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
SeminarGout
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
References (150)
- et al.
The prevalence and prophylaxis of gout in England
J Clin Epidemiol
(1995) - et al.
Alcohol intake and risk of incident gout in men: a prospective study
Lancet
(2004) - et al.
Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans
J Biol Chem
(2008) - et al.
Gout: update on some pathogenic and clinical aspects
Rheum Dis Clin North Am
(2006) - et al.
The inflammasome, autoinflammatory diseases, and gout
Joint Bone Spine
(2007) - et al.
Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study
Metabolism
(2005) - et al.
Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study
Lancet
(2008) - et al.
Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study
Am J Med
(1987) - et al.
Gouty attacks occur frequently in postoperative gastric bypass patients
Surg Obes Relat Dis
(2008) - et al.
Histopathologic examination of conjunctival tophi in gouty arthritis
Am J Ophthalmol
(2005)
A patient with arthritis, severe back pain, impaired wound healing, and perforated sigmoid colon
Lancet
Gout: a clinical and radiologic review
Radiol Clin North Am
“Crystal clear”—sonographic assessment of gout and calcium pyrophosphate deposition disease
Semin Arthritis Rheum
Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction: a randomised controlled study
Lancet
Gout and hyperuricemia
A brief history of the rheumatic diseases
Bull Rheum Dis
A concise history of gout and hyperuricemia and their treatment
Arthritis Res Ther
Gout: on the brink of novel therapeutic options for an ancient disease
Arthritis Rheum
Frequency and predictors of inappropriate management of recurrent gout attacks in a longitudinal study
J Rheumatol
Epidemiology, risk factors, and lifestyle modifications for gout
Arthritis Res Ther
Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population
J Rheumatol
Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000–2005
Ann Rheum Dis
The effect of control and self-medication of chronic gout in a developing country. Outcome after 10 years
J Rheumatol
Gout is on the increase in New Zealand
Ann Rheum Dis
Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China
J Rheumatol
Menopause, postmenopausal hormone use and serum uric acid levels in US women—the Third National Health and Nutrition Examination Survey
Arthritis Res Ther
Purine-rich foods, dairy and protein intake, and the risk of gout in men
N Engl J Med
Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study
Arch Intern Med
Coffee, tea, and caffeine consumption and serum uric acid level: the third national health and nutrition examination survey
Arthritis Rheum
Vitamin C intake and serum uric acid concentration in men
J Rheumatol
Uric acid nephrolithiasis
Curr Rheumatol Rep
Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics
Arthritis Res Ther
The pathogenesis of gout
Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome
Orphanet J Rare Dis
Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study
BMJ
Clinical practice. Gout
N Engl J Med
Urate excretion in normal and gouty men
Adv Exp Med Biol
Molecular identification of a renal urate anion exchanger that regulates blood urate levels
Nature
Molecular basis of primary renal hyperuricemia: role of the human urate transporter hURAT1
Z Rheumatol
Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease
Clin Exp Nephrol
Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients
Am J Hypertens
SLC2A9 is a high-capacity urate transporter in humans
PLoS Med
SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout
Nat Genet
SLC2A9 influences uric acid concentrations with pronounced sex-specific effects
Nat Genet
Pathogenesis of gout
Ann Intern Med
Are joints affected by gout also affected by osteoarthritis?
Ann Rheum Dis
Developments in the scientific and clinical understanding of gout
Arthritis Res Ther
Recent developments in crystal-induced inflammation pathogenesis and management
Curr Rheumatol Rep
Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation
Arthritis Rheum
The inflammatory process of gout and its treatment
Arthritis Res Ther
Cited by (818)
Sanmiao wan alleviates inflammation and exhibits hypouricemic effect in an acute gouty arthritis rat model
2024, Journal of EthnopharmacologyNanocomposite modified electrode based on polyaniline/Ti<inf>3</inf>C<inf>2</inf> for the simultaneous detection of purine bases and uric acid
2024, Materials Today CommunicationsA case of rheumatoid arthritis in a Nubian woman from the site of Sheikh Mohamed, near Aswan, Egypt
2024, International Journal of Paleopathology