Gout: Acute Attack, Crystals and Urate-Lowering Therapy

Gout is an inflammatory arthritis caused by deposition of monosodium urate crystals in and around joints, as a result of persistently high uric acid levels. It causes sudden, extremely painful attacks. With modern urate-lowering treatment it can be well controlled.

Risk factors

• Male sex and increasing age; postmenopausal women.
• Diet:
  • red meat and organ meats
  • seafood
  • beer and spirits
  • sugary drinks high in fructose
• Obesity and metabolic syndrome.
• Chronic kidney disease.
• Drugs:
  • thiazide and loop diuretics
  • low-dose aspirin
  • ciclosporin
  • pyrazinamide
• High cell turnover: psoriasis, haematological cancers, tumour lysis.

Clinical features

• Acute gout: sudden onset of severe pain, swelling and redness of a single joint, often overnight, peaking within 24 hours. The first metatarsophalangeal joint (big toe) is classic ("podagra"). Other sites include the ankle, midfoot, knee, wrist and fingers.
• Attacks settle over 1–2 weeks, but recur if urate stays high.
• Chronic tophaceous gout: deposits of urate (tophi) on the ears, fingers, elbows and Achilles tendon, with joint damage.
• Uric acid kidney stones.

Diagnosis

• Joint aspiration and polarised light microscopy: needle-shaped, negatively birefringent urate crystals. This is the gold standard. Always send fluid for Gram stain and culture, to exclude septic arthritis.
• Serum urate: may be normal during an acute attack. Recheck about 2 weeks after it settles.
• Other blood tests: kidney function, glucose, lipids and blood count.
• Imaging: X-ray (punched-out erosions with overhanging edges in chronic gout), ultrasound ("double contour" sign) or dual-energy CT.

A hot, swollen joint with fever must be treated as septic arthritis until proven otherwise.

Treatment of an acute attack

Start treatment as early as possible:

• NSAIDs (with gastroprotection if needed), or
• Colchicine at low dose. Diarrhoea is the main side effect; reduce the dose in kidney impairment and watch for drug interactions.
• Corticosteroids (oral, or intra-articular injection) when NSAIDs and colchicine are unsuitable.

Rest, elevate the joint, and apply ice packs.

Long-term urate-lowering therapy (ULT)

Indications:

• recurrent attacks
• tophi
• gouty arthritis with joint damage
• chronic kidney disease
• kidney stones

Many guidelines now offer ULT after the first attack.

Drugs and how to use them:

• Allopurinol is first-line. Start at a low dose and increase gradually ("treat to target").
• Febuxostat is an alternative. Use it with caution in cardiovascular disease.
• Target serum urate: below 360 µmol/L (6 mg/dL), or below 300 µmol/L (5 mg/dL) with tophi or frequent attacks.
• Give low-dose colchicine or an NSAID as prophylaxis for the first months of ULT, because flares can occur as urate falls.
• Do not stop ULT during an acute attack if the patient is already taking it.

Safety: allopurinol can rarely cause severe skin reactions. The HLA-B*5801 allele increases this risk, and testing is advised before starting in some populations.

Lifestyle

• Weight loss.
• Reduce alcohol, sugary drinks and high-purine foods.
• Stay hydrated.
• Review diuretics where possible.

Gout versus pseudogout

Pseudogout (calcium pyrophosphate deposition disease):

• often affects the knee or wrist in older people
• rhomboid-shaped, positively birefringent crystals
• chondrocalcinosis on X-ray

Exam pearls

• Negatively birefringent needles mean gout; positively birefringent rhomboids mean pseudogout.
• Serum urate can be normal during an attack.
• Always exclude septic arthritis in a hot, swollen joint.

For more, see our Exam Night Notes 1.0: Rheumatology and the Medicine Companion.

Test yourself

5 exam-style single-best-answer questions. Choose your answer, then tap “Show answer”.

1. Crystals in gout are:

   1. None
   2. Rhomboid, positively birefringent
   3. Cholesterol plates
   4. Calcium oxalate
   5. Needle-shaped, negatively birefringent
   Show answer

   Answer: E. Needle-shaped, negatively birefringent
   Monosodium urate crystals are needle-shaped and negatively birefringent.

2. Hot swollen knee with fever. What must be excluded first?

   1. Bursitis
   2. Osteoarthritis
   3. Tendinitis
   4. Fibromyalgia
   5. Septic arthritis
   Show answer

   Answer: E. Septic arthritis
   Aspirate and send for Gram stain and culture; septic arthritis destroys joints quickly.

3. A patient already on allopurinol has an acute flare. What should be done with allopurinol?

   1. Give it IV
   2. Stop it
   3. Continue it and treat the flare
   4. Double it immediately
   5. Switch to aspirin
   Show answer

   Answer: C. Continue it and treat the flare
   Do not stop urate-lowering therapy during an attack.

4. Target serum urate for most patients on urate-lowering therapy:

   1. Below 360 µmol/L (6 mg/dL)
   2. Below 600 µmol/L
   3. Any level
   4. Below 100 µmol/L
   5. Above 400 µmol/L
   Show answer

   Answer: A. Below 360 µmol/L (6 mg/dL)
   Aim for below 360 µmol/L, or below 300 with tophi or frequent attacks.

5. Which drug can raise uric acid and trigger gout?

   1. Vitamin C
   2. Losartan
   3. Thiazide diuretics
   4. Allopurinol
   5. Colchicine
   Show answer

   Answer: C. Thiazide diuretics
   Thiazide and loop diuretics reduce urate excretion.

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Disclaimer

For education and exam preparation only. This is not medical advice and must not be used to diagnose or treat patients. Always follow current clinical guidelines and the advice of qualified senior colleagues.