What is the significance of uric acid level during an acute flare-up of gout?

Uric Acid Levels During Acute Gout Flares

Key Clinical Point

Serum uric acid levels frequently drop to normal or near-normal during acute gout attacks and should NOT be used to exclude the diagnosis of gout. 1

Why Uric Acid Levels Fall During Acute Attacks

• Uric acid behaves as a negative acute phase reactant, meaning it temporarily decreases during episodes of acute inflammation and stress 1
• The systemic inflammatory response itself causes a reduction in serum uric acid levels, independent of gout pathophysiology 2
• Increased renal excretion of uric acid during acute episodes contributes to this temporary reduction 1
• Studies demonstrate that 63.3% of patients with acute gout attacks have normal serum uric acid levels at presentation 3

Diagnostic Implications

Do not rely on serum uric acid levels to diagnose or exclude gout during an acute attack. 1, 4

• The European League Against Rheumatism explicitly states that serum uric acid levels do not confirm or exclude gout, as patients with crystal-proven gout may have normal serum levels during acute attacks 4
• The absence of hyperuricemia after an acute arthritis episode has a markedly low negative likelihood ratio for excluding gout 1
• The gold standard for diagnosis remains identification of monosodium urate crystals in synovial fluid or tophus aspirates under polarized light microscopy 1, 4

Clinical Characteristics of Normouricemic Acute Gout

Patients presenting with normal uric acid during acute attacks show distinct patterns:

• Higher inflammatory activity with elevated ESR (76.6% of cases) and C-reactive protein (30% of cases) 3
• More commonly associated with postsurgical episodes (22.7% vs. 6.0% in hyperuricemic patients) 5
• More frequent in patients with preserved renal function (lower frequency of renal insufficiency: 25.0% vs. 53.4%) 5
• Increased urinary excretion of uric acid found in 55% of normouricemic patients during acute attacks 3

Recurrence Risk

Importantly, serum uric acid levels during an acute attack do NOT predict future recurrence risk. 5

• Multivariate analysis shows no association between normouricemia during acute attack and recurrent gout attacks (hazard ratio 1.075,95% CI 0.972-1.190, p=0.159) 5
• The recurrence rate is similar between normouricemic and hyperuricemic patients (24.7% vs. 33.0%, p=0.220) 5
• Careful follow-up should be considered in all gout patients regardless of serum urate levels during an acute attack 5

When to Measure Uric Acid

Serum uric acid should preferably be measured between attacks (intercritical periods) rather than during acute flares for accurate assessment. 1

• Measurements during acute attacks have limited diagnostic value due to fluctuation 1
• For monitoring urate-lowering therapy, the target is <6.0 mg/dL (360 μmol/L), and <5.0 mg/dL (300 μmol/L) in severe gout with tophi 4
• Patients who achieve serum urate levels below 6.0 mg/dL have approximately 5% risk for acute gout attacks, whereas those with levels ≥6.0 mg/dL have 10-15% risk 6

Critical Pitfall to Avoid

Never exclude gout based solely on normal uric acid levels if clinical manifestations are suggestive (rapid onset of severe pain reaching maximum within 6-12 hours, especially podagra with overlying erythema). 1, 7

• If gout is suspected clinically, proceed with joint aspiration for crystal analysis regardless of serum uric acid level 1, 4
• Remember that gout and septic arthritis may coexist, so Gram stain and culture should still be performed even if monosodium urate crystals are identified when infection is suspected 4