Which laboratory tests should be ordered for a patient with an acute gout flare to assess inflammation, renal and hepatic function, and exclude infection?

Laboratory Tests for Acute Gout Flare

For a patient presenting with an acute gout flare, order synovial fluid analysis with crystal identification (if feasible), serum uric acid, complete blood count, inflammatory markers (ESR/CRP), renal function tests (creatinine, eGFR), and liver function tests—while recognizing that synovial fluid analysis remains the gold standard but is often not performed in primary care settings. 1, 2, 3

Essential Diagnostic Laboratory Tests

Synovial Fluid Analysis (Gold Standard)

• Joint aspiration with polarized light microscopy to identify needle-shaped, negatively birefringent monosodium urate crystals is the reference standard for definitive gout diagnosis, with sensitivity 63-78% and specificity 93-100%. 1, 2, 4
• Perform arthrocentesis when septic arthritis cannot be clinically excluded, when the diagnosis is uncertain, or when this is the patient's first suspected gout attack. 1, 2
• Always obtain Gram stain and culture even when MSU crystals are identified, because gout and septic arthritis can coexist. 2, 3
• Synovial fluid analysis can detect MSU crystals in approximately 70% of patients with known gout even during intercritical (pain-free) periods. 3

Serum Uric Acid Level

• Measure serum uric acid, but understand that hyperuricemia alone cannot diagnose gout and normal levels do not exclude it. 2, 3
• Approximately 10% of patients with acute gout have normal serum uric acid levels during an attack because uric acid behaves as a negative acute phase reactant during inflammation. 2, 3
• Only 22% of asymptomatic patients with serum uric acid >9 mg/dL develop gout over 5 years, highlighting that hyperuricemia is not synonymous with gout. 2
• Serum uric acid has limited diagnostic value during an acute attack but is essential for long-term management decisions and monitoring urate-lowering therapy. 3

Inflammatory Markers

• Order ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) to assess inflammation severity and help differentiate gout from septic arthritis. 4
• Elevated inflammatory markers support the diagnosis of acute inflammatory arthritis but are nonspecific. 4

Complete Blood Count

• Obtain CBC to assess for leukocytosis, which may suggest infection, and to evaluate overall inflammatory burden. 4
• An elevated white blood cell count raises concern for septic arthritis and strengthens the indication for joint aspiration. 4

Renal and Hepatic Function Assessment

Renal Function Tests

• Check serum creatinine and calculate eGFR (estimated glomerular filtration rate) because chronic kidney disease is a major risk factor for gout (relative risk 4.95) and influences medication selection and dosing. 2, 3
• Renal function testing is critical before initiating NSAIDs, colchicine, or urate-lowering therapy, as dosing adjustments are required in renal impairment. 3, 5
• Consider 24-hour urinary uric acid excretion in selected patients—specifically those with family history of young-onset gout, onset of gout under age 25, or history of renal calculi—to identify urate overproducers versus underexcretors. 2, 3

Liver Function Tests

• Obtain baseline liver function tests (AST, ALT, alkaline phosphatase, bilirubin) because many gout medications require hepatic monitoring. 3
• Febuxostat and other urate-lowering agents require baseline and periodic liver function monitoring. 3

Urinalysis

• Perform urinalysis to evaluate for crystalluria, proteinuria, and renal involvement. 3
• Urinalysis helps assess for concurrent urolithiasis, which occurs in approximately 20% of patients with gout. 6

Assessment of Comorbidities and Risk Factors

Cardiovascular and Metabolic Screening

• Systematically screen for associated comorbidities including obesity, hypertension, ischemic heart disease, heart failure, diabetes mellitus, and dyslipidemia, as these frequently coexist with gout and influence management decisions. 2, 4
• Consider fasting glucose or HbA1c to screen for diabetes, and lipid panel to assess cardiovascular risk. 2

Medication Review

• Review current medications, particularly thiazide diuretics (relative risk 1.72), loop diuretics, low-dose aspirin, cyclosporine, tacrolimus, and niacin, which can elevate serum urate levels. 2, 3

Practical Algorithm for Laboratory Testing

When joint aspiration is feasible:

1. Perform arthrocentesis with synovial fluid analysis for MSU crystals under polarized light microscopy 1, 2
2. Send synovial fluid for Gram stain and culture simultaneously 2, 3
3. Order serum uric acid, CBC, ESR/CRP 2, 3, 4
4. Check renal function (creatinine, eGFR) and liver function tests 3
5. Obtain urinalysis 3

When joint aspiration is not feasible (most primary care settings):

1. Order serum uric acid (recognizing its diagnostic limitations during acute attacks) 2, 3
2. Check CBC, ESR/CRP to assess inflammation and exclude infection 4
3. Obtain renal function tests (creatinine, eGFR) and liver function tests 3
4. Perform urinalysis 3
5. Consider 24-hour urinary uric acid if patient has early-onset gout, family history, or renal stones 2, 3
6. Use validated clinical criteria combined with ultrasound imaging if available 1, 2

Critical Pitfalls to Avoid

• Do not rely solely on serum uric acid for diagnosis—it may be normal during acute attacks and hyperuricemia alone does not confirm gout. 2, 3
• Do not skip Gram stain and culture when performing arthrocentesis, even if MSU crystals are identified, because gout and septic arthritis may coexist. 2, 3
• If septic arthritis cannot be excluded clinically, joint aspiration with Gram stain and culture is mandatory regardless of gout suspicion. 2
• Do not overlook medication-induced hyperuricemia—thiazide and loop diuretics are common culprits that should be identified and potentially discontinued. 2, 3
• Do not fail to assess renal function before prescribing NSAIDs, colchicine, or urate-lowering therapy, as dosing adjustments are critical in renal impairment. 3, 5