Gout is a form of inflammatory arthritis. The disease is very painful. Prof. Herbert S. B. Baraf from George Washington University helps to understand better gout.
Why is gout so painful?
I don’t know that I can provide you with a specific reason, but it surely is quite painful. The pain is the result of an intense inflammatory reaction triggered by crystal shedding in the affected joint. The joint swells, turns red and is typically extremely sensivitive to the lightest of touches. When a gout flare involves the feet, usually the great toe, which is where the first attacks of gouty arthritis usually occur, the pressure of the bedsheets or even of someone walking in the same room can cause exquisite jolt of pain.
Against pain caused by gout, what drug (molecule) do you prescribe or recommend the most?
There are 3 classes of medication that can be helpful to someone in the throes of an attack. The first is colchicine, which has been used for more than 200 years. NSAIDs are the second class of drug, all of which can be very helpful (indomethacin, celecoxib, ibuprofen and naproxen are some well know and frequently prescribed NSAIDs). Finally, corticosteroids either in tablet form, injected intramuscularly or injected directly into the inflamed joint, can control an attack of gout.
Is allopurinol still the best drug to prevent gout or do you suggest other drugs (molecules)?
I find it useful to regard gout as two disorders. The first is the arthritis and the second is a disorder of the metabolism that causes the blood level of uric acid to be elevated. Since uric acid is not very soluble in the blood (not easily disolved) when the blood level is elevated, crystals of uric acid are deposited in the joints where they build up. This occurs silently for months and years. The first attack of the arthritis occurs as a consequence of that build up. Allopurinol is used to allow those crystal deposits to be removed. A second common oral drug used to lower uric acid is febuxostat. Both are effective, particularly when the patient’s doctor monitors the blood level of uric acid, adjusting the dose of the medication to depress the value enough to allow the crystals to be dissolved so that they can be passed out through the kidneys, in the urine.
Gout is a disease well studied and documented, but is there some new interesting information about gout that came out in the last 3 years (about the disease, treatment, diagnosis)?
There is always new and interesting information coming out about gout. The newest treatment, pegloticase, was introduced more than 10 years ago. It is an enzyme the converts uric acid on contact to a substance that is easily passed out through the urine. It is used for patients whose gout is particularly severe and it is given by an intravenous infusion. Pegloticase, however, frequently stimulates people’s immune system to make antibodies. These antibodies cause the drug to stop working and can even lead to allergic reactions to the drug. Half of the patients treated with pegloticase will lose their response to the drug before it has a chance to work. We are learning that by adding medications that suppress the immune response and antibody formation, the drug can be effective in a larger proportion of treated patient. Finally, there is a new drug, also an enzyme that helps eliminate uric acid, that is currently under investigation.
What are the main reasons (or culprits) for gout, especially in the United States?
The elevated uric acid that causes gout may be the result of many things. Genetics play a big role in how the kidneys dispose of uric acid. Diuretic medications given to patients with heart and kidney disease, may raise the blood uric acid level. We often see elevations of uric acid in individuals who are overweight or diabetic. As our population gets older, more and more people develop elevated uric acid levels and then gout.
Do we know why the men are more affected than women?
Men have higher blood uric acid levels. Female hormones keep the uric acid lower in women and protect against gout. Once menopause occurs, estrogen levels fall in women and the serum uric acid rises. Women who are past menopause start developing gout at the same rate as men. Of course men may start developing gout in their 20’s and 30’s which is very unusual in women and as a result there are many more men than women with gout, overall.
Athletes are more at risk of suffering from gout like marathon runners (some sources speak of a risk 5 times higher), do we know why?
I have not seen this association before. I don’t know if it is true and if it is, other than repetitive trauma to the feet, i don’t have an explanation for you.
Finally, apart from medication, what good advice would you give to prevent gout?
Keeping control of your weight and avoiding excessive alcohol intake are the best advice. Increased blood levels of uric acid in large measure, though, are due to genetic defects in the kidneys that impair how individuals eliminate uric acid.
Interview by Xavier Gruffat (pharmacist, MBA). In October and November 2020.