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?

Pseudogout (Calcium Pyrophosphate Deposition Disease) is the Most Likely Diagnosis

Given the presentation of recurrent monoarticular knee pain over 3 months with normal uric acid levels and normal WBC count, pseudogout is the most probable diagnosis, though synovial fluid analysis remains essential to definitively distinguish between crystal arthropathies and exclude septic arthritis.

Why Each Diagnosis Does or Does Not Fit

Gout - Unlikely

• Normal serum uric acid essentially rules out gout in this clinical context 1
• While approximately 10% of gout patients may have normal uric acid during acute attacks, the absence of hyperuricemia has a markedly low likelihood ratio, making gout diagnosis very unlikely 1
• Hyperuricemia alone has only 53-61% specificity for gout, but its absence is highly predictive against gout 1
• The EULAR guidelines explicitly state that diagnosis of gout should not be made on hyperuricemia alone, and conversely, normal uric acid makes gout improbable 1

Septic Arthritis - Excluded

• Absence of fever, systemic manifestations, and normal WBC count effectively excludes septic arthritis 2, 3
• Septic arthritis characteristically presents with acute onset, fever, and systemic toxicity—none of which are present here 2
• The 3-month duration of recurrent episodes is inconsistent with untreated bacterial infection 4

Reactive Arthritis - Excluded

• The explicit absence of recent illness history rules out reactive arthritis 2, 3
• Reactive arthritis requires a preceding infection (typically gastrointestinal or genitourinary), which is not present in this case 2

Pseudogout - Most Likely

• Recurrent monoarticular knee involvement with normal uric acid is the classic presentation of calcium pyrophosphate deposition disease (CPPD/pseudogout) 4, 5
• The knee is the most commonly affected joint in pseudogout 4, 5
• Pseudogout can present with recurrent episodes similar to gout but without hyperuricemia 4, 6
• In elderly patients particularly, pseudogout can be challenging to differentiate from gout based on clinical features alone 4

Critical Next Step: Synovial Fluid Analysis is Mandatory

Joint aspiration with synovial fluid analysis must be performed to confirm the diagnosis and exclude other conditions 1, 3:

• Monosodium urate crystals (needle-shaped, negatively birefringent) confirm gout with sensitivity and specificity approaching 100% 1, 3
• Calcium pyrophosphate crystals (rhomboid-shaped, weakly positively birefringent) confirm pseudogout 4, 5
• Gram stain and culture must be performed even when crystals are identified, as crystal arthritis and septic arthritis can coexist 3
• The EULAR guidelines strongly recommend that synovial fluid aspiration and crystal examination be undertaken in any patient with undiagnosed inflammatory arthritis 1

Common Pitfalls to Avoid

• Do not rely on serum uric acid alone: Normal uric acid does not completely exclude gout, but makes it highly unlikely in this presentation 1
• Do not assume clinical diagnosis is sufficient: Even typical presentations require crystal confirmation for definitive diagnosis 1
• Do not skip joint aspiration: The risk of missing septic arthritis or making an incorrect diagnosis outweighs the discomfort of the procedure 1, 3
• Do not confuse classification criteria with diagnostic criteria: Most published algorithms are for classification, not individual patient diagnosis 1

If Joint Aspiration Cannot Be Performed

If aspiration is technically impossible, consider advanced imaging 1:

• Ultrasound can detect the "double contour sign" (sensitivity 74%, specificity 88% for gout) 1, 3
• Dual-energy CT (DECT) has 85-100% sensitivity and 83-92% specificity for detecting monosodium urate deposits, though less sensitive in early disease 1, 3
• Plain radiography may show chondrocalcinosis in pseudogout but has limited value for acute diagnosis 4, 5