What initial tests and investigations are recommended for a patient presenting with polyarthritis?

Initial Testing for Polyarthritis

Order rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA/anti-CCP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complete blood count with differential, comprehensive metabolic panel, and bilateral hand, wrist, and foot radiographs immediately for any patient presenting with polyarthritis. 1

Essential First-Line Laboratory Tests

Autoantibody Panel

• RF and ACPA testing must be ordered simultaneously at initial presentation—these are the cornerstone serologic tests with ACPA having 90% specificity and 60% sensitivity, while RF has 70% specificity with similar sensitivity 1
• Both tests should be performed together because seronegative RA (negative RF and ACPA) accounts for 20-30% of cases and does not exclude the diagnosis 1
• Low-positive results score 2 points and high-positive results score 3 points in the 2010 ACR/EULAR classification criteria 1

Inflammatory Markers

• CRP is preferred over ESR because it is more reliable, not age-dependent, and provides superior disease activity assessment 1
• Both ESR and CRP should be measured at baseline for diagnostic and prognostic purposes, with abnormal values contributing 1 point to the classification score 2, 1
• Elevated CRP, especially at high levels, has diagnostic value for predicting rheumatoid arthritis and indicates active inflammatory disease 2, 1
• Normal inflammatory markers do not exclude inflammatory arthritis—ESR and CRP are poor predictors and can be normal even in active disease 1

Baseline Safety Laboratory Panel

• Complete blood count with differential is required to detect cytopenias before starting DMARDs and to calculate disease activity scores 1
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and urate levels is mandatory prior to methotrexate therapy 2, 1
• Urinalysis is part of the standard initial workup for undifferentiated peripheral inflammatory arthritis 2, 1

Essential Imaging Studies

Baseline Radiographs

• Bilateral hand, wrist, and foot X-rays must be obtained at presentation to identify periarticular osteopenia, uniform joint space narrowing, and marginal erosions 1
• The presence of erosions on baseline radiographs is highly predictive of RA diagnosis and disease persistence 1, 3
• Conventional radiography remains the standard for initial imaging evaluation despite MRI's higher sensitivity 1, 4
• Repeat radiographs at 6 months and 12 months to monitor radiographic progression 1

Advanced Imaging (When Diagnosis Uncertain)

• Ultrasound with Power Doppler should be considered when clinical examination shows no definite synovitis but suspicion remains high—it is 75% more accurate than physical examination alone in detecting subclinical synovitis 1
• 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
• Power Doppler ultrasound is particularly useful when patients do not meet the 2010 ACR/EULAR criteria but clinical suspicion persists 1

Conditional Testing Based on Clinical Presentation

When Diagnosis Remains Uncertain

• Antinuclear antibodies (ANA) should be ordered if diagnosis is uncertain to screen for other connective tissue diseases like systemic lupus erythematosus 2, 1
• If ANA is positive, order anti-dsDNA and extractable nuclear antigen (ENA) panels to exclude SLE, though symmetric polyarthritis with elevated CRP is more characteristic of RA 1

When Spondyloarthropathy Suspected

• HLA-B27 typing should be considered if clinical features suggest axial involvement, enthesitis, reactive arthritis, or spondyloarthropathy 2, 1
• ESR has limited utility (50% sensitivity, 80% specificity) for screening spondyloarthropathy, and inflammatory back pain with HLA-B27 are superior screening parameters 1

Before Initiating Biologic Therapy

• Hepatitis B, hepatitis C, and tuberculosis screening is mandatory before starting any biologic DMARD therapy 1

Critical Clinical Assessment Points

Joint Examination

• Perform a 28-joint count assessment examining proximal interphalangeal joints (PIPs), metacarpophalangeal joints (MCPs), wrists, elbows, shoulders, and knees for tenderness and swelling 1
• The squeeze test of MCPs and metatarsophalangeal joints (MTPs) helps assess for clinical synovitis—pain on compression indicates inflammatory arthritis 1
• Document the number and pattern of involved joints: 1-3 small joints = 2 points, 4-10 small joints = 3 points, >10 joints = 5 points 1

Clinical Features Predictive of RA

• Morning stiffness ≥30 minutes (ideally ≥1 hour) strongly indicates inflammatory arthritis and distinguishes it from osteoarthritis 1, 5
• Advanced age, female gender, greater morning stiffness, higher number of tender and swollen joints, involvement of small joints of hands and feet, and symmetric involvement predict progression to RA 2, 3
• Duration of symptoms ≥6 weeks contributes 1 point to the classification score 1

Algorithmic Approach to Diagnosis

Step 1: Confirm Clinical Synovitis

• 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
• Look for soft, boggy joint swelling from synovitis rather than hard, bony enlargement from osteophytes 1

Step 2: Apply 2010 ACR/EULAR Classification Criteria

• Calculate a score based on four domains: joint involvement (0-5 points), serology (0-3 points), acute-phase reactants (0-1 point), and symptom duration (0-1 point) 1
• A score ≥6/10 confirms definite RA classification 1

Step 3: Consider Advanced Imaging if Score <6

• If the score is <6 but clinical suspicion remains high, order ultrasound with Power Doppler or MRI to detect subclinical synovitis 1

Step 4: Urgent Rheumatology Referral

• Refer to rheumatology within 6 weeks of symptom onset if inflammatory arthritis is suspected, as early treatment prevents irreversible joint damage 1

Common Diagnostic Pitfalls to Avoid

• Do not delay treatment waiting for positive serology—seronegative RA is common (20-30% of cases) and has similar prognosis to seropositive disease 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 2, 1
• Do not rely on autoantibody positivity alone—clinical context with definite synovitis takes precedence over serologic findings 1
• Anemia and azotemia can artificially elevate ESR independent of inflammatory activity 3
• Serum uric acid may be normal during acute gout flare, so normal urate does not exclude crystal arthropathy 3

Monitoring After Initial Diagnosis

• Repeat CRP and ESR every 4-6 weeks after treatment initiation to monitor disease activity and treatment response 1, 5
• Use composite disease activity measures (SDAI or CDAI) at each visit, with a target of remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 1
• Serial inflammatory markers are useful for longitudinal monitoring but should not be the sole determinant of treatment decisions 1