Gout and African Americans: Reducing disparities

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Gout and African Americans: Reducing disparities
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Bharat Kumar, MD
Petar Lenert, MD, PhD

Despite the historic association of gout with royalty and “rich eating,” gout disproportionately affects those of lower socioeconomic status.1 Risk factors for gout, including obesity, chronic kidney disease, diabetes, and hypertension, are more common in African Americans, resulting in a higher prevalence of the disease. In addition, African Americans are less likely to receive the aggressive treatment for gout advocated by professional societies, such as anti-inflammatory medications during flares and prophylactic urate-lowering therapy.

This article reviews the epidemiology of gout and its pathophysiology, risk factors, and optimal management, focusing on African Americans and strategies to reduce healthcare disparities in this patient population.

GOUT IS COMMON AND SERIOUS

Gout is the most common inflammatory arthritis in the United States today, affecting 4% of the adult US population.2 It is a chronic disease associated with high levels of uric acid, usually manifesting as intermittent attacks of painful monoarthritis, although multiple joints may be involved.

Despite a popular misconception that gout is merely an episodic nuisance, it is a serious disease that can significantly affect physical function and quality of life.3 A 2013 systematic review found that quality of life was significantly reduced in patients with gout, particularly those with polyarticular gout, tophi, comorbidities, and radiographic damage.4

Economic costs include decreased worker productivity and increased absences from work.5,6 From 2001 to 2005, an estimated 2 million visits were made to primary care providers due to gout.7 Because gout frequently coexists with diabetes, hypertension, coronary artery disease, and kidney disease, it is often overlooked during routine clinic visits.3

HIGH URIC ACID HAS MANY EFFECTS

Uric acid, a product of purine metabolism, is the key mediator of gouty arthritis. Accumulation of uric acid in joints and other tissues leads to an exuberant inflammatory response manifesting as a gouty attack. When uncontrolled, uric acid may crystallize in joints and other structures, leading to tophi formation, which can cause chronic deforming and erosive arthritis, known as chronic tophaceous gout.8

Although gout is considered to be a musculoskeletal disorder, recent evidence indicates that hyperuricemia plays an important role in the development of renal disease and contributes to cardiovascular morbidity and death.9 Several studies have found that reducing uric acid levels lowers cardiovascular mortality rates and retards the progression of chronic kidney disease.10

MEN AND CERTAIN RACIAL GROUPS MOST AFFECTED

Large-scale epidemiologic surveys have established that prevalence varies widely among population groups. Premenopausal women are less likely to be affected than men, presumably due to the effect of female hormones on renal tubular excretion of uric acid.11

Certain Asian populations (Filipinos, Taiwanese, Micronesians, the Maoris of New Zealand, Hmong Chinese immigrants in Minnesota) and African Americans have a high prevalence, while people from several sub-Saharan African countries have a very low prevalence. These differences are likely due to a variety of reasons, including genetic predisposition; diet (Table 1); risk factors such as obesity, diabetes, and hypertension; less access to healthcare resources; and inappropriate treatment.12,13

AFRICAN AMERICANS ARE A DIVERSE GROUP

“African Americans” are a highly heterogeneous group making up about 13% of the US population. Most scholars now consider racial identity largely a product of socioeconomic and political circumstances rather than a scientific concept.14 The US Census Bureau defines African Americans (or “blacks”) as those having origins in the black racial groups of Africa,15  but even this is problematic, since it combines people as diverse as descendants of 17th, 18th, and 19th century enslaved Africans with recent first-generation African immigrants, as well as with Caribbean- and Latino-Americans of African heritage.

In addition, many African Americans trace their ancestry to other racial and ethnic groups, especially European and Native American. A study of nine European DNA markers among 10 African American populations in the United States and one population of Jamaicans of African descent found a range of frequencies from 7% among Jamaicans to 23% among African Americans living in New Orleans.16

Although such diversity argues against generalizing healthcare needs for the entire African American community, some evidence indicates that genetic markers for gene-disease associations may be consistent across traditional racial boundaries.17

GENETIC FACTORS CANNOT EXPLAIN GOUT DISPARITIES

Several small studies have found evidence of genetic factors mediating the risk for hyperuricemia and gout. Twin studies indicate that hyperuricemia is highly heritable,18 although they do not show a concordance in the heritability of gout, suggesting that environmental factors also have an important role in developing clinical manifestations of the disease.12

Genome-wide association studies have identified 28 separate loci influencing uric acid levels, including genes for uric acid transporters (eg, SLC2A9 and ABCG2), and metabolic pathway regulators (eg, PDZK1, SCL22A12, and PRPSAP1), but the distribution among African Americans is largely unknown.19 One important exception is SLC2A9, a renal tubular transporter of uric acid: variants of SLC2A9 were found exclusively in African Americans, but the clinical significance of this association is unclear.20

Several epidemiologic studies have looked at gout in African Americans.

In the Coronary Artery Risk Development in Young Adults study,21 young African Americans had lower levels of uric acid than whites after adjusting for body mass index (BMI), glomerular filtration rate (GFR), diet, and medications. But after up to 20 years of follow-up, the risk of hyperuricemia was 2.3 times higher in African American women than in white women (95% confidence interval [CI] 1.34–3.99). Such differences were not found between African American and white men.

The National Health and Nutritional Examination Survey (NHANES) found that African American adolescents had lower uric acid levels than white adolescents after taking into account sugar intake, GFR, BMI, and onset of puberty.22

The Multiple Risk Factor Intervention Trial23 also found that among those with high cardiovascular risk, the incidence of hyperuricemia and gout was lower in African Americans than in whites.

COMORBID DISEASES MAY EXPLAIN DISPARITIES

Despite some evidence that African Americans have genetic factors that are protective against gout, they have a much greater frequency of acquired risk factors for gout, including obesity, physical inactivity, hypertension, diabetes mellitus, renal failure, high intake of seafood, elevated blood lead levels, and use of antihypertensive medications (Table 2).

Hochberg et al24 examined the incidence of gout in 352 African American and 571 white physicians and found higher rates in African Americans (9% vs 5%). The authors suggested different rates of hypertension as an explanation, although the use of antihypertensive medications such as diuretics that promote hyperuricemia confounds the strength of this conclusion.

AFRICAN AMERICANS NEED STANDARD TREATMENT . . .

Unlike for heart failure, in which subgroup analyses of large prospective studies have found different efficacies of medications in African Americans than in whites, no such data exist for gout. Although there is a higher risk of allopurinol hypersensitivity in ethnic groups that express the HLA-B*5801 polymorphism (eg, Han Chinese, Korean, Thai, Japanese, Portuguese), African Americans are not known to be at greater risk.25 There are also no special precautions for using febuxostat or probenecid in African Americans.

Absent any compelling reason, gout management should be the same regardless of ethnicity.26 Patients should be counseled on primary prevention measures such as dietary and behavioral modification and, if necessary, started on aggressive urate-lowering therapy.27

. . . BUT ARE LESS LIKELY TO HAVE GOUT APPROPRIATELY TREATED

African Americans with gout are less likely to receive urate-lowering therapy.28 According to the 2002 National Ambulatory Medical Care Survey in the United States, African Americans with gout are far less likely to receive allopurinol than whites (42% vs 80%; odds ratio [OR] 0.18; 95% CI 0.04–0.78).23 Even when therapy is prescribed, rates of nonadherence are greater in African Americans than in whites (OR 1.86, 95% CI 1.52–2.27), though the authors do not speculate why this is so.29 No studies have compared rates of prescribing febuxostat to African Americans vs whites.

African Americans are also less likely to receive ongoing routine care for their gout. A 2007 study30 of 663 veterans found that physicians were 1.41 times less likely to adhere to three selected quality indicators when dealing with nonwhite than white patients (95% CI 0.52–3.84). The three quality indicators studied were:

  • Lowering of daily allopurinol dose to below 300 mg/day in the presence of renal insufficiency (no longer considered a quality measure)
  • Monitoring of serum urate level at least once during the first 6 months of continued use of a xanthine oxidase inhibitor, such as allopurinol
  • Monitoring of complete blood cell count and creatinine kinase at least every 6 months in patients with renal impairment receiving long-term prophylactic oral colchicine (> 0.5 mg/day for at least 6 months).

The finding was independent of age, comorbidity index, healthcare access, and utilization characteristics (eg, number of inpatient and outpatient visits, type of physician, most frequently seen physician).

 

 

LIFESTYLE MODIFICATION

Dietary modification is a useful initial step toward reducing uric acid levels (Table 1).27 The following measures are recommended:

Reduce alcohol intake. Alcoholic beverages, particularly beer, are strongly linked to hyperuricemia, according to a 2013 meta-analysis.31 Although alcohol consumption is lower in African Americans than in whites, mortality rates from cirrhosis and other alcohol-related diseases are 10% higher, suggesting metabolic differences that render African Americans more susceptible to the negative health effects of alcohol.32

Avoid sugary drinks. Sweetened beverages, especially those rich in fructose, are also implicated in hyperuricemia and gout. NHANES found an increase in serum uric acid of 0.33 mg/dL (95% CI, 0.11–0.73) in those consuming one to three sugar-sweetened drinks per day compared with nonconsumers, adjusting for total energy intake, age, sex, medications, hypertension, and GFR.33 A prospective study also found a relative risk of 1.85 for those who drink two or more sugar-sweetened beverages per day compared with those who drink fewer than one per month (95% CI 1.08–3.16).34

Unfortunately, African Americans consume a disproportionate amount of sugar from all sources: 17% of African Americans are considered heavy consumers vs 9% of whites.35

Limit foods rich in purines. Red meat, seafood, and some vegetables, including asparagus, spinach, peas, cauliflower, and mushrooms, are associated with increased serum uric acid levels. NHANES found that greater meat and seafood consumption was associated with increased uric acid levels. Choi et al36 found that the risk of gout increased by 21% with each additional daily serving of meat; the relative risk of developing gout was 1.41 (95% CI 1.07–1.86) in the fifth quintile of meat intake compared with the first quintile, and 1.51 (95% CI 1.17–1.95) in the fifth quintile of seafood consumption.

Despite these associations with high-purine food consumption and gout, many purine-rich foods may not contribute to hyperuricemia, and therefore a low-purine diet may not be protective. Interestingly, purine-rich vegetable protein intake is not associated with increased gout risk.37

Increase dairy consumption. Dairy in the diet is associated with a lower incidence of gout, with a decrease of 0.21 mg/dL (95% CI –0.37 to –0.04) in serum uric acid levels between the highest and lowest quintiles of dairy consumption.38 A randomized controlled trial found a 10% reduction in serum uric acid levels with milk consumption.39

Enjoy coffee. Coffee intake has been inversely correlated with gout. Daily intake of 4 to 5 cups of coffee is associated with a relative risk of 0.60 (95% CI 0.41–0.87) vs no coffee.40

Vitamin C and cherry juice41,42 have also been linked to lower gout risk, but the data are less robust.

Control weight. Primary care providers should advise patients to increase physical activity and maintain a healthy weight.

In a prospective study, Choi et al43 found that, in men, the risk of gout increased with the BMI. Compared with men with BMIs in the range of 21 to 22.9 kg/m2, the relative risks were:

  • 1.95 (95% CI 1.44–2.65) at BMI 25 to 29.9 kg/m2
  • 2.33 (95% CI 1.62–3.36) at BMI 30 to 34.9 kg/m2
  • 2.97 (95% CI 1.73–5.10) at BMI > 35 kg/m2.

In addition, those who gained more than 13.6 kg since age 21 had a relative risk of 1.99 (95% CI 1.49–2.66) of developing gout compared with those whose weight remained within 1.8 kg.  

For those who cannot achieve weight loss through conservative measures, bariatric surgery has shown promise. In a prospective study of 60 obese patients (BMI > 35 kg/m2) with gout and type 2 diabetes mellitus, uric acid steadily declined during the first year after bariatric surgery.44

TREATMENT OF ACUTE ATTACKS

Gout can be effectively managed in most patients. Behavioral and pharmacologic interventions are cheap and effective and have been shown to halt further damage to joints as well as retard the progression of renal disease and reduce cardiovascular morbidity.

During acute attacks, anti-inflammatory medications, principally glucocorticoids, nonsteroidal anti-inflammatory drugs, and colchicine, should be given promptly to reduce the intensity and duration of flares.

Although traditional teaching has been that urate-lowering therapy should not be initiated during an acute gout attack because it could prolong the duration of the attack, guidelines now permit it, based on studies showing that therapy does not prolong attacks.45,46

AGGRESSIVE URATE-LOWERING THERAPY FOR PROPHYLAXIS

Long-term treatment of gout is aimed at reducing uric acid levels by mitigating modifiable risk factors and through urate-lowering therapy.46 For many patients, conservative management with dietary and other behavioral changes is not sufficient to prevent further attacks of gout, necessitating urate-lowering therapy. Comorbid diseases such as obesity, hypertension, chronic kidney disease, and diabetes should also be addressed because they promote hyperuricemia and gouty attacks.47

A number of organizations have issued gout management guidelines over the past decade, including the American College of Rheumatology (ACR) in 2012, the European League Against Rheumatism (2006, updated in 2014), and the British Society of Rheumatology (2007). All recommend urate-lowering therapy to prevent gout flares.

The American and European guidelines recommend a target uric acid level below 6 mg/dL, and the British guidelines recommend a target below 5 mg/dL.48 For patients with palpable and visible tophi, the ACR guidelines state that lowering to below 5 mg/dL may be needed.46

First-line agents for urate-lowering therapy are xanthine oxidase inhibitors, which include allopurinol (costing $0.48 per generic 100-mg tablet or $0.92 per 300-mg tablet), and febuxostat ($5.38 per 40-mg or 80-mg tablet). For patients with contraindications or intolerances to allopurinol or febuxostat, probenecid ($1.15 per 500-mg tablet), which functions as a uricosuric agent (ie, increases urinary excretion of uric acid), may be used.

Losartan ($1.68 per 25-mg tablet) and fenofibrate ($1.91 per 48-mg tablet) are also often used to reduce uric acid levels, but they have only modest effects and are not approved for this indication in the United States.49

MANAGE CHRONIC CASES WITH CONTINUED THERAPY

ACR guidelines strongly emphasize continuing prophylaxis in case of ongoing gout activity (ie, detection of tophi on examination, recent gout attacks, or chronic gouty arthritis) (Table 3). The following durations have been proposed for prophylaxis:

  • 6 months after an attack
  • 6 months after achieving target uric acid level in patients with evidence of tophi
  • 3 months after achieving target uric acid level in patients with resolved tophi. 

Two randomized controlled trials support the use of the anti-inflammatory agent colchicine ($4.30 per tablet) for prophylaxis when initiating urate-lowering therapy.50,51

Monitor uric acid levels, renal function, adverse effects

The initial dosage of urate-lowering agents depends on the presence of kidney disease (Table 3).

Allopurinol is typically started at 50 mg to 100 mg oral daily, and titrated upward in increments of 100 mg depending on uric acid levels. According to the ACR guidelines, uric acid levels should be measured every 2 to 5 weeks.46 The Febuxostat vs Allopurinol Streamline Trial found that 97% of patients reached target uric acid levels within two titrations.52

Especially during the first months of therapy, physicians should be vigilant for adverse effects of allopurinol, including hypersensitivity reaction (rash, fever, Stevens-Johnson syndrome), hepatotoxicity, and myelotoxicity (bone marrow suppression), and for effects of febuxostat, such as rash, diarrhea, elevations in aminotransferase levels, and upper respiratory tract infections.53 Although the maximum acceptable dose of allopurinol is 800 mg even in chronic kidney disease, regularly monitoring for hypersensitivity reactions and other adverse effects is needed if doses are above 300 mg per day.46

Routine follow-up is essential

Adherence to therapy should be assessed at every visit. Patients should be counseled that gout is a chronic disease and that they should continue on urate-lowering therapy even if they are not having acute attacks. Adverse effects of medications should be monitored and addressed, although for allopurinol and febuxostat these are rare beyond the first few months of initiation and titration. If worsening of gout or uric acid levels occurs, therapy should be augmented and contributors to hyperuricemia reviewed. In refractory cases, rheumatology consultation may be needed; medications such as pegloticase ($16,800/mL) may be deemed necessary for severe tophaceous gout or for patients who need more rapid reduction of urates.49

STRATEGIES TO ADDRESS DISPARITIES

Creative approaches are needed to engage African American communities to reduce the burden of gout. No trials have been published evaluating methods for reducing health disparities with gout, but strategies for other chronic conditions may be applicable.

Incorporate guidelines better. Although setting and disseminating guidelines should ensure that care is standardized, studies have found that primary care physicians and rheumatologists frequently do not implement them.3,54 Reasons cited for poor adherence to gout guidelines include their relatively recent release, poor patient adherence, lack of measurement tools, and inadequate education of primary care physicians. Incorporating the guidelines as “best practice advisories” into electronic medical record systems has been proposed to improve their implementation.46

Use a team approach. Some quality improvement projects have used pharmacists and nurses to help implement gout guidelines. In two studies, empowering nurses and pharmacists to better educate patients and implement standardized protocols for titrating urate-lowering medications led to sustained improvements in maintaining serum uric acid levels less than 6 mg/dL.55–57

Multidisciplinary involvement by nutritionists, physicians, and community health workers have been found to help improve glycemic control in African Americans.58 Similar efforts can be undertaken to improve control of uric acid levels through dietary modification and improved compliance.

Address patient concerns. Substantial gaps exist in knowledge about gout between providers and the general population, although large studies specifically focusing on African Americans are lacking.59 Qualitative studies suggest that patient experience of gout may vary depending on race, with African Americans more likely than whites to rank the following concerns regarding gout as high: dietary restrictions, emotional burden, severe pain, the need for canes or crutches during flares, and gout bringing their day to a halt.60 Another study among African Americans with gout found concerns about the effectiveness of urate-lowering therapy, side effects of medications, polypharmacy, pill size, cost, refill issues, and forgetting to take medications regularly.61

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Author and Disclosure Information

Bharat Kumar, MD
Allergy/Immunology and Rheumatology Fellow, Division of Immunology, University of Iowa Hospitals and Clinics, Iowa City, IA

Petar Lenert, MD, PhD
Clinical Associate Professor of Internal Medicine, Division of Immunology, University of Iowa Hospitals and Clinics, Iowa City, IA

Address: Bharat Kumar, MD, Division of Immunology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242; Bharat-Kumar@UIowa.edu

Issue
Cleveland Clinic Journal of Medicine - 83(9)
Publications
Cleveland Clinic Journal of Medicine
Topics
Rheumatology
Pain
Page Number
665-674
Legacy Keywords
gout, uric acid, hyperuricemia, African American, disparities
Sections
Addressing Disparities in Health Care
Author(s)
Bharat Kumar, MD
Petar Lenert, MD, PhD
Author(s)
Bharat Kumar, MD
Petar Lenert, MD, PhD
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Bharat Kumar, MD
Allergy/Immunology and Rheumatology Fellow, Division of Immunology, University of Iowa Hospitals and Clinics, Iowa City, IA

Petar Lenert, MD, PhD
Clinical Associate Professor of Internal Medicine, Division of Immunology, University of Iowa Hospitals and Clinics, Iowa City, IA

Address: Bharat Kumar, MD, Division of Immunology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242; Bharat-Kumar@UIowa.edu

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Bharat Kumar, MD
Allergy/Immunology and Rheumatology Fellow, Division of Immunology, University of Iowa Hospitals and Clinics, Iowa City, IA

Petar Lenert, MD, PhD
Clinical Associate Professor of Internal Medicine, Division of Immunology, University of Iowa Hospitals and Clinics, Iowa City, IA

Address: Bharat Kumar, MD, Division of Immunology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242; Bharat-Kumar@UIowa.edu

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Despite the historic association of gout with royalty and “rich eating,” gout disproportionately affects those of lower socioeconomic status.1 Risk factors for gout, including obesity, chronic kidney disease, diabetes, and hypertension, are more common in African Americans, resulting in a higher prevalence of the disease. In addition, African Americans are less likely to receive the aggressive treatment for gout advocated by professional societies, such as anti-inflammatory medications during flares and prophylactic urate-lowering therapy.

This article reviews the epidemiology of gout and its pathophysiology, risk factors, and optimal management, focusing on African Americans and strategies to reduce healthcare disparities in this patient population.

GOUT IS COMMON AND SERIOUS

Gout is the most common inflammatory arthritis in the United States today, affecting 4% of the adult US population.2 It is a chronic disease associated with high levels of uric acid, usually manifesting as intermittent attacks of painful monoarthritis, although multiple joints may be involved.

Despite a popular misconception that gout is merely an episodic nuisance, it is a serious disease that can significantly affect physical function and quality of life.3 A 2013 systematic review found that quality of life was significantly reduced in patients with gout, particularly those with polyarticular gout, tophi, comorbidities, and radiographic damage.4

Economic costs include decreased worker productivity and increased absences from work.5,6 From 2001 to 2005, an estimated 2 million visits were made to primary care providers due to gout.7 Because gout frequently coexists with diabetes, hypertension, coronary artery disease, and kidney disease, it is often overlooked during routine clinic visits.3

HIGH URIC ACID HAS MANY EFFECTS

Uric acid, a product of purine metabolism, is the key mediator of gouty arthritis. Accumulation of uric acid in joints and other tissues leads to an exuberant inflammatory response manifesting as a gouty attack. When uncontrolled, uric acid may crystallize in joints and other structures, leading to tophi formation, which can cause chronic deforming and erosive arthritis, known as chronic tophaceous gout.8

Although gout is considered to be a musculoskeletal disorder, recent evidence indicates that hyperuricemia plays an important role in the development of renal disease and contributes to cardiovascular morbidity and death.9 Several studies have found that reducing uric acid levels lowers cardiovascular mortality rates and retards the progression of chronic kidney disease.10

MEN AND CERTAIN RACIAL GROUPS MOST AFFECTED

Large-scale epidemiologic surveys have established that prevalence varies widely among population groups. Premenopausal women are less likely to be affected than men, presumably due to the effect of female hormones on renal tubular excretion of uric acid.11

Certain Asian populations (Filipinos, Taiwanese, Micronesians, the Maoris of New Zealand, Hmong Chinese immigrants in Minnesota) and African Americans have a high prevalence, while people from several sub-Saharan African countries have a very low prevalence. These differences are likely due to a variety of reasons, including genetic predisposition; diet (Table 1); risk factors such as obesity, diabetes, and hypertension; less access to healthcare resources; and inappropriate treatment.12,13

AFRICAN AMERICANS ARE A DIVERSE GROUP

“African Americans” are a highly heterogeneous group making up about 13% of the US population. Most scholars now consider racial identity largely a product of socioeconomic and political circumstances rather than a scientific concept.14 The US Census Bureau defines African Americans (or “blacks”) as those having origins in the black racial groups of Africa,15  but even this is problematic, since it combines people as diverse as descendants of 17th, 18th, and 19th century enslaved Africans with recent first-generation African immigrants, as well as with Caribbean- and Latino-Americans of African heritage.

In addition, many African Americans trace their ancestry to other racial and ethnic groups, especially European and Native American. A study of nine European DNA markers among 10 African American populations in the United States and one population of Jamaicans of African descent found a range of frequencies from 7% among Jamaicans to 23% among African Americans living in New Orleans.16

Although such diversity argues against generalizing healthcare needs for the entire African American community, some evidence indicates that genetic markers for gene-disease associations may be consistent across traditional racial boundaries.17

GENETIC FACTORS CANNOT EXPLAIN GOUT DISPARITIES

Several small studies have found evidence of genetic factors mediating the risk for hyperuricemia and gout. Twin studies indicate that hyperuricemia is highly heritable,18 although they do not show a concordance in the heritability of gout, suggesting that environmental factors also have an important role in developing clinical manifestations of the disease.12

Genome-wide association studies have identified 28 separate loci influencing uric acid levels, including genes for uric acid transporters (eg, SLC2A9 and ABCG2), and metabolic pathway regulators (eg, PDZK1, SCL22A12, and PRPSAP1), but the distribution among African Americans is largely unknown.19 One important exception is SLC2A9, a renal tubular transporter of uric acid: variants of SLC2A9 were found exclusively in African Americans, but the clinical significance of this association is unclear.20

Several epidemiologic studies have looked at gout in African Americans.

In the Coronary Artery Risk Development in Young Adults study,21 young African Americans had lower levels of uric acid than whites after adjusting for body mass index (BMI), glomerular filtration rate (GFR), diet, and medications. But after up to 20 years of follow-up, the risk of hyperuricemia was 2.3 times higher in African American women than in white women (95% confidence interval [CI] 1.34–3.99). Such differences were not found between African American and white men.

The National Health and Nutritional Examination Survey (NHANES) found that African American adolescents had lower uric acid levels than white adolescents after taking into account sugar intake, GFR, BMI, and onset of puberty.22

The Multiple Risk Factor Intervention Trial23 also found that among those with high cardiovascular risk, the incidence of hyperuricemia and gout was lower in African Americans than in whites.

COMORBID DISEASES MAY EXPLAIN DISPARITIES

Despite some evidence that African Americans have genetic factors that are protective against gout, they have a much greater frequency of acquired risk factors for gout, including obesity, physical inactivity, hypertension, diabetes mellitus, renal failure, high intake of seafood, elevated blood lead levels, and use of antihypertensive medications (Table 2).

Hochberg et al24 examined the incidence of gout in 352 African American and 571 white physicians and found higher rates in African Americans (9% vs 5%). The authors suggested different rates of hypertension as an explanation, although the use of antihypertensive medications such as diuretics that promote hyperuricemia confounds the strength of this conclusion.

AFRICAN AMERICANS NEED STANDARD TREATMENT . . .

Unlike for heart failure, in which subgroup analyses of large prospective studies have found different efficacies of medications in African Americans than in whites, no such data exist for gout. Although there is a higher risk of allopurinol hypersensitivity in ethnic groups that express the HLA-B*5801 polymorphism (eg, Han Chinese, Korean, Thai, Japanese, Portuguese), African Americans are not known to be at greater risk.25 There are also no special precautions for using febuxostat or probenecid in African Americans.

Absent any compelling reason, gout management should be the same regardless of ethnicity.26 Patients should be counseled on primary prevention measures such as dietary and behavioral modification and, if necessary, started on aggressive urate-lowering therapy.27

. . . BUT ARE LESS LIKELY TO HAVE GOUT APPROPRIATELY TREATED

African Americans with gout are less likely to receive urate-lowering therapy.28 According to the 2002 National Ambulatory Medical Care Survey in the United States, African Americans with gout are far less likely to receive allopurinol than whites (42% vs 80%; odds ratio [OR] 0.18; 95% CI 0.04–0.78).23 Even when therapy is prescribed, rates of nonadherence are greater in African Americans than in whites (OR 1.86, 95% CI 1.52–2.27), though the authors do not speculate why this is so.29 No studies have compared rates of prescribing febuxostat to African Americans vs whites.

African Americans are also less likely to receive ongoing routine care for their gout. A 2007 study30 of 663 veterans found that physicians were 1.41 times less likely to adhere to three selected quality indicators when dealing with nonwhite than white patients (95% CI 0.52–3.84). The three quality indicators studied were:

  • Lowering of daily allopurinol dose to below 300 mg/day in the presence of renal insufficiency (no longer considered a quality measure)
  • Monitoring of serum urate level at least once during the first 6 months of continued use of a xanthine oxidase inhibitor, such as allopurinol
  • Monitoring of complete blood cell count and creatinine kinase at least every 6 months in patients with renal impairment receiving long-term prophylactic oral colchicine (> 0.5 mg/day for at least 6 months).

The finding was independent of age, comorbidity index, healthcare access, and utilization characteristics (eg, number of inpatient and outpatient visits, type of physician, most frequently seen physician).

 

 

LIFESTYLE MODIFICATION

Dietary modification is a useful initial step toward reducing uric acid levels (Table 1).27 The following measures are recommended:

Reduce alcohol intake. Alcoholic beverages, particularly beer, are strongly linked to hyperuricemia, according to a 2013 meta-analysis.31 Although alcohol consumption is lower in African Americans than in whites, mortality rates from cirrhosis and other alcohol-related diseases are 10% higher, suggesting metabolic differences that render African Americans more susceptible to the negative health effects of alcohol.32

Avoid sugary drinks. Sweetened beverages, especially those rich in fructose, are also implicated in hyperuricemia and gout. NHANES found an increase in serum uric acid of 0.33 mg/dL (95% CI, 0.11–0.73) in those consuming one to three sugar-sweetened drinks per day compared with nonconsumers, adjusting for total energy intake, age, sex, medications, hypertension, and GFR.33 A prospective study also found a relative risk of 1.85 for those who drink two or more sugar-sweetened beverages per day compared with those who drink fewer than one per month (95% CI 1.08–3.16).34

Unfortunately, African Americans consume a disproportionate amount of sugar from all sources: 17% of African Americans are considered heavy consumers vs 9% of whites.35

Limit foods rich in purines. Red meat, seafood, and some vegetables, including asparagus, spinach, peas, cauliflower, and mushrooms, are associated with increased serum uric acid levels. NHANES found that greater meat and seafood consumption was associated with increased uric acid levels. Choi et al36 found that the risk of gout increased by 21% with each additional daily serving of meat; the relative risk of developing gout was 1.41 (95% CI 1.07–1.86) in the fifth quintile of meat intake compared with the first quintile, and 1.51 (95% CI 1.17–1.95) in the fifth quintile of seafood consumption.

Despite these associations with high-purine food consumption and gout, many purine-rich foods may not contribute to hyperuricemia, and therefore a low-purine diet may not be protective. Interestingly, purine-rich vegetable protein intake is not associated with increased gout risk.37

Increase dairy consumption. Dairy in the diet is associated with a lower incidence of gout, with a decrease of 0.21 mg/dL (95% CI –0.37 to –0.04) in serum uric acid levels between the highest and lowest quintiles of dairy consumption.38 A randomized controlled trial found a 10% reduction in serum uric acid levels with milk consumption.39

Enjoy coffee. Coffee intake has been inversely correlated with gout. Daily intake of 4 to 5 cups of coffee is associated with a relative risk of 0.60 (95% CI 0.41–0.87) vs no coffee.40

Vitamin C and cherry juice41,42 have also been linked to lower gout risk, but the data are less robust.

Control weight. Primary care providers should advise patients to increase physical activity and maintain a healthy weight.

In a prospective study, Choi et al43 found that, in men, the risk of gout increased with the BMI. Compared with men with BMIs in the range of 21 to 22.9 kg/m2, the relative risks were:

  • 1.95 (95% CI 1.44–2.65) at BMI 25 to 29.9 kg/m2
  • 2.33 (95% CI 1.62–3.36) at BMI 30 to 34.9 kg/m2
  • 2.97 (95% CI 1.73–5.10) at BMI > 35 kg/m2.

In addition, those who gained more than 13.6 kg since age 21 had a relative risk of 1.99 (95% CI 1.49–2.66) of developing gout compared with those whose weight remained within 1.8 kg.  

For those who cannot achieve weight loss through conservative measures, bariatric surgery has shown promise. In a prospective study of 60 obese patients (BMI > 35 kg/m2) with gout and type 2 diabetes mellitus, uric acid steadily declined during the first year after bariatric surgery.44

TREATMENT OF ACUTE ATTACKS

Gout can be effectively managed in most patients. Behavioral and pharmacologic interventions are cheap and effective and have been shown to halt further damage to joints as well as retard the progression of renal disease and reduce cardiovascular morbidity.

During acute attacks, anti-inflammatory medications, principally glucocorticoids, nonsteroidal anti-inflammatory drugs, and colchicine, should be given promptly to reduce the intensity and duration of flares.

Although traditional teaching has been that urate-lowering therapy should not be initiated during an acute gout attack because it could prolong the duration of the attack, guidelines now permit it, based on studies showing that therapy does not prolong attacks.45,46

AGGRESSIVE URATE-LOWERING THERAPY FOR PROPHYLAXIS

Long-term treatment of gout is aimed at reducing uric acid levels by mitigating modifiable risk factors and through urate-lowering therapy.46 For many patients, conservative management with dietary and other behavioral changes is not sufficient to prevent further attacks of gout, necessitating urate-lowering therapy. Comorbid diseases such as obesity, hypertension, chronic kidney disease, and diabetes should also be addressed because they promote hyperuricemia and gouty attacks.47

A number of organizations have issued gout management guidelines over the past decade, including the American College of Rheumatology (ACR) in 2012, the European League Against Rheumatism (2006, updated in 2014), and the British Society of Rheumatology (2007). All recommend urate-lowering therapy to prevent gout flares.

The American and European guidelines recommend a target uric acid level below 6 mg/dL, and the British guidelines recommend a target below 5 mg/dL.48 For patients with palpable and visible tophi, the ACR guidelines state that lowering to below 5 mg/dL may be needed.46

First-line agents for urate-lowering therapy are xanthine oxidase inhibitors, which include allopurinol (costing $0.48 per generic 100-mg tablet or $0.92 per 300-mg tablet), and febuxostat ($5.38 per 40-mg or 80-mg tablet). For patients with contraindications or intolerances to allopurinol or febuxostat, probenecid ($1.15 per 500-mg tablet), which functions as a uricosuric agent (ie, increases urinary excretion of uric acid), may be used.

Losartan ($1.68 per 25-mg tablet) and fenofibrate ($1.91 per 48-mg tablet) are also often used to reduce uric acid levels, but they have only modest effects and are not approved for this indication in the United States.49

MANAGE CHRONIC CASES WITH CONTINUED THERAPY

ACR guidelines strongly emphasize continuing prophylaxis in case of ongoing gout activity (ie, detection of tophi on examination, recent gout attacks, or chronic gouty arthritis) (Table 3). The following durations have been proposed for prophylaxis:

  • 6 months after an attack
  • 6 months after achieving target uric acid level in patients with evidence of tophi
  • 3 months after achieving target uric acid level in patients with resolved tophi. 

Two randomized controlled trials support the use of the anti-inflammatory agent colchicine ($4.30 per tablet) for prophylaxis when initiating urate-lowering therapy.50,51

Monitor uric acid levels, renal function, adverse effects

The initial dosage of urate-lowering agents depends on the presence of kidney disease (Table 3).

Allopurinol is typically started at 50 mg to 100 mg oral daily, and titrated upward in increments of 100 mg depending on uric acid levels. According to the ACR guidelines, uric acid levels should be measured every 2 to 5 weeks.46 The Febuxostat vs Allopurinol Streamline Trial found that 97% of patients reached target uric acid levels within two titrations.52

Especially during the first months of therapy, physicians should be vigilant for adverse effects of allopurinol, including hypersensitivity reaction (rash, fever, Stevens-Johnson syndrome), hepatotoxicity, and myelotoxicity (bone marrow suppression), and for effects of febuxostat, such as rash, diarrhea, elevations in aminotransferase levels, and upper respiratory tract infections.53 Although the maximum acceptable dose of allopurinol is 800 mg even in chronic kidney disease, regularly monitoring for hypersensitivity reactions and other adverse effects is needed if doses are above 300 mg per day.46

Routine follow-up is essential

Adherence to therapy should be assessed at every visit. Patients should be counseled that gout is a chronic disease and that they should continue on urate-lowering therapy even if they are not having acute attacks. Adverse effects of medications should be monitored and addressed, although for allopurinol and febuxostat these are rare beyond the first few months of initiation and titration. If worsening of gout or uric acid levels occurs, therapy should be augmented and contributors to hyperuricemia reviewed. In refractory cases, rheumatology consultation may be needed; medications such as pegloticase ($16,800/mL) may be deemed necessary for severe tophaceous gout or for patients who need more rapid reduction of urates.49

STRATEGIES TO ADDRESS DISPARITIES

Creative approaches are needed to engage African American communities to reduce the burden of gout. No trials have been published evaluating methods for reducing health disparities with gout, but strategies for other chronic conditions may be applicable.

Incorporate guidelines better. Although setting and disseminating guidelines should ensure that care is standardized, studies have found that primary care physicians and rheumatologists frequently do not implement them.3,54 Reasons cited for poor adherence to gout guidelines include their relatively recent release, poor patient adherence, lack of measurement tools, and inadequate education of primary care physicians. Incorporating the guidelines as “best practice advisories” into electronic medical record systems has been proposed to improve their implementation.46

Use a team approach. Some quality improvement projects have used pharmacists and nurses to help implement gout guidelines. In two studies, empowering nurses and pharmacists to better educate patients and implement standardized protocols for titrating urate-lowering medications led to sustained improvements in maintaining serum uric acid levels less than 6 mg/dL.55–57

Multidisciplinary involvement by nutritionists, physicians, and community health workers have been found to help improve glycemic control in African Americans.58 Similar efforts can be undertaken to improve control of uric acid levels through dietary modification and improved compliance.

Address patient concerns. Substantial gaps exist in knowledge about gout between providers and the general population, although large studies specifically focusing on African Americans are lacking.59 Qualitative studies suggest that patient experience of gout may vary depending on race, with African Americans more likely than whites to rank the following concerns regarding gout as high: dietary restrictions, emotional burden, severe pain, the need for canes or crutches during flares, and gout bringing their day to a halt.60 Another study among African Americans with gout found concerns about the effectiveness of urate-lowering therapy, side effects of medications, polypharmacy, pill size, cost, refill issues, and forgetting to take medications regularly.61

Despite the historic association of gout with royalty and “rich eating,” gout disproportionately affects those of lower socioeconomic status.1 Risk factors for gout, including obesity, chronic kidney disease, diabetes, and hypertension, are more common in African Americans, resulting in a higher prevalence of the disease. In addition, African Americans are less likely to receive the aggressive treatment for gout advocated by professional societies, such as anti-inflammatory medications during flares and prophylactic urate-lowering therapy.

This article reviews the epidemiology of gout and its pathophysiology, risk factors, and optimal management, focusing on African Americans and strategies to reduce healthcare disparities in this patient population.

GOUT IS COMMON AND SERIOUS

Gout is the most common inflammatory arthritis in the United States today, affecting 4% of the adult US population.2 It is a chronic disease associated with high levels of uric acid, usually manifesting as intermittent attacks of painful monoarthritis, although multiple joints may be involved.

Despite a popular misconception that gout is merely an episodic nuisance, it is a serious disease that can significantly affect physical function and quality of life.3 A 2013 systematic review found that quality of life was significantly reduced in patients with gout, particularly those with polyarticular gout, tophi, comorbidities, and radiographic damage.4

Economic costs include decreased worker productivity and increased absences from work.5,6 From 2001 to 2005, an estimated 2 million visits were made to primary care providers due to gout.7 Because gout frequently coexists with diabetes, hypertension, coronary artery disease, and kidney disease, it is often overlooked during routine clinic visits.3

HIGH URIC ACID HAS MANY EFFECTS

Uric acid, a product of purine metabolism, is the key mediator of gouty arthritis. Accumulation of uric acid in joints and other tissues leads to an exuberant inflammatory response manifesting as a gouty attack. When uncontrolled, uric acid may crystallize in joints and other structures, leading to tophi formation, which can cause chronic deforming and erosive arthritis, known as chronic tophaceous gout.8

Although gout is considered to be a musculoskeletal disorder, recent evidence indicates that hyperuricemia plays an important role in the development of renal disease and contributes to cardiovascular morbidity and death.9 Several studies have found that reducing uric acid levels lowers cardiovascular mortality rates and retards the progression of chronic kidney disease.10

MEN AND CERTAIN RACIAL GROUPS MOST AFFECTED

Large-scale epidemiologic surveys have established that prevalence varies widely among population groups. Premenopausal women are less likely to be affected than men, presumably due to the effect of female hormones on renal tubular excretion of uric acid.11

Certain Asian populations (Filipinos, Taiwanese, Micronesians, the Maoris of New Zealand, Hmong Chinese immigrants in Minnesota) and African Americans have a high prevalence, while people from several sub-Saharan African countries have a very low prevalence. These differences are likely due to a variety of reasons, including genetic predisposition; diet (Table 1); risk factors such as obesity, diabetes, and hypertension; less access to healthcare resources; and inappropriate treatment.12,13

AFRICAN AMERICANS ARE A DIVERSE GROUP

“African Americans” are a highly heterogeneous group making up about 13% of the US population. Most scholars now consider racial identity largely a product of socioeconomic and political circumstances rather than a scientific concept.14 The US Census Bureau defines African Americans (or “blacks”) as those having origins in the black racial groups of Africa,15  but even this is problematic, since it combines people as diverse as descendants of 17th, 18th, and 19th century enslaved Africans with recent first-generation African immigrants, as well as with Caribbean- and Latino-Americans of African heritage.

In addition, many African Americans trace their ancestry to other racial and ethnic groups, especially European and Native American. A study of nine European DNA markers among 10 African American populations in the United States and one population of Jamaicans of African descent found a range of frequencies from 7% among Jamaicans to 23% among African Americans living in New Orleans.16

Although such diversity argues against generalizing healthcare needs for the entire African American community, some evidence indicates that genetic markers for gene-disease associations may be consistent across traditional racial boundaries.17

GENETIC FACTORS CANNOT EXPLAIN GOUT DISPARITIES

Several small studies have found evidence of genetic factors mediating the risk for hyperuricemia and gout. Twin studies indicate that hyperuricemia is highly heritable,18 although they do not show a concordance in the heritability of gout, suggesting that environmental factors also have an important role in developing clinical manifestations of the disease.12

Genome-wide association studies have identified 28 separate loci influencing uric acid levels, including genes for uric acid transporters (eg, SLC2A9 and ABCG2), and metabolic pathway regulators (eg, PDZK1, SCL22A12, and PRPSAP1), but the distribution among African Americans is largely unknown.19 One important exception is SLC2A9, a renal tubular transporter of uric acid: variants of SLC2A9 were found exclusively in African Americans, but the clinical significance of this association is unclear.20

Several epidemiologic studies have looked at gout in African Americans.

In the Coronary Artery Risk Development in Young Adults study,21 young African Americans had lower levels of uric acid than whites after adjusting for body mass index (BMI), glomerular filtration rate (GFR), diet, and medications. But after up to 20 years of follow-up, the risk of hyperuricemia was 2.3 times higher in African American women than in white women (95% confidence interval [CI] 1.34–3.99). Such differences were not found between African American and white men.

The National Health and Nutritional Examination Survey (NHANES) found that African American adolescents had lower uric acid levels than white adolescents after taking into account sugar intake, GFR, BMI, and onset of puberty.22

The Multiple Risk Factor Intervention Trial23 also found that among those with high cardiovascular risk, the incidence of hyperuricemia and gout was lower in African Americans than in whites.

COMORBID DISEASES MAY EXPLAIN DISPARITIES

Despite some evidence that African Americans have genetic factors that are protective against gout, they have a much greater frequency of acquired risk factors for gout, including obesity, physical inactivity, hypertension, diabetes mellitus, renal failure, high intake of seafood, elevated blood lead levels, and use of antihypertensive medications (Table 2).

Hochberg et al24 examined the incidence of gout in 352 African American and 571 white physicians and found higher rates in African Americans (9% vs 5%). The authors suggested different rates of hypertension as an explanation, although the use of antihypertensive medications such as diuretics that promote hyperuricemia confounds the strength of this conclusion.

AFRICAN AMERICANS NEED STANDARD TREATMENT . . .

Unlike for heart failure, in which subgroup analyses of large prospective studies have found different efficacies of medications in African Americans than in whites, no such data exist for gout. Although there is a higher risk of allopurinol hypersensitivity in ethnic groups that express the HLA-B*5801 polymorphism (eg, Han Chinese, Korean, Thai, Japanese, Portuguese), African Americans are not known to be at greater risk.25 There are also no special precautions for using febuxostat or probenecid in African Americans.

Absent any compelling reason, gout management should be the same regardless of ethnicity.26 Patients should be counseled on primary prevention measures such as dietary and behavioral modification and, if necessary, started on aggressive urate-lowering therapy.27

. . . BUT ARE LESS LIKELY TO HAVE GOUT APPROPRIATELY TREATED

African Americans with gout are less likely to receive urate-lowering therapy.28 According to the 2002 National Ambulatory Medical Care Survey in the United States, African Americans with gout are far less likely to receive allopurinol than whites (42% vs 80%; odds ratio [OR] 0.18; 95% CI 0.04–0.78).23 Even when therapy is prescribed, rates of nonadherence are greater in African Americans than in whites (OR 1.86, 95% CI 1.52–2.27), though the authors do not speculate why this is so.29 No studies have compared rates of prescribing febuxostat to African Americans vs whites.

African Americans are also less likely to receive ongoing routine care for their gout. A 2007 study30 of 663 veterans found that physicians were 1.41 times less likely to adhere to three selected quality indicators when dealing with nonwhite than white patients (95% CI 0.52–3.84). The three quality indicators studied were:

  • Lowering of daily allopurinol dose to below 300 mg/day in the presence of renal insufficiency (no longer considered a quality measure)
  • Monitoring of serum urate level at least once during the first 6 months of continued use of a xanthine oxidase inhibitor, such as allopurinol
  • Monitoring of complete blood cell count and creatinine kinase at least every 6 months in patients with renal impairment receiving long-term prophylactic oral colchicine (> 0.5 mg/day for at least 6 months).

The finding was independent of age, comorbidity index, healthcare access, and utilization characteristics (eg, number of inpatient and outpatient visits, type of physician, most frequently seen physician).

 

 

LIFESTYLE MODIFICATION

Dietary modification is a useful initial step toward reducing uric acid levels (Table 1).27 The following measures are recommended:

Reduce alcohol intake. Alcoholic beverages, particularly beer, are strongly linked to hyperuricemia, according to a 2013 meta-analysis.31 Although alcohol consumption is lower in African Americans than in whites, mortality rates from cirrhosis and other alcohol-related diseases are 10% higher, suggesting metabolic differences that render African Americans more susceptible to the negative health effects of alcohol.32

Avoid sugary drinks. Sweetened beverages, especially those rich in fructose, are also implicated in hyperuricemia and gout. NHANES found an increase in serum uric acid of 0.33 mg/dL (95% CI, 0.11–0.73) in those consuming one to three sugar-sweetened drinks per day compared with nonconsumers, adjusting for total energy intake, age, sex, medications, hypertension, and GFR.33 A prospective study also found a relative risk of 1.85 for those who drink two or more sugar-sweetened beverages per day compared with those who drink fewer than one per month (95% CI 1.08–3.16).34

Unfortunately, African Americans consume a disproportionate amount of sugar from all sources: 17% of African Americans are considered heavy consumers vs 9% of whites.35

Limit foods rich in purines. Red meat, seafood, and some vegetables, including asparagus, spinach, peas, cauliflower, and mushrooms, are associated with increased serum uric acid levels. NHANES found that greater meat and seafood consumption was associated with increased uric acid levels. Choi et al36 found that the risk of gout increased by 21% with each additional daily serving of meat; the relative risk of developing gout was 1.41 (95% CI 1.07–1.86) in the fifth quintile of meat intake compared with the first quintile, and 1.51 (95% CI 1.17–1.95) in the fifth quintile of seafood consumption.

Despite these associations with high-purine food consumption and gout, many purine-rich foods may not contribute to hyperuricemia, and therefore a low-purine diet may not be protective. Interestingly, purine-rich vegetable protein intake is not associated with increased gout risk.37

Increase dairy consumption. Dairy in the diet is associated with a lower incidence of gout, with a decrease of 0.21 mg/dL (95% CI –0.37 to –0.04) in serum uric acid levels between the highest and lowest quintiles of dairy consumption.38 A randomized controlled trial found a 10% reduction in serum uric acid levels with milk consumption.39

Enjoy coffee. Coffee intake has been inversely correlated with gout. Daily intake of 4 to 5 cups of coffee is associated with a relative risk of 0.60 (95% CI 0.41–0.87) vs no coffee.40

Vitamin C and cherry juice41,42 have also been linked to lower gout risk, but the data are less robust.

Control weight. Primary care providers should advise patients to increase physical activity and maintain a healthy weight.

In a prospective study, Choi et al43 found that, in men, the risk of gout increased with the BMI. Compared with men with BMIs in the range of 21 to 22.9 kg/m2, the relative risks were:

  • 1.95 (95% CI 1.44–2.65) at BMI 25 to 29.9 kg/m2
  • 2.33 (95% CI 1.62–3.36) at BMI 30 to 34.9 kg/m2
  • 2.97 (95% CI 1.73–5.10) at BMI > 35 kg/m2.

In addition, those who gained more than 13.6 kg since age 21 had a relative risk of 1.99 (95% CI 1.49–2.66) of developing gout compared with those whose weight remained within 1.8 kg.  

For those who cannot achieve weight loss through conservative measures, bariatric surgery has shown promise. In a prospective study of 60 obese patients (BMI > 35 kg/m2) with gout and type 2 diabetes mellitus, uric acid steadily declined during the first year after bariatric surgery.44

TREATMENT OF ACUTE ATTACKS

Gout can be effectively managed in most patients. Behavioral and pharmacologic interventions are cheap and effective and have been shown to halt further damage to joints as well as retard the progression of renal disease and reduce cardiovascular morbidity.

During acute attacks, anti-inflammatory medications, principally glucocorticoids, nonsteroidal anti-inflammatory drugs, and colchicine, should be given promptly to reduce the intensity and duration of flares.

Although traditional teaching has been that urate-lowering therapy should not be initiated during an acute gout attack because it could prolong the duration of the attack, guidelines now permit it, based on studies showing that therapy does not prolong attacks.45,46

AGGRESSIVE URATE-LOWERING THERAPY FOR PROPHYLAXIS

Long-term treatment of gout is aimed at reducing uric acid levels by mitigating modifiable risk factors and through urate-lowering therapy.46 For many patients, conservative management with dietary and other behavioral changes is not sufficient to prevent further attacks of gout, necessitating urate-lowering therapy. Comorbid diseases such as obesity, hypertension, chronic kidney disease, and diabetes should also be addressed because they promote hyperuricemia and gouty attacks.47

A number of organizations have issued gout management guidelines over the past decade, including the American College of Rheumatology (ACR) in 2012, the European League Against Rheumatism (2006, updated in 2014), and the British Society of Rheumatology (2007). All recommend urate-lowering therapy to prevent gout flares.

The American and European guidelines recommend a target uric acid level below 6 mg/dL, and the British guidelines recommend a target below 5 mg/dL.48 For patients with palpable and visible tophi, the ACR guidelines state that lowering to below 5 mg/dL may be needed.46

First-line agents for urate-lowering therapy are xanthine oxidase inhibitors, which include allopurinol (costing $0.48 per generic 100-mg tablet or $0.92 per 300-mg tablet), and febuxostat ($5.38 per 40-mg or 80-mg tablet). For patients with contraindications or intolerances to allopurinol or febuxostat, probenecid ($1.15 per 500-mg tablet), which functions as a uricosuric agent (ie, increases urinary excretion of uric acid), may be used.

Losartan ($1.68 per 25-mg tablet) and fenofibrate ($1.91 per 48-mg tablet) are also often used to reduce uric acid levels, but they have only modest effects and are not approved for this indication in the United States.49

MANAGE CHRONIC CASES WITH CONTINUED THERAPY

ACR guidelines strongly emphasize continuing prophylaxis in case of ongoing gout activity (ie, detection of tophi on examination, recent gout attacks, or chronic gouty arthritis) (Table 3). The following durations have been proposed for prophylaxis:

  • 6 months after an attack
  • 6 months after achieving target uric acid level in patients with evidence of tophi
  • 3 months after achieving target uric acid level in patients with resolved tophi. 

Two randomized controlled trials support the use of the anti-inflammatory agent colchicine ($4.30 per tablet) for prophylaxis when initiating urate-lowering therapy.50,51

Monitor uric acid levels, renal function, adverse effects

The initial dosage of urate-lowering agents depends on the presence of kidney disease (Table 3).

Allopurinol is typically started at 50 mg to 100 mg oral daily, and titrated upward in increments of 100 mg depending on uric acid levels. According to the ACR guidelines, uric acid levels should be measured every 2 to 5 weeks.46 The Febuxostat vs Allopurinol Streamline Trial found that 97% of patients reached target uric acid levels within two titrations.52

Especially during the first months of therapy, physicians should be vigilant for adverse effects of allopurinol, including hypersensitivity reaction (rash, fever, Stevens-Johnson syndrome), hepatotoxicity, and myelotoxicity (bone marrow suppression), and for effects of febuxostat, such as rash, diarrhea, elevations in aminotransferase levels, and upper respiratory tract infections.53 Although the maximum acceptable dose of allopurinol is 800 mg even in chronic kidney disease, regularly monitoring for hypersensitivity reactions and other adverse effects is needed if doses are above 300 mg per day.46

Routine follow-up is essential

Adherence to therapy should be assessed at every visit. Patients should be counseled that gout is a chronic disease and that they should continue on urate-lowering therapy even if they are not having acute attacks. Adverse effects of medications should be monitored and addressed, although for allopurinol and febuxostat these are rare beyond the first few months of initiation and titration. If worsening of gout or uric acid levels occurs, therapy should be augmented and contributors to hyperuricemia reviewed. In refractory cases, rheumatology consultation may be needed; medications such as pegloticase ($16,800/mL) may be deemed necessary for severe tophaceous gout or for patients who need more rapid reduction of urates.49

STRATEGIES TO ADDRESS DISPARITIES

Creative approaches are needed to engage African American communities to reduce the burden of gout. No trials have been published evaluating methods for reducing health disparities with gout, but strategies for other chronic conditions may be applicable.

Incorporate guidelines better. Although setting and disseminating guidelines should ensure that care is standardized, studies have found that primary care physicians and rheumatologists frequently do not implement them.3,54 Reasons cited for poor adherence to gout guidelines include their relatively recent release, poor patient adherence, lack of measurement tools, and inadequate education of primary care physicians. Incorporating the guidelines as “best practice advisories” into electronic medical record systems has been proposed to improve their implementation.46

Use a team approach. Some quality improvement projects have used pharmacists and nurses to help implement gout guidelines. In two studies, empowering nurses and pharmacists to better educate patients and implement standardized protocols for titrating urate-lowering medications led to sustained improvements in maintaining serum uric acid levels less than 6 mg/dL.55–57

Multidisciplinary involvement by nutritionists, physicians, and community health workers have been found to help improve glycemic control in African Americans.58 Similar efforts can be undertaken to improve control of uric acid levels through dietary modification and improved compliance.

Address patient concerns. Substantial gaps exist in knowledge about gout between providers and the general population, although large studies specifically focusing on African Americans are lacking.59 Qualitative studies suggest that patient experience of gout may vary depending on race, with African Americans more likely than whites to rank the following concerns regarding gout as high: dietary restrictions, emotional burden, severe pain, the need for canes or crutches during flares, and gout bringing their day to a halt.60 Another study among African Americans with gout found concerns about the effectiveness of urate-lowering therapy, side effects of medications, polypharmacy, pill size, cost, refill issues, and forgetting to take medications regularly.61

References
  1. Hayward RA, Rathod T, Roddy E, Muller S, Hider SL, Mallen CD. The association of gout with socioeconomic status in primary care: a cross-sectional observational study. Rheumatology (Oxford) 2013; 52:2004–2008.
  2. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum 2011; 63:3136–3141.
  3. Oderda GM, Shiozawa A, Walsh M, et al. Physician adherence to ACR gout treatment guidelines: perception versus practice. Postgrad Med 2014; 126:257–267.
  4. Chandratre P, Roddy E, Clarson L, Richardson J, Hider SL, Mallen CD. Health-related quality of life in gout: a systematic review. Rheumatology (Oxford) 2013; 52:2031–2040.
  5. Kleinman NL, Brook RA, Patel PA, et al. The impact of gout on work absence and productivity. Value Health 2007; 10:231–237.
  6. Edwards NL, Sundy JS, Forsythe A, Blume S, Pan F, Becker MA. Work productivity loss due to flares in patients with chronic gout refractory to conventional therapy. J Med Econ 2011; 14:10–15.
  7. Sacks JJ, Luo YH, Helmick CG. Prevalence of specific types of arthritis and other rheumatic conditions in the ambulatory health care system in the United States. Arthritis Care Res (Hoboken) 2010; 62:460–464.
  8. Juraschek SP, Kovell LC, Miller ER 3rd, Gelber AC. Gout, urate-lowering therapy, and uric acid levels among adults in the United States. Arthritis Care Res (Hoboken) 2015; 67:588–592.
  9. Grassi D, Desideri G, Di Giacomantonio AV, Di Giosia P, Ferri C. Hyperuricemia and cardiovascular risk. High Blood Press Cardiovasc Prev 2014; 21:235–242.
  10. Karis E, Crittenden DB, Pillinger MH. Hyperuricemia, gout, and related comorbidities: cause and effect on a two-way street. South Med J 2014; 107:235–241.
  11. Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in US women—the Third National Health and Nutrition Examination Survey. Arthritis Res Ther 2008; 10:R116.
  12. MacFarlane LA, Kim SC. Gout: a review of nonmodifiable and modifiable risk factors. Rheum Dis Clin North Am 2014; 40:581–604.
  13. Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol 2015 Nov; 11:649–662.
  14. Rivas-Drake D, Seaton EK, Markstrom C, et al; Ethnic and Racial Identity in the 21st Century Study Group. Ethnic and racial identity in adolescence: implications for psychosocial, academic, and health outcomes. Child Dev 2014; 85:40–57.
  15. US Commission on Civil Rights. Racial categorization in the 2010 census. www.usccr.gov/pubs/RC2010Web_Version.pdf. Accessed August 12, 2016.
  16. Parra EJ, Marcini A, Akey J, et al. Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet 1998; 63:1839–1851.
  17. Ioannidis JP, Ntzani EE, Trikalinos TA. ‘Racial’ differences in genetic effects for complex diseases. Nat Genet 2004; 36:1312–1218.
  18. Emmerson BT, Nagel SL, Duffy DL, Martin NG. Genetic control of the renal clearance of urate: a study of twins. Ann Rheum Dis 1992; 51:375–377. 
  19. Merriman TR, Choi HK, Dalbeth N. The genetic basis of gout. Rheum Dis Clin North Am 2014; 40:279–290.
  20. Rule AD, de Andrade M, Matsumoto M, Mosley TH, Kardia S, Turner ST. Association between SLC2A9 transporter gene variants and uric acid phenotypes in African American and white families. Rheumatology (Oxford) 2011; 50: 871–878.
  21. Gaffo AL, Jacobs DR Jr, Lewis CE, Mikuls TR, Saag KG. Association between being African-American, serum urate levels and the risk of developing hyperuricemia: findings from the Coronary Artery Risk Development in Young Adults cohort. Arthritis Res Ther 2012; 14:R4.
  22. DeBoer MD, Dong L, Gurka MJ. Racial/ethnic and sex differences in the relationship between uric acid and metabolic syndrome in adolescents: an analysis of National Health and Nutrition Survey 1999-2006. Metabolism 2012; 61: 554–561.
  23. Krishnan E. Gout in African Americans. Am J Med 2014; 127:858–864.
  24. Hochberg MC, Thomas J, Thomas DJ, Mead L, Levine DM, Klag MJ. Racial differences in the incidence of gout. The role of hypertension. Arthritis Rheum 1995; 38:628–632.
  25. Jarjour S, Barrette M, Normand V, Rouleau JL, Dubé MP, de Denus S. Genetic markers associated with cutaneous adverse drug reactions to allopurinol: a systematic review. Pharmacogenomics 2015; 16:755–767.
  26. Singh JA. Can racial disparities in optimal gout treatment be reduced? Evidence from a randomized trial. BMC Med 2012; 10:15.
  27. Nasser-Ghodsi N, Harrold LR. Overcoming adherence issues and other barriers to optimal care in gout. Curr Opin Rheumatol 2015; 27:134–138.
  28. Krishnan E, Lienesch D, Kwoh CK. Gout in ambulatory care settings in the United States. J Rheumatol 2008; 35:498–501.
  29. Solomon DH, Avorn J, Levin R, Brookhart MA. Uric acid lowering therapy: prescribing patterns in a large cohort of older adults. Ann Rheum Dis 2008; 67:609–613.
  30. Singh JA, Hodges JS, Toscano JP, Asch SM. Quality of care for gout in the US needs improvement. Arthritis Rheum 2007; 57:822–829.
  31. Wang M, Jiang X, Wu W, Zhang D. A meta-analysis of alcohol consumption and the risk of gout. Clin Rheumatol 2013; 32:1641–1648.
  32. Zapolski TC, Pedersen SL, McCarthy DM, Smith GT. Less drinking, yet more problems: understanding African American drinking and related problems. Psychol Bull 2014; 140:188–223.
  33. Choi JW, Ford ES, Gao X, Choi HK. Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2008; 59:109–116.
  34. Choi HK, Curhan G. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ 2008; 336:309–312.
  35. Schmidt LA. New unsweetened truths about sugar. JAMA Intern Med 2014; 174:525–526.
  36. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004; 350:1093–1103.
  37. Choi HK. A prescription for lifestyle change in patients with hyperuricemia and gout. Curr Opin Rheumatol 2010; 22:165–172.
  38. Choi HK, Liu S, Curhan G. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2005; 52:283–289. 
  39. Dalbeth N, Wong S, Gamble GD, et al. Acute effect of milk on serum urate concentrations: a randomised controlled crossover trial. Ann Rheum Dis 2010; 69:1677–1682. 
  40. Choi HK, Willett W, Curhan G. Coffee consumption and risk of incident gout in men: a prospective study. Arthritis Rheum 2007; 56:2049–2055.
  41. Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi HK. Cherry consumption and decreased risk of recurrent gout attacks. Arthritis Rheum 2012; 64:4004–4011.
  42. Schlesinger N, Schlesinger M. Previously reported prior studies of cherry juice concentrate for gout flare prophylaxis: comment on the article by Zhang et al. Arthritis Rheum 2013; 65:1135–1136. 
  43. Choi HK, Atkinson K, Karlson EW, Curhan G. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med 2005; 165:742–748.
  44. Dalbeth N, Chen P, White M, et al. Impact of bariatric surgery on serum urate targets in people with morbid obesity and diabetes: a prospective longitudinal study. Ann Rheum Dis 2014; 73:797–802.
  45. Hill EM, Sky K, Sit M, Collamer A, Higgs J. Does starting allopurinol prolong acute treated gout? A randomized clinical trial. J Clin Rheumatol 2015; 21:120–125.
  46. Khanna D, Fitzgerald JD, Khanna PP, et al; American College of Rheumatology. 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; 64:1431–1446.
  47. Puig JG, Martínez MA. Hyperuricemia, gout and the metabolic syndrome. Curr Opin Rheumatol 2008; 20:187–191.
  48. Wise E, Khanna PP. The impact of gout guidelines. Curr Opin Rheumatol 2015; 27:225–230.
  49. Becker MA. Urate-lowering medications. www.uptodate.com. Accessed August 15, 2016.
  50. Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol 2004; 31:2429–2432.
  51. Paulus HE, Schlosstein LH, Godfrey RG, Klinenberg JR, Bluestone R. Prophylactic colchicine therapy of intercritical gout. A placebo-controlled study of probenecid-treated patients. Arthritis Rheum 1974; 17:609–614.
  52. Jennings CG, Mackenzie IS, Flynn R, et al; FAST study group. Up-titration of allopurinol in patients with gout. Semin Arthritis Rheum 2014; 44:25–30.
  53. Becker MA, Schumacher HR, Espinoza LR, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther 2010; 12: R63.
  54. Cottrell E, Crabtree V, Edwards JJ, Roddy E. Improvement in the management of gout is vital and overdue: an audit from a UK primary care medical practice. BMC Fam Pract 2013; 14:170.
  55. Goldfien RD, Ng MS, Yip G, et al. Effectiveness of a pharmacist-based gout care management programme in a large integrated health plan: results from a pilot study. BMJ Open 2014; 4:e003627.
  56. Lim AY, Shen L, Tan CH, Lateef A, Lau TC, Teng GG. Achieving treat to target in gout: a clinical practice improvement project. Scand J Rheumatol 2012; 41:450–457.
  57. Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis 2013; 72:826–830.
  58. Smalls BL, Walker RJ, Bonilha HS, Campbell JA, Egede LE. Community interventions to improve glycemic control in African Americans with type 2 diabetes: a systemic review. Glob J Health Sci 2015; 7:171–182.
  59. Harrold LR, Mazor KM, Peterson D, Naz N, Firneno C, Yood RA. Patients’ knowledge and beliefs concerning gout and its treatment: a population based study. BMC Musculoskelet Disord 2012; 13:180.
  60. Singh JA. The impact of gout on patient’s lives: a study of African American and Caucasian men and women with gout. Arthritis Res Ther 2014; 16:R132.
  61. Singh JA. Facilitators and barriers to adherence to urate-lowering therapy in African Americans with gout: a qualitative study. Arthritis Res Ther 2014; 16:R82.
References
  1. Hayward RA, Rathod T, Roddy E, Muller S, Hider SL, Mallen CD. The association of gout with socioeconomic status in primary care: a cross-sectional observational study. Rheumatology (Oxford) 2013; 52:2004–2008.
  2. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum 2011; 63:3136–3141.
  3. Oderda GM, Shiozawa A, Walsh M, et al. Physician adherence to ACR gout treatment guidelines: perception versus practice. Postgrad Med 2014; 126:257–267.
  4. Chandratre P, Roddy E, Clarson L, Richardson J, Hider SL, Mallen CD. Health-related quality of life in gout: a systematic review. Rheumatology (Oxford) 2013; 52:2031–2040.
  5. Kleinman NL, Brook RA, Patel PA, et al. The impact of gout on work absence and productivity. Value Health 2007; 10:231–237.
  6. Edwards NL, Sundy JS, Forsythe A, Blume S, Pan F, Becker MA. Work productivity loss due to flares in patients with chronic gout refractory to conventional therapy. J Med Econ 2011; 14:10–15.
  7. Sacks JJ, Luo YH, Helmick CG. Prevalence of specific types of arthritis and other rheumatic conditions in the ambulatory health care system in the United States. Arthritis Care Res (Hoboken) 2010; 62:460–464.
  8. Juraschek SP, Kovell LC, Miller ER 3rd, Gelber AC. Gout, urate-lowering therapy, and uric acid levels among adults in the United States. Arthritis Care Res (Hoboken) 2015; 67:588–592.
  9. Grassi D, Desideri G, Di Giacomantonio AV, Di Giosia P, Ferri C. Hyperuricemia and cardiovascular risk. High Blood Press Cardiovasc Prev 2014; 21:235–242.
  10. Karis E, Crittenden DB, Pillinger MH. Hyperuricemia, gout, and related comorbidities: cause and effect on a two-way street. South Med J 2014; 107:235–241.
  11. Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in US women—the Third National Health and Nutrition Examination Survey. Arthritis Res Ther 2008; 10:R116.
  12. MacFarlane LA, Kim SC. Gout: a review of nonmodifiable and modifiable risk factors. Rheum Dis Clin North Am 2014; 40:581–604.
  13. Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol 2015 Nov; 11:649–662.
  14. Rivas-Drake D, Seaton EK, Markstrom C, et al; Ethnic and Racial Identity in the 21st Century Study Group. Ethnic and racial identity in adolescence: implications for psychosocial, academic, and health outcomes. Child Dev 2014; 85:40–57.
  15. US Commission on Civil Rights. Racial categorization in the 2010 census. www.usccr.gov/pubs/RC2010Web_Version.pdf. Accessed August 12, 2016.
  16. Parra EJ, Marcini A, Akey J, et al. Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet 1998; 63:1839–1851.
  17. Ioannidis JP, Ntzani EE, Trikalinos TA. ‘Racial’ differences in genetic effects for complex diseases. Nat Genet 2004; 36:1312–1218.
  18. Emmerson BT, Nagel SL, Duffy DL, Martin NG. Genetic control of the renal clearance of urate: a study of twins. Ann Rheum Dis 1992; 51:375–377. 
  19. Merriman TR, Choi HK, Dalbeth N. The genetic basis of gout. Rheum Dis Clin North Am 2014; 40:279–290.
  20. Rule AD, de Andrade M, Matsumoto M, Mosley TH, Kardia S, Turner ST. Association between SLC2A9 transporter gene variants and uric acid phenotypes in African American and white families. Rheumatology (Oxford) 2011; 50: 871–878.
  21. Gaffo AL, Jacobs DR Jr, Lewis CE, Mikuls TR, Saag KG. Association between being African-American, serum urate levels and the risk of developing hyperuricemia: findings from the Coronary Artery Risk Development in Young Adults cohort. Arthritis Res Ther 2012; 14:R4.
  22. DeBoer MD, Dong L, Gurka MJ. Racial/ethnic and sex differences in the relationship between uric acid and metabolic syndrome in adolescents: an analysis of National Health and Nutrition Survey 1999-2006. Metabolism 2012; 61: 554–561.
  23. Krishnan E. Gout in African Americans. Am J Med 2014; 127:858–864.
  24. Hochberg MC, Thomas J, Thomas DJ, Mead L, Levine DM, Klag MJ. Racial differences in the incidence of gout. The role of hypertension. Arthritis Rheum 1995; 38:628–632.
  25. Jarjour S, Barrette M, Normand V, Rouleau JL, Dubé MP, de Denus S. Genetic markers associated with cutaneous adverse drug reactions to allopurinol: a systematic review. Pharmacogenomics 2015; 16:755–767.
  26. Singh JA. Can racial disparities in optimal gout treatment be reduced? Evidence from a randomized trial. BMC Med 2012; 10:15.
  27. Nasser-Ghodsi N, Harrold LR. Overcoming adherence issues and other barriers to optimal care in gout. Curr Opin Rheumatol 2015; 27:134–138.
  28. Krishnan E, Lienesch D, Kwoh CK. Gout in ambulatory care settings in the United States. J Rheumatol 2008; 35:498–501.
  29. Solomon DH, Avorn J, Levin R, Brookhart MA. Uric acid lowering therapy: prescribing patterns in a large cohort of older adults. Ann Rheum Dis 2008; 67:609–613.
  30. Singh JA, Hodges JS, Toscano JP, Asch SM. Quality of care for gout in the US needs improvement. Arthritis Rheum 2007; 57:822–829.
  31. Wang M, Jiang X, Wu W, Zhang D. A meta-analysis of alcohol consumption and the risk of gout. Clin Rheumatol 2013; 32:1641–1648.
  32. Zapolski TC, Pedersen SL, McCarthy DM, Smith GT. Less drinking, yet more problems: understanding African American drinking and related problems. Psychol Bull 2014; 140:188–223.
  33. Choi JW, Ford ES, Gao X, Choi HK. Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2008; 59:109–116.
  34. Choi HK, Curhan G. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ 2008; 336:309–312.
  35. Schmidt LA. New unsweetened truths about sugar. JAMA Intern Med 2014; 174:525–526.
  36. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004; 350:1093–1103.
  37. Choi HK. A prescription for lifestyle change in patients with hyperuricemia and gout. Curr Opin Rheumatol 2010; 22:165–172.
  38. Choi HK, Liu S, Curhan G. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2005; 52:283–289. 
  39. Dalbeth N, Wong S, Gamble GD, et al. Acute effect of milk on serum urate concentrations: a randomised controlled crossover trial. Ann Rheum Dis 2010; 69:1677–1682. 
  40. Choi HK, Willett W, Curhan G. Coffee consumption and risk of incident gout in men: a prospective study. Arthritis Rheum 2007; 56:2049–2055.
  41. Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi HK. Cherry consumption and decreased risk of recurrent gout attacks. Arthritis Rheum 2012; 64:4004–4011.
  42. Schlesinger N, Schlesinger M. Previously reported prior studies of cherry juice concentrate for gout flare prophylaxis: comment on the article by Zhang et al. Arthritis Rheum 2013; 65:1135–1136. 
  43. Choi HK, Atkinson K, Karlson EW, Curhan G. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med 2005; 165:742–748.
  44. Dalbeth N, Chen P, White M, et al. Impact of bariatric surgery on serum urate targets in people with morbid obesity and diabetes: a prospective longitudinal study. Ann Rheum Dis 2014; 73:797–802.
  45. Hill EM, Sky K, Sit M, Collamer A, Higgs J. Does starting allopurinol prolong acute treated gout? A randomized clinical trial. J Clin Rheumatol 2015; 21:120–125.
  46. Khanna D, Fitzgerald JD, Khanna PP, et al; American College of Rheumatology. 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; 64:1431–1446.
  47. Puig JG, Martínez MA. Hyperuricemia, gout and the metabolic syndrome. Curr Opin Rheumatol 2008; 20:187–191.
  48. Wise E, Khanna PP. The impact of gout guidelines. Curr Opin Rheumatol 2015; 27:225–230.
  49. Becker MA. Urate-lowering medications. www.uptodate.com. Accessed August 15, 2016.
  50. Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol 2004; 31:2429–2432.
  51. Paulus HE, Schlosstein LH, Godfrey RG, Klinenberg JR, Bluestone R. Prophylactic colchicine therapy of intercritical gout. A placebo-controlled study of probenecid-treated patients. Arthritis Rheum 1974; 17:609–614.
  52. Jennings CG, Mackenzie IS, Flynn R, et al; FAST study group. Up-titration of allopurinol in patients with gout. Semin Arthritis Rheum 2014; 44:25–30.
  53. Becker MA, Schumacher HR, Espinoza LR, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther 2010; 12: R63.
  54. Cottrell E, Crabtree V, Edwards JJ, Roddy E. Improvement in the management of gout is vital and overdue: an audit from a UK primary care medical practice. BMC Fam Pract 2013; 14:170.
  55. Goldfien RD, Ng MS, Yip G, et al. Effectiveness of a pharmacist-based gout care management programme in a large integrated health plan: results from a pilot study. BMJ Open 2014; 4:e003627.
  56. Lim AY, Shen L, Tan CH, Lateef A, Lau TC, Teng GG. Achieving treat to target in gout: a clinical practice improvement project. Scand J Rheumatol 2012; 41:450–457.
  57. Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis 2013; 72:826–830.
  58. Smalls BL, Walker RJ, Bonilha HS, Campbell JA, Egede LE. Community interventions to improve glycemic control in African Americans with type 2 diabetes: a systemic review. Glob J Health Sci 2015; 7:171–182.
  59. Harrold LR, Mazor KM, Peterson D, Naz N, Firneno C, Yood RA. Patients’ knowledge and beliefs concerning gout and its treatment: a population based study. BMC Musculoskelet Disord 2012; 13:180.
  60. Singh JA. The impact of gout on patient’s lives: a study of African American and Caucasian men and women with gout. Arthritis Res Ther 2014; 16:R132.
  61. Singh JA. Facilitators and barriers to adherence to urate-lowering therapy in African Americans with gout: a qualitative study. Arthritis Res Ther 2014; 16:R82.
Issue
Cleveland Clinic Journal of Medicine - 83(9)
Issue
Cleveland Clinic Journal of Medicine - 83(9)
Page Number
665-674
Page Number
665-674
Publications
Cleveland Clinic Journal of Medicine
Publications
Cleveland Clinic Journal of Medicine
Topics
Rheumatology
Pain
Article Type
Article
Display Headline
Gout and African Americans: Reducing disparities
Display Headline
Gout and African Americans: Reducing disparities
Legacy Keywords
gout, uric acid, hyperuricemia, African American, disparities
Legacy Keywords
gout, uric acid, hyperuricemia, African American, disparities
Click for Credit Status
Eligible
Sections
Addressing Disparities in Health Care
Inside the Article

KEY POINTS

  • Gout is more common in African Americans mainly because of their higher prevalence of risk factors such as obesity, diabetes, chronic kidney disease, and hypertension.
  • Gout significantly reduces quality of life, economic productivity, and physical function and increases the risks of cardiovascular and renal disease.
  • Although professional guidelines and effective medications are widely available, studies have found low physician compliance with providing optimal gout treatment, especially for African American patients.
  • Treatment for gout in African Americans is the same as for all patients. Acute attacks should be treated promptly with anti-inflammatory agents, and uric acid levels should be aggressively lowered with drug therapy and diet modification.
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