Harvey's Garden

Gout

Properties2
tagst2
aliasesHyperuricemia

3 min read

Epidemiology

Etiology

Risk factors

  • Increased uric acid production
    • Dietary sources
      • Purine-rich foods (eg, seafood, red meat)
      • Fructose-containing & alcoholic beverages (particularly beer)
    • ↑ Cell turnover (eg, tumor lysis syndrome)
    • Lesch-Nyhan syndrome (deficiency of HGPRT)
    • ↑ Phosphoribosyl pyrophosphate activity
  • Decreased uric acid clearance
  • Rapid decline in uric acid levels
    • Xanthine oxidase inhibitors (eg, allopurinol)
    • Uricosuric drugs (eg, probenecid)

Pathophysiology

  • Gout
    • An inflammatory crystal arthropathy that is caused by the precipitation and deposition of uric acid crystals in synovial fluid and tissues.
    • It is typically associated with hyperuricemia, but can also occur if uric acid levels are normal.
  • Uric acid
    • An end-product of purine metabolism that is excreted by the kidneys
    • Has somewhat poor water solubility
    • Predisposes to gout
  • Triggers of urate crystal deposition
    • ↑ Uric acid levels (due to insufficient excretion or increased production of purines)
    • Acidosis
    • Low temperature (e.g., cool peripheral joints)
  • Crystalline arthritis: supersaturation of uric acid in extracellular fluid → intraarticular uric crystal precipitation (coated by IgGs) → phagocytosis by polymorphonuclear cells → release of inflammatory mediators and enzymes → local joint inflammation
  • Chronic effects: repeated attacks → aggregations of urate crystals and giant cells (tophi) → deformities and arthritis

Clinical features

  • Acute Gouty Arthritis:
    • Sudden, excruciating monoarticular joint pain, erythema, warmth, and marked swelling.
    • Peaks within 12–24 hours; often begins overnight or early morning.
    • Podagra: 1st metatarsophalangeal (MTP) joint is most common (> 50% initial flares); also affects midfoot, ankles, knees, wrists.
    • Triggers: Trauma, surgery, large meal, alcohol binge, dehydration, initiation of urate-lowering therapy (ULT).
  • Chronic Tophaceous Gout:
    • Develops after years of untreated/poorly controlled disease.
    • Tophi: Painless or tender nodular chalky deposits of MSU crystals in soft tissues, tendons, and cartilage (helix of ear, olecranon bursa, Achilles tendon).
    • Can lead to chronic joint deformities mimicking rheumatoid arthritis (RA).

Diagnostics

  • Synovial fluid leukocyte count
  • Imaging:
    • Plain Radiographs (X-ray):
      • Acute: Soft tissue swelling only.
      • Chronic: “Punched-out” lytic bone erosions with sclerotic margins and overhanging edges (“rat-bite” lesions), preservation of joint space until late.
    • Ultrasound / DECT: “Double contour sign” on articular cartilage; useful if arthrocentesis is inconclusive or inaccessible.

Treatment

Tip

  • NSAIDs (e.g., naproxen, indomethacin) preferred if no contraindications
  • Colchicine used as second-line therapy

Acute gout flare

NSAIDs

  • Naproxen or an alternative (e.g., indomethacin, ibuprofen)
  • Contraindicated in PUD

Colchicine

  • Mechanism of action: binds and stabilizes tubulin subunits → inhibits microtubule polymerization → inhibits phagocytosis of urate crystals, neutrophil activation, migration, and degranulation
  • Adverse effects
    • Gastrointestinal symptoms, e.g., diarrhea, nausea, vomiting, and abdominal pain, are the most common.
    • Rhabdomyolysis , myopathy
    • Polyneuropathy
    • Cardiac toxicity, arrhythmias
    • Nephrotoxicity
    • Myelosuppression
    • CNS symptoms (e.g., fatigue, headache)

Tip

Colchicine is unlikely to be effective when initiated > 24–36 hours after symptom onset. Colchicine is preferable in patients who cannot tolerate NSAIDs or systemic glucocorticoids (e.g., patients with PUD)

Chronic gout

  • Urate-lowering therapy (ULT) is recommended for chronic gout.
    • First-line: xanthine-oxidase inhibitors (allopurinol)
    • Second-line: uricosurics (probenecid)
    • Third-line: recombinant uricase (pegloticase, rasburicase)
  • Administer anti-inflammatory prophylaxis before initiating ULT as ULT may trigger, prolong, or worsen an acute gout flare.
    • Lowering of serum urate levels likely causes preexisting urate crystal deposits to dissolve and become mobile.

Uricosurics

  • Probenecid
  • Mechanism of action
    • Inhibition of uric acid reabsorption along renal proximal convoluted tubules → increased renal elimination
  • Side effects

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