What are the differential diagnoses and management options for monoarthritis?

Monoarthritis: Differential Diagnosis and Management

Immediate Priority: Exclude Septic Arthritis

Septic arthritis must be ruled out first in any patient presenting with acute monoarthritis, as diagnostic delay leads to irreversible joint destruction, sepsis, and death. 1, 2

• Perform arthrocentesis immediately if joint effusion is present, particularly when fever, erythema, or warmth accompany the swelling 3
• Send synovial fluid for cell count with differential, Gram stain, and aerobic/anaerobic culture before starting antibiotics 4, 2
• Synovial fluid white blood cell count >50,000 cells/μL strongly suggests septic arthritis, though counts vary widely and should be interpreted cautiously 2
• Start empiric antibiotics immediately after aspiration if infection is suspected—do not delay treatment waiting for culture results 2, 3

Key Differential Diagnoses

The most common causes of monoarthritis are:

Crystal-Induced Arthropathy

• Gout: Examine synovial fluid under polarized microscopy for needle-shaped, negatively birefringent monosodium urate crystals 2, 3
• Pseudogout: Look for rhomboid-shaped, positively birefringent calcium pyrophosphate crystals 1, 2
• Monoarthritis of the first metatarsophalangeal joint has 99% sensitivity for gout but only 8% specificity (many other conditions can present similarly) 5

Trauma

• Obtain plain radiographs when focal bone pain or recent trauma is present to exclude fracture, metabolic bone disease, or tumor 3
• Trauma is the most common cause of monoarthritis in emergency department settings 6

Inflammatory Arthritis

• Early rheumatoid arthritis or psoriatic arthritis: In patients with monoarthritis/oligoarthritis and poor prognostic factors (structural damage, elevated ESR/CRP, dactylitis, or nail involvement), initiate a conventional synthetic DMARD rapidly, preferably within 3 months of symptom onset 5
• Methotrexate is preferred when clinically relevant skin involvement is present 5
• Consider NSAIDs and local glucocorticoid injections for symptomatic relief, but these should not be used as monotherapy for more than 4 weeks in peripheral arthritis 5

Immune Checkpoint Inhibitor-Related Arthritis

• In patients receiving cancer immunotherapy, inflammatory arthritis occurs in approximately 5-10% 5
• Grade 1 (mild pain with inflammation): Continue immunotherapy and use NSAIDs 5
• Grade 2 (moderate pain limiting instrumental activities): Hold immunotherapy, use prednisone 10-20 mg/day, and refer to rheumatology if symptoms persist >4 weeks 5
• Grade 3-4 (severe/disabling): Hold immunotherapy, use prednisone 0.5-1 mg/kg, and consider DMARDs if no improvement after 4 weeks 5

Diagnostic Workup Algorithm

Clinical Assessment

• Document disease chronology: acute onset (<6 weeks) suggests viral infection, crystal arthritis, or serum sickness; chronic (≥6 weeks) suggests RA or other chronic arthritides 4
• Morning stiffness >30-60 minutes strongly indicates inflammatory arthritis 4
• Assess for extra-articular manifestations: rash, fever, constitutional symptoms 4, 7

Laboratory Testing

• Obtain ESR and CRP to assess for inflammation 4
• Order RF, anti-CCP antibodies, and ANA if inflammatory arthritis is suspected 5, 4
• Consider HLA-B27 if reactive arthritis or axial involvement is present 5

Imaging

• Plain radiographs are the initial imaging modality for most cases to screen for erosions, structural damage, and alternative diagnoses 4
• Ultrasound or MRI may be indicated for persistent arthritis unresponsive to treatment or when metastatic lesions/septic arthritis are suspected 5

Critical Pitfalls to Avoid

• Never administer antibiotics before performing arthrocentesis when septic arthritis is suspected, as this reduces culture yield 3
• Never start treatment based solely on elevated uric acid levels—synovial fluid crystal analysis is required for gout diagnosis 3
• Never use NSAIDs alone for >4 weeks in patients with peripheral inflammatory arthritis—this delays definitive DMARD therapy and allows joint damage to progress 5
• Never delay DMARD initiation beyond 3 months from symptom onset in patients with persistent/erosive arthritis risk, as this represents a critical "window of opportunity" 5

When to Refer

• Refer to rheumatology immediately if joint swelling (synovitis) persists or if symptoms of arthralgia continue >4 weeks 5
• Urgent rheumatology consultation is needed for suspected septic arthritis or when unable to taper corticosteroids below 10 mg/day after 3 months 5