What is the likely diagnosis and treatment for a patient with hyperuricemia and chronic foot pain?

Elevated Uric Acid and Chronic Foot Pain: Diagnosis and Management

The most likely diagnosis is chronic gouty arthritis, and you should pursue synovial fluid aspiration for monosodium urate (MSU) crystal identification to confirm the diagnosis before initiating long-term urate-lowering therapy. 1

Diagnostic Approach

Step 1: Crystal Identification (Gold Standard)

• Synovial fluid aspiration with polarized light microscopy for MSU crystals is mandatory and provides definitive diagnosis with a likelihood ratio of 566.60. 1, 2
• This should be performed in any patient with undiagnosed inflammatory arthritis, regardless of how typical the presentation appears. 1
• MSU crystals appear needle-shaped with strong negative birefringence under polarized microscopy. 3

Step 2: Clinical Diagnosis (When Aspiration Not Feasible)

If joint aspiration is not possible, gout is highly suggested by the following features: 1

• Monoarticular foot involvement (especially first metatarsophalangeal joint) - this is the initial presentation in 50% of cases 3
• Previous similar acute episodes with pain-free intervals
• Rapid onset of severe pain and swelling (worst within 24 hours)
• Erythema overlying the joint
• Male gender
• Associated cardiovascular diseases
• Hyperuricemia

Critical caveat: The diagnosis should NOT be made on hyperuricemia alone - only 22% of patients with uric acid >9 mg/dL develop gout over 5 years, and uric acid levels frequently drop to normal during acute inflammatory episodes. 1, 4

Step 3: Imaging (When Clinical Diagnosis Uncertain)

• Ultrasound is superior to plain radiographs for detecting tophi and the "double contour sign" at cartilage surfaces, which is highly specific for urate deposits. 1
• Plain radiographs have limited value for acute flares but can show chronic MSU deposition. 1

Essential Workup Before Treatment

Identify Contributing Factors

Screen for these specific causes of hyperuricemia in every patient: 1

• Medications: thiazide/loop diuretics, low-dose aspirin, cyclosporine, tacrolimus, niacin 1
• Dietary factors: excess alcohol (especially beer and spirits), non-diet sodas, high-purine foods (meat, shellfish) 1
• Metabolic conditions: chronic kidney disease, obesity 1

Assess Comorbidities

Systematically evaluate for: 1

• Renal impairment (check creatinine, urinalysis)
• Hypertension
• Ischemic heart disease and heart failure
• Diabetes mellitus
• Dyslipidemia
• Obesity

Special consideration: Screen for uric acid overproduction (24-hour urine uric acid) if disease onset before age 25 or history of kidney stones. 1

Treatment Strategy

Acute Management (If Currently Flaring)

• First-line: NSAIDs or corticosteroids (choice depends on comorbidities) 5, 6
• Second-line: Colchicine 5, 6
• Do NOT discontinue treatment during a flare - gout flares frequently occur when initiating urate-lowering therapy. 7

Long-Term Urate-Lowering Therapy

Initiate after confirming diagnosis and addressing acute symptoms: 1

• Target serum uric acid <6 mg/dL (360 μmol/L), or <5 mg/dL (300 μmol/L) for tophaceous gout 2, 6

• First-line agent: Allopurinol - inhibits xanthine oxidase, reducing uric acid formation 8, 5

  • Start low and titrate upward until target achieved 5
  • Reduces both serum and urinary uric acid within 2-3 days 8
  • Full effects manifest after one week or more 8

• Alternative: Uricosuric agents (probenecid) - only in patients with preserved renal function and no nephrolithiasis history 1, 5

• Refractory cases: Pegloticase - PEGylated uric acid enzyme for chronic gout refractory to conventional therapy 7

  • Requires premedication with antihistamines and corticosteroids 7
  • Must be administered in healthcare settings prepared for anaphylaxis 7

Flare Prophylaxis During Urate-Lowering Initiation

• Mandatory: Low-dose colchicine for at least 6 months when starting urate-lowering therapy 4, 5
• This prevents flares triggered by rapid uric acid fluctuations 4

Medication Adjustments

• Discontinue non-essential medications that elevate uric acid: thiazide/loop diuretics, niacin, calcineurin inhibitors 1
• Do NOT discontinue low-dose aspirin (≤325 mg daily) for cardiovascular prophylaxis - its modest effect on uric acid is negligible 1

Lifestyle Modifications

Implement these evidence-based changes: 1

• Limit: alcohol (especially beer/spirits), high-purine meats, shellfish, high-fructose corn syrup
• Encourage: weight loss if obese, adequate hydration
• Avoid: crash diets and dehydration

Monitoring Strategy

• Measure serum uric acid before each follow-up to guide dose titration 2
• Consider discontinuing therapy if uric acid rises above 6 mg/dL on treatment, particularly with 2 consecutive elevated levels, as this indicates loss of therapeutic response and increased infusion reaction risk (for biologic agents) 7

Referral Indications

Consider rheumatology referral for: 1

• Unclear etiology of hyperuricemia
• Refractory symptoms despite treatment
• Difficulty reaching target uric acid with renal impairment
• Multiple adverse events from urate-lowering therapy