Serum Uric Acid in Active Gout
Serum uric acid levels are frequently normal during active gout attacks and should not be used to confirm or exclude the diagnosis, as uric acid behaves as a negative acute phase reactant that temporarily decreases during acute inflammation. 1, 2
The Paradox of Normal Uric Acid During Acute Attacks
Approximately 10-63% of patients with acute gout attacks have normal serum uric acid levels at the time of the flare. 3, 4
During acute inflammatory episodes, serum uric acid temporarily decreases compared to intercritical periods due to increased renal excretion and its behavior as a negative acute phase reactant. 2, 5
The EULAR guidelines explicitly state that serum uric acid levels do not confirm or exclude gout, as many people with hyperuricemia never develop gout, and patients with crystal-proven gout may have normal levels during acute attacks (strength of recommendation: 95% CI 92-99). 1, 5
Why This Occurs
Acute inflammation and stress cause temporary lowering of serum uric acid levels through physiological mechanisms. 2, 5
Increased renal excretion of uric acid occurs specifically during acute gout episodes, contributing to the paradoxical drop in serum levels. 2, 5
One study found that 63.3% of patients with acute gout attacks had normal serum uric acid levels, with 76.6% showing elevated ESR and increased urinary uric acid excretion in 55% of tested patients. 4
Diagnostic Implications
The gold standard for gout diagnosis is identification of needle-shaped, negatively birefringent monosodium urate crystals in synovial fluid or tophus aspirates—not serum uric acid measurement. 1, 3
Synovial fluid aspiration and crystal examination should be undertaken in any patient with undiagnosed inflammatory arthritis, even when serum uric acid is normal. 3
The absence of hyperuricemia after an acute arthritis episode has a markedly low negative likelihood ratio, meaning normal uric acid does not rule out gout. 2
When to Measure Serum Uric Acid
For diagnostic purposes, serum uric acid should be measured during the intercritical period (between attacks) rather than during acute flares, as levels are typically higher when inflammation has resolved. 5
Serum uric acid has limited diagnostic value during acute gout flares and should preferably be measured at distance from a flare. 2, 5
For monitoring treatment efficacy, regular measurements are essential to ensure target levels below 6 mg/dL are maintained. 5
Common Pitfalls
Never exclude gout based solely on normal serum uric acid levels if clinical manifestations are suggestive (rapid onset severe pain, podagra, overlying erythema, or positive response to colchicine). 2, 4
Conversely, hyperuricemia alone should not be used to diagnose gout, as it has relatively low specificity (53-61%) and many people with elevated uric acid never develop gout. 3
If septic arthritis is suspected, perform Gram stain and culture even if crystals are identified, as gout and sepsis can coexist in the same joint. 1, 3