Below is a reprint of an article I wrote for Just Joints, an online newsletter for health professionals distributed by the Arthritis Foundation Upper Midwest Region. This article will be posted in the archives eventually, but be sure to check out the other articles in this series.
Also, be sure to check out Episode 2 of The Rheumatology Podcast, where we discuss an article looking at starting allopurinol during acute gout attacks, as well as some of our other experiences with gout.
The incidence of gout has risen dramatically in the U.S. population, likely driven by the increased incidence of comorbid risk factors that include obesity, diabetes, chronic kidney disease, cardiovascular disease, and hypertension. Despite advances in current therapies for gout that can prevent unnecessary joint damage, tophi, and recurrent flares, many patients remain undertreated. In October 2012, the American College of Rheumatology (ACR) released guidelines on the management of gout in two parts. This article will briefly review part one of the recent ACR guidelines, which focus on nonpharmacologic and pharmacologic management of hyperuricemia, which is often misunderstood and mismanaged, but likely plays the biggest role in long term control of gout.
Beginning with focus on patient education on diet and lifestyle changes, most physicians are aware of recommendations on the avoidance of organ meats in the management of hyperuricemia, and are also aware of limiting servings of seafood, beef, lamb, and pork. Avoidance of alcohol, especially beer, is also widely recognized. Newer recommendations that clinicians might not be aware of are to avoid foods and beverages containing high-fructose corn syrup, which has recently been associated with gout.
One of the most important parts of the recent guidelines is the recommendation to lower serum uric acid levels to less than 6 mg/dl at a minimum, and to less than 5 mg/dl in more severely affected patients, such as those with tophi present. Initial treatment of hyperuricemia should begin with one of the xanthine oxidase inhibitors (XOI), typically allopurinol. The initial allopurinol starting dose recommended was 100 mg daily in patients with normal renal function (50mg daily in stage 4 or higher CKD), which needs to be titrated upward until uric acid is at target. Failure to titrate the dose of allopurinol until uric acid levels are at goal is a common mistake in the management of gout.
Some physicians might be undertreating hyperuricemia over concern regarding side effects when increasing the dose of allopurinol, stopping long before reaching the maximal FDA approved dose of 800mg per day. Even in the setting of CKD, with proper monitoring for toxicity, studies have shown that allopurinol doses can safely be increased above 300mg per day, which is also pointed out in the recent recommendations. There are certain patient populations who are considered high risk of severe allopurinol hypersensitivity reactions, especially Koreans with CKD, and those of Han Chinese or Thai descent, and these patients should be screened for the HLA-B*5801 allele prior to starting allopurinol, which is associated with increased risk of hypersensitivity in these groups.
The newer XOI, febuxostat, is typically reserved for patients who have experienced adverse events from allopurinol, or have not achieved uric acid target despite maximal doses of allopurinol. Additional uric acid lowering therapy with uricosuric agents, typically probenecid in the U.S., is advised in patients who do not reach target uric acid levels with an XOI, given they do not have contraindications to these agents such as nephrolithiasis or significant renal impairment. A newer agent given intravenously, pegloticase, which is a recombinant uricase that metabolizes uric acid, can be given to patients with refractory disease.
Part two of the recent gout guidelines give advice on prophylaxis for patients recently started on uric acid lowering therapy to prevent attacks, usually with colchicine, and also discusses management of acute gout flares. Current knowledge of therapeutic strategies for gout has become increasingly important, especially as we are likely to see more patients with this condition in the upcoming years.