Ted R. Mikuls, MD, MSPH, Umbach Professor of Rheumatology, Vice Chair for Research, Department of Internal Medicine, University of Nebraska Medical Center

According to studies, gout is strongly associated with several comorbidities—including cardiovascular disease, hypertension, diabetes, and chronic kidney disease (CKD)—and increases mortality risk. The comorbidities linked to gout can increase risks for lower extremity amputations (LEA). “Many patients with gout have either undergone LEA or are being considered for it,” says Ted R. Mikuls, MD, MSPH. “In at least some of these cases, there may be an underappreciation for the role gout played in the clinical presentation. For example, gout is well known to mimic common indications for amputation, such as non-healing wounds or osteomyelitis.”


Seeking a Better Understanding of LEA in Patients With Gout

Despite the disease burden, gout can be effectively treated with anti-inflammatory agents for flares and urate-lowering therapy (ULT) to reduce or stop disease progression. For a study published in JAMA Network Open, Dr. Mikuls and colleagues examined rates and factors associated with LEA in patients with gout. “Recognizing that LEA is associated with significant morbidity and poor long-term outcomes, we wanted to understand whether gout sufferers more commonly undergo amputation,” explains Dr. Mikuls. “We also wanted to see if this risk was due to comorbidities or other factors commonly seen in gout and to what degree LEA might be preventable among those with gout.”

For the study, investigators used national administrative data and multivariable Cox proportional hazards regression models to examine the associations of gout with LEA. The study included patients who used United States Department of Veterans Affairs services from 2000 to 2015. Patients with gout were identified using diagnostic codes and matched with up to 10 controls by age, sex, and year of benefit enrollment. Overall, the study included data on nearly 6 million patients, including 556,521 with gout and 5,368,397 without gout.


At Least Some LEAs in Patients With Gout Might Be Preventable

“Our study showed that U.S. veterans with gout were 20% more likely than those without it to undergo LEA,” Dr. Mikuls says. “Moreover, increased rates of amputation among those with gout were independent of other risk factors, such as age, sex, comorbidities, cigarette smoking, and BMI. Among those with gout, we also found that amputation rates were lower for patients with evidence of optimal serum urate control. Given the wide availability of highly effective ULT, our results suggest that at least some of these amputations might have been preventable.”

Patients with gout who had poor serum urate control—defined as higher than 7 mg/dL during the preceding year, on average—was associated with a 25% to 37% increase in the rate of amputation. Conversely, treatment with ULT was not associated with the LEA rates. The highest rate of LEA was seen in patients with gout and diabetes (Figure). Of note, the authors extrapolated their data to the general U.S. adult population with gout and observed an approximately 2% cumulative incidence of gout during the 15-year period assessed. This suggests as many as 184,000 patients with gout are at risk of undergoing LEA during the coming years in the U.S. alone.


Call to Action: Determine if Gout Is Contributing to the Clinical Picture

“Our results serve as an important reminder to healthcare providers to pause and ask the important question of whether gout might be contributing to the clinical picture when evaluating patients for possible LEA,” says Dr. Mikuls. “Studies are needed to find effective strategies to systematically screen patients who are being considered for LEA, perhaps by checking serum urate concentrations or seeing if there is a history of gout or gout-related symptoms. Such efforts could help identify subsets of patients that might benefit from further evaluation. For patients with a history of gout or marked hyperuricemia, non-invasive imaging techniques could help identify gout as a mimic in some circumstances and might lead to different sets of interventions, but this warrants more research using prospective study designs.”