A 55-year-old man presents to the emergency department with right knee pain. He woke last night with sudden-onset, sharp, 10/10 non-radiating pain in his right knee. He denies recent trauma and he has no known medical problems. He denies tobacco use and will often drink 6-8 beers or spirits on weekend nights. His temperature is 98.6°F (37.0°C), pulse is 90/min, blood pressure is 140/90 mmHg, respirations are 16/min, and oxygen saturation is 97% on room air. Physical exam reveals an erythematous, edematous right knee. Passive extension of the knee is limited by pain. Synovial fluid aspiration is performed and sent for analysis, which reveals 20,000 leukocytes/mm^3, and no organisms visualized. Microscopic examination of synovial fluid is shown in Figure A. Which of the following is the most likely diagnosis?
Gout
Septic arthritis
Lyme arthritis
Pseudogout
Gout
The patient’s sudden-onset knee pain with effusion and synovial fluid findings are characteristic of gout.

Gout is caused by monosodium urate crystal deposition in joint spaces, most commonly in the big toe, ankle, or knee. Crystal deposition in the joint space leads to an intense inflammatory reaction that causes severe pain and joint effusion. Gout is most commonly due to lifestyle factors including a diet high in red meat and alcohol. Medications that cause elevated uric acid levels (such as thiazide diuretics) may also play a role. Conditions resulting in high cell turnover and therefore excessive purine release such as hematologic malignancies may also lead to the development of gout. Patients typically present with sudden-onset, severe pain, erythema, and joint effusion. Synovial fluid analysis will reveal an elevated leukocyte count and negatively birefringent, needle-shaped crystals. Treatment of acute gout is with NSAID medications, colchicine, or steroids depending on presentation and patient-specific factors. Prevention of further attacks is centered around lifestyle changes such as avoidance of red meat and alcohol. Xanthine oxidase inhibitors such as allopurinol are also often used for prevention of further episodes.

Neogi discusses the management of acute gout. She comments that, while synovial fluid analysis is the gold standard of diagnosis, many physicians do not routinely perform it, instead relying on clinical judgment to diagnose gout. The differential diagnosis for a gout-like presentation includes pseudogout, septic arthritis, Lyme arthritis, reactive arthritis, and rheumatoid arthritis.

Figure A shows monosodium urate crystals, which appear as negatively birefringent, needle-shaped crystals under polarized light.

Incorrect Answers:
Answer B: Lyme disease may also presents as a monoarticular arthritis in later stages. However, a recent history of tick exposure and preceding flu-like illness would also be expected.

Answer C: Pseudogout presents similar to gout, but is caused by calcium pyrophosphate deposition. Crystals appear rhomboid shaped and are positively birefringent under polarized light.

Answer D: Septic arthritis typically has higher leukocyte counts (> 50,000/mm^3) in the synovial fluid with organisms visualized on gram stain. Fever would also be expected.

Answer E: Rheumatoid arthritis may present as a monoarticular arthritis with acute flairs. However, crystals visualized in synovial fluid are more suggestive of acute gout.

Bullet Summary:
Acute gout presents with sudden-onset, severe joint pain and is characterized by needle-shaped negatively birefringent crystals visualized under polarized light.