Susceptibility to gout
Historically, gout was viewed as a disease of wealthy men who could afford rich foods and plentiful alcohol. The risk factors that predisposed to gout in the past are present today for most American middle-aged men and postmenopausal women (whose susceptibility rises once uric-acid control by estrogen is no longer present). Obesity and weight gain are strong risk factors for gout, and there is an epidemic in industrialized countries of the now familiar metabolic syndrome.
Over recent decades, several large population studies indicate that uric acid levels are increasing in the general population.1 This epidemiologic evidence has implications not only for gout, but perhaps also for cardiovascular disease (hyperuricemia has deleterious effects on vascular endothelium) and other significant comorbidities.4
Men tend to have higher serum urate levels, but women catch up after menopause. Regardless of age or gender, urate crystallizes at a serum level of 6.8 mg/dL. Thus men or women whose serum urate is >6.0 are at risk for developing gout. The ranges considered “normal” by most clinical labs typically include values for serum urate above its solubility. Clinical manifestations increase with the length of time cells are surrounded by high levels of serum urate.
Aggressive treatment of the comorbidities of gout often affects serum urate. Diuretics, which are still first-line treatment for hypertension and heart failure, lead to increased uric acid reabsorption. The thiazides in particular are notorious for this effect. Use of this class of antihypertensive is associated with increased acute flares of gout. The first thing often noted in a patient suspected of having gout is recent treatment with hydrochlorothiazide (HCTZ) or furosemide (Lasix).
Transplant patients have a uniquely high risk of gout. Cyclosporine is a widely used antirejection agent, which rapidly and significantly increases serum urate through its effects on the kidney. With the increase in organ and stem-cell transplantation, it is important to remember that gout develops quickly and with impressively high serum urate levels (often >10) in this group. Furthermore, be alert to atypical manifestations. While gout in the non-transplanted individual affects primarily the lower extremities, gout in the transplant patient is often found in the upper extremities and axial joints.
In general, alcohol consumption raises serum urate levels. Purine-rich beer confers the greatest risk, followed by hard liquor. Modest intake of wine does not increase risk, but heavy consumption might.6 Patients whose gout is generally well controlled with medication often experience a flare after binge drinking.
Food with high purine content similarly leads to an overproduction of serum urate. A recent study found the highest risk for gout was associated with consumption of large amounts of red meat and seafood. Dairy-based foods were negatively correlated. Fructose is not a purine, but new research links it to hyperuricemia as well as cardiovascular risk.
Extremely purine-rich foods are not typically eaten often or in large quantities. These include anchovies, herring, sardines, mussels, clams, organ meats, and beer in excess. While these foods are best avoided, most gout sufferers need more significant uric acid reductions than the 1 mg/dL drop gained by eliminating these foods.
Making the diagnosis
The definitive diagnosis of gout is made by tapping a joint effusion or suspected tophaceous deposit and examining the aspirate under a compensated polarizing microscope. Monosodium urate crystals have a characteristic needle shape and show strong negative birefringence (Figure 2). It is best to use a clinical lab staffed with medical technicians trained in the accurate use of a compensated polarizing microscope.
Sending the fluid for cell count as well as culture will rule out other causes of an inflamed joint (e.g., septic, traumatic, or rheumatoid arthritis or other crystal disorder).
The common practice of making the diagnosis of “presumed gout” based on an acute hot joint, hyperuricemia, and a good response to colchicine treatment leads to diagnostic errors. A good clinical response to oral colchicine is not pathognomonic for gout, although many clinicians erroneously jump to that conclusion.
Repeated presentations of a warm swollen joint in the appropriate physical distribution with a background setting of sustained hyperuricemia may well be “presumed gout.” Unfortunately, many busy clinicians are not comfortable aspirating a warm tender joint or do not have a clinical lab available for rapid, reliable crystal analysis of synovial fluid aspirates.
In early gout, x-rays are not diagnostic, but in late-stage gout, there are characteristic x-ray changes. Overhanging edges on the margins of the bones and punched-out lesions can be dramatic (Figure 3).