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New concepts in the management of Gout

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Gout, one of the most common rheumatic diseases in adulthood, is often inadequately treated. Even though understanding of the molecular basis of hyperuricaemia and gouty inflammation has advanced, gaps in the quality-of-care remain and patient education about the condition and adherence with therapy are often inadequate. In addition, clinicians have questions about new pharmacologic options for uric acid-lowering therapy and for acute attacks.

Some new concepts have emerged in the management of gout. Below are some key points:

Cardiovascular disease link

Hyperuricaemia is strongly associated with metabolic syndrome. The metabolic syndrome is a cluster of symptoms that can include increased blood pressure, elevated insulin levels, high triglycerides, low HDL cholesterol, and high LDL cholesterol, and excess body fat around the waist.

Presence of metabolic syndrome results in a three-fold increased risk of atherosclerotic cardiovascular disease and a five-fold increased risk of type 2 diabetes. Higher insulin levels are known to reduce renal excretion of urate.

Several studies have shown an independent association with serum uric acid and future risk of cardiovascular disease, stroke, and hypertension. The Coronary Artery Risk Development in Young Adults (CARDIA) study with 4,053 young adults found significantly higher BMI, fasting insulin, and triglycerides and lower HDL cholesterol in patients with hyperuricaemia.

Any patient with gout or hyperuricaemia should trigger a high clinical suspicion and investigation for potential coexistence of the metabolic syndrome and associated comorbidities.

Biologic activity of uric acid

Uric acid is a danger signal that acts as endogenous adjuvant when tissue is injured during immune presentation. In gout, the uric acid crystals activate complement by the alternative pathway, but also by the classical pathway through the accumulation of immunoglobulin. The crystals interact with macrophages, produce cytokine interleukin-1, and then generate other cytokines.

Gouty arthritis

The diagnosis of gout is not made on the basis of a high uric acid. Rather, there should be a history of acute, intermittent attacks of pain, swelling and tenderness in between 1-4 joints, usually involving the toes, ankles and knees. It is rare to encounter polyarticular gout or persistent inflammatory arthritis. The gold standard for diagnosis is aspiration of joint and demonstration of needle shaped, negatively birefrigent cryslas. Alternatively, a typical clinical presentation may also be sufficient to diagnose gout. Uric acid levels can be normal during an acute attack.


Gout management should also include pain control. The most effective pain reduction therapies include:

  • NSAIDs and glucocorticoids
  • Colchicine: The Acute Gout Flare Receiving Colchicine Evaluation (AGREE) trial considered the efficacy of high-dose versus low-dose colchicine versus placebo and found less toxicity with the low dose (0.5mg, 1-3 times daily)
  • Newer interleukin-1 inhibitors: anakinra, rilonacept, and canakinumab. All have been found effective for significant reduction in gout pain and chronic pain.


Gout treatment should mirror treatment for hypertension, with lifestyle and dietary changes. The prevalence of gout has doubled since the 1970s, which could be related to the prevalence of high-fructose corn syrup in the American diet. Sweetened soft drinks should be eliminated because they have been found to increase the risk of gout twofold. Hypertensive patients with gout and metabolic syndrome should be treated with losartan or amlodipine, which has a better risk-benefit ratio than diuretics for these patients.

Diet for gout

Many fallacies exist regarding the low purine diet. Firstly it has to be recognised that very high levels of uric acid cannot be lowered through diet alone. The target for uric acid is less than 6mg/dL to prevent future attacks. Decreasing foods rich in high fructose corn syrup, reducing fruit juices, red meats, organ meats, shellfish and alcohol consumption are beneficial. In addition, studies have shown benefits to eating cherries or concentrated cherry juice and at least two servings of low fat dairy products per day. It is not required to stop consumption of normal amounts of lentils or any kind of vegetable.

Urate-lowering therapies

Therapies used for urate-lowering will have no effect on pain but are necessary for renal function and to reduce gout attacks. Indications for urate-lowering include multiple gout flares each year, advanced gouty arthritis, presence of tophi, gout with chronic kidney disease, recurring renal stones, and daily urinary urate excretion of 1,000mg or more.

When the urate level is lower than 6mg/dL, the patient’s flares can be eliminated, the tophi resolve, and quality-of-life improves.

Current therapies for urate-lowering include:

  • Allopurinol: Most physicians prescribe a 300mg allopurinol dose or lower, and only 3% of physicians prescribe a dose higher than 300mg, even though the US Food and Drug Administration (FDA) has approved doses up to 800mg. A 300mg, or lower dose, has been found ineffective in many cases, even though some published guidelines recommend the 300 mg dose. The allopurinol dose should be tailored for the individual patient to bring uric acid levels under 6 mg/dL. Maximum doses in patients with normal renal function can be up to 800mg/day
  • Febuxostat: A new selective xanthine oxidase inhibitor and nonpurine analogue, febuxostat is metabolised in the liver, orally administered, rapidly absorbed, and highly protein bound. A phase III trial, the CONFIRMS trial, found that more patients reached the target of lower than 6mg/dL at six months with an 80mg dose. The 40mg dose outperformed the 80mg dose in renally impaired patients, and 44% of patients reached a 5mg/dL target with the higher dose
  • Pegloticase: Not yet approved by the FDA, pegloticase is a purified recombinant porcine urate oxidase that catalyses the conversion of uric acid to allantoin, a more soluble and readily excretable form. With injections given every two weeks, there was a remarkable decline in baseline, resolution of tophi, and impressive lowering of uric acid.

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This web site is run by an Arthritis Specialist based in Dubai, United Arab Emirates. On this site you will find news about the latest in arthritis, information about research results in the field, tips and information and diet and exercise, and much more.



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