Epidemiology and classification of gout

Historical Perspective

Gout is an inflammatory arthritis caused by the crystallization of urate within the joints and is associated with hyperuricemia. Once known as a “disease of kings and king of diseases,” gout was described by Hippocrates during the Golden Age of Greece and was previously considered a disease of the affluent, primarily observed in middle-aged men of the wealthy upper class (“the Patrician malady”). Based on these historical descriptions, gout had often affected the wealthy and the educated, particularly those who not only could afford the comforts of life but also enjoyed its excesses, with lifestyles that bordered on overindulgence, gluttony, and intemperance. As these lifestyles have become affordable and prevalent among the general public in the modern era, particularly in Western societies with abundantly available foods and a strong tendency toward a sedentary lifestyle, gout has changed its epidemiology from a “disease of kings” to a “disease of commoners.”

Westernization and Gout Trends

Humans are the only mammals that are known to develop gout spontaneously, probably because hyperuricemia commonly develops only in humans. The diet and urate levels in species that lack uricase but do not suffer gout provide insight into why the serum urate levels in the great apes (1.5–3.0 mg/dL) are substantially lower than those in humans in the modern era (mean, 6.1 mg/dL among men in the U.S. general population). The great apes primarily consume vegetables and fruit, and their animal protein intake is minimal. Early humans in indigenous scavenging and gathering societies consumed diets primarily derived from vegetables and fruits with sporadic supplementation of fish and game and likely had serum urate levels similar to those of the great apes.

A number of epidemiologic studies from various countries suggest that gout prevalence has increased in the past few decades. This increase is likely explained by trends in lifestyle factors associated with westernization. For example, since the introduction of Western culture and dietary habits, gout has become epidemic among some native peoples, such as the Maori of New Zealand. After the introduction of a diet high in fatty meats and carbohydrates and low in dairy products in the early 1900s, an epidemic of obesity and gout developed. Three similarly conducted serial surveys in New Zealand show an increase in the prevalence of gout in European, U.S., and Maori descendants ( Table 192.1 ). Findings from the United States, United Kingdom, and China also suggest that the disease burden of gout is similarly increasing (see Table 192.1 ).

Similarly, gout was considered rare among African Americans in the early 1900s, but changes in diet have led to a rapid development of obesity, diabetes, and hypertension. Today, mean serum urate levels are higher, and gout is more common among African Americans than among Whites. Furthermore, ecologic studies of Japanese and Filipino populations have found that U.S. immigrants from these countries had increases in serum urate levels, the incidence of gout, or both, compared with their nonmigrant counterparts.

Case Definitions and Classification Criteria

Epidemiologic estimates of the disease burden of gout (e.g., prevalence or incidence) depend on case definition, as with any other condition. A definitive diagnosis of gout requires either the presence of monosodium urate monohydrate crystals in the joint fluid or tophus presence. However, in population surveys designed to estimate the prevalence of gout, this method of identification is impractical. For this reason, several case definitions have been developed, including self-reports; the Rome criteria ; the New York criteria ; the American College of Rheumatology (ACR) preliminary criteria; and most recently, the 2015 ACR/European League Against Rheumatism (EULAR) gout classification criteria. For example, the prevalence of gout has been estimated using self-reported data from various years of the U.S. National Health Interviews Surveys (NHIS). Data from the Sudbury study showed that 44% of self-reported cases could be validated according to the Rome or New York criteria. However, the validation rate from a physician cohort (the Johns Hopkins Precursor Study) was much higher—80% according to the ACR survey criteria applied by mail and 100% by mail combined with medical record review. Similarly, the validation rate of self-reported gout in a recent large prospective cohort of male health professionals was approximately 70% according to the ACR survey criteria assessed by a mailed survey. The difference in the validation rates of self-reported gout between these studies likely reflects differences in the level of health knowledge in the study populations.

Recent epidemiologic studies have used large-scale population-based electronic medical records (EMRs) and administrative health databases, whereby gout cases are identified using physician diagnoses or the International Classification of Diseases (ICD) coding system. Validation studies have found positive predictive values of ICD codes ranging from 61% in a U.S. managed care setting to 86% in a Veterans Affairs database. Moreover, the combination of a physician diagnosis and antigout drug use in EMRs has shown a positive predictive value of 90% in a general population context. Finally, the 2015 ACR/EULAR gout classification criteria are based on clinical features, laboratory findings (e.g., serum uric acid levels), and imaging modalities (e.g., dual energy computed tomography and ultrasound) and showed a sensitivity of 92% and specificity of 89%, which is superior to any other previous criteria.

Prevalence of Gout

Prevalence estimates from various countries and timeframes along with their definitions of gout are summarized in Table 192.1 . The disease burden of gout is substantial and increasing worldwide, with the latest estimates ranging from 2.7% to 6.7% in Western lifestyle countries and Taiwan. The latest prevalence of self-reported gout (diagnosed by health professionals) in the United States was estimated in 2015 to 2016 to be 4% of U.S. adults, which translates into 9.2 million individuals. This recent prevalence estimate is significantly higher than the 1988 to 1994 estimate (2.7%; an absolute difference of 1.2%). Furthermore, the prevalence of hyperuricemia and mean serum urate levels in 2007 to 2008 were significantly higher than the 1988 to 1994 estimates. Similarly, serial U.S. NHIS that used the same survey instrument showed that the annual prevalence of gout doubled between 1969 and 1996, and the steepest increase occurred between 1969 and 1976 (see Table 192.1 ), closely coinciding with the obesity epidemic due to Western diet and lifestyle trends. UK studies based on general practice diagnostic indices found similarly increasing prevalence estimates of gout between the 1970s and 1990s (see Table 192.1 ). The latest study based on the same UK database found a prevalence of 2.49% in 2012. An Italian study also found an increasing trend from 0.7% to 0.9% between 2005 and 2009, although the prevalence estimates seemed lower than those of other Western countries, which may be explained by the potential urate-lowering benefit of the Mediterranean diet. Whereas a Taiwanese Nutrition and Health Survey conducted during the mid-1990s found a prevalence similar to the United States (3.4%), a more recent study using the National Health Insurance Research Database in 2010 found a higher prevalence of 6.24%.

Incidence of Gout

A number of prospective cohort studies from the United States as well as EMR or administrative database analyses from other countries have estimated the contemporary incidence rates of gout ranging from 1.5 to 4.1 cases among men and 0.4 to 1.5 cases among women per 1000 person-years ( Table 192.2 ). Furthermore, these incidence estimates have increased in recent years, consistent with gout prevalence estimates. For example, the Framingham Heart Study followed 5209 people for a median of 28 years and documented 104 incident cases of gout (clinically diagnosed by typical symptoms and medications) in women and 200 cases in men, resulting in incidence rates of 1.4 and 4.0 per 1000 person-years, respectively. Furthermore, serial investigations of the Rochester Epidemiology Project showed that the incidence of gout without diuretic exposure (using the ACR survey criteria ) doubled from 20.2 per 100,000 in 1977 to 1978 to 45.9 per 100,000 in 1995 to 1996, paralleling the obesity epidemic. Similarly, studies based on UK general practice databases spanning between the 1990s and 2012 found rising trends of gout incidence (see Table 192.2 ) over the past several decades. These studies all found that the incidence of gout was higher in men than in women and increased with age regardless of sex.