What laboratory tests are used to diagnose and monitor rheumatoid arthritis (RA) in an adult patient?

Laboratory Tests for Rheumatoid Arthritis

Order rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA/anti-CCP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complete blood count with differential, comprehensive metabolic panel (including liver and renal function), and urinalysis as your core initial laboratory workup for any patient with suspected RA. 1, 2

Essential Serologic Tests

Autoantibody Testing

• Rheumatoid Factor (RF) is essential for diagnosis and prognosis, though it has moderate sensitivity (70%) and specificity (70%) 1, 2
• Anti-CCP antibodies (ACPA) have superior specificity (90%) compared to RF, with moderate sensitivity (60%), making them highly valuable when positive 1, 2
• Order both RF and ACPA simultaneously at initial presentation—they are the cornerstone autoantibody tests, and ordering both increases diagnostic sensitivity 3, 2
• High-positive RF or ACPA carries more diagnostic weight (3 points) than low-positive results (2 points) in the 2010 ACR/EULAR Classification Criteria 2

Critical Clinical Pearl on Serology

Do not dismiss RA diagnosis based on negative RF or ACPA—seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease. 1, 4 Negative tests do not exclude RA, and treatment should not be delayed waiting for positive serology 1

Inflammatory Markers

Acute Phase Reactants

• C-reactive protein (CRP) is preferred over ESR because it is more reliable, not age-dependent, and provides better reproducibility 1, 2
• Measure both ESR and CRP at baseline for diagnostic and prognostic purposes 1, 3, 2
• Normal ESR/CRP does not exclude RA—more than 40% of RA patients have normal acute phase reactants at presentation 4, 5
• Repeat ESR and CRP every 4-6 weeks after treatment initiation to monitor disease activity and treatment response 1, 2

Important Limitation

Acute phase reactants are poor predictors of RA diagnosis and can be normal even in active disease—prioritize clinical synovitis over laboratory values in diagnostic decisions 1, 5

Baseline Hematologic and Metabolic Assessment

Complete Blood Count

• Order CBC with differential to assess for cytopenias before starting treatment 1, 6
• This is essential baseline information as many RA medications can cause hematologic abnormalities 1

Comprehensive Metabolic Panel

• Include liver function tests, renal function, glucose, and urate levels 1
• Liver and renal function are critical for monitoring methotrexate and other DMARD safety 6
• Normal uric acid helps exclude gout as a differential diagnosis 1

Urinalysis

• Perform urinalysis as part of the standard initial workup 1, 3

Additional Testing Based on Clinical Context

When Diagnosis Remains Uncertain

• Antinuclear antibodies (ANA) can screen for other connective tissue diseases like lupus if the diagnosis is uncertain 1, 2
• HLA-B27 typing should be considered if spondyloarthropathy is suspected (axial or entheseal involvement) 1

Pre-Treatment Screening

• Test for hepatitis B, hepatitis C, and tuberculosis before starting any biologic therapy—this is required by guidelines 1, 6

Monitoring Strategy After Diagnosis

Serial Laboratory Monitoring

• Repeat inflammatory markers (CRP and ESR) at each visit to monitor disease activity 1
• Use composite disease activity measures (DAS28, SDAI, or CDAI) every 4-6 weeks after treatment initiation, with target of remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 1, 2
• SDAI is preferred over DAS28 when CRP is elevated, as it provides more stringent disease activity assessment 1

Imaging as Complementary Assessment

• Obtain baseline X-rays of hands, wrists, and feet bilaterally at initial presentation—erosions on baseline radiographs are highly predictive for RA diagnosis and disease persistence 1, 2
• Repeat X-rays at 6 months and 12 months to monitor radiographic progression 1
• Consider ultrasound with Power Doppler or MRI if clinical examination shows no definite synovitis but suspicion remains high—these detect subclinical synovitis that predicts disease progression 1

Common Pitfalls to Avoid

• Never delay treatment waiting for positive serology—seronegative RA is common and requires equally aggressive treatment 1
• Do not dismiss RA diagnosis based solely on normal ESR/CRP—clinical synovitis and composite disease activity measures should guide treatment decisions 1, 5
• Failing to order both RF and ACPA reduces diagnostic sensitivity—always order both tests simultaneously 3, 2
• Laboratory tests should complement, not replace, careful clinical examination with 28-joint count assessment 1, 3