What lab tests are recommended for a patient suspected of having rheumatoid arthritis?

Laboratory Tests for Suspected Rheumatoid Arthritis

For any patient with suspected rheumatoid arthritis, order rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complete blood count with differential, comprehensive metabolic panel, and bilateral X-rays of hands, wrists, and feet at initial presentation. 1

Essential Serologic Tests

Autoantibody Testing

• Both RF and anti-CCP should be ordered simultaneously at initial presentation, as these are the cornerstone autoantibody tests for RA diagnosis and prognosis 1, 2
• Anti-CCP has higher specificity (90%) than RF (70%) for RA, though both have similar sensitivity around 60% 1, 2
• RF testing is essential for diagnosis and prognosis, as recommended by the European League Against Rheumatism 1
• High-positive RF or anti-CCP carries more diagnostic weight (3 points) than low-positive results (2 points) in the 2010 ACR/EULAR Classification Criteria 1
• The presence of RF and/or anti-CCP significantly increases the probability of developing RA 1

Critical Clinical Pearl

• Negative RF does not exclude RA—seronegative RA accounts for 20-30% of cases 2
• Anti-CCP should be measured in RF-negative patients, as 30-40% of RA patients may be RF-negative 1

Inflammatory Markers

Acute Phase Reactants

• CRP is preferred over ESR as it is more reliable, not age-dependent, and provides better correlation with disease activity 1, 2
• Both ESR and CRP should be measured at baseline for diagnostic and prognostic purposes 1
• Do not dismiss the diagnosis based on normal inflammatory markers—40% of RA patients have normal ESR or CRP, and these are poor predictors even in active disease 2, 3
• Repeat CRP and ESR at each visit to monitor disease activity and treatment response 1, 2

Baseline Laboratory Panel

Complete Blood Count and Metabolic Assessment

• CBC with differential should be ordered to assess for cytopenias (anemia, thrombocytosis common in active RA) and calculate neutrophil-to-lymphocyte ratio 1, 4, 2
• Comprehensive metabolic panel including liver function tests (ALT, AST), renal function (creatinine), glucose, and uric acid levels is required for baseline assessment and monitoring 1, 2
• Urinalysis is part of the standard initial workup 1, 2

Pre-Treatment Screening

Infectious Disease Screening (Before Starting Biologics or DMARDs)

• Screen for hepatitis B surface antigen, surface antibody, core antibody, and hepatitis C antibody before starting biologic therapy 4, 2, 5
• Tuberculin skin test or interferon-gamma release assay (IGRA preferred over TST in patients with prior BCG vaccination) should be done regardless of risk factors 4
• HBV reactivation is a potentially serious complication—measure HBc and/or HBs antibodies even if HBs antigen is negative 6

Baseline Imaging

Radiographic Assessment

• Bilateral hand, wrist, and foot X-rays should be obtained at initial presentation—the presence of erosions on baseline radiographs is highly predictive for RA diagnosis and disease persistence 1, 2
• X-rays should be repeated within 6-12 months to monitor for radiographic progression 1, 2
• Look for periarticular osteopenia, uniform joint space narrowing, and marginal erosions as characteristic features 2

Advanced Imaging When Diagnosis Uncertain

• If clinical examination shows no definite synovitis but suspicion remains high, consider ultrasound with Power Doppler or MRI 1, 2
• Ultrasound with Power Doppler is superior to clinical examination for detecting subclinical synovitis and is 75% more accurate than physical examination alone 2
• MRI with IV contrast is more sensitive than ultrasound in early stages and detects bone marrow edema (osteitis), which is the best single predictor of future disease progression 2

Additional Testing When Diagnosis Uncertain

Expanded Autoimmune Panel

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

Common Pitfalls to Avoid

• Never delay treatment waiting for positive serology—seronegative RA is common and has similar prognosis to seropositive disease 2
• Do not rely solely on inflammatory markers for diagnosis—more than 30-40% of RA patients have negative RF/anti-CCP or normal ESR/CRP 3
• Refer to rheumatology within 6 weeks of symptom onset if inflammatory arthritis is suspected, as early treatment prevents irreversible joint damage 2
• Joint swelling (synovitis) is the cornerstone finding—look specifically for soft tissue swelling around joints, not bony enlargement 2