What laboratory and imaging studies should be ordered to diagnose and manage suspected gout?

Diagnostic Testing for Gout

Joint aspiration with synovial fluid analysis for monosodium urate (MSU) crystals using polarized light microscopy is the gold standard diagnostic test and should be performed whenever feasible, particularly when the diagnosis is uncertain, this is the first attack, or septic arthritis cannot be excluded. 1, 2

Essential Diagnostic Tests

Synovial Fluid Analysis (Gold Standard)

• MSU crystals appear as needle-shaped, negatively birefringent crystals under polarizing microscopy with 84% sensitivity and 100% specificity 1, 2
• Perform arthrocentesis when septic arthritis cannot be clinically excluded, the clinical presentation is atypical or uncertain, or when it is the patient's first suspected gout attack 1, 3
• Gram stain and culture must be performed on all synovial fluid samples even when MSU crystals are identified, because gout and septic arthritis can coexist 1, 2
• Synovial fluid analysis can still detect MSU crystals in approximately 70% of patients with known gout during intercritical (symptom-free) periods 2, 3

Serum Uric Acid Level

• Measure serum uric acid, but recognize that hyperuricemia alone cannot diagnose gout and normal levels do not exclude it 1, 2
• Serum uric acid has moderate sensitivity (53-67%) and specificity (78-92%) for gout diagnosis 1, 2
• 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 1, 2
• Only 22% of asymptomatic patients with serum uric acid levels above 9 mg/dL develop gout over 5 years 1
• Serum uric acid is essential for long-term management decisions and monitoring treatment efficacy, with a target of <6 mg/dL for most patients 2

Renal Function Assessment

• Check creatinine, BUN, and eGFR to evaluate renal function, which is critical for medication selection and dosing, especially for urate-lowering therapy 2
• Assess for chronic kidney disease, which has a relative risk of 4.95 for gout 1

24-Hour Urinary Uric Acid Excretion (Selected Patients)

• Determine renal uric acid excretion in patients with family history of young-onset gout, onset of gout under age 25, or history of renal calculi 2, 3
• This test helps identify uric acid overproducers versus underexcretors, which may influence treatment selection 4, 2

Imaging Studies

First-Line Imaging: Ultrasound

• Ultrasound is the first-line imaging modality when joint aspiration is not feasible or when clinical diagnosis is uncertain 1
• The "double contour sign" on cartilage surfaces has 74% sensitivity and 88% specificity for detecting MSU crystal deposition 1
• Always scan the first metatarsophalangeal joint bilaterally, even if asymptomatic, as this is the disease-specific target site 1
• Ultrasound detects tophi with 65% sensitivity and 80% specificity 1
• Ultrasound performs better in late disease (>2 years duration) with 63% sensitivity compared to 50% in early disease (<2 years) 1

Second-Line Imaging: Dual-Energy CT (DECT)

• Consider DECT when ultrasound is negative but clinical suspicion remains high, particularly in patients with disease duration >2 years 1
• DECT has 85-100% sensitivity and 83-92% specificity for detecting MSU crystal deposition 1
• DECT is more expensive and involves radiation exposure, making it second-line 1

Plain Radiographs (Limited Role)

• Plain radiographs are useful only for assessing chronic structural damage or excluding alternative diagnoses and should not be used as the primary diagnostic modality for acute gout 4, 1
• Radiographs are frequently normal in early or acute gout apart from non-specific soft tissue swelling 4

Additional Laboratory Tests

Inflammatory Markers

• Check ESR and CRP to assess inflammation severity and help rule out infection 1
• Complete blood count to evaluate for infection and assess overall inflammatory burden 1

Urinalysis

• Perform urinalysis to evaluate for crystalluria and renal involvement 2

Liver Function Tests

• Baseline and periodic liver function tests are recommended if initiating febuxostat therapy 2

Assessment of Risk Factors and Comorbidities

Systematically screen for the following comorbidities and risk factors: 1, 3

• Chronic kidney disease (relative risk 4.95)
• Obesity (relative risk 3.81)
• Hypertension (relative risk 3.93)
• Diuretic use (relative risk 1.72), including thiazides, loop diuretics, low-dose aspirin
• Cardiovascular disease (ischemic heart disease, heart failure)
• Diabetes mellitus
• Dyslipidemia
• Alcohol consumption (especially beer)
• Diet high in meat, shellfish, and high-fructose corn syrup

Diagnostic Algorithm When Joint Aspiration Is Not Feasible

When synovial fluid analysis cannot be performed, use validated clinical criteria combined with ultrasound imaging to achieve diagnostic accuracy exceeding 80%: 1

Clinical features supporting gout diagnosis include:

• Rapid onset of severe pain reaching maximum intensity within 6-24 hours 1
• Monoarticular arthritis affecting the first metatarsophalangeal joint (podagra) 1
• Erythema over the affected joint 1
• History of previous similar acute arthritis episodes 1
• Male gender 1
• Associated cardiovascular diseases 1
• Hyperuricemia (though not diagnostic alone) 1

Common Pitfalls to Avoid

• Do not diagnose gout based on hyperuricemia alone—up to 80% of patients with hyperuricemia never develop gout 1
• Do not exclude gout based on normal serum uric acid during an acute attack 1, 2
• Failing to perform synovial fluid analysis can lead to less accurate diagnosis, especially in atypical presentations 2
• Do not overlook the possibility of coexisting septic arthritis—always perform Gram stain and culture even when MSU crystals are identified 1, 2
• Consider medication effects on serum urate levels (thiazides, loop diuretics, low-dose aspirin, niacin, cyclosporine, tacrolimus) 2
• Do not rely on imaging alone—patient history, physical examination, and laboratory findings must be integrated into the diagnostic assessment 1