Laboratory Tests are Essential for Confirming Rheumatoid Arthritis in Symptomatic Patients
Laboratory testing is necessary to confirm a diagnosis of rheumatoid arthritis in symptomatic patients, with rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA/anti-CCP) being the essential serological markers. 1
Key Laboratory Tests for RA Diagnosis
Essential Tests:
Rheumatoid Factor (RF)
Anti-CCP (Anti-Cyclic Citrullinated Peptide) Antibodies
Inflammatory Markers
- Erythrocyte Sedimentation Rate (ESR)
- C-Reactive Protein (CRP)
- Help assess disease activity 1
Diagnostic Value of Combined Testing
- When RF and anti-CCP are used together, specificity increases to 99.6% 3
- Combined detection of RF, anti-CCP, CRP, and ESR provides 89.5% accuracy in diagnosis 2
Diagnostic Algorithm for Suspected RA
Initial Assessment:
- Evaluate for persistent joint symptoms (>6 weeks)
- Check for functional limitations affecting daily activities
- Assess joint distribution pattern (symmetrical small joint involvement is typical for RA)
Laboratory Testing:
- Order RF, anti-CCP, ESR, and CRP tests
- Positive RF with inflammatory joint symptoms warrants referral to rheumatology 1
Interpretation of Results:
- Positive anti-CCP (>50 units): Highly specific for RA (97.8% specificity) 3
- Positive RF with negative anti-CCP: Consider other diagnoses
- Negative RF with positive anti-CCP: Likely early or seronegative RA
- Both positive: Strong evidence for RA (specificity 99.6%) 3
- Both negative: Does not rule out RA (consider clinical presentation)
Additional Considerations:
- Anti-CCP positive patients often have more severe disease and higher risk of erosive arthritis
- Seronegative RA (negative RF and anti-CCP) still requires clinical diagnosis
Important Caveats
- False Positives: RF can be positive in other conditions including Sjögren's syndrome (73.3%), chronic hepatitis (24.7%), and SLE (18.3%) 4
- Early Disease: Laboratory tests may be negative in early disease; clinical suspicion should prompt referral to rheumatology regardless
- Differential Diagnosis: Consider psoriatic arthritis (may target DIPJs or affect just one ray), gout (which may superimpose on pre-existing HOA), and other inflammatory arthritides 5
Imaging Considerations
- Plain radiographs provide the gold standard for morphological assessment of hand arthritis 5
- A posteroanterior radiograph of both hands on a single film is adequate for diagnosis 5
- Ultrasound may be useful when there is doubt about inflammatory activity 1
Laboratory testing is not just helpful but necessary for confirming RA diagnosis, monitoring disease activity, and guiding treatment decisions. The combination of RF and anti-CCP testing provides the highest diagnostic accuracy and should be ordered in all patients with suspected RA.