What laboratory and imaging tests should be ordered to diagnose arthritis?

Laboratory and Imaging Tests for Arthritis Diagnosis

Order rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), ESR, CRP, complete blood count with differential, comprehensive metabolic panel, and bilateral hand/wrist/foot X-rays as the initial diagnostic workup for suspected inflammatory arthritis. 1

Essential Laboratory Tests

First-Line Serologic Testing

• RF and ACPA testing should be ordered simultaneously at initial presentation, as these are the cornerstone autoantibody tests for rheumatoid arthritis diagnosis 1
• ACPA has high specificity (90%) with moderate sensitivity (60%), making it the strongest predictor of RA (OR 13.8) 1
• RF has lower specificity (70%) with similar sensitivity to ACPA, but negative RF does not exclude RA—seronegative RA accounts for 20-30% of cases 1

Inflammatory Markers

• CRP is preferred over ESR as it is more reliable, not age-dependent, and provides a simple, validated, reproducible test 1
• Both ESR and CRP should be measured at baseline for diagnostic and prognostic purposes, though CRP is superior for ongoing monitoring 1, 2
• Markedly elevated inflammatory markers (CRP >10 mg/L, ESR >30 mm/hr) strongly suggest inflammatory arthritis, though normal values do not exclude it 1

Baseline Safety Panel

• Complete blood count with differential to assess for cytopenias before starting disease-modifying antirheumatic drugs (DMARDs) 1
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and urate levels is required before initiating methotrexate 1
• Urinalysis as part of the standard initial workup 1

Conditional Testing Based on Clinical Suspicion

• Antinuclear antibodies (ANA) should be ordered if diagnosis remains uncertain to screen for other connective tissue diseases like systemic lupus erythematosus 1, 2
• HLA-B27 typing should be considered if spondyloarthropathy is suspected (axial or entheseal involvement) 1, 2
• Hepatitis B, Hepatitis C, and tuberculosis screening before starting any biologic therapy 1, 3

Imaging Studies

Initial Imaging

• Conventional radiography (X-rays) of hands, wrists, and feet bilaterally should be obtained at initial presentation as the standard investigation to assess for erosions 1
• The presence of erosions on baseline radiographs is highly predictive for RA diagnosis and disease persistence 1
• Radiographic hallmarks include periarticular osteopenia, uniform joint space narrowing, and osseous erosions 1

Advanced Imaging When Diagnosis is Uncertain

• Ultrasound with Power Doppler is superior to clinical examination for detecting inflammation and structural damage, detecting synovitis 2.18-fold more frequently than clinical examination 4
• Power Doppler ultrasound is particularly useful when patients with early arthritis do not meet the 2010 ACR/EULAR criteria, with OR 9.9 if one joint is involved and 48.7 if more than three joints are involved 4
• 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
• MRI bone marrow edema is a strong independent predictor of subsequent radiographic progression in early RA (coefficient 0.75, p<0.001) 4
• The presence of bone marrow edema or both synovitis and erosion on MRI increases likelihood of developing RA (positive likelihood ratio 4.5 and 4.8, respectively) 4

Diagnostic Algorithm

Step 1: Clinical Assessment

• Identify definite clinical synovitis in at least one joint not better explained by another disease 1
• Assess for symmetric involvement of small joints (MCPs, PIPs, wrists, MTPs) 1
• Document morning stiffness duration (>30 minutes suggests inflammatory arthritis) 1

Step 2: Apply 2010 ACR/EULAR Classification Criteria

• Joint involvement scoring: 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 1
• Serology scoring: negative RF and ACPA = 0 points, low positive RF or ACPA = 2 points, high positive RF or ACPA = 3 points 1
• Acute phase reactants: normal CRP and ESR = 0 points, abnormal CRP or ESR = 1 point 1
• Duration of symptoms: <6 weeks = 0 points, ≥6 weeks = 1 point 1
• Score ≥6/10 indicates definite RA 1

Step 3: Advanced Imaging if Score <6/10 but High Clinical Suspicion

• Order ultrasound with Power Doppler to detect subclinical synovitis 1
• Consider MRI if ultrasound is negative but clinical suspicion remains high 1

Critical Pitfalls to Avoid

• Do not delay treatment waiting for positive serology—seronegative RA is common (20-30% of cases) and has similar prognosis 1
• Do not dismiss the diagnosis based on normal ESR/CRP—acute phase reactants are poor predictors and can be normal even in active disease 1
• Do not rely solely on RF testing—ACPA is more specific and should always be ordered simultaneously 1
• Do not overlook the need for repeat testing—serological markers may evolve over time, and inflammatory markers should be repeated every 4-6 weeks after treatment initiation 1, 2

Monitoring After Diagnosis

• Repeat hand, wrist, and foot X-rays at 6 months and 12 months to monitor radiographic progression 1
• Repeat inflammatory markers (CRP and ESR) at each visit to monitor disease activity 1
• Use composite disease activity measures (SDAI or CDAI) every 4-6 weeks to guide treatment decisions, with target of remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 1