What are the next lab orders for an adult patient with an elevated rheumatoid factor level, suspected of having rheumatoid arthritis, and possibly a history of autoimmune disorders?

Next Laboratory Orders for Elevated Rheumatoid Factor

Order anti-CCP antibodies, CRP, ESR, CBC with differential, comprehensive metabolic panel, and baseline bilateral hand/wrist/foot X-rays immediately to confirm rheumatoid arthritis diagnosis and establish baseline disease activity. 1

Essential Confirmatory Serology

• Anti-citrullinated protein antibodies (anti-CCP/ACPA) must be ordered as they have high specificity (90%) with moderate sensitivity (60%) for rheumatoid arthritis, and when combined with positive RF, significantly increase diagnostic certainty 1, 2
• Both RF and anti-CCP should be interpreted together, as dual positivity strongly predicts rheumatoid arthritis and aggressive disease course 1

Inflammatory Markers for Disease Activity

• C-reactive protein (CRP) is preferred over ESR as it is more reliable, not age-dependent, and provides better monitoring of disease activity 3, 1
• ESR should also be measured at baseline for comprehensive inflammatory marker assessment, though CRP will be used for ongoing monitoring 1
• These markers establish baseline disease activity and will be repeated every 4-6 weeks after treatment initiation 1

Complete Blood Count and Metabolic Assessment

• CBC with differential is essential to assess for cytopenias (anemia, thrombocytopenia, leukopenia) commonly seen in rheumatoid arthritis and to establish baseline before starting disease-modifying therapy 3, 1
• Comprehensive metabolic panel including liver function tests, renal function (creatinine/eGFR), glucose, and uric acid levels is required for baseline assessment and to ensure safe medication initiation 3, 1
• Urinalysis should be performed as part of the standard initial workup to assess for renal involvement 3, 1

Baseline Imaging Studies

• Bilateral hand, wrist, and foot X-rays are mandatory at initial presentation as the presence of erosions on baseline radiographs is highly predictive for rheumatoid arthritis diagnosis and disease persistence 1
• These baseline films will be repeated at 6 and 12 months to monitor radiographic progression 1

Additional Screening Tests

• ANA testing should be ordered if the diagnosis remains uncertain to screen for other connective tissue diseases such as systemic lupus erythematosus or mixed connective tissue disease 4, 1
• HLA-B27 typing may be considered if there is axial involvement, entheseal involvement, or spondyloarthropathy is being considered in the differential diagnosis 1

Pre-Treatment Infectious Disease Screening

• Hepatitis B surface antigen, surface antibody, core antibody, and hepatitis C antibody must be tested before starting any biologic therapy, as required by treatment guidelines 3, 2
• Tuberculosis screening with either tuberculin skin test or interferon-gamma release assay (IGRA preferred if prior BCG vaccination) should be performed before initiating biologic agents 3

Critical Clinical Pearls

• Do not delay treatment or dismiss rheumatoid arthritis diagnosis based solely on normal inflammatory markers, as approximately 40% of patients with active rheumatoid arthritis have normal ESR or CRP at presentation 5, 6
• Seronegative rheumatoid arthritis (negative RF and anti-CCP) accounts for 20-30% of cases and has similar prognosis to seropositive disease, so negative serology does not exclude the diagnosis 1
• RF positivity occurs in approximately 15% of first-degree relatives of rheumatoid arthritis patients and in other conditions (hepatitis C, cryoglobulinemia, Sjögren's syndrome), so clinical context is essential 1
• Referral to rheumatology should occur within 6 weeks of symptom onset if inflammatory arthritis is suspected, as early treatment with disease-modifying antirheumatic drugs prevents irreversible joint damage 1

Clinical Assessment to Accompany Laboratory Orders

• Perform a detailed 28-joint count examination assessing proximal interphalangeal joints (PIPs), metacarpophalangeal joints (MCPs), wrists, elbows, shoulders, and knees for tenderness and swelling 1
• Document duration of morning stiffness (>30 minutes suggests inflammatory arthritis), number and pattern of involved joints, and presence of symmetric small joint involvement 1, 2
• Calculate baseline disease activity using SDAI or CDAI to establish treatment targets of remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 1