What are the initial steps to diagnose and treat a patient suspected of having rheumatoid arthritis (RA)?

Testing for Rheumatoid Arthritis

For any patient with suspected rheumatoid arthritis, immediately order rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP), CRP, ESR, complete blood count with differential, comprehensive metabolic panel, and bilateral hand, wrist, and foot X-rays—do not delay treatment waiting for results if clinical synovitis is present. 1, 2, 3

Essential Laboratory Tests

First-Line Serologic Testing

• Order both RF and anti-CCP antibodies simultaneously at initial presentation, as these are the cornerstone autoantibody tests for RA diagnosis and prognosis 1, 2
• Anti-CCP has superior diagnostic value with 90% specificity and 60% sensitivity, compared to RF which has 70% specificity with similar sensitivity 1, 3, 4
• High-positive RF or anti-CCP carries more diagnostic weight (3 points) than low-positive results (2 points) in the 2010 ACR/EULAR Classification Criteria 1
• The presence of RF and/or anti-CCP significantly increases the probability of developing RA, with RF positivity predicting more aggressive disease and erosive progression 1, 2

Inflammatory Markers

• CRP is preferred over ESR as it is more reliable, not age-dependent, and provides better correlation with clinical assessment and radiographic changes 1, 3, 5
• Both ESR and CRP should be measured at baseline for diagnostic and prognostic purposes, though normal values do not exclude RA 1, 2
• Persistently elevated CRP at diagnosis predicts severe disease with high risk of progressive joint erosions and functional deterioration 2

Additional Baseline Testing

• Complete blood count with differential to assess for cytopenias before starting treatment 1, 2, 3
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and urate levels 1, 2
• Urinalysis as part of the standard initial workup 1, 2, 3
• Hepatitis B, Hepatitis C, and tuberculosis screening before starting any biologic therapy 1, 2, 4

Imaging Studies

Baseline Radiography

• Obtain bilateral hand, wrist, and foot X-rays at initial presentation to assess for erosions, periarticular osteopenia, and uniform joint space narrowing 1, 2, 3
• The presence of erosions on baseline radiographs is highly predictive for RA diagnosis and disease persistence 1, 2, 3
• Repeat X-rays at 6 and 12 months to monitor radiographic progression 2, 3

Advanced Imaging When Diagnosis Uncertain

• Ultrasound with Power Doppler is superior to clinical examination for detecting subclinical synovitis and is 75% more accurate than physical examination alone 2, 3
• MRI with IV contrast is the most sensitive imaging modality in early stages, detecting bone marrow edema (osteitis) which is the best single predictor of future disease progression and functional deterioration 2, 3
• Consider ultrasound or MRI if clinical examination shows no definite synovitis but suspicion remains high, as these can detect inflammation that predicts disease progression 1, 2, 3

Clinical Assessment

Key Physical Examination Findings

• Identify definite clinical synovitis (soft tissue swelling) in at least one joint not better explained by another disease—this is the cornerstone of RA diagnosis 1, 2, 3
• Look for symmetric involvement of small joints, particularly MCPs, PIPs, wrists, and MTPs, with DIPs typically spared 2, 3, 5
• Perform a squeeze test of MCPs and MTPs to assess for tenderness, which is characteristic of inflammatory arthritis 2, 3
• Document morning stiffness duration >30 minutes, often lasting hours, which is characteristic of RA 3, 5, 6

Diagnostic Scoring System

• Apply the 2010 ACR/EULAR Classification Criteria requiring a score of ≥6/10 points based on: 1, 2
  • Joint involvement: 1 large joint = 0 points; 2-10 large joints = 1 point; 1-3 small joints = 2 points; 4-10 small joints = 3 points; >10 joints = 5 points 2
  • Serology: Negative RF and anti-CCP = 0 points; low positive = 2 points; high positive = 3 points 2
  • Acute phase reactants: Normal CRP and ESR = 0 points; abnormal = 1 point 2
  • Duration of symptoms: <6 weeks = 0 points; ≥6 weeks = 1 point 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 the diagnosis based on normal ESR/CRP—inflammatory markers can be normal even in active disease and are poor predictors of RA 1, 2
• Do not limit HRCT to symptomatic patients only—any RA patient with risk factors for interstitial lung disease or who develops respiratory symptoms, impaired lung function, or crackles on chest auscultation should be referred for HRCT 7
• Refer urgently to rheumatology within 6 weeks of symptom onset if inflammatory arthritis is suspected, as early treatment prevents irreversible joint damage 1, 2, 3

Conditional Testing

• Order ANA if diagnosis remains uncertain to screen for other connective tissue diseases like lupus 1, 2
• Consider HLA-B27 typing if spondyloarthropathy is suspected (axial or entheseal involvement) 1, 2
• Repeat ESR and CRP every 4-6 weeks after treatment initiation to monitor disease activity and treatment response 1, 2