What is the initial approach to a patient presenting with asymmetric polyarthritis, right ankle swelling, restricted range of motion (ROM), pain, and erythema, without a history of apparent trauma?

Asymmetric Polyarthritis with Acute Monoarticular Ankle Involvement: Initial Diagnostic Approach

In a patient presenting with asymmetric polyarthritis and acute right ankle swelling with erythema, pain, and restricted ROM without trauma, septic arthritis must be excluded first through joint aspiration, followed by systematic evaluation for crystal arthropathy, reactive arthritis, and inflammatory arthritides including psoriatic arthritis and HCV-related arthritis. 1

Immediate Exclusion of Septic Arthritis

• Joint aspiration with synovial fluid analysis is mandatory when a single joint presents with swelling, erythema, and warmth to exclude septic arthritis, which represents a medical emergency 1
• Synovial fluid should be sent for cell count with differential, Gram stain, culture, and crystal analysis 1
• The presence of erythema and warmth strongly suggests inflammatory synovitis requiring urgent evaluation 1, 2

Essential Laboratory Evaluation

Complete the following laboratory studies to assess inflammation and guide differential diagnosis: 1

• Complete blood count with differential 1
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) - typically markedly elevated in inflammatory arthritis 1
• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies 1
• Antinuclear antibodies (ANA) 1
• Urinalysis 1
• Transaminases 1
• Serum uric acid for gout evaluation 2

Pattern Recognition for Differential Diagnosis

Asymmetric Oligoarthritis Pattern (Most Likely)

The asymmetric pattern involving large joints, particularly the ankle, suggests several specific diagnoses: 1

• Reactive arthritis: Look for conjunctivitis, urethritis, back pain suggestive of sacroiliitis, and recent gastrointestinal or genitourinary infection 1
• Psoriatic arthritis: Examine for psoriatic skin lesions (may be subtle), nail changes, dactylitis, and DIP joint involvement 1, 3
• HCV-related intermittent mono-oligoarthritis: Typically involves medium and large joints of lower limbs, especially ankles, with acute course and frequent relapses often concurrent with cutaneous vasculitis 1
• Crystal arthropathy (gout or pseudogout): Sudden onset, severe pain, and erythema are characteristic 1

Key Distinguishing Features

Psoriatic arthritis presents with asymmetric involvement and can manifest as: 3

• Distal interphalangeal joint involvement
• Dactylitis ("sausage digits")
• Nail pitting or onycholysis
• Enthesitis
• Skin lesions may be minimal or in hidden areas (scalp, gluteal cleft)

HCV-related arthritis has two distinct patterns: 1

• Symmetric polyarthritis (less common, resembles RA but non-erosive)
• Intermittent mono-oligoarthritis (more common): acute flares involving ankles and large joints, associated with cryoglobulinemic vasculitis
• RF may be positive, but anti-CCP antibodies are rarely detected 1

Reactive arthritis features include: 1

• Asymmetric oligoarthritis of large joints (knees, ankles, wrists)
• Extra-articular manifestations: conjunctivitis, urethritis
• Preceding infection (1-4 weeks prior)
• Possible sacroiliitis or cervical pain

Imaging Strategy

Clinical examination is the primary method for detecting arthritis, but imaging aids in uncertain cases: 1

• Plain radiographs of the affected ankle and other symptomatic joints to assess for erosions, joint space narrowing, or fracture 1
• Ultrasound or power Doppler can detect synovitis when clinical examination is equivocal 1
• MRI may be helpful to detect synovitis and assess for enthesitis if spondyloarthropathy is suspected 1

Critical Pitfalls to Avoid

• Never dismiss acute monoarticular swelling with erythema without joint aspiration - septic arthritis can coexist with inflammatory arthritis and requires immediate treatment 1
• Do not assume symmetric polyarthritis is required for rheumatoid arthritis - RA can present with asymmetric involvement initially, though this is less common 4
• Seronegative arthritis requires broader differential consideration - if RF and anti-CCP are negative, consider infectious causes (including leprosy in endemic areas), HCV-related arthritis, psoriatic arthritis, and reactive arthritis 1, 5
• Inflammatory markers (ESR, CRP) are usually markedly elevated in immune checkpoint inhibitor-induced arthritis and help differentiate from degenerative disease 1
• Screen for HCV infection in patients with asymmetric arthritis, especially if cryoglobulinemia or vasculitis is present 1

Urgent Rheumatology Referral Criteria

Refer to rheumatology ideally within 6 weeks when: 1

• Arthritis involves more than one joint
• Joint swelling not caused by trauma or bony enlargement is present
• Morning stiffness exceeds 30 minutes
• Metacarpophalangeal or metatarsophalangeal joints are involved