Laboratory Workup for Rheumatoid Arthritis
Test for both Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP) in all patients with suspected RA presenting with synovitis, along with acute-phase reactants (ESR and CRP), complete blood count, and baseline renal and hepatic function tests. 1, 2
Essential Diagnostic Laboratory Tests
Autoantibody Testing
- Rheumatoid Factor (RF) should be measured in all patients with suspected RA who present with synovitis, recognizing that 30-40% of RA patients may be RF-negative 1, 3
- Anti-CCP antibodies should be measured, particularly in RF-negative patients and when combination therapy is being considered 1, 2
- Anti-CCP antibodies have significant prognostic value; high levels and dual positivity with RF are associated with higher risk of persistent and erosive disease 1
Inflammatory Markers
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should be obtained to assess systemic inflammation 4
- C-reactive protein correlates well with clinical assessment and radiographic changes 5
- Approximately 40% of RA patients may have normal ESR or CRP, so normal values do not exclude the diagnosis 3
Baseline Laboratory Assessment
- Complete blood count with differential to identify anemia, thrombocytosis, or other hematologic abnormalities associated with RA 4
- Renal function tests (creatinine, BUN) as baseline before initiating disease-modifying antirheumatic drugs 4
- Hepatic function tests (AST, ALT, albumin) as baseline before starting DMARDs, particularly methotrexate 4
Critical Clinical Pearls
When to Refer Despite Negative Labs
- Urgently refer patients with suspected persistent synovitis for specialist evaluation, even with normal acute-phase reactants or negative RF, especially when small joints of hands/feet are affected 1, 2
- Multiple joint involvement or symptoms persisting ≥3 months warrant urgent rheumatology referral regardless of laboratory results 2
Understanding Laboratory Limitations
- More than 30% of RA patients have negative tests for RF or anti-CCP antibodies 3
- Laboratory measures cannot serve as a gold standard for diagnosis in all individual patients 3
- The diagnosis of RA is clinical, supported but not defined by laboratory findings 4
Additional Testing for Patients Starting Biologic Therapy
- Hepatitis B screening before initiating biologic agents 4
- Hepatitis C screening before initiating biologic agents 4
- Tuberculosis testing (typically interferon-gamma release assay or tuberculin skin test) before initiating biologic agents 4