should not be the sole determinant of treatment decisions 1

Algorithmic Approach to Laboratory Testing

1. Initial presentation with suspected inflammatory arthritis:

   • Order RF, anti-CCP, CRP, ESR, CBC with differential, comprehensive metabolic panel, and urinalysis 1, 2, 3

2. If RF and anti-CCP are both negative but clinical suspicion remains high:

   • Do not exclude rheumatoid arthritis based on serology alone 1, 3
   • Consider ANA and ENA panel to evaluate for alternative connective tissue diseases 1
   • Proceed with imaging (ultrasound with Power Doppler or MRI) to detect subclinical synovitis 1, 3

3. Before initiating DMARD therapy:

   • Ensure comprehensive metabolic panel, CBC, and urinalysis are completed 1, 3

4. Before initiating biologic therapy:

   • Complete hepatitis B, hepatitis C, and tuberculosis screening 1, 5

5. During ongoing treatment:

   • Repeat CRP/ESR at each visit (every 4-6 weeks during active disease) 1, 2