CHAPTER 10 Martin Underwood Warwick Clinical Trials Unit, Warwick Medical School, The University of Warwick Coventry, UK; Department of Epidemiology and Preventive Medicine Monash University, Clayton, Australia Gout is a common metabolic disorder, typically presenting as an acute monoarthritis, most commonly of the first metatarsal phalangeal joint. The term ‘gout’ includes an acute attack, the propensity for repeated episodes and also for chronic gouty arthritis. The underlying problem is a build‐up of urate, a purine breakdown product. Humans, and some primates, lack uricase, which in other mammals oxidizes urate to allantoin, which is readily soluble. Both an increased dietary purine intake and an increased breakdown of endogenous proteins (e.g. cancer treatment or haematological malignancy) can increase urate levels. Urate excretion is mainly renal. The rate of renal excretion is affected by urine flow, pH and competition for renal tubular exchange (e.g. diuretics). People whose problems are primarily due to increased purine turnover will have a high urinary urate and those whose problems are primarily renal will have a low urinary urate. This distinction is rarely of clinical importance. For uric acid crystals to form, the serum needs to be saturated with urate, i.e. >0.42 mmol/L (>7.0 g/dL). This is coincidentally the upper limit of the reference range in men and postmenopausal women in many laboratories. For premenopausal women, the upper limit of the reference range for serum urate is commonly 0.36 mmol/L (6.0 mg/dL). Globally, the age‐standardized prevalence of gout is 0.076% (95% uncertainty interval (UI) 0.072–0.082). This overall figure, from the Global Burden of Disease, conceals striking differences in prevalence between regions and within regions according to age and sex. Population prevalences range from 0.39% (95% UI 0.35–0.43) in Australasia to 0.03% (95% UI 0.02–0.05) in parts of sub‐Saharan Africa. For men living in Australasia, southern Latin America, North America (high income) and western Europe, prevalences all exceed 1% by the age of 60, peaking at over 2.5% in elderly Australasian men (Figure 10.1). Even in high‐prevalence regions, only around 0.5% of elderly women are affected. See http://vizhub.healthdata.org/gbd‐compare/ for detailed breakdown. Figure 10.1 Prevalence of gout by region, 1990 and 2010. Source: Redrawn from Smith et al. (2014) There is no pattern of change of age‐standardized prevalence of gout over time. Nevertheless, with an ageing population, the absolute number of people affected and the disease burden are increasing. However, there are few reliable data on how many people are affected each year or how many people are taking prophylactic drugs. Some non‐white populations are more prone to gout/hyperuricaemia; there is generally a higher prevalence of gout in indigenous ethnic groups around the Pacific Rim. Environmental factors also have a part to play; for example, increasing age and obesity have resulted in a >50% increase in disease burden from gout in high‐income Asian Pacific countries in the 20 years to 2010. Age and sex – Gout becomes more common with increasing age. The diagnosis is rare in premenopausal women. It is more common in older women but still much less prevalent than in men (see Figure 10.1). The later age of onset in women may relate to the uricosuric effects of oestrogens. Obesity – Relative risk of gout increases with increasing body mass index (BMI). Compared to people with a BMI of 21–25, those with BMI of >35 are four times as likely to develop gout (Figure 10.2). Figure 10.2 Obesity and the incidence of a first attack of gout in men. Source: Data from Choi et al. (2005) Diet – Each additional portion of meat per day increases the risk of gout by 20%. Purine‐rich vegetables do not appear to increase the risk, whilst consuming more dairy products reduces the risk of developing gout (Table 10.1). Dietary fructose may also increase the risk of developing gout. This occurs naturally and is also present in high fructose corn syrup (HFCS) which is commonly used as a sweetener for soft drinks and other foods in the USA. Its use in the European Union, where it is known as isoglucose, is set to increase with planned lifting of production quotas in 2017. Table 10.1 Effect of diet and alcohol on incidence of a first attack of gout in men*. Source: Data from Choi et al. (2014a & b) Data from the professionals follow‐up‐study. * Additional weekly serving. Drugs – A number of drugs can increase serum urate; diuretics are common culprits. Aspirin and salicylates at low doses decrease urate excretion but at high doses (4–6 g/day) they have a uricosuric effect. Alcohol – Compared to non‐drinkers, people consuming >50 g alcohol per day are 2.5 times as likely to develop gout. Whilst there is a strong relationship between beer intake and gout, there is only a weak relationship between intake of spirits and gout. There does not appear to be a relationship between wine intake and gout. Alcohol is catabolized to ketones that compete with urate for excretion by the renal tubule. Beer typically contains substantial amounts of purines, from yeast, that are catabolized to urate by gut bacteria. Alcohol may also increase the dose of allopurinol needed by decreasing the conversion of allopurinol to its effective metabolite, oxipurinol (Figure 10.3). Figure 10.3 Effect of total alcohol intake on the relative risk of a first attack of gout. Source: Data from Choi et al. (2005)
Gout, Hyperuricaemia and Crystal Arthritis
Gout and hyperuricaemia
Epidemiology
Risk factors for gout/hyperuricaemia
Portion
Relative risk (95% Cl)
Alcohol
Beer 335 ml
1.49 (1.32 to 1.70)
Sprits 44 ml
1.15 (1.04 to 1.28)
Wine 118 ml
1.04 (1.88 to 1.22)
Food:
Meat
1.21 (1.04 to 1.41)
Seafood (fish)*
1.07 (1.01 to 1.12)
Purine rich vegetables
0.97 (0.79 to 1.19)
Total dairy products
0.82 (0.75 to 0.90)
Low fat dairy products
0.79 (0.71 to 0.87)
High fat dairy products
0.99 (0.89 to 1.10)
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