What bloodwork is recommended to diagnose rheumatoid arthritis in a patient, particularly a woman between 30 and 60 years old, presenting with joint pain, swelling, and stiffness?

Bloodwork for Rheumatoid Arthritis Diagnosis

The essential bloodwork for diagnosing rheumatoid arthritis includes anti-citrullinated protein antibody (ACPA/anti-CCP), rheumatoid factor (RF), and C-reactive protein (CRP), with ACPA being the most specific test at 90% specificity. 1

First-Line Serologic Tests

Anti-CCP (ACPA) and rheumatoid factor should be ordered simultaneously at initial presentation, as these are the cornerstone autoantibody tests for RA diagnosis and prognosis. 1, 2

• ACPA has 90% specificity with 60% sensitivity, making it the most specific test for RA 1
• RF has 70% specificity with 60-80% sensitivity, providing complementary diagnostic information 1
• Both tests can be negative in 20-30% of RA cases (seronegative RA), so negative results do not exclude the diagnosis 2, 3
• High-positive RF or high-positive ACPA predicts aggressive disease with increased risk of extra-articular manifestations and shortened life expectancy 1

Inflammatory Markers

C-reactive protein (CRP) is preferred over erythrocyte sedimentation rate (ESR) because it correlates more closely with disease activity and is not age-dependent. 1

• Both CRP and ESR should be measured at baseline for diagnostic and prognostic purposes 2
• 40% of RA patients can have normal ESR or CRP, so normal inflammatory markers do not exclude active disease 3
• Markedly elevated CRP predicts severe disease with high risk of progressive joint erosions and functional deterioration 2

Complete Metabolic and Hematologic Assessment

A complete blood count with differential and comprehensive metabolic panel are essential to assess for cytopenias and establish baseline organ function before treatment. 1, 2

• CBC evaluates for anemia, leukopenia, and thrombocytopenia, which correlate with disease activity 4
• Comprehensive metabolic panel includes liver function tests, renal function, glucose, and urate levels 2
• Urinalysis is part of the standard initial workup 2

Conditional Testing Based on Clinical Presentation

Antinuclear antibodies (ANA) should be ordered if the diagnosis remains uncertain to screen for other connective tissue diseases like lupus. 2

• HLA-B27 testing should be considered if symptoms suggest spondyloarthropathy, particularly if there is axial or entheseal involvement 5, 2
• Hepatitis B, Hepatitis C, and tuberculosis screening are required before starting any biologic therapy 2, 6

Critical Clinical Pearls

Do not delay treatment or dismiss the diagnosis based solely on negative serology or normal inflammatory markers. 2

• Seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease 2
• The 2010 ACR/EULAR criteria assign only 1 point for abnormal CRP or ESR while joint involvement contributes up to 5 points, emphasizing that clinical synovitis is more important than laboratory values 2
• Repeat inflammatory markers (CRP and ESR) every 4-6 weeks after treatment initiation to monitor disease activity and treatment response 2

Diagnostic Algorithm

1. Order ACPA, RF, and CRP simultaneously as first-line tests 1, 2
2. Add CBC with differential and comprehensive metabolic panel for baseline assessment 1, 2
3. If diagnosis uncertain, add ANA to exclude other connective tissue diseases 2
4. If spondyloarthropathy suspected, add HLA-B27 5, 2
5. Before starting biologics, screen for hepatitis B, C, and tuberculosis 2, 6

The presence of clinical synovitis on physical examination remains more important than any laboratory test, and treatment should not be delayed waiting for positive serology in patients with definite clinical findings. 2