What is the likely diagnosis and management for a middle-aged patient with recurrent knee pain and swelling, no history of trauma or infection, and lab results showing hyperuricemia (high uric acid level) and elevated urea?

Diagnosis: Gout (Answer: A)

The most likely diagnosis is gout, given the combination of recurrent knee monoarthritis with markedly elevated serum uric acid (600 mg/dL, which is approximately 10 mg/dL) and hyperuricemia in a middle-aged patient without trauma or infection. 1

Diagnostic Reasoning

Why Gout is Most Likely

• Hyperuricemia with joint inflammation strongly suggests gout, with a likelihood ratio of 9.74 when hyperuricemia is defined as mean + 2SD above normal population values 1
• The combination of recurrent monoarticular arthritis and hyperuricemia increases the probability of gout to approximately 60% based on composite diagnostic features 1
• Elevated urea suggests possible renal involvement, which is common in gout and can both result from and contribute to hyperuricemia 2
• The recurrent nature (episode 3 months ago) fits the pattern of intercritical gout with acute flares separated by asymptomatic periods 3

Why Other Diagnoses are Less Likely

• Septic arthritis (B) is excluded by the absence of infection history, and the patient would typically present with fever, acute onset, and systemic toxicity—none mentioned here 1
• Reactive arthritis (C) requires a preceding infection (typically genitourinary or gastrointestinal), which is explicitly absent in this case 1
• Calcium pyrophosphate deposition disease (D, pseudogout) does not cause hyperuricemia; it is associated with normal or low uric acid levels and would show calcium pyrophosphate crystals, not elevated uric acid 3

Critical Diagnostic Steps

Definitive Diagnosis Required

Joint aspiration with synovial fluid analysis for monosodium urate (MSU) crystals under polarized light microscopy is mandatory to confirm the diagnosis, as it provides near-definitive diagnosis with a likelihood ratio of 566.60 1

• Synovial fluid aspiration should be performed in any patient with undiagnosed inflammatory arthritis, regardless of how typical the clinical presentation appears 1
• Clinical diagnosis alone, even with hyperuricemia, is not definitive without crystal confirmation 1

Important Caveats

• Approximately 10% of patients with acute gout have normal serum uric acid levels during an attack because uric acid acts as a negative acute phase reactant during inflammation 1, 4
• Hyperuricemia alone should never be used to diagnose gout, as only 22% of patients with uric acid >9 mg/dL develop gout over 5 years, giving hyperuricemia a specificity of only 53-61% 1
• Gout and septic arthritis can coexist, so if there is any clinical suspicion of infection, Gram stain and culture must still be performed even if MSU crystals are identified 1

Management Approach

Acute Phase Management

• Treat the acute flare first with NSAIDs, colchicine, or corticosteroids before initiating urate-lowering therapy 3
• Do not start allopurinol during an acute attack, as it can paradoxically worsen or prolong the flare 2

Long-Term Urate-Lowering Therapy

Initiate urate-lowering therapy with allopurinol after the acute flare resolves, targeting serum uric acid below 6 mg/dL (360 μmol/L), or below 5 mg/dL (300 μmol/L) for tophaceous gout 5, 2

• Allopurinol inhibits xanthine oxidase, reducing both serum and urinary uric acid production by blocking uric acid formation rather than increasing excretion 2
• The elevated urea suggests possible renal impairment, which makes allopurinol preferable to uricosuric agents that increase renal uric acid excretion and could worsen renal function 2

Additional Evaluation

• Assess for metabolic syndrome components (obesity, hypertension, hyperlipidemia, hyperglycemia), as these are common comorbidities that require management 1, 5
• Evaluate renal function thoroughly given the elevated urea, as chronic hyperuricemia can cause urate nephropathy 2, 3
• Consider 24-hour urinary uric acid excretion if the patient is young (<25 years), has family history of early-onset gout, or has renal calculi to identify overproducers versus underexcretors 1