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Gout

Subjects

Abstract

Gout is a chronic disease caused by monosodium urate (MSU) crystal deposition. Gout typically presents as an acute, self-limiting inflammatory monoarthritis that affects the joints of the lower limb. Elevated serum urate level (hyperuricaemia) is the major risk factor for MSU crystal deposition and development of gout. Although traditionally considered a disorder of purine metabolism, altered urate transport, both in the gut and the kidneys, has a key role in the pathogenesis of hyperuricaemia. Anti-inflammatory agents, such corticosteroids, NSAIDs and colchicine, are widely used for the treatment of gout flare; recognition of the importance of NLRP3 inflammasome activation and bioactive IL-1β release in initiation of the gout flare has led to the development of anti-IL-1β biological therapy for gout flares. Sustained reduction in serum urate levels using urate-lowering therapy is vital in the long-term management of gout, which aims to dissolve MSU crystals, suppress gout flares and resolve tophi. Allopurinol is the first-line urate-lowering therapy and should be started at a low dose, with gradual dose escalation. Low-dose anti-inflammatory therapies can reduce gout flares during initiation of urate-lowering therapy. Models of care, such as nurse-led strategies that focus on patient engagement and education, substantially improve clinical outcomes and now represent best practice for gout management.

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Fig. 1: Disease progression in gout.
Fig. 2: Urate transporters in the kidneys and intestine in humans.
Fig. 3: Classification of the causes of hyperuricaemia.
Fig. 4: Mechanisms of initiation and resolution of the gout flare.
Fig. 5: Identification of MSU crystals using polarizing light microscopy.
Fig. 6: Typical clinical and imaging features of gout.
Fig. 7: Ultrasonography-based features of gout.
Fig. 8: Mechanism of action of urate-lowering drugs currently used for gout treatment.

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Acknowledgements

The authors are grateful to A. Nakayama for editing assistance. H.K.C. is supported by the US National Institutes of Health (AR060772).

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Introduction (N.D.); Epidemiology (H.K.C.); Mechanisms/pathophysiology (H.M. and L.A.B.J.); Diagnosis, screening and prevention (F.P.-R. and N.D.); Management (L.K.S.); Quality of life (P.P.K.); Outlook (N.D.); overview of the Primer (N.D.).

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Correspondence to Nicola Dalbeth.

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Competing interests

N.D. has received speaking fees from Pfizer, Horizon, Janssen and AbbVie; consulting fees from Horizon, Hengrui and Kowa; and research funding from Amgen and AstraZeneca; and is currently principal investigator on a clinical trial of intensive urate-lowering therapy (funded by the Health Research Council of New Zealand). Within the past 5 years, N.D. has been principal investigator on a clinical trial of febuxostat in early gout, and received consulting or speaking fees from Takeda, Menarini and Teijin. H.K.C. received research support from AstraZeneca and consulting fees from Takeda, Selecta, GSK and Horizon. L.A.B.J. has received a speaking fee from Novartis, research funding from Ardea Biosciences/AstraZeneca, and is Scientific Advisory Board member of Olatec Therapeutics LLC. P.P.K. has received research grants from Ironwood, Sobi and Horizon. F.P.-R. has been an advisor for Amgen, Horizon, Grünenthal, Menarini, Sanofi and Syneos-Health; a speaker for Amgen, Astellas, Grünenthal, Lilly, Logarithm, Menarini and the Spanish Foundation for Rheumatology; received investigation grants from Cruces Rheumatology Association and the Spanish Foundation for Rheumatology; and received congress funding from Lilly, Novartis and the European League Against Rheumatism (EULAR). L.K.S. has received speaking fees from Amgen and is currently principal investigator on a clinical trial of colchicine prophylaxis (funded by the Health Research Council of New Zealand). L.K.S. is a member of the Medicines Adverse Reaction Committee of New Zealand and the New Zealand Pharmaceutical Management Agency (PHARMAC) Rheumatology Subcommittee. H.M. declares no competing interests.

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Nature Reviews Disease Primers thanks J.G. Puig, M. Pillinger, P. Richette, M. Andrés and R. Burgos-Vargas for their contribution to the peer review of this work.

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Dalbeth, N., Choi, H.K., Joosten, L.A.B. et al. Gout. Nat Rev Dis Primers 5, 69 (2019). https://doi.org/10.1038/s41572-019-0115-y

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