Prophylaxis, Treatment, and Foods to Avoid in Gout

Hello. I am Jonathan Kay, Professor of Medicine and Director of Clinical Research in the Division of Rheumatology at the University of Massachusetts Medical School and UMass Memorial Medical Center, both in Worcester, Massachusetts.

Today I would like to talk about gout. Gout is a very common disease and one of the few curable diseases treated by rheumatologists. We have typically treated gout by lowering serum urate levels and using prophylactic medications or nonsteroidal anti-inflammatory drugs and perhaps corticosteroids, either orally or injected into the joint. We have treated gout on the basis of clinical experience and lessons passed down from generation to generation, but we have never had evidence-based guidelines to treat this very common and important condition.

In October 2012, the American College of Rheumatology published guidelines for the management of gout and urate-lowering treatment in 2 parts in Arthritis Care and Research.^[1,2] I would like to highlight some of the important features of these guidelines.

These recommendations included patient education on diet and lifestyle, reminding us of the secondary causes of hyperuricemia (such as comorbid conditions) and elimination of nonessential prescription medications (such as diuretics) that might produce hyperuricemia. Clinicians should evaluate the burden of disease (such as palpable tophi) and the frequency and severity of acute and chronic symptoms and signs and use all of this information to choose appropriate pharmacologic intervention.

To improve the signs and symptoms of gout, the serum urate target should be < 6 mg/dL, and ideally < 5 mg/dL, in patients with tophaceous gout. The guidelines recommend either allopurinol or febuxostat as the first-line urate-lowering treatment agent, or probenecid if at least 1 xanthine oxidase inhibitor is contraindicated or not tolerated.

During the first 6 months of urate-lowering therapy, concomitant pharmacologic anti-inflammatory gout attack prophylaxis is warranted. This is typically accomplished with colchicine (an expensive drug), but nonsteroidal anti-inflammatory drugs can be used as long as the patient does not have underlying kidney disease. If necessary, corticosteroids can be prescribed.

The long-term management of gout includes continuing prophylaxis in the patient with ongoing gout symptoms and signs and in patients with at least 1 tophus on physical examination, and regularly monitoring serum urate levels and side effects such as rash or allergic reactions to urate-lowering therapy. Once gouty attacks and all palpable tophi have resolved, treatment should be continued indefinitely to maintain a serum urate level of < 6 mg/dL.

The modifiable risk factors for gout include obesity and dietary excess, including excessive alcohol intake. Metabolic syndrome causes type 2 diabetes mellitus and can predispose to psoriasis, gout, hypertension, and hyperlipidemia. Modifying these risk factors will not only benefit the patient by reducing the risk for gout but will also reduce the risk for coronary artery disease and stroke. A history of urolithiasis is an indication for urate-lowering therapy, and chronic glomerular or interstitial renal disease may be a clue that the patient is at risk of developing a toxic gout.

The guidelines point out that a genetic mutation is common among Hon, Chinese, and Korean patients and can lead to a markedly increased occurrence of allopurinol hypersensitivity syndrome. Clinicians should consider testing for this gene in patients at risk.

For dietary recommendations, patients should be advised to avoid organ meats that are high in purine content (such as sweetbreads, liver, and kidney). Avoiding these foods is not problematic for most patients, but a few patients enjoy these delicacies. Patients should also avoid high fructose corn syrup, sweetened sodas, and other beverages or foods containing fructose. Alcohol should be restricted to 2 servings daily for men and 1 serving daily for women.

During periods of frequent gout attacks or when advanced gout is under poor control, patients should abstain from alcohol. They should limit serving sizes of beef, lamb, pork, and seafood with high purine content (such as sardines and shellfish), but limiting serving sizes is probably a good idea for everybody. Patients should limit serving sizes of naturally sweet fruit juices, table sugar, and sweetened beverages and desserts and reduce their intake of table salt, including high-sodium sauces and gravies. This is a good recommendation for all patients because these foods can increase blood pressure and predispose to cardiovascular disease. Patients should be encouraged to drink low-fat or nonfat dairy products and eat plenty of vegetables.

Patients who have no tophi on examination should be initiated on single-agent xanthine oxidase inhibitor therapy, titrated to a maximum appropriate dose. Allopurinol should be started at 100 mg daily and gradually increased to 300 mg daily, depending on the patient's response in terms of lowering of serum urate level. The dose can be increased to 800 mg daily, if needed. Typically, patients who don't respond to allopurinol are underdosed as long as they are not experiencing toxicity. If the serum urate target of < 6 mg/dL is not achieved, or if disease activity continues, a uricosuric agent, such as probenecid, should be added to the xanthine oxidase inhibitor, and both agents should be titrated to the maximum appropriate dose. If the serum urate target is still not achieved and disease activity persists with frequent flares, or if the patient has chronic tophaceous gouty arthropathy, consideration should be given to initiation of therapy with pegylated uricase (pegloticase).

To summarize, clinicians should recommend that patients maintain a healthy lifestyle, avoiding foods high in purines or fructose, limit portions of red meats, shellfish (high in purine content), salt, and sugar, and encourage dairy products and vegetables. Xanthine oxidase inhibition should be initiated to reduce the serum uric acid level to < 6 mg/dL, and ideally < 5 mg/dL. Xanthine oxidase inhibition should be continued as long as the disease remains active, with prophylaxis initiated for the first 6 months of therapy. It is unclear whether primary care physicians will adhere to the recommendations for prophylaxis, which might drive more of these patients to rheumatologists for appropriate management of gout.

Pegloticase is appropriate for patients with severe tophaceous disease who are refractory to or intolerant of conventional, appropriately dosed urate-lowering therapy. However, pegloticase must be administered carefully, making certain that a rise in serum uric acid level does not occur despite continued administration of the medication because that may be a harbinger of an allergic reaction.

The treatment of gout is now codified by the American College of Rheumatology guidelines, which include recommendations for management of acute gout attacks. Gout attacks are treated with nonsteroidal anti-inflammatory drugs, systemic corticosteroids, colchicine, or intra-articular corticosteroids along with initiation of appropriate urate-lowering therapy to manage the disease chronically. Of note, the recommendations say that it is not necessary to wait until after an acute attack of gout is over before initiating chronic urate-lowering therapy.

These guidelines are very timely and appropriate and will be very helpful in the management of gout.