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Recent Advances in Understanding and Managing Gout

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Recent Advances in Understanding and Managing Gout

Talia F Igel et al. F1000Res.

Abstract

Gout is the most common crystal arthropathy and the leading cause of inflammatory arthritis. It is associated with functional impairment and, for many, a diminished health-related quality of life. Numerous studies have demonstrated the impact of gout and its associated conditions on patient morbidity and mortality. Unfortunately, gout remains under-diagnosed and under-treated in the general community. Despite major advances in treatment strategies, as many as 90% of patients with gout are poorly controlled or improperly managed and their hyperuricemia and recurrent flares continue. The introduction of novel urate-lowering therapies, new imaging modalities, and a deeper understanding of the pathogenesis of gout raise the possibility of better gout care and improved patient outcomes. Here, we spotlight recent advances in the diagnosis and management of gout and discuss novel therapeutics in gout treatment.

Keywords: gout; gout treatment; urate-lowering therapy.

Conflict of interest statement

Competing interests: Talia F. Igel declares that she has no competing interests. Svetlana Krasnokutsky has served as a consultant for Crealta, Horizon and Ironwood. Michael H. Pillinger serves or has served as a consultant for AstraZeneca, Crealta, Horizon, Ironwood and Sobi and has been an investigative site for a sponsored trial by Takeda.No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. New imaging modalities for demonstrating serum urate deposition.
( A) Musculoskeletal ultrasound of a first metatarsal phalangeal joint (plantar longitudinal view) demonstrating a classic “double contour sign” (arrows), indicating the deposition of monosodium urate (MSU) crystals on the cartilage surface of the metatarsal head. ( B) Dual-energy computed tomography of a foot. Green areas indicate MSU deposition, and arrows indicate the presence of MSU deposition at the first distal interphalangeal joint, at the carpal metacarpal joint, and along the Achilles tendon.
Figure 2.
Figure 2.. Activation of the NLRP3 inflammasome and the production IL-1β.
( 1) Monosodium urate (MSU) crystal phagocytosis stimulates the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase to generate reactive oxygen species that in turn can activate the NLRP3 (NOD-like receptor protein 3) inflammasome. ( 2) MSU crystals may also stimulate the secretion of ATP, which can engage and activate the purinergic receptor P2X7, resulting in recruitment of pannexin-1 channels. The resultant rapid efflux of potassium, and the lowering of intracellular potassium, can also trigger inflammasome activation. ( 3) Concurrently, MSU crystal interactions with Toll-like receptors (TLRs) on the cell surface stimulate the production of pro-IL-1β via MyD88- and NF-κB-dependent pro-IL-1β gene transcription. ( 4) Once stimulated, the NLRP3 inflammasome’s enzymatic effector caspase-1 cleaves the pro-IL-1β to biologically active IL-1β. IL-1β is then secreted from the cell into the extra-cellular fluid of the site of inflammation. ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; IL-1β, interleukin-1 beta; NF-κB, nuclear factor-kappa B; NLRP3, NOD-like receptor protein 3; ROS, reactive oxygen species; TLR, Toll-like receptor.

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Cited by 3 PubMed Central articles

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Grant support

TFI was supported in part by a travel scholarship from Monash University. SK was supported in part by an Investigator Award from the Rheumatology Research Foundation and by a New York State Empire Clinical Research Investigator Program award. MHP receives salary support from NYU CTSA grant 1UL1TR001445 from the National Center for the Advancement of Translational Science, National Institutes of Health.

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