What is the appropriate diagnostic and treatment approach for a patient presenting with large joint polyarthritis?

Large Joint Polyarthritis: Diagnostic and Treatment Approach

For a patient presenting with large joint polyarthritis, immediately perform a comprehensive joint examination to identify the pattern of involvement, obtain inflammatory markers (CRP/ESR), RF, anti-CCP antibodies, and baseline radiographs, then refer to rheumatology within 6 weeks if inflammatory arthritis is suspected, as early treatment prevents irreversible joint damage. 1

Initial Clinical Assessment

The cornerstone of diagnosis is identifying definite clinical synovitis (soft, boggy joint swelling from inflammation, not hard bony enlargement) in at least one joint not better explained by another disease 1. For large joint polyarthritis specifically, focus your examination on:

• Shoulders, elbows, hips, knees, and ankles - these are the classic large joints that may be affected 2, 1
• Symmetric involvement is characteristic of rheumatoid arthritis, though large joint predominance may suggest alternative diagnoses 1
• Morning stiffness >30 minutes strongly indicates inflammatory arthritis rather than mechanical causes 1, 3
• Squeeze test of affected joints to assess for tenderness and synovitis 1

Critical pitfall: Do not dismiss inflammatory arthritis based on normal ESR/CRP alone - acute phase reactants can be normal even in active disease and are poor predictors, accounting for only 1 point in the ACR/EULAR classification criteria 1. Clinical synovitis takes precedence over laboratory values 1.

Essential Diagnostic Workup

First-Line Laboratory Tests (in order of priority):

• RF and anti-CCP antibodies - Anti-CCP has high specificity (90%) with moderate sensitivity (60%); RF has lower specificity (70%) but similar sensitivity 1. Both should be ordered simultaneously at initial presentation 1.
• CRP and ESR - CRP is preferred over ESR as it's more reliable and not age-dependent 1. Markedly elevated CRP (>10 mg/L) strongly suggests inflammatory arthritis and predicts aggressive disease with high risk of radiographic progression 1.
• Complete blood count with differential - to assess for cytopenias before starting treatment 1
• Comprehensive metabolic panel - including liver function, renal function, glucose, and urate levels 1
• Urinalysis - part of standard initial workup 1

Conditional Testing Based on Clinical Presentation:

• ANA and extractable nuclear antigens - if connective tissue disease suspected or diagnosis uncertain 1
• HLA-B27 - if spondyloarthropathy considered (axial or entheseal involvement) 1
• ASO titers and throat culture - if acute rheumatic fever suspected (migratory pattern, recent streptococcal infection) 3
• Lyme serology - if endemic area exposure and migratory arthritis 3
• Hepatitis B, C, and tuberculosis screening - required before starting any biologic therapy 1

Imaging Studies:

• Baseline bilateral hand, wrist, and foot X-rays - even for large joint predominant disease, as erosions predict RA diagnosis and disease persistence 1. Repeat at 6 and 12 months to monitor radiographic progression 1.
• X-rays of affected large joints - to assess for erosions, joint space narrowing, and exclude alternative diagnoses 4
• Ultrasound with Power Doppler - if clinical examination shows no definite synovitis but suspicion remains high; detects synovitis 2.18-fold more frequently than clinical examination and predicts disease progression 4
• 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, 4

Key Differential Diagnoses for Large Joint Polyarthritis

Seronegative Rheumatoid Arthritis

• Accounts for 20-30% of RA cases with similar prognosis to seropositive disease 1, 3
• Anti-CCP may be positive even when RF is negative 3
• Morning stiffness typically exceeds 30-60 minutes 3
• Do not delay treatment waiting for positive serology - seronegative RA is common and has similar prognosis 1

Acute Rheumatic Fever

• Most critical diagnosis to exclude due to potential cardiac complications 3
• Occurs 2-4 weeks following group A β-hemolytic streptococcal pharyngitis 3
• Migratory pattern: each joint affected for 1-4 days before symptoms migrate 3
• Look for other Jones criteria: carditis, chorea, erythema marginatum, subcutaneous nodules 3
• Dramatic response to NSAIDs within 24-48 hours is a diagnostic clue 3

Lyme Disease

• Presents with migratory joint pain weeks to months after infection 3
• Erythema migrans rash precedes arthritis in 60-80% of cases 3
• Essential to obtain history of tick exposure in endemic areas 3

Spondyloarthropathies

• Consider if axial or entheseal involvement present 1
• Psoriatic arthritis can present with polyarticular involvement including large joints 1
• HLA-B27 testing helpful if suspected 1

Crystal-Induced Arthritis

• Gout can present with polyarticular involvement 3
• Normal uric acid does not exclude gout 1
• Arthrocentesis mandatory if septic arthritis cannot be excluded 3

Disease Activity Assessment

Use validated composite measures to guide treatment decisions 1:

• Simplified Disease Activity Index (SDAI) - preferred when CRP is elevated; includes tender joint count (28 joints), swollen joint count (28 joints), patient global assessment, evaluator global assessment, and CRP 1

  • Remission: SDAI ≤3.3
  • Low disease activity: SDAI ≤11
  • Moderate: SDAI ≤26
  • High: >26

• Clinical Disease Activity Index (CDAI) - use when CRP is normal or near-normal; does not incorporate acute phase reactants 1

  • Remission: CDAI ≤2.8
  • Low disease activity: CDAI ≤10

• Perform 28-joint count examination assessing PIPs, MCPs, wrists, elbows, shoulders, and knees for tenderness and swelling 1

Initial Treatment Strategy (If RA Confirmed)

Start methotrexate 15 mg weekly immediately as first-line DMARD, without delaying for complete serologic workup, to prevent irreversible joint damage. 1, 5 Plan to escalate to 20-25 mg weekly 1.

Treatment Algorithm:

1. Methotrexate monotherapy - anchor drug for RA, indicated for severe active RA with insufficient response to NSAIDs 5
2. Short-term low-dose prednisone (10-20 mg daily) - as bridge therapy while awaiting DMARD effect 1
3. Reassess disease activity every 4-6 weeks using SDAI 1
4. If inadequate response after 3 months - consider triple DMARD therapy or adding a biologic agent (TNF inhibitor) 1

Target of Treatment:

• Primary target is remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 1
• Repeat inflammatory markers (CRP/ESR) at each visit to monitor disease activity 1

Non-Pharmacologic Interventions:

• Occupational therapy for joint protection education, assistive devices, and splinting 1
• Dynamic exercise program incorporating aerobic exercise and progressive resistance training 1
• Tobacco cessation - smoking is a modifiable predictor of adverse outcomes 1

Critical Pitfalls to Avoid

• Do not delay referral - refer to rheumatology within 6 weeks of symptom onset if inflammatory arthritis suspected 1
• Do not start corticosteroids before establishing diagnosis - they can mask symptoms and confound workup 3
• Do not dismiss diagnosis based on normal inflammatory markers - ESR/CRP are poor predictors and can be normal in active disease 1
• Do not use preserved methotrexate formulation for high-dose therapy - contains benzyl alcohol which can cause fatal "gasping syndrome" in neonates 5
• Avoid NSAIDs initially if acute rheumatic fever in differential - dramatic response is a diagnostic clue 3
• If septic arthritis cannot be excluded, arthrocentesis is mandatory before initiating any treatment 3

Monitoring and Follow-up

• Serial rheumatologic examinations and inflammatory markers every 4-6 weeks after treatment initiation 1
• Repeat hand, wrist, and foot X-rays at 6 months and 12 months to monitor radiographic progression 1
• Monitor for methotrexate toxicity - hepatic, bone marrow, and renal toxicity increase with age 5
• Screen for hepatitis B, C, and tuberculosis before starting biologic agents 1