What is the appropriate workup for a patient with suspected arthritis?

Arthritis Workup

Initial Clinical Assessment

Begin with a focused history and physical examination to distinguish inflammatory from non-inflammatory arthritis, as this fundamentally determines the diagnostic pathway and urgency of workup. 1, 2

Key Historical Features to Document

• Duration of symptoms: ≥6 weeks predicts persistent inflammatory arthritis 1
• Morning stiffness duration: >30 minutes to 1 hour strongly suggests inflammatory arthritis 1, 2, 3
• Pattern of joint involvement: Small joints (MCPs, PIPs, wrists, MTPs) versus large joints; symmetric versus asymmetric 2, 3
• Number of joints involved: ≥3 joints predicts persistence 1
• Response to medications: Improvement with NSAIDs/corticosteroids (not opioids) suggests inflammatory process 1
• Systemic symptoms: Fatigue, fever, weight loss, rash, dry eyes/mouth, Raynaud's phenomenon 4, 3

Physical Examination Priorities

• Complete 28-joint count examination: Assess PIPs, MCPs, wrists, elbows, shoulders, and knees for tenderness and swelling 2
• Distinguish soft tissue swelling from bony enlargement: Inflammatory arthritis produces soft, boggy joint swelling from synovitis; osteoarthritis causes hard, bony enlargement 2
• Squeeze test of MCPs and MTPs: Positive test indicates clinical synovitis 2
• Spine examination: Assess for axial involvement if spondyloarthropathy suspected 1
• Skin examination: Look for psoriatic plaques, rheumatoid nodules, vasculitic lesions 2, 4

Essential Laboratory Workup

First-Line Tests (Order Immediately)

• Rheumatoid factor (RF): Sensitivity ~60%, specificity ~70% for RA 2, 5
• Anti-citrullinated protein antibodies (ACPA/anti-CCP): Sensitivity ~60%, specificity ~90-96% for RA 1, 2, 6
• C-reactive protein (CRP): Preferred over ESR as it is more reliable and not age-dependent 2
• Erythrocyte sedimentation rate (ESR): Baseline inflammatory marker assessment 1, 2
• Complete blood count with differential: Assess for cytopenias before starting treatment 2, 4
• Comprehensive metabolic panel: Including liver function, renal function, glucose, and urate levels 2, 4
• Urinalysis: Part of standard initial workup 1, 2

Conditional Testing Based on Clinical Presentation

• Antinuclear antibodies (ANA): If diagnosis uncertain or to screen for other connective tissue diseases (SLE, Sjögren's) 1, 2, 4
• HLA-B27: If symptoms suggest spondyloarthropathy, reactive arthritis, or affect the spine 1, 2
• Anti-SSA/Ro and anti-SSB/La: If Sjögren's syndrome suspected (dry eyes, dry mouth) 4
• Hepatitis B, C, and tuberculosis screening: Required before initiating biologic therapy 2, 5

Imaging Studies

Initial Imaging (Obtain at Baseline)

Plain radiographs of bilateral hands, wrists, and feet are essential baseline imaging to assess for erosions, which predict RA diagnosis and disease persistence. 1, 2, 6

• Radiographic features of inflammatory arthritis: Periarticular osteopenia, uniform joint space narrowing, marginal erosions 1, 2
• Radiographic features of osteoarthritis: Asymmetric joint space narrowing, osteophytes, subchondral sclerosis 2

Advanced Imaging (When Diagnosis Uncertain)

• Ultrasound with Power Doppler: Superior to clinical examination for detecting subclinical synovitis; useful when patients don't meet 2010 ACR/EULAR criteria 1, 2
• MRI with IV contrast: More sensitive than ultrasound in early stages; detects bone marrow edema (osteitis), which is the best single predictor of future disease progression 1, 2

Do not delay joint aspiration to obtain advanced imaging if septic arthritis is suspected. 1

Diagnostic Algorithm

Step 1: Confirm Inflammatory Arthritis

If morning stiffness >30 minutes, positive squeeze test, soft tissue swelling, and symmetric small joint involvement → Refer to rheumatology within 6 weeks. 2

Step 2: Apply 2010 ACR/EULAR Classification Criteria

Score ≥6/10 points indicates definite RA classification: 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 ACPA = 0 points; low positive RF or ACPA = 2 points; high positive RF or ACPA = 3 points 2
• Acute phase reactants: Normal CRP and ESR = 0 points; abnormal CRP or ESR = 1 point 2
• Duration of symptoms: <6 weeks = 0 points; ≥6 weeks = 1 point 2

Step 3: Consider Key Differential Diagnoses

• Psoriatic arthritis: Polyarticular involvement, elevated CRP, negative RF/ACPA; examine for psoriatic plaques or nail changes 2
• Reactive arthritis: Recent conjunctivitis, urethritis, or GI/GU infection; consider HLA-B27 testing 2
• Polymyalgia rheumatica: Proximal muscle pain without true weakness, normal CK, absence of definite synovitis 2
• Erosive osteoarthritis: Typically affects DIP joints (which RA spares); look for proliferative marginal erosions on X-ray 6
• Septic arthritis: Aspirate joint if suspected; analyze cell count, Gram stain, cultures, and crystal analysis 1

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 diagnosis based on normal ESR/CRP: Acute phase reactants can be normal even in active inflammatory disease 1, 2
• Do not ignore DIP joint involvement: This pattern suggests erosive osteoarthritis or psoriatic arthritis rather than RA 2, 6
• Do not delay joint aspiration for imaging if infection suspected: Aspiration should not be delayed to obtain advanced imaging studies 1

Monitoring After Diagnosis

• Repeat inflammatory markers (CRP, ESR) every 4-6 weeks after treatment initiation 1, 2
• Repeat hand, wrist, and foot X-rays at 6 and 12 months to monitor radiographic progression 2
• Use composite disease activity measures (SDAI or CDAI) to guide treatment decisions, with target of remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 2