According to a recent study based on data from the National Health and Nutrition Examination Survey, gout affects an estimated 5.9 million men and 3.3 million women, comprising 3.9% of adults in the United States. The prevalence rates of hyperuricemia (serum urate level, >7.0 mg/dL in men and >5.7 mg/dL in women) were found to be about 20% in each group.1 Results from a study published in 2017 showed that all-cause hospitalizations among patients with gout in the United States increased by >410% between 1993 and 2014 compared with an increase of just 4.8% in the overall US population.2

Despite such findings, only 33% of patients with gout reported using urate-lowering therapy.1 The low rate of treatment among patients with gout may be because of a misconception that the condition can be effectively managed solely through lifestyle strategies. In addition, patients believe that control of flares is their only concern, although gout-related damage occurs even in the absence of flares.

“This calls for an increase need for identification and management of serious co-morbid conditions in patients with gout,” the authors of the 2017 study concluded.2 Although joint pain and swelling caused by gout flares are well-recognized, chronically elevated uric acid levels have also been implicated in a range of other adverse outcomes. In addition to gout-related bone and joint damage, including erosions, gout has been linked to numerous comorbidities, such as cardiovascular disease, chronic kidney disease, hypertension, and type 2 diabetes.3

These comorbidities and other complications of gout have been the focus of emerging research. Investigators of a 2019 study observed a greater prevalence of chronic kidney disease among patients with gout with uncontrolled serum uric acid levels vs patients with well-controlled levels (49% vs 32%), and more frequent hospitalizations for congestive heart failure (20% vs 7%) and acute kidney failure (20% vs 8%).4

Research has also indicated higher rates of hypertension (69%) and chronic kidney disease (23%) among patients with vs without gout, as well as a >2-fold increase in the risk for death from heart failure.5,6

“Gout remains [underrecognized] as a chronic, systemic and progressive disease, which means that too frequently, only acute and obvious symptoms like flares are addressed,” Brian LaMoreaux, MD, rheumatologist and medical director at Horizon Therapeutics, told Rheumatology Advisor. “Now is the time to reshape the conversation surrounding gout to focus on the implications of this…condition beyond just the flares.”

Rheumatology Advisor spoke with Dr LaMoreaux to gain additional insights on the systemic manifestations of gout and how physician education can improve patient outcomes.

Rheumatology Advisor: What are some of the effects of gout that healthcare providers commonly overlook or fail to adequately address?

Dr LaMoreaux: There are multiple factors driving the underdiagnosis and adequate treatment of gout. It begins with the decades of stigma surrounding the disease that perpetuate the misconceptions and hinder productive physician-patient conversations.

Despite gout [affecting] 4% of the US population, it is often not a [priority compared with] other rheumatologic diseases, sometimes even in rheumatology clinics. Clinicians readily understand the life-threatening aspects of conditions, including rheumatoid arthritis and lupus, but gout is not typically viewed in the same context, despite the associated comorbidities and mortality implications.

Moreover, gout does not always show in its classic presentation (i.e., podagra); there are some people who may not experience flares, and others who, despite taking oral medications and making lifestyle changes, continue to have signs and symptoms.

From recent research, we are beginning to understand the complex relationship between pain resolution and gout progression, as well as the implications of systemic urate deposition throughout the body. This brings about new conversations and encourages clinicians to see gout as a disease beyond the joints and outside of episodic flares, ultimately driving an appreciation of the effects of chronic urate deposition [with regard] to bone erosion, renal function, and cardiovascular disease.

Rheumatology Advisor: What would be a simple, systematic approach for clinicians to cover all the bases with patients with gout?

Dr LaMoreaux: The most important aspect is patient education about gout, and to ensure that they understand that the disease is not just a disease of flares, and that even without a flare they may still be patient of gout. The American College of Rheumatology guidelines provide a basis for treating and addressing flares while focusing on driving lower serum uric acid levels.7

Beyond the musculoskeletal manifestations, it can also be helpful to think about the management of cardiovascular risk in gout, similar to how we approach this in diabetes: regularly monitoring modifiable cardiovascular risk factors, including blood glucose or A1c, lipids, blood pressure, and smoking.

Related Articles

Rheumatology Advisor: How can healthcare providers manage comorbidities in these patients?

Dr LaMoreaux: Much of the approach remains patient-dependent, but we can look to research to provide [direction]. For example, more than 70% of patients with gout have chronic kidney disease stage 2 or higher; clinicians should remain aware of this and continue to monitor renal function and serum uric acid levels.8 In addition, it is well-known how chronic inflammation can affect the cardiovascular system, leading to early onset of heart disease and increased mortality.

Although the inflammatory process is different for diseases, including rheumatoid arthritis and lupus, the end result for a patient with gout is the same. As long as there are uric acid crystals in the body, there is subclinical inflammation; with gout, this inflammation becomes exacerbated by other cardiovascular risk factors.

When available, advanced imaging techniques, such as scans of dual-energy computed tomography, can uncover the true burden of urate throughout the body. Even without advanced imaging, viewing gout as a systemic metabolic disease and not as an articular-only process will help drive management approaches that best reflect the totality of the disease.

Rheumatology Advisor: What should be the focus of future research or educational efforts pertaining to this topic?

Dr LaMoreaux: There are many remaining needs. In terms of research, we’ve just begun to scratch the surface of what we understand about gout and urate deposition throughout the body and its downstream clinical implications. In terms of patient education, we’re trying to change the tide on understanding that gout is centered on diet, which is not true; in terms of a disease, we’re aiming to elevate gout as a disease that needs to be taken more seriously with respect to urgency of treatment and research efforts.

References

1. Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK. Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: The national health and nutrition examination survey, 2007-2016. Arthritis Rheumatol. 2019;71(6):991-999.

2. Singh G, Mithal A, Mithal A. THU0409 not just a swollen big toe: increasing all-cause hospitalizations in patients with gout in the United States: 1993-2014. Ann Rheum Dis. 2017;76:362.

3. Stamp LK, Chapman PT. Gout and its comorbidities: implications for therapy. Rheumatology. 2013;52(1):34-44.

4. Francis-Sedlak M, LaMoreaux B, Holt RJ. SAT0429 Comorbidities in an early diagnosed cohort of uncontrolled versus controlled gout: analysis of a large US payer database. Ann Rheumatic Dis. 2019;78:1303-1304.

5. Chen-Xu M, Yokose C, Pillinger M, Choi HK. Contemporary comorbidity burden of gout and hyperuricemia in the US during the past decade (National Health And Nutrition Examination Survey [NHANES] 2007-2016) [abstract]. Arthritis Rheumatol. 2018;70(suppl 10). Abstract 2236.

6. Pagidipati NJ, Clare RM, Keenan RT, Chiswell K, Roe MT, Hess CN. Association of gout with long-term cardiovascular outcomes among patients with obstructive coronary artery disease. J Am Heart Assoc. 2018;7(16):e009328.

7. Khanna D, FitzGerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-1446.

8. Vargas-Santos AB, Peloquin CE, Zhang Y, Neogi T. Association of chronic kidney disease with allopurinol use in gout treatment. JAMA Intern Med. 2018;178(11):1526-1533.