**Background:** This educational case addresses the clinical presentation, differential diagnosis, and management of acute monoarticular arthritis, with a focus on gout. Gout is a crystal-induced arthropathy caused by monosodium urate (MSU) crystal deposition in joints, driven by hyperuricemia (serum urate >6.8 mg/dL). The case contrasts gout with osteoarthritis (OA), rheumatoid arthritis (RA), septic arthritis, pseudogout, and Lyme arthritis, emphasizing synovial fluid analysis as the diagnostic gold standard.
**Methods:** A 52-year-old man presented with acute left knee pain and right first-toe pain after drinking alcohol. His history included prior episodes of first-toe pain during alcohol binges treated with ibuprofen, hydrochlorothiazide use for hypertension, and a family history of gout. Physical examination revealed left knee warmth, erythema, swelling, exquisite tenderness (pain 7/10), and right first metatarsophalangeal joint pain, warmth, swelling, and redness (podagra). Vital signs showed BP 138/78 mmHg, HR 100 bpm, temperature 100.4°F, and BMI 33.5 kg/m². Laboratory evaluation included an STI panel (all non-reactive), CBC (WBC 12,500/mm³, reference 4500–11,000), BMP (normal except non-fasting glucose 110 mg/dL), inflammatory markers (ESR 40 mm/hour, reference <20; CRP 5 mg/L, reference <1), and serum uric acid (12.0 mg/dL, reference 3.0–8.2). Arthrocentesis of the left knee was performed under sterile technique.
**Key Results:** Synovial fluid analysis showed yellow, turbid appearance; WBC count 48,000/mm³ (reference 0–200); 80% neutrophils (reference <25%); presence of needle-shaped, negatively birefringent crystals on compensated polarized light microscopy; and sterile culture. These findings confirmed the diagnosis of acute gouty arthritis. OA was ruled out (synovial fluid in OA shows 200–2000 WBCs/mm³, <25% neutrophils, no crystals). Septic arthritis was excluded by sterile culture and absence of >50,000 WBCs/mm³ (though 48,000 is near the threshold, the presence of crystals and negative Gram stain/culture supported gout). The patient's elevated uric acid (12.0 mg/dL) and history of hydrochlorothiazide use (which interacts with renal urate transporters causing underexcretion) were identified as contributing factors. The case notes that crystal-induced arthritis and septic arthritis may co-occur in up to 5% of cases.
**Clinical Implications:** The case reinforces that arthrocentesis with synovial fluid analysis is essential when septic arthritis is suspected, as physical examination alone may not differentiate inflammatory from septic joints. For this patient, management includes NSAIDs (e.g., Indomethacin) for acute flare, switching from hydrochlorothiazide to losartan (an angiotensin receptor blocker that lowers urate), dietary counseling to reduce alcohol and purine-rich foods, weight loss, and maintaining serum urate <5 mg/dL. Long-term urate-lowering therapy (e.g., Allopurinol, a xanthine oxidase inhibitor) may be considered. The case also reviews the pathogenesis of gout: hyperuricemia leads to MSU crystal precipitation, macrophage engulfment triggers NLRP3 inflammasome activation and IL-1β release, recruiting neutrophils and causing acute inflammation, with spontaneous resolution typically within 10–14 days due to anti-inflammatory cytokines like TGF-β. Primary gout (90% of cases) is usually due to uric acid underexcretion rather than overproduction.