Gout

Background

Gout is a common disorder, which affects around 1% of the population. It is caused by excess uric acid in the blood. Excess uric acid forms monosodium urate (MSU) crystals that are deposited in the joints, kidneys, and soft tissues, resulting in arthritis, kidney damage, and lumps under the skin respectively.

In healthy individuals, uric acid is formed after eating certain high-protein foods. Usually most of the uric acid is then excreted by the kidneys in the urine. Excess uric acid in the blood can result from:

• A diet that is high in animal-based protein, especially meat and seafood.
• Moderate-high alcohol intake, especially beer.
• Being overweight – gout is associated with the metabolic syndrome.
• Some medications, including diuretics and low-dose aspirin.
• Kidney disease can reduce urinary excretion of uric acid.
• Overproduction of uric acid can occur in disorders that cause high cell turnover, such as some myeloproliferative disorders (excessive numbers of cells produced by the bone marrow) and some types of anaemia (haemolytic anaemia and pernicious anaemia).

Other risk factors for gout include:

• Having a family history of gout.
• Age – in general, uric acid levels are elevated for 20 years before gout develops. In men uric acid levels rise at puberty so gout is often diagnosed in their 4th to 6th decade of life. Oestrogen protects young women from gout; uric acid levels rise at menopause and gout is often diagnosed in their 6th to 8th decade of life.

Clinical features

In most cases, the first attack of gout presents with extreme pain and swelling in a single joint, often the big toe (podagra). The pain begins abruptly and the joint is red, hot, and extremely tender. Occasionally the first attack of gout affects multiple joints simultaneously. Patients may have a fever, particularly if many joints are involved. Untreated attacks of gout usually last 7-10 days, following which the patient may be symptom-free until the next attack.

Acute gout

Initially, attacks of gout may be months or years apart. An attack of gout can be brought on by:

• A sudden increase in blood uric acid level, e.g. after an episode of binge-drinking, eating a large quantity of high-protein food, dehydration, trauma, or starting a medication that raises uric acid.
• A sudden decrease in blood uric acid level, e.g. after starting a medication that lowers uric acid.

If gout remains untreated, the following complications can occur:

• Attacks become more frequent, last for longer, and involve more joints.
• Collections of MSU crystals, called tophi, develop in the soft tissues and appear as firm lumps under the skin. Tophi generally develop around 10 years after the first attack of gout in untreated patients and are commonly found around the elbows, hands, and feet. Tophi contain a white pasty material and as they enlarge they work their way towards the skin surface to drain. Small sinus tracts (tunnels) may develop and secrete white pasty material. Alternatively a large blister may form, which ruptures leaving a continuously draining ulcer.
• Tophi develop in and around the joints leading to joint destruction and chronic (long-term, continuous) joint pain and stiffness.
• Panniculitis (inflammation of the fat under the skin) is a rare complication of gout. This presents as nodular (lumpy) lesions of the legs that ulcerate and drain a fluid that contains MSU crystals.
• MSU crystals can be deposited in the kidneys producing inflammation and scarring (called chronic urate nephropathy). Kidney stones are also common in patients with gout.

Gouty tophi

More images of gouty tophi ...

Diagnosis

• Gout is diagnosed in the initial attack by taking a small sample of fluid from around the affected joint space. MSU crystals can be identified under the microscope. This test is also important to rule out other causes of an inflamed joint, such as infection.
• Joint x-rays may show findings consistent with gout, but these findings are not diagnostic on their own. Furthermore, early on in the disease, x-rays may be normal or show soft tissue swelling only.
• Uric acid levels may be elevated in the blood, but this finding alone is not diagnostic.

Treatment

The treatment of gout is divided into 3 phases: treatment of the acute attack, uric acid-lowering therapy, and prevention of acute flares.

Treatment of the acute attack

Options for treatment to relieve the pain of an acute attack of gout include:

• NSAIDs (non-steroidal anti-inflammatory drugs) – These are generally the medicines of choice for most patients who do not have underlying health problems. Aspirin should be avoided as it can alter uric acid levels and worsen the attack.
• Corticosteroids – If only one joint is involved, corticosteroids can be injected directly into the joint space to help reduce the systemic effects of oral steroids.
• Colchicine – Up until recently, colchicine was the treatment of choice for acute gout. However, due to recent safety concerns, colchicine is now only recommended if NSAIDs or corticosteroids are inappropriate. High dose colchicine therapy is no longer recommended.

The above medicines do not prevent joint damage, tophi, or kidney disease.

Medicines to reduce uric acid

Long term management of gout focuses on lowering uric acid levels. These medicines can prevent attacks of gouty arthritis and prevent MSU crystals from being deposited in the tissues. Medicines that lower uric acid levels should not be started during an acute attack of gout; instead they should be started a few weeks after the attack has resolved.

• Allopurinol is the most effective uric-acid lowering therapy, but it has a number of side effects and interactions with other medicines. Dermatological side effects of allopurinol range from a mild morbilliform eruption (measles-like rash, which resolves when the drug is discontinued) to Stevens-Johnson syndrome / toxic epidermal necrolysis and drug hypersensitivity syndrome.
• Probenecid is an alternative uric acid lowering medicine with fewer significant side effects than allopurinol.

Prevention of acute flares

Acute flares of gout can be precipitated by the sudden reduction in blood uric acid that occurs when uric acid lowering medicines are started. For this reason it is important to take a low (preventative) dose of a NSAID or colchicine to reduce the likelihood of a flare developing. In patients unable to take either of these medicines, an oral corticosteroid can be considered. Patients who have only occasional attacks of gout, may only need to take these medicines for 2-3 weeks. Whereas patients with multiple tophi may need to continue treatment for months.

Draft 25 April 2010