What is the likely cause of repeated episodes of joint pain in a patient with normal white blood cell (WBC) count and normal uric acid levels, presenting with right knee pain but no fever, tenderness, or systemic manifestations?

Most Likely Diagnosis: Pseudogout (Calcium Pyrophosphate Deposition Disease)

Given the normal uric acid level in the context of recurrent monoarticular knee pain, gout is essentially ruled out, making pseudogout (CPPD) the most likely diagnosis among the options provided. 1

Why Gout is Effectively Excluded

• Normal serum uric acid levels essentially rule out gout in this clinical context of recurrent monoarticular knee pain, according to EULAR guidelines 1
• The absence of hyperuricemia has a markedly low likelihood ratio for gout diagnosis 1
• While hyperuricemia alone has only 53-61% specificity for gout, its absence is highly predictive against gout 1
• EULAR explicitly states that normal uric acid makes gout improbable 1

Why Other Diagnoses Are Unlikely

Septic arthritis is excluded by several key features 2:

• No fever present
• Normal WBC count
• No systemic manifestations
• Subacute 3-month course (septic arthritis presents acutely with fever and systemic toxicity) 2

Reactive arthritis is excluded because 2:

• No recent history of preceding infection (explicitly stated as absent)
• Reactive arthritis requires an antecedent infection 2

Diagnostic Approach Required

Joint aspiration with synovial fluid analysis is mandatory to definitively distinguish between crystal arthropathies 1:

• Look for calcium pyrophosphate crystals (rhomboid-shaped, weakly positively birefringent) for pseudogout
• Monosodium urate crystals (needle-shaped, negatively birefringent) would confirm gout with near 100% sensitivity/specificity 1
• Gram stain and culture must still be performed even when crystals are identified, as crystal arthritis and septic arthritis can coexist 1

Alternative Imaging if Aspiration Cannot Be Performed

• Ultrasound can detect the "double contour sign" (sensitivity 74%, specificity 88% for gout) 1
• Dual-energy CT has 85-100% sensitivity and 83-92% specificity for detecting monosodium urate deposits 1
• Plain radiographs may show chondrocalcinosis in CPPD but have limited value for acute diagnosis 1

Clinical Pitfall to Avoid

The knee is the most common joint affected by pseudogout, and the recurrent pattern with normal uric acid strongly points away from gout 3. Do not assume gout based solely on recurrent monoarticular arthritis—the normal uric acid is a critical distinguishing feature that shifts the diagnosis toward CPPD 1.