What is the cause of a patient's recurrent joint pain with normal uric acid levels and no systemic manifestations, presenting with right knee pain and normal white blood cell (WBC) count?

Pseudogout is the Most Likely Diagnosis

Given the presentation of recurrent joint pain with normal uric acid levels, normal WBC count, absence of fever, and no systemic manifestations, pseudogout (calcium pyrophosphate deposition disease) is the most probable diagnosis, though definitive diagnosis requires synovial fluid analysis demonstrating calcium pyrophosphate crystals.

Why Not Gout

Normal Uric Acid Does Not Exclude Gout, But Makes It Less Likely

• While serum uric acid can be normal during acute gout attacks (occurring in approximately 10-63% of cases), the absence of hyperuricemia makes gout significantly less likely 1, 2, 3
• Uric acid behaves as a negative acute phase reactant and temporarily decreases during acute inflammation, but this patient has no fever or systemic manifestations suggesting acute inflammation 2
• The diagnosis of gout should not be made on the presence of hyperuricemia alone, nor should it be excluded solely on normal levels, but normal uric acid substantially reduces the probability 1
• The specificity of hyperuricemia for gout diagnosis is only 53-61%, meaning normal levels argue against gout in the absence of crystal confirmation 1

Clinical Context Matters

• This patient has recurrent episodes over 3 months without the typical acute inflammatory presentation of gout (no fever, no erythema mentioned, no rapid onset reaching maximum in 6-12 hours) 1
• The absence of systemic manifestations and normal WBC count further reduces the likelihood of acute gout 1

Why Pseudogout is More Likely

Clinical Presentation Fits Better

• Pseudogout commonly presents with recurrent monoarticular or oligoarticular arthritis affecting large joints, particularly the knee 4
• The presentation can be subacute or chronic, matching this patient's 3-month history without acute systemic features
• Normal uric acid levels are expected in pseudogout, as it is caused by calcium pyrophosphate dihydrate crystal deposition, not monosodium urate 4

Why Not the Other Options

Reactive Arthritis is Unlikely

• Reactive arthritis typically follows a recent infection (gastrointestinal or genitourinary), which this patient lacks 4
• Usually presents with systemic features and extra-articular manifestations (conjunctivitis, urethritis), which are absent here

Septic Arthritis is Excluded

• Normal WBC count makes septic arthritis highly unlikely 5
• Absence of fever and systemic manifestations argues strongly against infection 1
• The recurrent nature over 3 months without progression is inconsistent with untreated septic arthritis

Definitive Diagnostic Approach Required

Synovial Fluid Analysis is Mandatory

• Joint aspiration with synovial fluid analysis for crystal identification is essential and should be performed in any patient with undiagnosed inflammatory arthritis 1
• For gout: look for needle-shaped, negatively birefringent monosodium urate crystals 1
• For pseudogout: look for rhomboid-shaped, weakly positively birefringent calcium pyrophosphate crystals 4
• Gram stain and culture should still be performed even if crystals are identified, as gout/pseudogout and sepsis can coexist 1

Imaging May Help

• Plain radiographs can show chondrocalcinosis in pseudogout, particularly in the knee menisci and triangular fibrocartilage of the wrist 4
• Ultrasound or dual-energy CT can detect monosodium urate crystal deposition if gout remains a consideration despite normal uric acid 1

Critical Pitfall to Avoid

Do not rely on serum uric acid levels alone to diagnose or exclude gout 1, 2. The gold standard remains crystal identification in synovial fluid, which will definitively distinguish between gout (monosodium urate crystals) and pseudogout (calcium pyrophosphate crystals) 1.