What is the diagnosis and treatment for a patient presenting with gout-like symptoms but normal uric acid levels?

Gout-Like Symptoms with Normal Uric Acid

A normal serum uric acid level does not exclude gout—you must aspirate the joint and examine synovial fluid for monosodium urate (MSU) crystals under polarized light microscopy to confirm or rule out the diagnosis. 1

Why Normal Uric Acid Doesn't Rule Out Gout

• Approximately 10% of patients with crystal-proven gout have normal serum uric acid levels during acute attacks. 1
• Serum uric acid behaves as a negative acute phase reactant, temporarily decreasing during episodes of acute inflammation and stress. 1
• Two studies demonstrated that uric acid levels measured during acute gout attacks were lower—even within the normal range—compared to elevated levels measured during intercritical periods. 1
• The specificity of hyperuricemia for diagnosing gout is only 53-61%, meaning hyperuricemia alone is a poor diagnostic marker. 1

Definitive Diagnostic Approach

Step 1: Synovial Fluid Aspiration and Crystal Analysis

• Aspirate the affected joint and examine synovial fluid under compensated polarized light microscopy—this is the gold standard for diagnosis. 1, 2, 3
• MSU crystals appear as needle-shaped, negatively birefringent crystals. 2
• This test has the highest strength of recommendation (96,95% CI 93-100) from the European League Against Rheumatism. 3
• Perform Gram stain and bacterial culture even if MSU crystals are identified, as gout and septic arthritis can coexist. 2, 3

Step 2: If Synovial Fluid Analysis Is Not Possible

• When crystal identification is not feasible and clinical features are atypical, use advanced imaging to search for MSU crystal deposition. 1
• Dual-energy CT (DECT) has sensitivity of 84-87% and specificity of 84-93% for detecting urate deposits. 1
• Ultrasound can detect the "double contour sign" (sensitivity 50-83%, specificity 76-92%) and tophi (sensitivity 33-65%, specificity 80-95%). 1

Step 3: Clinical Criteria When Imaging/Aspiration Unavailable

• Look for rapid onset of severe pain, swelling, and erythema, especially in the first metatarsophalangeal joint (podagra). 2, 4
• Presence of tophus (proven or suspected) has the highest clinical diagnostic value (likelihood ratio 15.56). 5
• Response to colchicine also has strong diagnostic value (likelihood ratio 4.33). 5
• Clinical algorithms have sensitivity of 85-92% and specificity of 78-93% compared to crystal identification. 1

Common Pitfall to Avoid

Never rely on serum uric acid levels alone for diagnosis—they have limited diagnostic value, especially during acute attacks. 1, 2, 3 The absence of hyperuricemia makes gout very unlikely but does not completely exclude it. 1

Treatment If Gout Is Confirmed

Immediate Management of Acute Flare:

• Initiate anti-inflammatory therapy within hours of symptom onset for maximum effectiveness. 5
• First-line options: 2
  • Colchicine: 1.2 mg loading dose followed by 0.6 mg one hour later (total 1.8 mg over one hour). 2, 6
  • NSAIDs: Full anti-inflammatory doses with proton pump inhibitor if gastrointestinal risk factors exist. 2
  • Corticosteroids: Oral prednisolone 30-35 mg/day for 3-5 days, or intra-articular injection after joint aspiration. 2
• Low-dose colchicine (1.8 mg total) is as effective as high-dose regimens but better tolerated (number needed to treat = 5). 5

Long-Term Urate-Lowering Therapy:

• Initiate urate-lowering therapy after the acute flare resolves (typically 2-4 weeks), as the presence of MSU crystals confirms chronic urate crystal deposition requiring definitive treatment. 2
• Start allopurinol at 100 mg daily and titrate upward by 100 mg weekly until serum uric acid is <6 mg/dL (or <5 mg/dL for severe disease with tophi). 2, 4, 5
• Provide flare prophylaxis with low-dose colchicine (0.5-0.6 mg daily) during urate-lowering therapy initiation and continue for at least 3-6 months after reaching target uric acid. 2, 6, 4
• Monitor serum uric acid every 2-4 weeks during dose titration. 2
• Maintain lifelong urate-lowering therapy once crystals are dissolved, as discontinuation leads to recurrence in approximately 40% of patients. 2

Alternative Diagnoses to Consider

If MSU crystals are not found, consider:

• Calcium pyrophosphate deposition disease (pseudogout): Look for positively birefringent rhomboid crystals in synovial fluid. 7, 8
• Septic arthritis: Gram stain and culture are mandatory to rule this out, as it can rapidly become lethal. 9, 8
• Rheumatoid arthritis: Particularly in elderly patients with polyarticular manifestations. 8
• Basic calcium phosphate deposition disease (calcific periarthritis/tendinitis). 7