Serum Uric Acid Levels in Patients with Gout Tophi
Serum uric acid levels are NOT reliably elevated in patients with gout tophi, and a normal uric acid level does not exclude the presence of tophi or active gout disease. 1
Key Clinical Principle
While hyperuricemia is the most important risk factor for developing gout, serum uric acid levels do not confirm or exclude gout at any stage of disease, including in patients with tophi. 1 This is a critical diagnostic pitfall that can lead to underdiagnosis and undertreatment.
Why Uric Acid Can Be Normal Despite Tophi
During acute gout attacks, serum uric acid acts as a negative acute-phase reactant and can drop to normal levels. 2 In the largest studies of acute gout treatment (339 patients), 14% had truly normal uric acid (≤6 mg/dL) and 32% had levels ≤8 mg/dL during acute attacks. 2
Patients on chronic allopurinol therapy frequently have normal or low uric acid levels but can still have persistent tophi and ongoing crystal deposition. 2 The mean baseline uric acid was 7.1 mg/dL in allopurinol users versus 8.5 mg/dL in non-users during acute attacks. 2
Even when uric acid is maintained below 6 mg/dL for extended periods, monosodium urate crystals can persist in joints. 3 In one study, 44% of asymptomatic patients who maintained uric acid ≤6 mg/dL for over 12 months still had MSU crystals in their knee joints on aspiration. 3
Clinical Implications for Tophaceous Gout
The presence of subcutaneous tophi on physical examination is an absolute indication to start urate-lowering therapy, regardless of the current serum uric acid level. 1, 4 This is because tophi represent a high body urate burden and ongoing tissue damage.
Tophi indicate chronic, advanced gout with significant crystal deposition that has accumulated over time, independent of the current serum uric acid measurement. 5 The body's total uric acid pool (reflected by tophi) is more clinically relevant than a single serum measurement.
In patients with tophi, the therapeutic target should be more aggressive: maintain uric acid <5 mg/dL (300 μmol/L) until complete crystal dissolution occurs, then maintain <6 mg/dL lifelong. 4, 6
Diagnostic Approach
Never rely on serum uric acid alone to diagnose or exclude gout in patients with suspected tophi. 1 The sensitivity of uric acid >6 mg/dL for gout is only 67% and specificity is 78%. 1
Definitive diagnosis requires identification of monosodium urate crystals from synovial fluid or tophus aspiration under polarized light microscopy. 4 This is the gold standard and should be performed whenever possible.
Physical examination for tophi is essential, as their presence changes management regardless of uric acid levels. 1 Imaging (ultrasound, dual-energy CT) can detect tophi not visible on exam.
Common Pitfall to Avoid
Do not withhold urate-lowering therapy or dismiss a gout diagnosis in a patient with clinical tophi simply because their serum uric acid is normal or only mildly elevated. 1, 2 This represents a failure to understand that serum uric acid is a poor marker of disease burden in established, chronic gout with tophi. The velocity of tophus reduction correlates directly with how low uric acid is maintained during treatment, not with the baseline level. 7