Gout

Gout is a crystal-induced arthropathy resulting from sustained hyperuricemia exceeding the physiologic saturation point of monosodium urate (6.8 mg/dL at 37°C). Urate crystal deposition activates the NLRP3 inflammasome in resident macrophages, triggering caspase-1-mediated IL-1β release and an intense neutrophilic inflammatory cascade. Chronic hyperuricemia leads to tophaceous disease with cartilage and bone erosion. The clinician must differentiate gout from septic arthritis and pseudogout, prescribe acute flare management, initiate and titrate urate-lowering therapy (ULT) to achieve target serum urate <6 mg/dL, manage comorbidities including CKD and cardiovascular disease, and consider pharmacogenomic testing (HLA-B*5801) before prescribing allopurinol in high-risk populations.

Diagnostics & workup: - Order synovial fluid aspiration and analysis: negatively birefringent needle-shaped MSU crystals under polarized microscopy (gold standard) - Send synovial fluid for Gram stain and culture to rule out septic arthritis (can coexist with gout) - Order serum uric acid (may be normal during acute flare; establish baseline after resolution) - Order CMP: creatinine, eGFR (renal function for drug dosing), electrolytes, hepatic panel - Order CBC with differential to assess for leukocytosis and rule out infection - Order ESR and CRP to quantify inflammatory burden - Consider dual-energy CT (DECT) for atypical presentations or chronic tophaceous gout evaluation - Order HLA-B*5801 testing before initiating allopurinol in Southeast Asian, African American, or Korean patients