Can Uric Acid Be Normal in Gout?
Yes, uric acid levels can be normal during acute gout attacks, occurring in approximately 10-40% of patients with crystal-proven gout, and a normal level should never be used to exclude the diagnosis. 1, 2
Why Uric Acid Drops During Acute Attacks
Serum uric acid behaves as a negative acute phase reactant, meaning it temporarily decreases during episodes of acute inflammation and stress. 3, 1 This phenomenon occurs through two key mechanisms:
- Increased renal excretion of uric acid during acute inflammatory episodes is the primary mechanism for this temporary reduction. 3, 4
- Studies demonstrate that clearance of uric acid and fractional excretion of uric acid (FEur) are notably increased in patients during acute attacks, especially in those with serum uric acid <420 μmol/L (approximately 7 mg/dL). 4
- The correlation between low uric acid levels and elevated inflammatory markers (ESR, CRP) during acute attacks has been well-documented. 2
Clinical Prevalence
The frequency of normal uric acid during acute gout is substantial and clinically important:
- 14% of patients had serum uric acid ≤6 mg/dL during acute attacks in large clinical trials. 5
- 32% of patients had serum uric acid ≤8 mg/dL during acute gout episodes. 5
- One study found 63.3% of patients with acute gout attacks had normal serum uric acid levels at presentation. 2
- 39.8% of gout patients were normouricemic during acute attacks in a retrospective cohort study. 6
Diagnostic Implications
Serum uric acid has limited diagnostic value during acute gout attacks and should preferably be measured during the intercritical period (between attacks) rather than during acute flares. 1
Key diagnostic considerations:
- The gold standard for gout diagnosis remains identification of monosodium urate (MSU) crystals in synovial fluid or tophus aspirates, not serum uric acid measurement. 3, 1
- The diagnosis of acute gout should not be excluded based solely on normal uric acid levels if clinical manifestations are suggestive. 3, 1, 2
- Clinical features supporting gout include rapid development of severe pain reaching maximum within 6-12 hours, podagra with overlying erythema, presence of tophi, or rapid response to colchicine. 1, 7
When to Measure Uric Acid
- For diagnostic purposes, measure serum uric acid during the intercritical period when levels are typically higher after inflammation has resolved. 1
- For monitoring treatment efficacy, regular measurements are essential to ensure target levels below 6 mg/dL (360 μmol/L) are maintained, or below 5 mg/dL (300 μmol/L) in severe gout with tophi. 1
- Hyperuricemia (male >7 mg/dL, female >6 mg/dL) has sensitivity of only 57% but specificity of 92% for clinical gout. 1
Common Pitfalls to Avoid
- Never exclude gout based on a single normal uric acid level during an acute presentation. 3, 1
- Patients taking chronic allopurinol are more likely to have lower serum uric acid at baseline during acute attacks compared to non-users. 5
- Prior risk factors for hyperuricemia may have been modified at presentation (cessation of diuretics, weight loss, reduced alcohol intake), resulting in normal levels despite active disease. 3
- Normouricemic patients during acute attacks show higher inflammatory activity but have similar recurrence rates as hyperuricemic patients, requiring equally careful follow-up. 6