Gout: On the brink of novel therapeutic options for an ancient disease

Bieber, Jeffry D; Terkeltaub, Robert

doi:10.1002/art.20438

Cited by 164 publications

(111 citation statements)

References 141 publications

(223 reference statements)

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“…Meanwhile, not all patients with gouty arthritis are found to have hyperuricemia. These findings may reveal the potential possibility that factors other than hyperuricemia initiate or precipitate gout (1).…”

Section: Introductionmentioning

confidence: 89%

“…Gouty arthritis is a common type of chronic arthritis in which high serum uric acid (sUA) levels and crystal deposition of monosodium urate (MSU) are considered to play crucial roles (1). The associations between hyperuricemia and comorbidities, such as hypertension, obesity, and metabolic syndrome, have been shown in many epidemiologic studies (2,3).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of obesity and hypertriglyceridemia on gout development with or without hyperuricemia: A prospective study

Chen

Pan

Hsu

et al. 2012

Arthritis Care & Research

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Impact of obesity and hypertriglyceridemia on gout development with or without hyperuricemia: A prospective study

Chen

Pan

Hsu

et al. 2012

Arthritis Care & Research

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“…Prevalence in the US has increased recently (1,3), nearly doubling between 1990 and 1999 in a study of health maintenance organization enrollees (3). The increase is thought to be partially due to aging of the population and to the increasing prevalence of renal failure, hypertension, diuretic therapy, and obesity (4,5).…”

Section: Introductionmentioning

confidence: 99%

Quality of care for gout in the US needs improvement

Singh

Hodges

Toscano

et al. 2007

Arthritis & Rheumatism

174

109

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Objective. To examine evidence-based quality indicators (QIs) in US veterans with gout diagnosis, and to examine the effect of demographics, heath care utilization/access, comorbid conditions, or physican characteristics as predictors of quality of gout care. Methods. Using the Minneapolis Veterans Affairs electronic medical record system, we identified a cohort of veterans receiving medication to treat gout between January 1, 1999 and December 31, 2003, and evaluated 3 recently published evidence-based QIs for gout management: QI 1 ‫؍‬ allopurinol dose <300 mg in gout patients with renal insufficiency, QI 2 ‫؍‬ uric acid check within 6 months of starting a new allopurinol prescription, and QI 3 ‫؍‬ complete blood count and creatine kinase check every 6 months for gout patients receiving prolonged colchicine therapy. We calculated the proportion of patients whose therapy adhered to each QI and to all applicable indicators (overall physician adherence). Logistic regression analysis examined association of overall physician adherence with sociodemographics, health care utilization, comorbidity, and provider characteristics. Results. Of 3,658 patients with a diagnosis of gout, 663 patients qualified for examination of >1 QI. Of these 663 patients, therapy in only 144 (22%) adhered to all applicable QIs; 59 (78%) of 76 adhered to QI 1, 155 (24%) of 643 adhered to QI 2, and 18 (35%) of 52 adhered to QI 3. Overall physician adherence to QIs was significantly lower in older veterans and in those with more inpatient visits per year, but was higher in those with more primary care visits or more health care providers. Conclusion. Suboptimal physician adherence to QIs was seen for all 3 QIs tested in this cohort of veterans with gout. These findings can guide quality improvement efforts.

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“…The deposition of monosodium urate monohydrate (MSU) crystals in articular joints and bursal tissues can be asymptomatic in gout or can erupt via incompletely defined factors into acute, episodic, selflimiting joint inflammation largely dependent on marked neutrophil influx (1)(2)(3). Because neutrophils are absent from normal joint fluid, the interaction of MSU crystals with resident cells in the joint is believed to be the primary factor stimulating neutrophilendothelial adhesion in the synovial microvasculature (4), acute neutrophil ingress, and paroxysms of gouty inflammation (1,4,5).…”

mentioning

confidence: 99%

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

et al. 2005

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Objective. In gout, incompletely defined molecular factors alter recognition of dormant articular and bursal monosodium urate monohydrate (MSU) crystal deposits, thereby inducing self-limiting bouts of characteristically severe neutrophilic inflammation. To define primary determinants of cellular recognition, uptake, and inflammatory responses to MSU crystals, we conducted a study to test the role of Toll-like receptor 2 (TLR-2), TLR-4, and the cytosolic TLR adapter protein myeloid differentiation factor 88 (MyD88), which are centrally involved in innate immune recognition of microbial pathogens.Methods. We isolated bone marrow-derived macrophages (BMDMs) in TLR-2 ؊/؊ , TLR-4 ؊/؊ , MyD88 ؊/؊ , and congenic wild-type mice, and assessed phagocytosis and cytokine expression in response to endotoxin-free MSU crystals under serum-free conditions. MSU crystals also were injected into mouse synovium-like subcutaneous air pouches.Results. TLR-2 ؊/؊ , TLR-4 ؊/؊ , and MyD88 ؊/؊ BMDMs demonstrated impaired uptake of MSU crystals in vitro. MSU crystal-induced production of interleukin-1␤ (IL-1␤), tumor necrosis factor ␣, keratinocyte-derived cytokine/growth-related oncogene ␣, and transforming growth factor ␤1 also were significantly suppressed in TLR-2 ؊/؊ and TLR-4 ؊/؊ BMDMs and were blunted in MyD88 ؊/؊ BMDMs in vitro. Neutrophil influx and local induction of IL-1␤ in subcutaneous air pouches were suppressed 6 hours after injection of MSU crystals in TLR-2 ؊/؊ and TLR-4 ؊/؊ mice and were attenuated in MyD88 ؊/؊ mice.Conclusion. The murine host requires TLR-2, TLR-4, and MyD88 for macrophage activation and development of full-blown neutrophilic, air pouch inflammation in response to MSU crystals. Our findings implicate innate immune cellular recognition of naked MSU crystals by specific TLRs as a major factor in determining the inflammatory potential of MSU crystal deposits and the course of gouty arthritis.

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Gout: On the brink of novel therapeutic options for an ancient disease

Cited by 164 publications

References 141 publications

Impact of obesity and hypertriglyceridemia on gout development with or without hyperuricemia: A prospective study

Impact of obesity and hypertriglyceridemia on gout development with or without hyperuricemia: A prospective study

Quality of care for gout in the US needs improvement

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

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