Clinical Pearls & Morning Reports
Published November 16, 2022
Gout is a chronic disease of monosodium urate deposition characterized by arthritis flares and disability. Lasting days to weeks if untreated, flares are inflammatory, often intensely painful, and debilitating. Read the NEJM Clinical Practice Article here.
Q: What are the risk factors for gout?
A: Hyperuricemia is a necessary but insufficient risk factor. This condition, which is defined as a circulating uric acid level that exceeds the solubility threshold for monosodium urate (>6.8 mg per deciliter), is three to five times as common as gout. Other risk factors for hyperuricemia and gout include male sex, older age, dietary and lifestyle factors, obesity, renal impairment, and the use of medications (e.g., diuretics) that increase urate concentrations.
Q: Describe a typical presentation of gout.
A: Patients typically present with an acute flare. Characteristic features of flare include monoarticular involvement of the foot — especially the first metatarsophalangeal joint or ankle — along with a history of similar episodes, rapid onset or escalation of pain or swelling (or both), erythema, associated coexisting conditions, and hyperuricemia. In patients who have had untreated disease for a long period of time but have not yet received a diagnosis, tophi may be present, most often detected over the extensor surface of the elbow or other joint areas.
A: The European League against Rheumatism has provided a framework for patient evaluation, calling for an approach centered on the identification of monosodium urate crystals in aspirates of synovial fluids or tophi. A positive result on polarized microscopy yields 100% specificity and is diagnostic in patients who present with suggestive symptoms and signs. Joint aspiration and other targeted testing procedures are critical to rule out mimics that occur in isolation or with gout, such as septic arthritis or pseudogout. In circumstances in which necessary equipment or technical skills are not available, a diagnosis can be made on the basis of suggestive clinical features and diagnostic algorithms. With persistent diagnostic uncertainty, imaging may be informative. Conventional radiography, most often targeting symptomatic joints in the feet or hands, may show bony erosions of advanced gout characterized by overhanging edges and sclerotic margins. Although hyperuricemia is a causal risk factor for gout, serum urate measurement has a limited role in diagnosis owing to low specificity.
A: Flares are treated with the goal of rapid pain resolution and restoration of function. Recommended first-line therapies should be individualized on the basis of coexisting conditions and include colchicine, nonsteroidal antiinflammatory drugs, and glucocorticoids. To expedite treatment, subspecialty guidelines recommend that patients keep medication readily available (the so-called “pill-in-a-pocket” approach) to take when initial symptoms occur. Allopurinol, a xanthine oxidase inhibitor available since the 1960s, remains the first-line urate-lowering therapy. Other options include febuxostat (a xanthine oxidase inhibitor), probenecid (a uricosuric), benzbromarone (a uricosuric not available in the United States), and less commonly, pegloticase. The guidelines of subspecialty societies recommend a treat-to-target approach characterized by the initiation of low-dose urate-lowering therapy with gradual adjustment to reach and maintain serum urate concentrations of less than 6.0 mg per deciliter. In contrast, the American College of Physicians, citing a lack of robust evidence to support this approach, advocates for a treat-to-avoid-symptoms strategy. Therapies for gout can affect patients’ coexisting conditions, and treatment of those co-existing conditions can affect gout. Although epidemiologic studies have linked dietary factors and obesity with gout risk, the efficacy of dietary and lifestyle interventions in management of gout has been the subject of limited study, with available data suggesting only modest benefit.