Snapshot A 46-year-old man presents to the emergency department due to severe pain of the first metatarsophalangeal (MTP) joint of acute onset. He describes the pain as 10/10 and sharp. Medical history is significant for obesity and hypertension and was recently started on furosemide. Social history is notable for alcohol use disorder managed with naltrexone. He reports to recently increasing his alcohol intake due to environmental stresses. On physical exam, the right first MTP joint appears erythematous, swollen, and is warm. Preparations are made to perform an arthrocentesis. Introduction Clinical definition deposition of monosodium urate crystals leading to a crystal-induced arthropathy Epidemiology demographics more common in men and the elderly risk factors conditions that increase serum urate levels (hyperuricemia) Etiology hyperuricemia defined as a serum urate level > 6.8 mg/dL causes of hyperuricemia include dietary habits alcohol red meat seafood medications thiazide diuretics loop diuretics cyclosporine low-dose aspirin pyrazinamide disorders of urate overproduction hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency also known as Lesch-Nyhan syndrome type I glycogen storage disease (Von Gierke disease) tumor lysis syndrome Pathogenesis purine catabolism results in uric acid production factors that influence serum uric acid level include purine intake purine synthesis uric acid excretion by the kidneys and gut conditions that increase the serum uric acid concentration increases the risk of crystal formation deposition of uric acid crystals lead to an inflammatory response resulting in a gout flare Prognosis acute attacks typically self-resolve patients have an increased risk of recurrence advanced gout and tophi may result without proper treatment Presentation Symptoms acute gout extreme pain of the affected joint (e.g., foot or ankle) chronic tophaceous gout stiff or swollen joint deformity of the affected joint (e.g., nodules) Physical exam acute gout typically mono-articular e.g., involvement of the first metatarsophalangeal joint (podagra) sudden onset of joint tenderness erythema and warmth swelling chronic tophaceous gout subcutaneous nodules typically non-tender overlying skin can be taut abnormal color white or yellow deposits Studies Labs hyperuricemia (> 6.8 mg/dL) not sufficient for the diagnosis the level may be lower during an attack Synovial fluid analysis joint fluid aspiration and crystal analysis is gold-standard negatively birefringent needle-shaped crystals under polarized light yellow under parallel light and blue under perpendicular light Making the diagnosis demonstrating monosodium urate crystals in an affected joint via polarizing light microscopy when this is not possible, the diagnosis can be clinically made Differential Septic arthritis this is a highly important differential diagnosis to exclude since this changes management distinguishing factors a synovial fluid analysis will demonstrate no crystals > 50,000 cells/mcL Gram stain may be positive Pseudogout distinguishing factors caused by deposition of calcium pyrophosphate crystals crystal analysis will demonstrate weakly positive birefringent rhomboid crystals under polarized light blue under parallel light Treatment Management approach acute attacks can be managed with nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or colchicine acute gout attacks typically self-resolve in 1-2 weeks; however, treatment will hasten recovery choice of treatment is dependent on certain patient factors (e.g., comorbidities, gout history, attack characteristics, availability, and cost) preventing future attacks are managed by urate-lowering therapy Conservative lifestyle modification indication a preventative measure for patients with gout examples decrease alcohol, red meat, and seafood consumption weight loss discontinuing or modifying medication (e.g., changing their loop diuretic) Medical medical management of acute attacks NSAIDs indication monotherapy agent for acute gout attacks colchicine indication monotherapy agent for acute gout attacks corticosteroids indication monotherapy agent for acute gout attacks medical management for preventing a future attack urate-lowering therapy indication to prevent future attacks medications xanthine oxidase inhibitors (first-line) e.g., allopurinol and febuxostat uricosuric agents (second-line) e.g., probenecid