Elsevier

Maturitas

Volume 78, Issue 4, August 2014, Pages 245-251
Maturitas

Review
Gout: Joints and beyond, epidemiology, clinical features, treatment and co-morbidities

https://doi.org/10.1016/j.maturitas.2014.05.001Get rights and content

Abstract

Gout is a common inflammatory arthritis precipitated by an inflammatory reaction to urate crystals in the joint. Gout is increasingly being recognised as a disease primarily of urate overload with arthritis being a consequence of this pathological accumulation. It is associated with a number of important co-morbidities including chronic kidney disease, obesity, diabetes and cardiovascular disease.

The prevalence of gout is increasing around the world. Significant progress has been made in determining the genetic basis for both gout and hyperuricaemia. Environmental risk factors for gout have been identified as certain foods, alcohol and several medications. There is, however, little evidence that changing these environmental risks improves gout on an individual level.

Treatment of gout encompasses two strategies: firstly treatment of inflammatory arthritis with non-steroidal anti-inflammatories, corticosteroids, colchicine or interleukin-1 inhibitors. The second and most important strategy is urate lowering, to a target of 0.36 mmol/L (6 mg/dL) or potentially lower in those with tophi (collections of crystalline urate subcutaneously). Along with urate lowering, adequate and prolonged gout flare prophylaxis is required to prevent the precipitation of acute attacks. Newer urate lowering agents are in development and have the potential to significantly expand the potential treatment options. Education of patients regarding the importance of life long urate lowering therapy and prophylaxis of acute attacks is critical to treatment success as adherence with medication is low in chronic diseases in general but especially in gout.

Introduction

Gout is a common inflammatory arthritis associated with important co-morbidities including cardiovascular disease, chronic kidney disease, obesity and type 2 diabetes. Gout is caused by an inflammatory reaction to urate crystals in joints. It is the commonest inflammatory arthritis in men and after the menopause is a common cause of inflammatory arthritis in women [1]. However, while historically gout has been viewed purely as a disease first manifesting as arthritis it is increasingly being recognised as a urate overload disease, often associated with extensive co-morbidities and with inflammatory arthritis being a manifestation of later stage disease [2]. A recent proposal to introduce disease stages is shown in Table 1. Gout has a significant impact on the working age population and impacts on work presenteeism, productivity and physical function [3], [4], [5]. Gout is growing in prevalence in developed countries and in addition is poorly recognised and treated [6], [7], [8], [9]. This manuscript aims to review the epidemiology of gout, its treatments and highlight its important co-morbidities.

Section snippets

Clinical features and impact of gout

The first attack (or ‘flare’) of gout commonly, although not universally, occurs in the first metatarsophalangeal joint and is referred to as ‘podagra’. Some individuals may only have one to two attacks of gout, or have extremely intermittent attacks months apart, but the majority will suffer from increasingly frequent attacks. Subsequent attacks commonly involve additional joints such as the knee and as gout progresses it can cause polyarticular attacks and tophus development, although tophi

Epidemiology of gout

Fundamentally gout is a urate overload disease, historically the mechanism of overload was divided into over production or under excretion [2]. Recently, the intestinal excretion of urate by the transporter ABCG2 has been identified as very important [11]. This has led to the proposal of new classification system for hyperuricaemia, see Table 2.

Clinical gouty arthritis is strongly linked to the level of serum urate, with increasing levels of hyperuricaemia leading to a progressively increasing

Treatment overview

Treatment of gout falls into two main categories: symptomatic relief during an acute episode of gout and urate lowering therapy (ULT) for long-term prevention of further flares. Integral to treatment is adequate prophylaxis of acute gout flares during ULT therapy. Historically ULT and the concomitant prevention of flares during ULT has often been managed sub-optimally.

Co-morbidities

Gout often occurs in the presence of other conditions, such as hypertension, renal impairment, diabetes mellitus and cardiovascular disease. Hyperuricaemia may actually be an independent risk factor for some of these conditions [66]. Likewise, some of these conditions and their associated treatments can influence SUA levels. In this sense gout truly is about ‘more than joints’ and can having wide-ranging health implications.

Conclusions

There is a growing body research into the causes, mechanisms and treatment of gout and this has, in part, been stimulated by the new therapeutics in development. There is, however, much further to learn. While there are readily available cheap therapies they are not being prescribed adequately, and even when they are not being taken as prescribed. This is undoubtedly multi-factorial, including, but not limited to, problems with disease education, literacy and numeracy and cross-cultural

Contributors

P.R. and S.H. contributed equally to the manuscript intellectual content, drafting, and approving the final draft of the manuscript.

Competing interest

Disclosure: P.R. has undertaken consulting for AstraZeneca Australia. S.H. has no disclosures.

Funding

S.H. has received no funding for this article. P.R. is funded by the National Health and Medical Research Council of Australia (NHMRC) grant no. GNT1017662.

Provenance and peer review

Commissioned and externally peer reviewed.

Acknowledgements

The authors would like to thank Nicola Dalbeth for her comments on a draft of this manuscript. P.R. is funded by the National Health and Medical Research Council of Australia (NHMRC).

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