What are the diagnostic criteria and management options for gout?

Gout Diagnosis

The definitive diagnosis of gout requires identification of monosodium urate (MSU) crystals in synovial fluid or tophus aspirate using polarized light microscopy, which remains the reference standard with specificity of 93-100%. 1, 2, 3

Diagnostic Algorithm

Step 1: Attempt Synovial Fluid Aspiration (Gold Standard)

• Perform arthrocentesis of the affected joint and analyze synovial fluid under polarizing microscopy to identify needle-shaped, negatively birefringent MSU crystals 1, 2, 3
• Sensitivity ranges from 63-78%, but specificity is excellent at 93-100% 3
• Critical pitfall: Always perform Gram stain and culture even when MSU crystals are identified, as gout and septic arthritis can coexist 1

Step 2: If Aspiration Not Possible, Apply Clinical Criteria

• Use the 2015 ACR/EULAR classification criteria (score ≥8 points is diagnostic) with sensitivity of 92% and specificity of 89% when imaging is available, or 85% sensitivity and 78% specificity without imaging 2
• Key high-value clinical features include:
  • Presence of tophi (odds ratio 7.29 - strongest predictor) 2, 3
  • Podagra (first metatarsophalangeal joint involvement) 2, 3
  • Resolution of pain within 2 weeks (odds ratio 3.58) 2
  • Maximal joint inflammation within 6-12 hours 3
  • Overlying erythema 3
  • Male sex (relative risk 7.64) 3

Step 3: Order Essential Laboratory Tests

• Serum uric acid (SUA) - essential for management but insufficient alone for diagnosis 1
  • Many patients with hyperuricemia never develop gout 1, 3
  • SUA may be normal during acute attacks 1
• Renal function tests (creatinine, BUN) - critical for medication selection and dosing 1
• Liver function tests - baseline assessment before initiating urate-lowering therapy 1
• Urinalysis - evaluate for crystalluria and renal involvement 1

Step 4: Consider Advanced Imaging When Diagnosis Uncertain

• Dual-Energy Computed Tomography (DECT) is the most accurate non-invasive imaging modality with sensitivity of 85-100% and specificity of 83-92% 2, 3
• Ultrasonography can detect the "double contour" sign on cartilaginous surfaces with pooled sensitivity of 74% and specificity of 88% 2, 3
• Important limitation: DECT is less sensitive in recent-onset acute gout 3

Step 5: Assess for Risk Factors and Comorbidities

• Evaluate medications that elevate serum urate: thiazide diuretics, loop diuretics, low-dose aspirin, niacin, cyclosporine, tacrolimus 1, 2
• Screen for cardiovascular risk factors in all patients with gout or hyperuricemia 1, 2
• Assess modifiable risk factors: obesity (relative risk 3.81), excessive alcohol consumption (especially beer), high-fructose corn syrup beverages, purine-rich foods (meat, seafood) 1, 2, 3
• Check for associated conditions: chronic kidney disease, hypertension, dyslipidemia 2, 4

Step 6: Special Laboratory Testing in Selected Patients

• 24-hour urine collection for uric acid excretion should be performed in patients with:
  • Family history of young-onset gout 1
  • Onset of gout under age 25 1
  • History of renal calculi 1

Critical Diagnostic Pitfalls to Avoid

• Never rely solely on serum uric acid for diagnosis - hyperuricemia alone does not confirm gout, and SUA may be normal during acute attacks 1
• Failing to perform synovial fluid analysis leads to less accurate diagnosis, especially in atypical presentations 1
• Clinical algorithms have higher sensitivity in patients with longer disease duration (>2 years) than in those with recent-onset symptoms 3
• Always consider septic arthritis in the differential and perform Gram stain/culture when aspirating joints 1

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Gout Management

For acute gout flares, initiate immediate anti-inflammatory therapy with first-line options including low-dose colchicine (1.2 mg followed by 0.6 mg one hour later), NSAIDs at full anti-inflammatory doses, or corticosteroids, followed by long-term urate-lowering therapy targeting serum uric acid <6 mg/dL. 1, 2

Acute Gout Attack Management

First-Line Treatment Options (Choose Based on Comorbidities)

Colchicine (Low-Dose Regimen):

• 1.2 mg loading dose, followed by 0.6 mg one hour later (total 1.8 mg) 1, 5
• Response rate of 38% vs 16% for placebo at 24 hours 5
• Do not repeat course for at least 3 days 5
• Critical FDA warning: This is NOT an innocuous drug 6

NSAIDs:

• Start at full anti-inflammatory doses as soon as possible 1, 2
• Add proton pump inhibitor if gastrointestinal risk factors exist 1
• Contraindicated in patients with renal disease, peptic ulcer, or high cardiovascular risk 2

Corticosteroids:

• Oral prednisolone 30-35 mg/day for 3-5 days 1
• OR intra-articular injection after joint aspiration 1
• Preferred in patients with contraindications to NSAIDs or colchicine 2

Dose Adjustments for Renal Impairment (Colchicine)

Mild to moderate renal impairment (CrCl 30-80 mL/min):

• No dose adjustment required, but monitor closely 5

Severe renal impairment (CrCl <30 mL/min):

• Treatment course should be repeated no more than once every two weeks 5

Dialysis patients:

• Single dose of 0.6 mg only 5
• Do not repeat more than once every two weeks 5

Long-Term Urate-Lowering Therapy (ULT)

Indications for Initiating ULT

• Presence of MSU crystals confirms need for definitive treatment regardless of serum uric acid level 1
• Two or more flare-ups per year 4
• Chronic kidney disease 4
• Urolithiasis 4
• Presence of tophi 4
• Chronic gouty arthritis or joint damage 4

Timing of ULT Initiation

• Start ULT after acute flare resolves, typically within 2-4 weeks 1

First-Line ULT: Allopurinol

• Start at 100 mg daily 1, 2
• Titrate upward by 100 mg weekly until target serum uric acid is achieved 1
• Target: <6 mg/dL (0.36 mmol/L) for most patients 1, 2
• Target: <5 mg/dL (0.30 mmol/L) for severe gout (tophi, frequent attacks) 1
• FDA indication: Management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, nephropathy) 6
• NOT recommended for asymptomatic hyperuricemia 6

Renal dose adjustment for allopurinol:

• Start with 50-100 mg in mild to moderate renal insufficiency 2
• Monitor closely for adverse events 2

Alternative ULT Options

• Febuxostat: Does not require dose adjustment in renal impairment 2
  • Important warning: Associated with increased all-cause and cardiovascular mortality; not routinely recommended 4
• Uricosuric agents (probenecid, benzbromarone): For allopurinol-allergic patients with normal renal function and no history of urolithiasis 2

Flare Prophylaxis During ULT Initiation

• Low-dose colchicine 0.5-0.6 mg daily OR low-dose NSAID 1
• Continue for at least 3 months after reaching target uric acid in patients without tophi 1
• Continue for 6 months in patients with history of tophi 1, 7
• Critical: Do NOT treat acute gout flares with colchicine in patients already receiving prophylactic colchicine 5

Monitoring Strategy

During ULT Dose Titration

• Check serum uric acid every 2-4 weeks during dose adjustment 1
• Monitor renal function at baseline and periodically 1
• Adjust allopurinol dose based on creatinine clearance 1

Long-Term Monitoring

• Maintain lifelong ULT once crystals are dissolved 1
• Discontinuation leads to recurrence in approximately 40% of patients 1
• Monitor frequency of gout attacks and size of tophi 2

Lifestyle Modifications (Essential Adjunct to Pharmacotherapy)

• Weight loss if obese 1, 2
• Limit alcohol consumption, especially beer 1, 2
• Avoid high-fructose corn syrup beverages 1, 2
• Reduce purine-rich foods (organ meats, shellfish) 1, 2
• Increase consumption of vegetables and low-fat/nonfat dairy products 1, 2, 7
• Regular exercise and smoking cessation 2

Special Considerations

Drug Interactions with Colchicine

• Strong CYP3A4 inhibitors (clarithromycin, ritonavir, indinavir, etc.) require dose reduction 5
• Maximum daily dose 0.6 mg when used with these agents 5
• Patients with renal or hepatic impairment should NOT receive colchicine with strong CYP3A4 inhibitors 5

Allopurinol Drug Interactions

• Check for interactions with azathioprine, mercaptopurine, or anticoagulants 1

Management of Tophi

• Treat medically through sustained reduction of serum uric acid, preferably below 5 mg/dL 2
• Surgery only indicated for nerve compression, mechanical impairment, or infection 2

Asymptomatic Hyperuricemia

• Do NOT treat pharmacologically to prevent gouty arthritis, renal disease, or cardiovascular events 2