What laboratory tests and treatment are recommended for a patient with Rheumatoid Arthritis (RA)?

Laboratory Testing for Rheumatoid Arthritis

For a patient with suspected or confirmed RA, order the following initial laboratory panel: RF, anti-CCP antibodies, CRP, ESR, CBC with differential, comprehensive metabolic panel (including liver and renal function), and urinalysis. 1, 2

Initial Diagnostic Laboratory Tests

Essential Serologic Tests

• Anti-CCP antibodies have the highest diagnostic value with 90% specificity and 60% sensitivity, making this the most important single serologic test for RA diagnosis 2
• Rheumatoid factor (RF) should be ordered simultaneously with anti-CCP, though it has lower specificity (70%) with similar sensitivity 2
• Both tests should be ordered together at initial presentation, as 20-30% of RA cases are seronegative, and negative results do not exclude the diagnosis 2

Inflammatory Markers

• C-reactive protein (CRP) is preferred over ESR because it is more reliable, not age-dependent, and provides better correlation with disease activity 1, 2
• Both CRP and ESR should be measured at baseline for diagnostic and prognostic purposes, though 40% of RA patients may have normal values despite active disease 1, 3
• Markedly elevated CRP at diagnosis predicts severe disease with high risk of progressive joint erosions and functional deterioration 1

Baseline Hematologic and Metabolic Testing

• CBC with differential to assess for cytopenias (anemia, thrombocytopenia, leukopenia) before starting therapy and to calculate neutrophil-to-lymphocyte ratio 1, 4
• Comprehensive metabolic panel including liver transaminases (ALT, AST), serum creatinine, glucose, and uric acid levels 1, 2
• Urinalysis as part of standard initial workup to assess renal involvement 1, 2

Additional Baseline Tests When Diagnosis is Uncertain

• ANA testing only if diagnosis remains uncertain or to screen for other connective tissue diseases like lupus 1, 2
• HLA-B27 typing only if spondyloarthropathy is suspected based on axial or entheseal involvement 1, 2

Pre-Treatment Screening (Before Starting Biologics or DMARDs)

Mandatory Infectious Disease Screening

• Tuberculosis screening with tuberculin skin test or interferon-gamma release assay (IGRA preferred over TST in patients with prior BCG vaccination) regardless of risk factors 1
• Hepatitis B panel: surface antigen, surface antibody, and core antibody 1
• Hepatitis C antibody 1
• These tests must be completed before initiating any biologic therapy 1, 2

Pregnancy-Related Testing

• Pregnancy testing before starting teratogenic medications (methotrexate, leflunomide) with mandatory contraception counseling 1

Ongoing Monitoring Laboratory Tests

For Patients on Methotrexate, Leflunomide, or Sulfasalazine

• First 3 months or after dose increases: CBC, liver transaminases, and serum creatinine every 2-4 weeks 1, 4
• Months 3-6 on stable therapy: Same labs every 8-12 weeks 1, 4
• After 6 months on stable therapy: Same labs every 12 weeks 1, 4
• Do not use less frequent monitoring intervals prematurely—maintain every 2-4 week monitoring for the full first 3 months 4

For Patients on Hydroxychloroquine

• No routine laboratory monitoring required after baseline labs 1

For Patients on NSAIDs

• CBC, liver function tests, and renal function tests every 6-12 months 1

For Patients on Tocilizumab or Tofacitinib

• CBC and liver function tests within the first 1-2 months, then every 3-4 months 1
• Lipid profiles at baseline and every 6 months 1

For Patients on Biologics with TB Risk

• Annual TB testing for patients who live, travel, or work where TB exposure is likely 1

Disease Activity Monitoring

Inflammatory Markers for Disease Activity Assessment

• CRP should be repeated at each visit (every 1-3 months during active disease, every 3-6 months once remission/low disease activity achieved) to monitor disease activity 1, 4
• CRP is incorporated into DAS28-CRP and SDAI composite disease activity measures 4
• Serial CRP measurements are useful for longitudinal disease monitoring but should not be the sole determinant of treatment decisions 1

Composite Disease Activity Measures

• Use one of six validated measures: CDAI, DAS28 (ESR or CRP), SDAI, RAPID-3, PAS, or PAS-II 4
• SDAI is preferred over CDAI when CRP is elevated, as it incorporates the inflammatory marker into the composite score 1, 4
• Continue using the same measure for consistency once selected 4

Baseline Imaging

Initial Radiographic Assessment

• Bilateral hand, wrist, and foot X-rays at baseline to assess for erosions, which predict RA diagnosis and disease persistence 1, 2
• Repeat X-rays at 6 months and 12 months to monitor radiographic progression 2

Advanced Imaging When Diagnosis is Uncertain

• Ultrasound with Power Doppler is superior to clinical examination for detecting subclinical synovitis and can predict disease progression 2
• MRI with IV contrast is more sensitive than ultrasound in early stages and detects bone marrow edema (osteitis), the best single predictor of future disease progression 2

Critical Pitfalls to Avoid

• Do not delay treatment waiting for positive serology—seronegative RA accounts for 20-30% of cases and has similar prognosis 2
• Do not dismiss RA diagnosis based on normal ESR/CRP—40% of RA patients have normal inflammatory markers even in active disease 1, 3
• Do not order ANA or HLA-B27 routinely—these tests are only indicated when specific alternative diagnoses are being considered 1, 2
• Do not use less frequent monitoring for methotrexate prematurely—maintain every 2-4 week laboratory monitoring for the full first 3 months 4
• Do not forget infectious disease screening before biologics—tuberculosis and hepatitis screening are mandatory before starting any biologic therapy 1, 2