New research reveals more on age-old bouts of gout

By Christiane Loell Dec 20, 2010, 3:06 GMT

Berlin - Gout is a form of arthritis, an acute attack of which often means a red, swollen and intensely painful big toe after a heavy meal. Recent scientific research has shed more light on the molecular processes that cause this joint disorder.

'Gout is a good example of how new findings on a disease known for millennia lead to the development of totally new therapeutic approaches,' noted Andreas Krause, chief physician in the Department of Internal Medicine, Rheumatology and Clinical Immunology at Immanuel Hospital in Berlin.

Gout results from a more or less strongly pronounced genetic defect in which the body is unable to excrete enough uric acid, which builds up in the blood, crystallizes and is deposited in the joints - usually the big toes but sometimes the ankles, knees or hands.

Since the body produces uric acid when it breaks down organic compounds called purines in food, gout attacks usually occur after heavy meals. Gout has therefore long been regarded as a 'disease of affluence.'

'Gout attacks are treated with non-steroidal anti-inflammatory drugs such as diclofenac, and sometimes with cortisone or colchicine,' said Sebastian Ullrich, senior physician in the Gastroenterology Department of Hamburg's Asklepios Clinic Altona.

A plant toxin extracted from the autumn crocus (Colchicum autumnale), colchicine is prescribed only for short periods because of its strong side-effects.

For years, the standard therapies for elevated levels of uric acid in the blood (hyperuricemia) have been allopurinol, a drug that inhibits uric acid production, and dietary changes.

Organ meats (liver, heart, kidneys, etc.), red meat, some kinds of saltwater fish and seafood, beer and sugary beverages are especially high in purines and, as such, conducive to raising uric acid levels.

However, 'allopurinol is of limited usefulness to people with poor kidney function, which is often the case when their uric acid levels are high,' according to Juergen Wollenhaupt, director of the Department of Rheumatology and Clinical Immunology at the Schoen Clinic Hamburg-Eilbek.

But what causes gout's symptoms? In recent years the immune system has been shown to play a large role.

'Uric acid crystals deposited in a joint are absorbed by certain immune cells,' Krause explained. The crystals activate the cells' inflammasome, a multi-protein complex discovered just a few years ago.

This triggers production of interleukin (IL)-1beta, which are signalling molecules that cause gout's characteristic redness, swelling, inflammation and a sensation of intense heat.

Researchers have discovered a number of drugs that inhibit either the production or action of IL-1beta. The drugs' efficacy in gout therapy is now being tested, mainly in the United States, Ullrich said.

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