What is the initial approach to diagnosing and treating migratory polyarthritis (inflammation of multiple joints) affecting large joints?

Differential Diagnoses for Migratory Polyarthritis Affecting Large Joints

The most critical differential diagnoses for migratory polyarthritis affecting large joints are acute rheumatic fever (ARF), Lyme disease, seronegative rheumatoid arthritis, post-streptococcal reactive arthritis, viral arthritis, and familial Mediterranean fever, with ARF being the classic presentation requiring urgent evaluation to prevent cardiac complications. 1, 2

Key Clinical Features to Identify

The hallmark of migratory polyarthritis is joint pain and swelling that moves from one joint to another over days, with previous joints improving as new joints become affected, predominantly involving knees, ankles, elbows, and wrists. 1 A critical diagnostic clue is rapid improvement (within 24-48 hours) with salicylates or NSAIDs, which is characteristic of ARF but can also mask the migratory pattern if given prematurely. 1, 2

• Each joint is typically affected for 1-4 days before symptoms migrate to another joint 1, 3
• The condition is self-limited, lasting approximately 4 weeks even without therapy 1
• No long-term joint deformity occurs, distinguishing it from chronic inflammatory arthritides 1
• Morning stiffness may be present but is typically mild and brief (less than 30-60 minutes), unlike rheumatoid arthritis 1, 2

Primary Differential Diagnoses

Acute Rheumatic Fever (ARF)

This is the most critical diagnosis to exclude due to potential cardiac complications. 1, 2

• Occurs 2-4 weeks following group A β-hemolytic streptococcal pharyngitis 1, 2
• Look for other Jones criteria manifestations: carditis (most serious), chorea, erythema marginatum, subcutaneous nodules 1
• More common in moderate to high-risk populations (developing countries, indigenous populations, lower socioeconomic groups) 1
• Obtain ASO titers and throat culture to document preceding streptococcal infection 2

Lyme Disease

• Presents with migratory joint pain and swelling, often weeks to months after initial infection 1
• Erythema migrans rash precedes arthritis in 60-80% of cases 1
• Essential to obtain history of tick exposure in endemic areas (northeastern and upper midwestern United States) 1
• Serologic testing (ELISA followed by Western blot if positive) confirms diagnosis 1

Seronegative Rheumatoid Arthritis

RF-negative RA accounts for 20-30% of all RA cases and has similar prognosis to seropositive disease. 2

• Can present with atypical migratory pattern, particularly in early disease 4
• Anti-CCP antibodies are critical - they may be positive even when RF is negative and have high specificity for RA 2, 4
• Morning stiffness typically exceeds 30-60 minutes, distinguishing it from mechanical causes 2
• Unlike ARF, symptoms do not respond dramatically to NSAIDs within 24-48 hours 1

Post-Streptococcal Reactive Arthritis

• Similar to ARF but does not fulfill all Jones criteria 1
• May have more prolonged arthritis (weeks to months) compared to ARF 2
• Less responsive to salicylates/NSAIDs than classic ARF 2
• Cardiac involvement is rare but should still be monitored 2

Viral Arthritis

Multiple viral infections cause migratory polyarthralgia and are typically self-limited. 2

• Parvovirus B19: Often presents with symmetric polyarthritis mimicking early RA, may have "slapped cheek" rash 2
• Hepatitis B and C: Arthritis may precede jaundice; check hepatitis serologies 2
• HIV: Can present with various rheumatic manifestations; obtain HIV serology 2
• Rubella, EBV, CMV: Less common but should be considered based on clinical context 2

Familial Mediterranean Fever (FMF)

• Consider in patients of Mediterranean, Middle Eastern, or North African descent 3
• Presents with recurrent episodes of migratory arthritis lasting 12-72 hours 3
• Associated with fever and serositis (peritonitis, pleuritis) 3
• Genetic testing for MEFV mutations confirms diagnosis 3

Drug-Induced Migratory Polyarthritis

• Clopidogrel is a recognized cause, typically occurring 2-7 days after initiation 5
• Symptoms completely resolve after discontinuing the offending medication 5
• Other medications to consider: hydralazine, procainamide, isoniazid 5

Essential Diagnostic Workup

Laboratory Evaluation (in order of priority)

• ASO titers and throat culture if ARF suspected 2
• Anti-CCP antibodies - high specificity for RA even when RF negative 2, 4
• ESR and CRP to assess inflammatory burden 2, 4
• Complete blood count with differential 2
• Comprehensive metabolic panel to assess renal and hepatic function 2
• RF and ANA - negative results do not exclude inflammatory arthritis 2, 4
• Lyme serology if endemic area exposure 1
• Hepatitis B, C, and HIV serologies 2
• HLA-B27 if spondyloarthropathy considered (though less likely with large joint involvement) 2

Imaging Studies

• Plain radiographs of affected joints to exclude structural pathology and establish baseline 4
• Echocardiography if ARF suspected to evaluate for carditis 1
• Ultrasound or MRI can detect synovitis when clinical examination is equivocal 4

Critical Diagnostic Pitfalls

• Prior NSAID use masks the migratory pattern of ARF - obtain detailed medication history before attributing lack of migration to alternative diagnosis 2
• Autoantibody positivity alone does not make a diagnosis - clinical context is paramount 2
• Negative RF does not exclude RA - always check anti-CCP antibodies 2, 4
• Antibiotics given for presumed infection can delay diagnosis of inflammatory conditions like FMF 3
• Overlapping osteoarthritis in older adults can obscure inflammatory arthritis - focus on presence of true synovitis (joint swelling, warmth, effusion) rather than just pain 4

When to Refer to Rheumatology

Urgent referral is indicated even with normal acute-phase response or negative RF if: 2

• Clinical synovitis is present (joint swelling on examination, not just arthralgia) 2
• Small joints of hands or feet are affected 2
• More than one joint is affected 2
• Symptoms persist despite initial management 2
• Diagnostic uncertainty with complex presentations 2

Initial Management Approach

While awaiting definitive diagnosis:

• Avoid NSAIDs initially if ARF is in the differential, as dramatic response is a diagnostic clue 1, 2
• If ARF is excluded and symptoms are severe, short-term NSAIDs can provide symptomatic relief 6
• Do not start corticosteroids before establishing diagnosis, as they can mask symptoms and confound workup 2
• Document the migratory pattern carefully - photograph affected joints, track duration at each site 1
• If septic arthritis cannot be excluded, arthrocentesis is mandatory before initiating any treatment 2