Elsevier

The Lancet

Volume 375, Issue 9711, 23–29 January 2010, Pages 318-328
The Lancet

Seminar
Gout

https://doi.org/10.1016/S0140-6736(09)60883-7Get rights and content

Summary

Gout is a common arthritis caused by deposition of monosodium urate crystals within joints after chronic hyperuricaemia. It affects 1–2% of adults in developed countries, where it is the most common inflammatory arthritis in men. Epidemiological data are consistent with a rise in prevalence of gout. Diet and genetic polymorphisms of renal transporters of urate seem to be the main causal factors of primary gout. Gout and hyperuricaemia are associated with hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular diseases. Non-steroidal anti-inflammatory drugs and colchicine remain the most widely recommended drugs to treat acute attacks. Oral corticosteroids could be an alternative to these drugs. Interleukin 1β is a pivotal mediator of acute gout and could become a therapeutic target. When serum uric acid concentrations are lowered below monosodium urate saturation point, the crystals dissolve and gout can be cured. Patient education, appropriate lifestyle advice, and treatment of comorbidities are an important part of management of patients with gout.

Introduction

Gout, “the king of diseases and the disease of kings”,1 was one of the earliest disorders to be recognised as a clinical entity. It was first identified by the Egyptians in 2640 BCE, and written evidence of the disease dates back to Hippocratic writings from about 400 BCE.2, 3 The most accurate early description of an acute attack of gout was made by Sydenham, an English physician, writing about himself in 1683.2, 3 Crystals from tophi were first described during the 18th and 19th centuries, and in the mid 20th century the role of excess urate production and impaired excretion in the pathogenesis of hyperuricaemia were reported. Finally, McCarty and Hollander3 showed that crystals from the synovial fluid of patients with gout were composed of monosodium urate.

Nowadays, gout is probably the best understood and most manageable of all common systemic rheumatic diseases.4 Most frequently it causes recurrent attacks of acute arthritis and sometimes can lead to chronic arthropathy, tophi depositions, and renal disease. Gout is a disorder of purine metabolism and results from urate crystal deposition in and around the joints caused by longstanding hyperuricaemia. Hyperuricaemia is a risk factor for gout but most people remain asymptomatic throughout their lives. In the past 10 years, the epidemiology of gout seems to have changed and great advances in the understanding of this disease have been made. We review data for epidemiology, pathophysiology, and diagnosis, and discuss present and future treatment for this disorder that is frequently inappropriately managed.5

Section snippets

Epidemiology

Data show a rise in the prevalence of gout that is potentially attributable to shifts in diet and lifestyle, improved medical care, and increased longevity.6 In England, rates of gout increased from 0·3% to 1·0% of the total population between 1970 and 1990,7 and a similar trend was reported in the USA during the 1990s—especially for men older than 75 years in whom rates nearly doubled from 2·1% in 1990 to 4·1% in 1999.8 From 2000 to 2005 in the UK, 1·4% of people were estimated to have gout.9

Pathophysiology

Uric acid is the final metabolite of endogenous and dietary purine metabolism. It is a weak acid with pKa of 5·75 (pH at which uric acid and urate concentrations are equal). At a physiological pH of 7·4 in the extracellular compartment, 98% of uric acid is in the ionised form of urate.19 Because of the high concentration of sodium in the extracellular compartment, urate is largely present as monosodium urate, with a low solubility limit of about 380 μmol/L. When urate concentrations exceed 380

Genetics and clinical features

Urate concentrations vary greatly between individuals, and although environmental factors are clearly implicated, results of studies45 have shown that inheritance also plays a part. Heritability of serum uric acid concentration accounts for about 60% of variability.46 Genome-wide studies31, 32, 33, 47, 48 have identified substantial associations between polymorphisms in the GLUT9 (SLC2A9) gene, urate concentrations, and gout, and a polymorphism in the URAT1 (SLC22CA12) gene was confirmed as a

Diagnosis and imaging

The European League Against Rheumatism (EULAR) developed recommendations51 in 2006, on the basis of both clinical practice and the best available evidence for diagnosis of gout. Panel 1 lists the ten key recommendations. Analysis of synovial fluid or tophus aspirate is a key diagnostic method for gout because identification of monosodium urate crystals in these samples enables a definite diagnosis to be made (Figure 3, Figure 4).51, 76 Aspiration of the small first metatarsophalangeal joint is

Primary and secondary gout

Gout can be classified as primary or secondary, depending on the presence or absence of an identified cause of hyperuricaemia.1, 53 Thus, primary gout is not a consequence of an acquired disorder or the result of a congenital defect. Other conditions often accompany primary gout, including obesity, alcohol consumption, hypertension, and hypertriglyceridaemia, which should be carefully assessed.1, 51, 53 Secondary gout is the consequence of use of specific drugs or develops in the course of

Hyperuricaemia, gout, and chronic diseases

The presence of kidney stones is the most frequent type of gout-related nephropathy, arising in about 10–40% of patients.19 Men with gout have a two-fold higher risk of kidney stones than do patients without gout.104 The likelihood of stones increases with serum urate concentration, extent of urinary uric acid excretion, and low urine pH.1, 105 A persistently low urinary pH is the most important pathogenic mechanism leading to stone formation because it favours excretion of uric acid (of low

Acute attacks

Standard management of acute attacks of gout consists of rest, application of ice to the affected joint,125, 126 and prescription of colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), or both,127, 128 which should be started immediately to be most effective. British rheumatology guidelines favour use of NSAIDs at maximum doses in cases of no contraindications and recommend that treatment be continued for 1–2 weeks.126 Colchicine can be poorly tolerated when given in high doses, and the

Search strategy and selection criteria

We searched the Cochrane library, Medline, and EmBase for reports published in English from Jan 1, 1998, to Nov 30, 2008 with the search terms “gout”, “hyperuricemia”, “uric acid”, “urate”, “purine”, and “tophus”. We also searched for “gout” or “hyperuricemia” combined with the terms “epidemiology”, “pathogenesis”, “genetic”, “pathophysiology”, “diagnosis”, “kidney stones”, “metabolic syndrome”, “diabetes”, “hypertension”, “cardiovascular”, and “treatment”. We mainly selected reports from

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