In a patient with acute warm wrist pain, markedly elevated C‑reactive protein and erythrocyte sedimentation rate, normal white blood cell count, and elevated serum uric acid, what is the most likely diagnosis and how should it be managed?

Acute Gout (Gouty Arthritis) with Septic Arthritis Exclusion Required

This presentation is most consistent with acute gouty arthritis of the wrist, but septic arthritis must be urgently excluded through joint aspiration with synovial fluid analysis before initiating definitive treatment. 1, 2

Why This Is Most Likely Gout

The combination of acute monoarticular wrist pain with warmth, markedly elevated inflammatory markers (CRP and ESR), normal white blood cell count, and elevated uric acid strongly suggests acute gouty arthritis. 2, 3

Key Supporting Features

• Acute gout commonly presents with markedly elevated ESR and CRP during flares, with the acute phase response correlating with the number of involved joints 3
• Normal serum uric acid does NOT exclude acute gout—63.3% of patients with confirmed acute gout attacks have normal serum uric acid levels during the acute flare, as uric acid is excreted more rapidly during inflammation 2
• The wrist is an established site for gouty arthritis, though less common than the first metatarsophalangeal joint 4
• Normal WBC count is typical in uncomplicated gout, distinguishing it from septic arthritis where leukocytosis is usually present 2, 3

Critical Inflammatory Marker Pattern

• CRP rises within 12–24 hours of gout onset and peaks at 48 hours, making it ideal for detecting acute inflammatory arthritis 5
• ESR elevation in gout correlates with disease severity, with higher values indicating more extensive joint involvement 3
• Both markers resolve rapidly with appropriate anti-inflammatory treatment in uncomplicated gout 3, 5

Why Septic Arthritis Must Be Excluded FIRST

Septic arthritis and gout can coexist in the same joint, and this combination has been specifically reported in the wrist. 4

Overlapping Clinical Features

• Both conditions present with acute monoarticular joint pain, warmth, and markedly elevated inflammatory markers 4, 6
• CRP levels >84 mg/L occur in both septic arthritis and acute gout, making CRP alone insufficient to distinguish them 6
• The presence of elevated uric acid does not exclude infection—bacterial infection can actually precipitate urate crystal deposition 4

Diagnostic Algorithm for Septic Arthritis Exclusion

Obtain synovial fluid analysis immediately before initiating treatment: 1, 6

1. Synovial fluid cell count and differential (septic arthritis typically shows >50,000 WBC/mm³ with >90% neutrophils) 1
2. Polarized light microscopy to identify negatively birefringent needle-shaped urate crystals (confirms gout) 1, 2
3. Gram stain and culture (gold standard for septic arthritis diagnosis) 6
4. Withhold antibiotics for at least 2 weeks prior to aspiration when clinically feasible to maximize culture yield 1

If septic arthritis is present alongside gout, CRP remains elevated significantly longer (11 ± 7 days vs. 6 ± 3 days for uncomplicated osteomyelitis) and reaches higher peak values. 6

Additional Diagnostic Workup

Essential Laboratory Tests

• Repeat serum uric acid measurement after the acute flare resolves, as levels normalize during attacks due to increased urinary excretion 2
• Comprehensive metabolic panel including renal function (creatinine, BUN) to assess for chronic kidney disease predisposing to gout 1
• Complete blood count with differential to confirm normal WBC and assess for cytopenias 1

Imaging Studies

• Plain radiographs of the wrist to assess for chronic gouty erosions (punched-out lesions with overhanging edges) or alternative diagnoses 1
• Ultrasound with Power Doppler can detect the "double contour sign" (urate crystal deposition on cartilage) and hyperemia, supporting gout diagnosis 1

Differential Diagnoses to Consider

Rheumatoid Arthritis (Less Likely)

• RA typically presents with symmetric polyarticular involvement, not acute monoarticular wrist pain 1
• Morning stiffness >1 hour and gradual onset distinguish RA from the sudden onset of gout 1
• Order RF and anti-CCP antibodies if symmetric small joint involvement develops over time 1

Pseudogout (CPPD Disease)

• Clinically indistinguishable from gout without synovial fluid analysis 1
• Polarized microscopy shows positively birefringent rhomboid-shaped calcium pyrophosphate crystals (vs. negatively birefringent needle-shaped urate crystals in gout) 1
• Radiographs may show chondrocalcinosis (cartilage calcification) 1

Reactive Arthritis

• Consider if recent genitourinary or gastrointestinal infection, conjunctivitis, or urethritis present 1
• HLA-B27 testing if axial or entheseal involvement develops 1

Management Once Septic Arthritis Is Excluded

Acute Gout Treatment

Initiate anti-inflammatory therapy immediately after confirming gout and excluding infection: 1

• NSAIDs (e.g., indomethacin 50 mg three times daily or naproxen 500 mg twice daily) as first-line therapy 1
• Colchicine 1.2 mg initially, then 0.6 mg one hour later, then 0.6 mg once or twice daily (reduce dose in renal impairment) 1
• Intra-articular corticosteroid injection if only one joint affected and infection definitively excluded 1
• Oral prednisone 0.5 mg/kg daily for 5–10 days if NSAIDs and colchicine contraindicated 1

Monitoring Treatment Response

• Repeat CRP every 2–4 weeks to confirm rapid normalization (within 6 ± 3 days in uncomplicated gout) 5, 6
• Persistent elevation of CRP beyond 2 weeks should prompt reassessment for concurrent infection or alternative diagnosis 6

Long-Term Urate-Lowering Therapy

Do NOT initiate urate-lowering therapy during the acute flare—wait until inflammation resolves (typically 2–4 weeks after attack). 1

• Target serum uric acid <6 mg/dL (or <5 mg/dL in patients with tophi) 1
• Allopurinol starting at 100 mg daily, titrating up by 100 mg every 2–4 weeks based on uric acid levels 1
• Febuxostat 40–80 mg daily as alternative if allopurinol not tolerated 1

Critical Pitfalls to Avoid

• Never dismiss gout based on normal serum uric acid during acute attack—63.3% of acute gout cases have normal uric acid levels 2
• Never assume elevated uric acid alone confirms gout—asymptomatic hyperuricemia is common and does not require treatment 1
• Never start antibiotics empirically without synovial fluid analysis unless patient is septic or immunocompromised 4, 6
• Never initiate urate-lowering therapy during acute flare—this can paradoxically worsen and prolong the attack 1
• Always consider coexistent septic arthritis in patients with known gout—the two conditions can occur simultaneously in the same joint 4