Elsevier

The Lancet

Volume 388, Issue 10055, 22–28 October 2016, Pages 2039-2052
The Lancet

Seminar
Gout

https://doi.org/10.1016/S0140-6736(16)00346-9Get rights and content

Summary

Gout is a chronic disease of deposition of monosodium urate crystals, which form in the presence of increased urate concentrations. Although environmental factors contribute to hyperuricaemia, renal and gut excretion of urate is central to regulation of serum urate, and genetic factors are important. Activation of the NLRP3 inflammasome and release of interleukin 1β have key roles in initiation of acute gout flares. A “treat to target serum urate” approach is essential for effective gout management; long-term lowering of serum urate to less than 360 μmol/L leads to crystal dissolution and ultimately to suppression of flares. An allopurinol dose-escalation strategy is frequently effective for achieving treatment targets, and several new urate-lowering drugs are also available. Worldwide, rates of initiation and continuation of urate-lowering therapy are very low, and, consequently, achievement of serum urate targets is infrequent. Strategies to improve quality of gout care are needed.

Introduction

Gout is a common and treatable form of inflammatory arthritis that affects almost 4% of adults in the USA.1 The central pathological feature of gout is chronic deposition of monosodium urate crystals, which form in the presence of increased urate concentrations.2 The clinical features of gout occur as a result of the inflammatory response to monosodium urate crystals, and treatment strategies that achieve crystal dissolution are central to effective gout management.3 In the past decade, major progress has been made in understanding of the pathogenesis, impact, diagnostic approaches to, and treatment of this disorder. In this Seminar, we provide a summary of these advances with a focus on clinical management of gout.

Section snippets

Hyperuricaemia

The progression of gout can be defined by four pathophysiological stages: hyperuricaemia without evidence of monosodium urate crystal deposition or gout, crystal deposition without symptomatic gout, crystal deposition with acute gout flares, and advanced gout characterised by tophi, chronic gouty arthritis, and radiographic erosions.4 Progression from one stage to the next is not inevitable.

Pathological hyperuricaemia has been defined as the serum urate concentration (408 μmol/L [6·8 mg/dL])

Incidence and prevalence

In UK and US studies, the incidence of gout varies from 0·30 per 1000 person-years in the 1970s, to 2·68 per 1000 person-years in the 2000s.20 In western developed countries, contemporary prevalence of gout is 3–6% in men and 1–2% in women.20 Prevalence steadily increases with age, but plateaus after 70 years of age.20 Lower prevalences have been reported in developing countries—typically less than 1%.20, 21 Differences in health-care systems or case ascertainment might account for some of

Presentation

Typically, gout presents for the first time as an acute episode of inflammation (flare) affecting the foot or ankle.18 The first flare occurs after an asymptomatic period of hyperuricaemia. It is self-limiting during 1–2 weeks, with complete resolution in signs and symptoms of joint inflammation during the so-called intercritical period. If hyperuricaemia persists, recurrent flares can occur, which become increasingly frequent and prolonged and affect many joints (polyarticular flares),

Principles of management

Gout management includes rapid treatment of acute flares and effective long-term management (table 2).3, 99, 100, 101 The central strategy for long-term management is reduction of serum urate to a concentration that achieves dissolution of monosodium urate crystals. According to the 2012 American College of Rheumatology guidelines, urate-lowering therapy is indicated for those with recurrent gout flares (>1 flare a year), tophi, stage 2 or worse chronic kidney disease, or kidney stones (table 2

Controversies and uncertainties

Although the central cause of gout is well known and effective treatments are available, many uncertainties remain and understanding about pathogenesis is incomplete (panel 2). For example, why some individuals with hyperuricaemia develop monosodium urate crystal deposition and others do not is unknown. Why monosodium urate crystals preferentially deposit at specific sites and why deposited crystals can be present in the joint without clinically apparent inflammation is also unclear. The causal

Conclusion

Despite major progress in the understanding of pathogenesis and therapeutic advances, the prevalence of gout is increasing and many patients have poorly controlled disease. Gout is a treatable disease and the strategy of long-term lowering of serum urate concentrations is highly effective in removing monosodium urate crystals. Implementation of this strategy necessitates focused attention to prevent the serious consequences of this disease.

Search strategy and selection criteria

We searched the Cochrane Library and MEDLINE with the term “gout” for articles published in English between Aug 1, 2010, and Jan 31, 2016. We largely selected publications from the past 5 years, but did not exclude commonly referenced and highly regarded older publications. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Review articles and book chapters are cited to provide readers with more details and more references

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