A 3-month history of recurrent joint pain, currently presenting with right knee pain, no fever, tenderness, or systemic manifestations, normal White Blood Cell (WBC) count, and normal uric acid levels, what is the likely cause of this patient's symptoms?

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Calcium Pyrophosphate Deposition Disease (CPPD/Pseudogout)

The most likely diagnosis is D - Calcium Pyrophosphate Deposition Disease (CPPD), also known as pseudogout, given the recurrent monoarticular knee pain over 3 months with normal uric acid levels and normal WBC count, which effectively rules out both gout and septic arthritis. 1

Why Normal Uric Acid Rules Out Gout

  • Normal serum uric acid levels essentially rule out gout in the clinical context of recurrent monoarticular knee pain, according to the European League Against Rheumatism 1
  • The absence of hyperuricemia has a markedly low likelihood ratio for gout diagnosis, making it very unlikely 1
  • While serum uric acid can be normal during acute gout attacks, this applies to acute presentations, not a 3-month history of recurrent episodes 2
  • Hyperuricemia alone has only 53-61% specificity for gout, but its absence is highly predictive against gout 1

Why CPPD (Pseudogout) Fits Best

  • CPPD is the second most common crystal arthropathy and frequently affects the knee joint 3
  • CPPD characteristically presents with recurrent episodes of monoarticular arthritis without systemic manifestations, exactly matching this clinical picture 4
  • The knee is one of the most commonly affected joints in CPPD, along with wrists and ankles 4
  • Risk factors for CPPD include advanced age, osteoarthritis, hyperparathyroidism, hemochromatosis, and hypomagnesemia 3

Why Not Reactive or Septic Arthritis

  • Reactive arthritis (B) is excluded by the absence of recent illness history and the 3-month duration of recurrent episodes 2
  • Septic arthritis (C) is ruled out by normal WBC count, absence of fever, and absence of systemic manifestations 3
  • Normal inflammatory markers and lack of acute systemic signs make infection highly unlikely 3

Definitive Diagnostic Approach

  • Joint aspiration with synovial fluid analysis is mandatory to confirm the diagnosis and exclude other conditions 1
  • CPPD diagnosis requires identification of calcium pyrophosphate crystals in synovial fluid—these appear as rhomboid-shaped, weakly positively birefringent crystals under polarized microscopy 3
  • Gram stain and culture must still be performed even when crystals are identified, as crystal arthritis and septic arthritis can coexist 1, 3

Imaging Considerations

  • Look for chondrocalcinosis on plain radiographs of the knee, which appears as linear calcifications in the cartilage 3
  • Conventional radiography and ultrasound are the recommended initial imaging modalities for CPPD diagnosis 3
  • Radiographic evidence of chondrocalcinosis supports CPPD but is not always present, particularly in early disease 5

Common Pitfall to Avoid

  • Do not assume gout based on recurrent monoarticular arthritis alone—normal uric acid makes this diagnosis extremely unlikely, and CPPD is a common mimic that requires crystal identification for definitive diagnosis 1, 4
  • Crystal deposits in joints can be destructive as well as painful, so early identification and management prevents degenerative disease 4

References

Guideline

Diagnosis of Gout

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Differential Diagnosis of Left Hand Swelling and Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Crystal-induced arthritis: an overview.

The American journal of medicine, 1996

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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