Gout: New Guidelines for Managing An Ancient Disease
Gout has inflicted pain on humanity for thousands of years. From Egyptian royal mummies—whose skeletons show gout-associated arthropathy—to the highly descriptive depictions of suffering by Greek and Roman playwrights, into generations of England’s aristocracy (most notably Henry VIII); gout has taken a toll on many notable historical figures.
In contrast, gout in the 21st century has not been so discriminating. Gout’s worldwide prevalence has been dramatically increasing in men and women irrespective of class, nationality, or ethnicity.1 Gout is now the most common inflammatory arthropathy in the United States,2 where it is estimated to affect more than 8 million people, or 3.9% of adults.
Gout presents as an acute mono- to poly-articular joint inflammation. Exquisite pain, redness, and swelling occur along with the potential for serum leukocytosis, low-grade fever, and elevated blood inflammatory markers.3 Gout has a predilection for the big toe, called podagra (up to 50% of first-time attacks); although ankles, knees, elbows, wrists, and hands also may be affected. An early gout attack mimics how the innate immune system treats infection, with the body going into overdrive to fight off this “foreign” invader.4
That foreign material in gout is uric acid (UA) crystals, which are deposited into the joint and soft tissue. This occurs when soluble serum urate precipitates out of solution and forms monosodium urate crystals, usually when the bloodstream concentration is >6.8 mg/dL (the point of physiologic saturation).5,6 By lowering and maintaining UA levels <6 mg/dL, the UA crystal burden will eventually resolve, eliminating acute attacks.
Since the symptoms of infection may mimic acute gout, or even co-exist, it is ideal to make a diagnosis by joint fluid analysis, looking for negatively birefringent monosodium urate crystals. In between acute gout flares, while the serum urate remains greater than the point of solubility, the deposition of UA crystals—forming a tophus—continues when the patient is asymptomatic (Figure 1). This process, called the intercritical period, is associated with low-grade joint inflammation and continued joint destruction. Visible and even deforming tophi can develop within 5 years of onset of gout in 30% of untreated patients.7
New Treatment Recommendations
It is not coincidental that the rising prevalence of gout has paralleled the rise in metabolic syndrome, renal impairment, transplant medicine, and cardiovascular disease. Gout is associated with multiple disease states and risk factors (Table 1), and gout patients often require complex medical management. They may have contraindications to common treatments, and require medications that may alter uric acid levels, making overall management challenging.8 Concomitant with a better understanding of pathophysiology and the increased prevalence of gout, a greater pharmacologic armamentarium has come to fruition over the last decade.
Responding to this increasing prevalence as well as to new therapies based on our improved understanding of gout pathophysiology, the American College of Rheumatology (ACR) recently developed non-pharmacologic and pharmacologic treatment recommendations for both acute and chronic gout.
For this directive the ACR brought together two groups of experts: a core expert panel that provided input into case scenario development, and a task force that voted on the scenarios. Using the RAND/UCLA consensus guidelines, this committee of “goutologists,” general rheumatologists, primary care providers, a nephrologist, and a patient representative went to work to develop guidelines that improve the quality and care of gout patients.9,10
After an approximately 2-year endeavor, the ACR task force (TF) published guidelines and recommendations in the October 2012 issue of Arthritis Care & Research. Four aspects of gout management were highlighted between two publications (Part 1 and Part 2). The first of these addressed urate-lowering therapy (ULT) options and their indications in managing gout and tophaceous gouty arthropathy. The second manuscript outlined recommendations regarding prophylaxis and treatment of acute gouty attacks. The TF did not focus on diagnosis and imaging but rather presumed the diagnosis of gout in all scenarios was correctly made. Importantly, the level of opinion designated referred to the efficacy, safety, and quality of treatments, and made no comparisons for cost or cost effectiveness.9,10 This review will highlight some of those TF recommendations.
Part 1: Recommendations for Treating the Hyperuricemia Of Gouty Arthritis
Like all medical interventions, ULTs have unique mechanisms of action, side-effect profiles, and patient risk profiles that must be considered and discussed with the patient to arrive at the best therapeutic option. The new recommendations outline those who definitely need intervention and medical management of their gout and symptoms while prioritizing the prevention of adverse effects. As not all gout patients are alike, the TF distinguished those who have only one attack (or no more than one every 12 months) and those with gout causing greater disability. Indications for ULT include patients with any gouty tophus or tophi; patients who experience at least one attack along with continued renal impairment (chronic kidney disease II or higher); or if a patient has two or more attacks in a 12-month period. Additionally, uric acid urolithiasis at any time was also a consensus indication for treatment with ULT.
Part 1 of the guidelines emphasizes the necessity of lowering serum urate to reduce a gout patient’s crystal burden even in the absence of clinically evident tophi; and regarded reducing and maintaining serum urate concentrations below a specific target, or “treating to target,” as paramount. The recommended target, based upon the physiological saturation of serum urate, is below 6 mg/dL, and less than 5 mg/dL in some cases when the crystal burden and associated morbidity is high.
Recommendations for Non-pharmacological and Pharmacological ULT
Once gout has been established, regardless of the severity, the TF agreed that the first step in lowering a patient’s serum urate levels was through prevention; including education, dietary changes, lifestyle modification, and control of co-morbid, predisposing conditions (Figure 2). For patients with a first attack, this represents an opportunity to lower serum urate levels with lifestyle changes such as weight loss, therefore potentially preventing further crystal deposition. Although there are no randomized controlled trials evaluating the efficacy of lifestyle changes, epidemiologically, studies have shown lower serum urate levels can be achieved with weight loss in the obese, eating a healthy diet, exercise, staying well hydrated, reduction in alcohol consumption, and smoking cessation.9,11,12 Providers encouraging such lifestyle changes will benefit their patients’ overall health and address co-morbidities in addition to gout.