How do I test for rheumatoid arthritis?

How to Test for Rheumatoid Arthritis

Order rheumatoid factor (RF) and anti-CCP antibodies simultaneously in every patient with joint swelling, obtain baseline CRP (preferred over ESR), and get plain radiographs of hands, wrists, and feet bilaterally—these three tests form the diagnostic cornerstone. 1

Essential Serologic Testing

• Both RF and anti-CCP must be ordered together at initial presentation, as they are the cornerstone autoantibody tests for RA diagnosis and provide complementary diagnostic information 1
• Anti-CCP has high specificity (90%) with moderate sensitivity (60%), making it especially valuable for confirming RA when positive 1
• RF shows sensitivity of 60-80% and specificity of ~70%, rising to ~80% in longstanding disease 1
• Seronegative RA accounts for 20-30% of cases—negative RF does not exclude RA, so clinical synovitis takes precedence over serology 1, 2
• High-positive RF or ACPA contributes 3 points to the 2010 ACR/EULAR classification criteria, while low-positive results contribute 2 points 1

Inflammatory Marker Assessment

• Measure CRP at baseline for both diagnostic and prognostic purposes—it is preferred over ESR because it is more reliable, simpler, and not age-dependent 1
• ESR should also be obtained at baseline as it contributes to the 2010 ACR/EULAR classification criteria 1
• Do not dismiss RA based on normal CRP/ESR—acute phase reactants are poor predictors and can be normal even in active disease 2
• Abnormal CRP or ESR adds 1 point to the classification score 1
• Simultaneous measurement of CRP and ESR does not provide additional clinical value 1

Baseline Imaging Studies

• Obtain plain radiographs of hands, wrists, and feet bilaterally at initial presentation—these are the initial imaging modality of choice 1
• The presence of erosions on baseline X-rays predicts RA development and persistence, contributing 5 points in the classification criteria 1
• Look for periarticular osteopenia, uniform joint space narrowing, and marginal erosions on radiographs 2
• Repeat plain radiographs within 6-12 months to evaluate radiographic progression 1, 2

Advanced Imaging When Diagnosis Is Uncertain

• Consider ultrasound with Power Doppler when clinical examination is inconclusive—it is superior to clinical examination for detecting inflammation and increases detection of subclinical synovitis by approximately 75% 1, 2
• MRI with IV contrast is more sensitive than ultrasound in early stages and detects bone marrow edema (osteitis), which is the best single predictor of future disease progression and functional deterioration 1, 2
• Power Doppler ultrasound is particularly useful when patients with early arthritis do not meet the 2010 ACR/EULAR criteria 2
• Routine use of MRI or ultrasound for initial RA assessment is not recommended because evidence for diagnostic or prognostic benefit in undifferentiated arthritis is insufficient 1

Clinical Assessment Requirements

• Perform a 28-joint count examining bilateral PIPs 1-5, MCPs 1-5, wrists, elbows, shoulders, and knees for tenderness and swelling 1
• Morning stiffness lasting >30 minutes (ideally ≥1 hour) is indicative of inflammatory arthritis and distinguishes RA from osteoarthritis 1, 3, 4, 5
• Look for soft tissue swelling, not bony enlargement—inflammatory arthritis produces soft, boggy joint swelling from synovitis 2
• The MCP and MTP joint squeeze test—pain on compression—indicates synovitis and supports inflammatory arthritis 2
• Assess pain using a visual analog scale, obtain patient global assessment, and evaluate functional status with the Health Assessment Questionnaire Disability Index 1

Baseline Safety Laboratory Panel (Before Starting Treatment)

• Complete blood count with differential to assess for cytopenias before starting DMARDs 1, 2
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and urate levels—required prior to methotrexate therapy 1, 2
• Urinalysis as part of standard initial workup 1, 2
• Hepatitis B, Hepatitis C, and tuberculosis screening before starting any biologic therapy 2, 6

Additional Testing When Diagnosis Is Uncertain

• ANA testing can screen for other connective tissue diseases like lupus if the diagnosis remains uncertain 1, 2
• HLA-B27 typing should be reserved for clinical scenarios suggesting spondyloarthropathy (e.g., axial or enthesitis involvement) rather than routine RA workup 1, 2
• Synovial biopsy is not required routinely; it should be limited to persistent monoarthritis when the differential diagnosis remains unclear 1
• Genetic testing has no role in standard RA diagnosis and should not be ordered routinely 1

2010 ACR/EULAR Classification Criteria

A total score ≥6 out of 10 classifies a patient as having definite RA, provided at least one joint exhibits definite clinical synovitis not better explained by another disease 1, 2

Scoring components:

• Joint involvement (0-5 points): 1 large joint = 0; 2-10 large joints = 1; 1-3 small joints = 2; 4-10 small joints = 3; >10 joints with at least one small joint = 5 1, 2
• Serology (0-3 points): Negative RF and ACPA = 0; low-positive RF or ACPA = 2; high-positive RF or ACPA = 3 1, 2
• Acute-phase reactants (0-1 point): Normal CRP and ESR = 0; abnormal CRP or ESR = 1 1, 2
• Symptom duration: <6 weeks = 0; ≥6 weeks = 1 1, 2

Critical Pitfalls to Avoid

• Do not delay treatment waiting for positive serology—seronegative RA is common (20-30% of cases) and has similar prognosis 2
• Do not dismiss the diagnosis based on normal ESR/CRP—inflammatory markers can be normal even in active disease 1, 2
• Do not rely solely on clinical examination—imaging studies may reveal subclinical inflammation not apparent on physical exam 1, 3
• Refer to rheumatology within 6 weeks of symptom onset if inflammatory arthritis is suspected, as early treatment prevents irreversible joint damage 1, 2, 6, 7

Key Differential Diagnoses to Consider

• Psoriatic arthritis can present with polyarticular involvement and elevated CRP while remaining anti-CCP negative—examine carefully for psoriatic plaques, nail pitting, or dactylitis 2
• Reactive arthritis should be considered with recent conjunctivitis, urethritis, or GI/GU infection—HLA-B27 testing is recommended when axial or entheseal manifestations are present 2
• Polymyalgia rheumatica manifests with proximal muscle pain without true weakness, normal CK levels, and absence of definite synovitis 2
• Viral arthritis (parvovirus B19, hepatitis B/C, EBV) can produce an RA-like picture—symptoms resolving within 6 weeks suggest viral arthritis, whereas persistence beyond 6 weeks supports true RA 2