Gout

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

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