Gout and hyperuricaemia

Causes of hyperuricaemia:

Impaired excretion of uric acid:

• Chronic renal disease
• Drug therapy:
• Thiazide diuretics
• Low-dose aspirin
• Lead toxicity
• 1˚ hyperparathyroidism
• Hypothyroidism

Increased production of uric acid:

• Myeloproliferative disorders (e.g. polycythaemia vera)
• Lymphoproliferative disorders (e.g. leukaemia)
• Carcinoma
• Severe psoriasis

Uric acid synthesis:

• Uric acid is the last step in the breakdown pathway of purines
• The last 2 steps are catalysed by xanthine oxidase and are:

1. Conversion of hypoxanthine to xanthine
2. Conversion of xanthine to uric acid

Clinical features:

Hyperuricaemia causes 4 clinical syndromes:

• Acute urate synovitis – gout
• Chronic polyarticular gout
• Chronic tophaceous gout
• Urate renal stone formation

Acute gout:

• Typically middle-aged men
• Sudden onset of agonising pain, swelling and redness of the first MTP joint
• The attack occurs at any time but may be precipitated by:
• Too much food or alcohol
• Dehydration
• Commencement of a diuretic

• Untreated attacks last ~7 days
• In 25% of attacks, a joint other than the great toe is affected

Chronic polyarticular gout:

Is unusual, except for elderly people:

• On longstanding diuretic treatment
• In renal failure

Chronic tophaceous gout:

• Sodium urate forms smooth white deposits (tophi) in skin and around joints
• They may occur on the:
• Ear lobe
• Fingers
• Achilles tendon

• Large deposits are unsightly and ulcerate
• There is chronic joint pain and sometimes superimposed acute gouty attacks

Investigations:

Joint fluid microscopy

Serum urate:

• Is usually raised (>600μmol/L)
• If normal, re-check it several weeks after the attack as the level falls immediately after an acute attack

Serum urea and creatinine:

• For signs of renal impairment

Treatment:

The use of NSAIDs in high doses rapidly reduces the pain and swelling. Initial doses (taken with food) are:

• Naproxen 750mg immediately, then 500mg 8-12 hourly
• Diclofenac 75-100mg immediately, then 50mg 6-8 hourly
• Indomethacin 75mg immediately, then 50mg 6-8 hourly

After 24-48 hours, reduced doses are given for a further week. In individuals with a history of peptic ulceration, alternative treatments include:

• Colchicine 1mg immediately, then 0.5mg 6-12 hourly (but this causes diarrhoea)
• Methylprednisolone IM or intra-articular depot

Treatment with agents which reduce serum urate levels:

• Only when the attacks are frequent, severe or associated with renal impairment or when the patient finds NSAIDs or colchicine difficult to tolerate should allopurinol or a uricosuric agent be used
• They should never be started within a month of an acute attack and always be under cover of a course of NSAID or colchicine for the first 4-6 weeks
• Allopurinol (300-600mg):
• Blocks xanthine oxidase, which converts xanthine into urate
• Reduces serum urate levels rapidly and is relatively non-toxic (but should be used in low doses (50-100mg) in renal impairment
• Skin rashes are the most common side-effect

• Uricosuric agents:
• E.g. probenecid
• Increase urate excretion
• Used in individuals who are allergic to allopurinol
• Should NOT be used in renal failure or in patients with urate stones