By Dr John Riordan FRACP, Consultant Rheumatologist

1. Urate can accumulate for more than 10 years before clinical features of gout develop
Gout is due to the accumulation and deposition of monosodium urate crystals. The incidence and prevalence of gout is increasing because of a number of factors including longevity, ageing population, chronic kidney disease, dietary factors and medications such as diuretics and low-dose aspirin.

It is likely that urate accumulates for at least 10 years before clinical features develop.

While gout is a common condition in general practice, the principles of management may be poorly understood.

2. Chronic, often migratory, joint inflammation may occur in long-standing gout

The first acute attack usually presents with an exquisitely painful, swollen and tender first metatarsophalangeal joint. Other joints may also be involved in the initial attack, particularly the mid and hind foot joints.

Over time, further joints including wrists and knees, may suffer acute attacks. Initially, the patient is asymptomatic between attacks. Chronic joint inflammation may occur in some patients, usually after many acute attacks of gout. Tophi may also become apparent in long-term sufferers but do occasionally develop without any clear history of acute attacks of gout.

3. An elevated serum urate alone is not sufficient to diagnose gout
Although the diagnosis of gout is often made on the typical clinical features, if possible, diagnosis should be confirmed by the identification of monosodium urate crystals in a joint aspirate.

The presence of hyperuricaemia is not diagnostic of gout. Indeed, most patients with hyperuricaemia do not develop the clinical features of gout. In up to 40% of cases, serum urate may be within the normal range during the acute attack.

Although there is some evidence that hyperuricaemia may be a cardiovascular risk factor, treating hyperuricaemia with urate-lowering therapy is not regarded as appropriate unless the patient also has proven gout.

4. An acute gout flare can re-occur after the first attack within 6 months to 2 years

After the first acute flare, if not treated with urate-lowering therapy, 62% of patients encounter a second flare within one year, 78% of patients within two years and 89% of patients by five years.

With this in mind, gout management must address two main aspects – treatment of acute attacks and prevention of consequences of ongoing urate accumulation, including tophaceous deposits, recurrent acute attacks, kidney stones and joint damage.

Acute attacks of gout should be treated with colchicine (500 microgram tablets – two tablets (1 mg) stat, then one tablet an hour later and then one tablet twice daily) or a nonsteroidal anti-inflammatory drug (NSAID), provided they are not contraindicated. Where these options are not available or the attack is difficult to control, intra-articular corticosteroids, or occasionally a short course of oral corticosteroids, may be used.

Prevention of the consequences of ongoing urate accumulation and recurrent flares should be treated with a urate-lowering therapy such as allopurinol or febuxostat.
5. 30% of patients with untreated gout and not prescribed preventive medication develop tophi within five years.
Failure to deplete urate stores in gout patients will result in the development of clinically apparent tophi within five years in 30% of cases.

Tophi are most commonly recognised in or around joints. However, they may deposit in almost any tissue. Tophi frequently cause local tissue damage, including joint destruction, and may ulcerate or even “burst”, especially on the toes and fingers.

Tophi on the olecranon regions and hands are unsightly and may cause embarrassment. Tophi may become acutely inflamed with the tophaceous material being confused with pus, resulting in inappropriate use of antibiotics for what is a chemical – rather than infective – inflammation.
Bone erosion in left foot due to gouty tophi build up

6. Treating to target cures gout

To cure gout, urate stores must be fully depleted. To achieve this, the serum urate must be maintained at a level below the solubility of urate in extracellular fluid thus enabling its mobilisation and excretion.

The target serum urate level is <0.36 mmol/L or preferably <0.30 mmol/L, especially in patients with tophi or large urate loads. Achieving and maintaining serum urate below the target is imperative in the treatment of gout.

Two types of urate-lowering therapy are available:

Xanthine oxidase inhibitors: Allopurinol is the traditional xanthine oxidase inhibitor. Febuxostat is a recently approved non-purine, selective xanthine oxidase inhibitor indicated for the treatment of symptomatic hyperuricaemia in conditions where urate deposition has already occurred (gouty arthritis and/or tophus formation) in adults with gout.

Uricosurics: Probenecid is the only uricosuric available in Australia.

Xanthine oxidase inhibitors are usually the first choice as they are effective and well tolerated. Probenecid is rarely used as first line and may not be effective in chronic renal insufficiency.

Because of the risk of precipitating an acute attack, urate-lowering therapy should be started at a low dose (eg allopurinol 50 mg daily or febuxostat 40 mg daily) and slowly increased (every 2-4 weeks) until target serum urate level is achieved (allopurinol in 50 or 100 mg increments and febuxostat from 40 mg to 80 mg). A low starting dose also minimises the risk of precipitating a severe cutaneous reaction to allopurinol.

Caution should be used when allopurinol is prescribed to Han Chinese people because of the high risk of a life threatening skin reaction, unless they are proven to be HLA-B5801 negative.

7. Acute gout attacks can still occur with urate-lowering therapy

While urate stores are being depleted with urate-lowering therapy (both allopurinol and febuxostat), acute gout attacks may still occur.

Prophylactic therapy is usually required during this time (which can last months) to reduce the frequency and severity of such attacks.

Low-dose colchicine (500 micrograms once or twice daily) or NSAIDs are the usual prophylactic therapies advised but must be used cautiously in some patients, especially in chronic kidney disease.

Once urate-lowering therapy has depleted the urate stores, no further attacks of gout should occur. To prevent reaccumulation of urate, urate-lowering therapy must be maintained long-term to keep serum urate below the target level of 0.36 mmol/L.

By following these management principles, acute attacks of gout and long-term consequences of urate accumulation can be avoided and gout therefore cured.

References available on request.

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