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Gout: HELP
Articles from Bilbao
Based on 44 articles published since 2009

These are the 44 published articles about Gout that originated from Bilbao during 2009-2019.
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline 2016 updated EULAR evidence-based recommendations for the management of gout. 2017

Richette, P / Doherty, M / Pascual, E / Barskova, V / Becce, F / Castañeda-Sanabria, J / Coyfish, M / Guillo, S / Jansen, T L / Janssens, H / Lioté, F / Mallen, C / Nuki, G / Perez-Ruiz, F / Pimentao, J / Punzi, L / Pywell, T / So, A / Tausche, A K / Uhlig, T / Zavada, J / Zhang, W / Tubach, F / Bardin, T. ·AP-HP, hôpital Lariboisière, service de Rhumatologie, F-75010 Paris, France; Inserm, UMR1132, Hôpital Lariboisière, F-75010 Paris, France; Universitè Paris Diderot, Sorbonne Paris Citè, F-75205 Paris, France. · Academic Rheumatology, University of Nottingham, Nottingham, UK. · Department of Rheumatology, Hospital General Universitario de Alicante, Alicante, Spain. · Institute of Rheumatology RAMS, Moscow, Russia. · Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland. · AP-HP, Dèpartement d'Epidèmiologie et Recherche Clinique, Hôpital Bichat, Paris, France: APHP, Centre de Pharmacoèpidèmiologie, Paris, France: Univ Paris Diderot, Paris, France: INSERM UMR 1123 ECEVE, Paris, France. · Patient from Nottingham, UK, Paris. · Department of Rheumatology, VieCuri Medical Centre, Venlo, and Scientific IQ HealthCare, Radboud UMC, Nijmegen, The Netherlands. · Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Netherlands. · Arthritis Research UK Primary Care Centre University of Keele, Keele, UK. · Osteoarticular Research Group, University of Edinburgh, Edinburgh, UK. · Seccion de Rheumatologia, Hospital de Cruces, Baracaldo, Spain. · Rheumatology Unit, Clínica Coração de Jesus, Lisbon, Portugal. · Rheumatology Unit, University of Padova, Padova, Italy. · Service de Rhumatologie, CHUV and Universitè de Lausanne, Lausanne, Switzerland. · Department of Rheumatology, University Clinic at the Technical University Dresden, Germany. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Czech Republic. ·Ann Rheum Dis · Pubmed #27457514.

ABSTRACT: BACKGROUND: New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations. METHODS: The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach. RESULTS: Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended. CONCLUSIONS: These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.

2 Review Combination urate-lowering therapy in the treatment of gout: What is the evidence? 2019

Perez-Ruiz, Fernando / Dalbeth, Nicola. ·Rheumatology Division, Hospital Universitario Cruces, University of the Basque Country, Bilbao 48903, Spain. Electronic address: fperezruiz@telefonica.net. · Bone and Joint Research Group, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand. ·Semin Arthritis Rheum · Pubmed #30075988.

ABSTRACT: BACKGROUND: Combination therapy that includes a uricosuric and xanthine oxidase inhibitor (XOI) is recommended in guidelines for patients with gout who do not meet treatment targets with XOI monotherapy alone. While the use of combination therapies has been investigated for many years, we reviewed data from the published studies to investigate the efficacy and safety of this approach. METHODS: Relevant published papers were identified by keyword search on PubMed and categorized according to the types of combination therapies included. Study methods and results were summarized. Outcomes of combination therapy were compared with respective monotherapies, where possible. RESULTS: Efficacy was assessed by changes in serum urate (sUA), urinary uric acid, gout flare rates, and /or tophi. Safety assessments, where reported, included adverse events and, for more recent studies, laboratory assessments. Early studies in the 1960s based on case reports or open-label designs and more recent, well-designed studies with large patient numbers provided consistent outcomes: that combination therapy with a uricosuric and a XOI provides substantially greater sUA lowering than achieved by either monotherapy. Greater sUA lowering translated to greater gout symptom control, including improved tophus resolution. CONCLUSIONS: Combination therapy with a uricosuric and an XOI offers additional sUA lowering compared to monotherapy alone and can provide benefit for achieving therapeutic targets in patients with gout who do not achieve target sUA or are intolerant of XOIs at appropriate monotherapy dosing.

3 Review International position paper on the appropriate use of uricosurics with the introduction of lesinurad. 2018

Jansen, Tim L / Perez-Ruiz, Fernando / Tausche, Anne-Kathrin / Richette, Pascal. ·Department of Rheumatology, VieCuri MC, Tegelseweg 210, 5912 BL, Venlo, The Netherlands. tjansen@viecuri.nl. · Medicine Department of Medicine and Nursery School, University of the Basque Country, Leioa, Spain. · Department of Rheumatology, University Clinic "Carl Gustav Carus" at the Technical University, Fetscherstrasse 74, D-01309, Dresden, Germany. · Service de Rhumatologie, Inserm, UMR1132, Hôpital Lariboisière, F-75010, Paris, France. · Université Paris Diderot, Sorbonne Paris Cité, F-75205, Paris, France. ·Clin Rheumatol · Pubmed #30244431.

ABSTRACT: Over the last 70 years, pharmacotherapy in gout with urate-lowering drugs has consisted of four drugs only: In 1952, a mild uricosuric probenecid became available, the xanthine oxidase inhibitor Allopurinol in 1964, and the latter became the most frequently used urate-lowering drug worldwide; in the Eurozone, the uricosuric benzbromarone was welcomed in 1977. Only in 2002, the potent non-purine xanthine oxidase inhibitor febuxostat was introduced. In many countries, uricosurics such as probenecid and benzbromarone have not been available up to now, and these days, the new uricosuric lesinurad is the first uricosuric that may be introduced in these countries, which is the reason for describing the position this novel uricosuric deserves in treating gout. Recent literature will be shortly reviewed, and the current proposed position for lesinurad will be given as an aid for clinicians.

4 Review Treat to target in gout. 2018

Perez-Ruiz, Fernando / Moreno-Lledó, Aitana / Urionagüena, Irati / Dickson, Alastair J. ·Rheumatology Division, Hospital Universitario Cruces, Biocruces Health Research Institute, and University of the Basque Country. · Family physician, Las Arenas Healthcare Centre, Biscay, Spain. · Primary Care Rheumatology Society & Honorary Associate, Centre of Health Economics, University of York, UK. ·Rheumatology (Oxford) · Pubmed #29272512.

ABSTRACT: The treat-to-target (T2T) approach has been successfully implemented in a number of diseases. T2T has been proposed for rheumatic diseases such as RA, spondyloarthritis, lupus, and recently for gout. The level of evidence for such approaches differs from one condition to the other (moderate to high for hyperlipidaemia, for example). Practice is based on the best available evidence at any time, and in absence of good evidence for T2T in gout, some suggest a conservative only-treat-symptoms approach. Evidence suggests that not treating gout to target in the long term is overall associated with worsening outcomes, such as flares, tophi and structural damage, which is associated to loss of quality of life and mortality. Different targets have been proposed for hyperuricaemia in gout; lower than 6 mg/dl (0.36 mmol/l) for all patients, at least <5 mg/dl (0.30 mmol/l) for patients with severe-polyarticular or tophaceous-gout.

5 Review Weight loss for overweight and obese individuals with gout: a systematic review of longitudinal studies. 2017

Nielsen, Sabrina M / Bartels, Else M / Henriksen, Marius / Wæhrens, Eva E / Gudbergsen, Henrik / Bliddal, Henning / Astrup, Arne / Knop, Filip K / Carmona, Loreto / Taylor, William J / Singh, Jasvinder A / Perez-Ruiz, Fernando / Kristensen, Lars E / Christensen, Robin. ·The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. · Department of Physical and Occupational Therapy, Bispebjerg and Frederiksberg, Copenhagen, Denmark. · The Research Initiative for Activity Studies and Occupational Therapy, General Practice, Department of Public Health, University of Southern Denmark, Odense, Denmark. · Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark. · Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. · Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Institutode Salud Musculoesquelética, Madrid, Spain. · Department of Medicine, University of Otago, Wellington, New Zealand. · Department of Medicine, University of Alabama at Birmingham, & Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA. · Rheumatology Division, Hospital de Cruces, Baracaldo, Spain. ·Ann Rheum Dis · Pubmed #28866649.

ABSTRACT: OBJECTIVES: Weight loss is commonly recommended for gout, but the magnitude of the effect has not been evaluated in a systematic review. The aim of this systematic review was to determine benefits and harms associated with weight loss in overweight and obese patients with gout. METHODS: We searched six databases for longitudinal studies, reporting the effect of weight loss in overweight/obese gout patients. Risk of bias was assessed using the tool Risk of Bias in Non-Randomised Studies of Interventions. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. RESULTS: From 3991 potentially eligible studies, 10 were included (including one randomised trial). Interventions included diet with/without physical activity, bariatric surgery, diuretics, metformin or no intervention. Mean weight losses ranged from 3 kg to 34 kg. Clinical heterogeneity in study characteristics precluded meta-analysis. The effect on serum uric acid (sUA) ranged from -168 to 30 μmol/L, and 0%-60% patients achieving sUA target (<360 μmol/L). Six out of eight studies (75%) showed beneficial effects on gout attacks. Two studies indicated dose-response relationship for sUA, achieving sUA target and gout attacks. At short term, temporary increased sUA and gout attacks tended to occur after bariatric surgery. CONCLUSIONS: The available evidence is in favour of weight loss for overweight/obese gout patients, with low, moderate and low quality of evidence for effects on sUA, achieving sUA target and gout attacks, respectively. At short term, unfavourable effects may occur. Since the current evidence consists of a few studies (mostly observational) of low methodological quality, there is an urgent need to initiate rigorous prospective studies (preferably randomised controlled trials). SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016037937.

6 Review Imaging of gout: New tools and biomarkers? 2016

Araujo, Elizabeth G / Manger, Bernhard / Perez-Ruiz, Fernando / Thiele, Ralf G. ·Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany. · Rheumatology Division, Hospital de Cruces, Baracaldo, Vizcaya, Spain. · Department of Medicine, Allergy/Immunology & Rheumatology Division, University of Rochester, School of Medicine and Dentistry, Rochester, NY, USA. Electronic address: Ralf_Thiele@URMC.Rochester.edu. ·Best Pract Res Clin Rheumatol · Pubmed #27931959.

ABSTRACT: While joint aspiration and crystal identification by polarizing microscopy remain the gold standard for diagnosing tophaceous gout, agreement among medical and ancillary health personnel examining synovial fluid using polarizing microscopy for the detection of monosodium urate (MSU) crystals appears to be poor. Imaging modalities, including conventional radiography (CR), ultrasonography (US), magnetic resonance imaging (MRI), and dual-energy computed tomography (DECT), have been found to provide information on the deposition of MSU crystals in tissues, and the consequences of such deposition. CR can demonstrate typical "punched out lesions" with marginal overhangs, but the sensitivity for erosion detection is better for DECT and US. US is inexpensive and can identify tophus deposition in and around joints, erosions, and tissue inflammation if power Doppler US is used. MRI can show tophi, bone marrow edema, and inflammation, but MRI findings of tophi may be nonspecific. DECT can identify and color-code tophaceous material, and provide an overview of the tophus burden of a joint area. Because of the lower number of available studies, the strength of evidence for the newer imaging can be improved through further research.

7 Review Febuxostat for the chronic management of hyperuricemia in patients with gout. 2016

Chinchilla, Sandra Pamela / Urionaguena, Irati / Perez-Ruiz, Fernando. ·a Rheumatology Division , Hospital Universitario Cruces, OSI EE-Cruces , Baracaldo , Spain. · b Biocruces Health Research Institute , Baracaldo , Spain. ·Expert Rev Clin Pharmacol · Pubmed #26942273.

ABSTRACT: Febuxostat is a non-purine, selective inhibitor of both isoforms of xanthine oxido-reductase (XOR), and a major alternative to the scarce number of urate-lowering medications available in the last decades. Its inhibition of XOR is more potent than allopurinol in a mg to mg comparison, what is associated to achievement of serum urate target more frequently than allopurinol at doses tested in clinical trials, especially in patients with the highest baseline serum urate levels. Its pharmacokinetics is not greatly dependent on renal clearance, contrary to allopurinol, what may be an advantage in patients with chronic kidney disease. Several trials are further evaluating both the cardiovascular safety of febuxostat and its possible beneficial effect on renal function preservation. Still scarce, but clinically interesting, evidence on its use in transplant patients has been recently released.

8 Review Epidemiology and health-related services. 2016

Perez-Ruiz, Fernando / Urionagüena, Irati / Carmona-Ortells, Loreto. ·aRheumatology Division, Biocruces Health Research Institute bRheumatology Division, Hospital Universitario Cruces, OSI EE-Cruces, Baracaldo cInstituto de Salud Musculoesquelética, Madrid, Spain. ·Curr Opin Rheumatol · Pubmed #26807788.

ABSTRACT: PURPOSE OF REVIEW: This article presents recent epidemiologic contributions focusing on gout-related conditions, especially if controversial, to find plausible, despite hypothetical, mechanistic explanations from the clinician perspective. RECENT FINDINGS: The prevalence of gout is increasing, but it is only partially clear that the incidence may be increasing as well. Direct associations of gout with increased risk of diabetes, black races, neurodegenerative disorders, and sugar-enriched foods have been recently questioned. A negative association with smoking has been reported, and new evidence shows that the impact of diet may be independent of obesity. Kidney disease and diuretics have been confirmed to be associated with gout, whereas new data on aging and menopause have come to challenge apparently established disease mechanisms. Regarding treatments, increase in bladder cancer associated with chronic allopurinol use has been reported, and the positive effect of urate-lowering treatment on cardiovascular events has been contested. SUMMARY: Epidemiological data in gout-related conditions are still evolving and claim for future cohort or intervention studies to prove causality. Controversies in epidemiological results fertilize the ground for studies to prove mechanisms and causality and provides a unique opportunity for clinical intervention to improve outcomes, especially with regard to treatments.

9 Review Inflammation: a possible mechanism for a causative role of hyperuricemia/gout in cardiovascular disease. 2015

Perez-Ruiz, F / Becker, M A. ·a a Servicio de Reumatología, Hospital Universitario Cruces, Instituto de Investigación Biomédica BioCruces , Vizcaya , Spain. · b b Department of Medicine , The University of Chicago Pritzker School of Medicine , Chicago , Illinois , USA. ·Curr Med Res Opin · Pubmed #26414731.

ABSTRACT: Hyperuricemia and gout are independent risk factors associated with the development of hypertension, metabolic syndrome, vascular damage, and renal disease. Whether these risk factors are causally related to these important chronic co-morbidities remains uncertain, but inflammation may provide a mechanistic explanation. Hyperuricemia and gout negatively affect vascular function by exerting pro-oxidant effects and by decreasing nitric oxide bioavailability, thus inducing inflammation and endothelial dysfunction, which may promote hypertension, metabolic syndrome, and cardiovascular (CV) disease. This paper presents and discusses current understanding of the diverse influences promoting hyperuricemia and gout and the basis of acute and chronic hyperuricemia/gout-related inflammation. This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.

10 Review Imaging as an Outcome Measure in Gout Studies: Report from the OMERACT Gout Working Group. 2015

Grainger, Rebecca / Dalbeth, Nicola / Keen, Helen / Durcan, Laura / Lawrence Edwards, N / Perez-Ruiz, Fernando / Diaz-Torne, Cesar / Singh, Jasvinder A / Khanna, Dinesh / Simon, Lee S / Taylor, William J. ·From the Department of Medicine, University of Otago Wellington, Wellington; Department of Medicine, University of Auckland, New Zealand; Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Medicine, University of Florida, Gainesville, Florida, USA; Rheumatology Division, Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya; Division of Rheumatology, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama; Division of Rheumatology, Department of Medicine, University of Michigan, Ann Arbor, Michigan; SDG LLC, Cambridge, Massachusetts, USA.R. Grainger, PhD, FRACP, Senior Lecturer, Rheumatologist, Department of Medicine, University of Otago Wellington; N. Dalbeth, MD, FRACP, Associate Professor, Department of Medicine, University of Auckland; L. Durcan, Rheumatology Fellow, MD, Mater Misericordiae University Hospital; H. Keen, PhD, Associate Professor, School of Medicine and Pharmacology, University of Western Australia; N.L. Edwards, MD, Professor of Medicine, Department of Medicine, University of Florida; F. Perez-Ruiz, MD, Professor, Rheumatology Division, Hospital Universitario Cruces and BioCruces Health Research Institute; C. Diaz-Torne, PhD, Associate Professor and Rheumatologist; J.A. Singh, MBBS, MPH, Associate Professor of Medicine; Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham; D. Khanna, MD, MSc, Associate Professor of Medicine, Division of Rheumatology, Department of Medicine, University of Michigan; L.S. Simon, MD, Principal Advisor, SDG LLC; W.J. Taylor, PhD, FRACP, Associate Professor and Rheumatologist, Department of Medicine, University of Otago Wellington. ·J Rheumatol · Pubmed #25641895.

ABSTRACT: OBJECTIVE: The gout working group at the Outcome Measures in Rheumatology (OMERACT) 12 meeting in 2014 aimed to determine which imaging modalities show the most promise for use as measurement instruments for outcomes in studies of people with chronic gout and to identify the key foci for future research about the performance of these imaging techniques with respect to the OMERACT filter 2.0. METHODS: During the gout session, a systematic literature review of the data addressing imaging modalities including plain radiography (XR), conventional computed tomography (CT), dual-energy computed tomography (DECT), magnetic resonance imaging (MRI), and ultrasound (US) and the fulfillment of the OMERACT filter 2.0 was presented. RESULTS: The working group identified 3 relevant domains for imaging in gout studies: urate deposition (tophus burden), joint inflammation, and structural joint damage. CONCLUSION: The working group prioritized gaps in the data and identified a research agenda.

11 Review New medications in development for the treatment of hyperuricemia of gout. 2015

Diaz-Torné, Cesar / Perez-Herrero, Nuria / Perez-Ruiz, Fernando. ·aDivision of Rheumatology, Hospital Santa Creu i San Pau, Barcelona bBiomedical Sciences School, Universidad Rey Juan Carlos, Madrid cDivision of Rheumatology, Hospital Universitario Cruces, and BioCruces Health Research Institute, Vizcaya, Spain. ·Curr Opin Rheumatol · Pubmed #25603039.

ABSTRACT: PURPOSE OF REVIEW: To update recent developments in medications targeting hyperuricemia, but not including medications recently labelled in the European Union and the United States. RECENT FINDINGS: A new xanthine oxidase inhibitor, Topiloric (Fujiyakuhin Co., Ltd. Japan) Uriadec (Sanwa Kagaku Kenkyusho Co., Ltd. Japan), has been developed and labelled in Japan. An inhibitor of purine nucleoside phosphorylase, Ulodesine, is in development in combination with allopurinol. The rest of the medications in the pipeline for hyperuricemia are targeting renal transporters of uric acid, mainly URAT1 and OAT4, acting as uricosuric agents. Most of them, such as lesinurad and arhalofenate, are being tested in trials in combination with allopurinol and febuxostat. The most potent RDEA3170 is being tested in monotherapy, but also associated with febuxostat. Recently, medications showing dual activity, inhibiting both xanthine oxidoreductase and URAT1, have been communicated or started exploratory clinical trials. There is no report of medications targeting other transporters such as Glut9 or ABCG2. SUMMARY: There are a number of medications in the pipeline targeting hyperuricemia, mostly uricosurics in combination with xanthine oxidase inhibitors, but some targeting both xanthine oxidoreductase and URAT1. Increasing the number of available medications will ensure proper control of hyperuricemia to target serum urate levels in the near future for most, if not all, patients with hyperuricemia.

12 Review A review of uric acid, crystal deposition disease, and gout. 2015

Perez-Ruiz, Fernando / Dalbeth, Nicola / Bardin, Tomas. ·Servicio de Reumatologia, Hospital Universitario Cruces, and BioCruces Health Research Institute, 48903, Baracaldo, Vizcaya, Spain, fernando.perezruiz@osakidetza.net. ·Adv Ther · Pubmed #25533440.

ABSTRACT: There has been increased interest in gout in both academic and clinical practice settings. Several reasons may explain this. The prevalence of both hyperuricemia and gout has risen in the last decades in developed countries and therefore the burden of gout has increased. The association of hyperuricemia and gout with cardiovascular outcomes and the opportunity of further benefits of intervention on hyperuricemia have been recently highlighted in the literature. Imaging techniques have proven to be useful for detection of urate deposition, even prior to the first clinical symptoms, enabling the evaluation of the extent of deposition and providing objective measurement of crystal depletion during urate-lowering treatment. Treating to target is increasingly used as the approach to treatment of diverse diseases. Therefore, different targets have been recommended for different stages of the burden of disease and for different stages of treatment. The final strategic target, to which any effort should be taken into consideration, is to completely dissolve urate crystals in tissues and therefore avoid further symptoms and structural damage of involved musculoskeletal structures. In summary, evidence suggest that an early approach to the treatment of gout and associated comorbidities is advisable, that new imaging techniques may help to evaluate both the burden of deposition and response to urate-lowering treatment in selected patients, and finally that the final strategic objective of healthcare for patients with gout is to completely resolve urate crystal deposits.

13 Review Improving cardiovascular and renal outcomes in gout: what should we target? 2014

Richette, Pascal / Perez-Ruiz, Fernando / Doherty, Michael / Jansen, Tim L / Nuki, George / Pascual, Eliseo / Punzi, Leonardo / So, Alexander K / Bardin, Thomas. ·Hôpital Lariboisière, Fédération de Rhumatologie, Centre Viggo Petersen 2, rue Ambroise Parè 75475 Cedex 10, Paris, France. · Servicio de Reumatología and BioCruces Health Research Institute, Cruces University Hospital, Plaza Cruces S/N, 48903 Barakaldo, Spain. · Division of Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital Nottingham, Hucknall Road, Nottingham NG5 1PB, UK. · Department of Rheumatology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, Netherlands. · Department of Rheumatology, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK. · Department of Medicine, Rheumatology Section, Alicante University and General Hospital, University Miguel Hernández, Av. Pintor Baeza 12, Alicante 03010, Spain. · Department of Rheumatology, Rheumatology Unit, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. · Service of Rheumatology, Centre Hospitalier Universitaire Vaudois, Avenue Pierre Decker 4, 1011 Lausanne, Switzerland. ·Nat Rev Rheumatol · Pubmed #25136785.

ABSTRACT: Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.

14 Review Clinical manifestations and diagnosis of gout. 2014

Perez-Ruiz, Fernando / Castillo, Edwin / Chinchilla, Sandra P / Herrero-Beites, Ana M. ·Division of Rheumatology, BioCruces Health Institute, Hospital Universitario Cruces, Pza Cruces sn, Baracaldo 48903, Spain. Electronic address: fernando.perezruiz@osakidetza.net. · Division of Rheumatology, Hospital Universitario Cruces, Pza Cruces sn, Baracaldo 48903, Spain. · Division of Physical Medicine, Hospital de Górliz, Astondo Ibiltoki, km. 2, Górliz 48630, Spain. ·Rheum Dis Clin North Am · Pubmed #24703343.

ABSTRACT: Gout has been academically considered to be a step-up disease consisting of different stages: acute gout, intercritical gout, and chronic gout. This simple approach may lead to misinterpretation and misdiagnosis. In clinical practice, we should consider gout as a single disease with either or both acute (most commonly, episodes of acute inflammation) and persistent clinical manifestations, but not restricted to chronic synovitis. In this article, an innovative, practical, and rational approach to the clinical manifestations and diagnosis of gout is presented, which may be supportive for clinicians involved in everyday care and management of patients with gout.

15 Review Canakinumab for gout: a specific, patient-profiled indication. 2014

Perez-Ruiz, Fernando / Chinchilla, Sandra P / Herrero-Beites, Ana María. ·Rheumatology Division, Hospital Universitario Cruces, Vizcaya, Spain. ·Expert Rev Clin Immunol · Pubmed #24451032.

ABSTRACT: The role of interleukin-1 (IL-1) in inflammation induced by crystals, and especially by monosodium urate crystals (MSUCs), has raised much interest in both basic and clinical investigation. Several drugs have been developed, and more are still in development, to block IL-1 driven inflammation, though to date only canakinumab (blocking IL-1β) has been labelled, yet limited to the European Union, with a restricted indication to treat episodes of acute inflammation (EAIs) in patients with gout in whom other therapeutic choices are unacceptable. Other medications developed for IL-1 blocking, such as anakinra and rilonacept, have been tested in gout patients in clinical trials, but lack label approval and may be further restricted to orphan indication in gout. Notwithstanding, the use of IL-1 blockade to prevent EAIs in gout looks promising, but no drug has yet obtained approval for such an indication.

16 Review Systematic review of the value of ultrasound and magnetic resonance musculoskeletal imaging in the evaluation of response to treatment of gout. 2014

Villaverde, Virginia / Rosario, María Piedad / Loza, Estíbaliz / Pérez, Fernando. ·Sección de Reumatología, Hospital Universitario de Móstoles, Móstoles, Madrid, España. Electronic address: virginia.villaverde@yahoo.es. · Unidad de Investigación, Sociedad Española de Reumatología, España. · Instituto de Enfermedades Musculoesqueléticas de Madrid, Madrid, España. · Sección de Reumatología, Hospital de Cruces, Baracaldo, Vizcaya, España. ·Reumatol Clin · Pubmed #24296268.

ABSTRACT: BACKGROUND: Imaging may be useful for monitoring response to therapy. Within the OMERACT proposal for the core set domains for outcome measures in chronic gout, serum urate levels, recurrence of gouty flares, tophus regression, and joint damage imaging have been included, among other proposed issues. OBJECTIVES: To perform a systematic literature review of the usefulness of magnetic resonance imaging (MRI) and ultrasound (US) on assessment of treatment response in patients with gout. METHODS: MEDLINE, EMBASE, Cochrane Library (up to February 2012), and abstracts presented at the 2010 and 2011 meetings of the American College of Rheumatology and European League Against Rheumatism, were searched for treatment studies of any duration and therapeutic options, examining the ability of MRI/US to assess treatment response in gouty patients. Meta-analyses, systematic reviews, randomized clinical trials, cohort and case-control studies and validation studies were included. Quality was appraised using validated scales. RESULTS: There were only 3 US published studies in the literature that analysed US utility on assessment of response to treatment in patients with gout. All of them were prospective case studies with a small number of patients and they were reviewed in detailed. A total of 36 patients with gout were examined with US. All of them had a baseline serum urate >6mg/dL. US features of gout (double contour sign, hyperechoic spots in synovial fluid, hyperechoic cloudy areas, tophus diameter and volume) achieved significant reduction in patients who reached the objective of uricemia ≤6mg/dL in all the studies; however, patients in whom levels did not drop below 6mg/dL had no change of US features of gout. Other parameters evaluated in one study included ESR, CRP, number of tender joints (TRN), number of swollen joints, and pain score (SP). All of them decreased with uricemia reduction, but only TRN and SP were statistically significant. No data was found on the value of MRI on treatment response assessment in patients with gout. CONCLUSIONS: The improvement in ultrasound features shows concurrent validity with uric acid reduction. According to the published evidence, US can be a useful tool for monitoring treatment of gouty patients, although more research is needed. The value of MRI on treatment response assessment in patients with gout remains to be determined.

17 Review Evaluation and treatment of gout as a chronic disease. 2012

Perez-Ruiz, Fernando / Herrero-Beites, Ana Maria. ·Rheumatology Division, Hospital Universitario Cruces, Pza Cruces, Baracaldo, Vizcaya, Spain. fperezruiz@telefonica.net ·Adv Ther · Pubmed #23104464.

ABSTRACT: Gout is a disease caused by deposition of monosodium urate crystals in tissues. One of the limitations for successful treatment of gout is to consider it as an intermittent disease rather than a chronic inflammatory disease which, if improperly treated, leads to chronic clinical manifestations. In addition, gout is linked to increased cardiovascular morbidity and mortality.Urate-lowering therapy comprises both nonpharmacologic and pharmacologic interventions, but most patients will need urate-lowering drugs to achieve target therapeutic serum urate levels. Reaching target serum urate levels is associated with improvement in clinical outcomes, including a reduction of acute inflammation episodes, resolution of tophi, and improvement in health-related quality of life perception.A number of urate-lowering drugs are available but a number of patients fail to achieve or maintain therapeutic serum urate levels and go on to develop refractory chronic gout. For such patients, efforts have been made to develop new treatments (e.g., febuxostat or pegloticase).This review intends to increase the awareness of gout as a chronic deposition disease, and show that efforts should be made to properly control serum urate levels in order to achieve complete disappearance of urate crystal deposition.

18 Review Imaging of gout: findings and utility. 2009

Perez-Ruiz, Fernando / Dalbeth, Nicola / Urresola, Aranzazu / de Miguel, Eugenio / Schlesinger, Naomi. ·Rheumatology Division, Hospital de Cruces, Baracaldo, Vizcaya, Spain. fernando.perezruiz@osakidetza.net ·Arthritis Res Ther · Pubmed #19591633.

ABSTRACT: Imaging is a helpful tool for clinicians to evaluate diseases that induce chronic joint inflammation. Chronic gout is associated with changes in joint structures that may be evaluated with diverse imaging techniques. Plain radiographs show typical changes only in advanced chronic gout. Computed tomography may best evaluate bone changes, whereas magnetic resonance imaging is suitable to evaluate soft tissues, synovial membrane thickness, and inflammatory changes. Ultrasonography is a tool that may be used in the clinical setting, allowing evaluation of cartilage, soft tissues, urate crystal deposition, and synovial membrane inflammation. Also ultrasound-guided puncture may be useful for obtaining samples for crystal observation. Any of these techniques deserve some consideration for feasibility and implementation both in clinical practice and as outcome measures for clinical trials. In clinical practice they may be considered mainly for evaluating the presence and extent of crystal deposition, and structural changes that may impair function or functional outcomes, and also to monitor the response to urate-lowering therapy.

19 Review Treating to target: a strategy to cure gout. 2009

Perez-Ruiz, Fernando. ·Rheumatology Division, Hospital de Cruces, 48600 Baracaldo, Vizcaya, Spain. fernando.perezruiz@osakidetza.net ·Rheumatology (Oxford) · Pubmed #19447780.

ABSTRACT: Acute gout attacks and the long-term complications of gout are associated with the deposition of monosodium urate (MSU) monohydrate crystals in the joints and soft tissues, causing acute and chronic inflammation. The aim of long-term treatment is to reduce the serum urate (sUA) level to 6 mg/dl (< or =360 micromol/l), below the saturation point of MSU, so that new crystals cannot form and existing crystals are dissolved. Serial joint aspiration studies confirmed the disappearance of crystals with effective urate-lowering therapy. There is good evidence that achieving sUA <6 mg/dl (360 micromol/l) results in freedom from acute gout attacks, and shrinkage and eventual disappearance of tophi. Gout patients must be informed about their diagnosis and educated about gout management including the importance of compliance with long-term treatment. Patients starting urate-lowering therapy need to understand the importance of prophylactic therapy with colchicine or NSAIDs to reduce the risk of 'mobilization flares' in the first few months. In the long term, reduction in the sUA below the target level will result in gout being effectively cured.

20 Clinical Trial Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial. 2017

Dalbeth, Nicola / Jones, Graeme / Terkeltaub, Robert / Khanna, Dinesh / Kopicko, Jeff / Bhakta, Nihar / Adler, Scott / Fung, Maple / Storgard, Chris / Baumgartner, Scott / Perez-Ruiz, Fernando. ·University of Auckland, Auckland, New Zealand. · University of Tasmania, Hobart, Tasmania, Australia. · University of California, San Diego. · University of Michigan, Ann Arbor. · Ardea Biosciences, Inc., San Diego, California. · AstraZeneca Pharmaceuticals, Gaithersburg, Maryland. · Hospital Universitario Cruces, Baracaldo, Spain. ·Arthritis Rheumatol · Pubmed #28597604.

ABSTRACT: OBJECTIVE: To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout. METHODS: Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ≥1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data. RESULTS: Patients (n = 324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P < 0.0001), but not 200 mg (56.6%; P = 0.13), to the febuxostat therapy as compared with febuxostat alone (46.8%). At all other time points, significantly more patients in the lesinurad 200 mg group achieved the serum UA target. The number of patients with complete tophus resolution was not different between groups. Treatment with lesinurad (200 mg and 400 mg) plus febuxostat reduced the total target tophi area as compared with febuxostat alone (50.1% and 52.9% versus 28.3%, respectively; P < 0.05). Safety was generally comparable with that of febuxostat alone, except for higher rates of predominantly reversible elevations in the serum creatinine level, particularly with lesinurad 400 mg. CONCLUSION: Treatment with lesinurad in combination with febuxostat demonstrated superior lowering of serum UA levels as compared with febuxostat alone, with clinically relevant added effects on tophi and an acceptable safety profile with lesinurad 200 mg in patients with tophaceous gout warranting additional therapy.

21 Clinical Trial Patients with gout differ from healthy subjects in renal response to changes in serum uric acid. 2017

Liu, Sha / Perez-Ruiz, Fernando / Miner, Jeffrey N. ·Biology Department, Ardea Biosciences Inc., 92121 San Diego, CA, USA. Electronic address: liusha168@gmail.com. · Hospital Universitario Cruces, Biocruces Health Research Institute, and Basque Country University, Vizcaya, Spain. · Biology Department, Ardea Biosciences Inc., 92121 San Diego, CA, USA. ·Joint Bone Spine · Pubmed #27324603.

ABSTRACT: OBJECTIVE: Our objectives were to determine whether a change in serum uric acid (sUA) resulted in a corresponding change in the fractional excretion of uric acid (FEUA) and whether the renal response was different in patients with gout versus healthy subjects. METHODS: FEUA was calculated from previously published studies and four new phase I studies in healthy subjects and/or patients with gout before and after treatment to lower or raise sUA. Treatments included xanthine oxidase inhibitors to lower sUA as well as infusion of uric acid and provision of a high-purine diet to raise sUA. Plots were created of FEUA versus sUA before and after treatment. For the phase I studies, percent change in FEUA per mg/dL change in sUA was calculated separately for healthy subjects and patients with gout, and compared using Student's t test. RESULTS: Analysis of previously published data and the new phase I clinical data indicates that changing sUA by a non-renal mechanism leads to a change in FEUA. The magnitude of change is greater in subjects with higher baseline FEUA versus patients with gout. Healthy subjects excrete more urate than do patients with gout at physiological urate-filtered load; this difference disappears when the urate-filtered load is decreased to ∼5000mg/24hours. CONCLUSION: These observations are consistent with a less saturated urate reabsorption system in patients with gout versus healthy subjects, resulting in elevated retention of uric acid. Further investigation could lead to the discovery of mechanisms responsible for the etiology of hyperuricemia/gout.

22 Clinical Trial Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. 2016

Perez-Ruiz, Fernando / Sundy, John S / Miner, Jeffrey N / Cravets, Matthew / Storgard, Chris / Anonymous791036. ·Rheumatology Division, Hospital Universitario Cruces, Barakaldo, Spain. · Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA Gilead Sciences, Foster City, California, USA. · Ardea Biosciences, San Diego, California, USA. · Ardea Biosciences, San Diego, California, USA Receptos, San Diego, California, USA. ·Ann Rheum Dis · Pubmed #26742777.

ABSTRACT: OBJECTIVES: To assess the efficacy and tolerability of lesinurad, an oral selective uric acid reabsorption inhibitor, in combination with allopurinol versus allopurinol alone in patients with gout and an inadequate response to allopurinol. METHODS: Patients (N=227) with an inadequate response to allopurinol, defined as serum urate (sUA) ≥6 mg/dL on ≥2 occasions ≥2 weeks apart despite ≥6 weeks of allopurinol, were randomised 2:1 to 4 weeks of double-blind treatment with lesinurad (200, 400 or 600 mg/day) or matching placebo in combination with their prestudy allopurinol dose (200-600 mg/day). Colchicine prophylaxis for gout flares was required. The primary end point was percent reduction from baseline sUA levels at 4 weeks. A pharmacokinetic substudy was also conducted. Safety was assessed throughout. RESULTS: Patients (n=208) received ≥1 dose of blinded medication. Lesinurad 200, 400 and 600 mg in combination with allopurinol produced significant mean percent reductions from baseline sUA of 16%, 22% and 30%, respectively, versus a mean 3% increase with placebo (p<0.0001, all doses vs placebo). Similar results were observed in patients with mild or moderate renal insufficiency (estimated creatinine clearance 30 to <90 mL/min). The incidence of ≥1 treatment-emergent adverse event was 46%, 48% and 54% with lesinurad 200, 400 and 600 mg, respectively, and 46% with placebo (most frequent, gout flares, arthralgia, headache and nasopharyngitis), with no deaths or serious adverse events. CONCLUSIONS: Lesinurad achieves clinically relevant and statistically significant reductions in sUA in combination with allopurinol in patients who warrant additional therapy on allopurinol alone. TRIAL REGISTRATION NUMBER: NCT01001338.

23 Article Brief Report: Validation of a Definition of Flare in Patients With Established Gout. 2018

Gaffo, Angelo L / Dalbeth, Nicola / Saag, Kenneth G / Singh, Jasvinder A / Rahn, Elizabeth J / Mudano, Amy S / Chen, Yi-Hsing / Lin, Ching-Tsai / Bourke, Sandra / Louthrenoo, Worawit / Vazquez-Mellado, Janitzia / Hernández-Llinas, Hansel / Neogi, Tuhina / Vargas-Santos, Ana Beatriz / da Rocha Castelar-Pinheiro, Geraldo / Amorim, Rodrigo B C / Uhlig, Till / Hammer, Hilde B / Eliseev, Maxim / Perez-Ruiz, Fernando / Cavagna, Lorenzo / McCarthy, Geraldine M / Stamp, Lisa K / Gerritsen, Martijn / Fana, Viktoria / Sivera, Francisca / Taylor, William. ·University of Alabama at Birmingham and Birmingham VA Medical Center, Birmingham, Alabama. · University of Auckland, Auckland, New Zealand. · University of Alabama at Birmingham. · Taichung Veterans General Hospital, Taichung, Taiwan. · Chiang Mai University, Chiang Mai, Thailand. · Hospital General de Mexico, Mexico City, Mexico. · Boston University School of Medicine, Boston, Massachusetts. · Boston University School of Medicine, Boston, Massachusetts, and Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. · Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. · Diakonhjemmet Hospital, Oslo, Norway. · Research Institute of Rheumatology of Russia, Moscow, Russia. · University of the Basque Country, Cruces University Hospital, and Biocruces Health Research Institute, Vizcaya, Spain. · University and IRCCS Policlinico S. Matteo Foundation, Pavia, Italy. · Mater Misericordiae University Hospital, Dublin, Ireland. · University of Otago, Christchurch, New Zealand. · Westfries Gasthuis, Hoorn, The Netherlands. · Rigshospitalet Glostrup, Copenhagen, Denmark. · Hospital General Universitario Elda, Elda, Spain. · University of Wellington, Wellington, New Zealand. ·Arthritis Rheumatol · Pubmed #29161469.

ABSTRACT: OBJECTIVE: To perform external validation of a provisional definition of disease flare in patients with gout. METHODS: Five hundred nine patients with gout were enrolled in a cross-sectional study during a routine clinical care visit at 17 international sites. Data were collected to classify patients as experiencing or not experiencing a gout flare, according to a provisional definition. A local expert rheumatologist performed the final independent adjudication of gout flare status. Sensitivity, specificity, predictive values, and receiver operating characteristic (ROC) curves were used to determine the diagnostic performance of gout flare definitions. RESULTS: The mean ± SD age of the patients was 57.5 ± 13.9 years, and 89% were male. The definition requiring fulfillment of at least 3 of 4 criteria (patient-defined gout flare, pain at rest score of >3 on a 0-10-point numerical rating scale, presence of at least 1 swollen joint, and presence of at least 1 warm joint) was 85% sensitive and 95% specific in confirming the presence of a gout flare, with an accuracy of 92%. The ROC area under the curve was 0.97. The definition based on a classification and regression tree algorithm (entry point, pain at rest score >3, followed by patient-defined flare "yes") was 73% sensitive and 96% specific. CONCLUSION: The definition of gout flare that requires fulfillment of at least 3 of 4 patient-reported criteria is now validated to be sensitive, specific, and accurate for gout flares, as demonstrated using an independent large international patient sample. The availability of a validated gout flare definition will improve the ascertainment of an important clinical outcome in studies of gout.

24 Article Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study. 2018

Latourte, Augustin / Soumaré, Aicha / Bardin, Thomas / Perez-Ruiz, Fernando / Debette, Stéphanie / Richette, Pascal. ·Université Paris Diderot, UFR médicale, Paris, France. · Hôpital Lariboisière, Service de Rhumatologie, Paris, Cedex, France. · INSERM 1132, Université Paris-Diderot, Hôpital Lariboisière, Paris, France. · Inserm Centre Bordeaux Population Health (U1219), Bordeaux, France. · Division of Rheumatology, Hospital Universitario Cruces, Biocruces Health Research Institute, and Basque Country University, Biscay, Spain. · University of Bordeaux, Bordeaux, France. · Department of Neurology, Memory Clinic, Bordeaux, France. · Department of Neurology, Framingham Heart Study, Boston University School of Medicine, Boston, Massachusetts, USA. ·Ann Rheum Dis · Pubmed #28754803.

ABSTRACT: OBJECTIVES: In patients with gout, maintaining too low serum uric acid (SUA) level with urate-lowering therapy is a concern because uric acid is thought to be neuroprotective. However, the relation between SUA and dementia remains debated. This study aimed to investigate the impact of SUA level on the incidence of dementia. METHODS: We assessed the longitudinal association between SUA level and incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria) in a large cohort of healthy older people from the community (Three-City Dijon cohort). Additionally, we investigated the relation between SUA level and MRI markers of brain ageing (white matter hyperintensity volume (WMHV), lacunes and hippocampal volume). RESULTS: The study sample comprised 1598 people (mean (SD) age 72.4(4.1) years, 38.3% male). During the 13,357 person-years of follow-up (median duration: 10.1 years), dementia developed in 110 participants (crude incidence rate: 8.2/1000 person-years). After multiple adjustments, the multivariate HR with the highest (≥75th percentile) versus lowest SUA level was 1.79 (95% CI 1.17 to 2.73; p=0.007). The association was stronger with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to 10.41), p=0.015) than Alzheimer's disease (HR=1.55 (95% CI 0.92 to 2.61), p=0.10). There was a non-significant trend towards an association between high SUA level and extensive WMHV (p=0.10), a biomarker of small vessel disease, but not hippocampal volume (p=0.94) or lacunes (p=0.86). The association between SUA level and vascular or mixed dementia might be affected by interim strokes. CONCLUSIONS: Risk of dementia, especially vascular or mixed dementia, may be increased with high SUA levels in elderly people.

25 Article Performance of Ultrasound in the Diagnosis of Gout in a Multicenter Study: Comparison With Monosodium Urate Monohydrate Crystal Analysis as the Gold Standard. 2017

Ogdie, Alexis / Taylor, William J / Neogi, Tuhina / Fransen, Jaap / Jansen, Tim L / Schumacher, H Ralph / Louthrenoo, Worawit / Vazquez-Mellado, Janitzia / Eliseev, Maxim / McCarthy, Geraldine / Stamp, Lisa K / Perez-Ruiz, Fernando / Sivera, Francisca / Ea, Hang-Korng / Gerritsen, Martijn / Cagnotto, Giovanni / Cavagna, Lorenzo / Lin, Chingtsai / Chou, Yin-Yi / Tausche, Anne-Kathrin / Lima Gomes Ochtrop, Manuella / Janssen, Matthijs / Chen, Jiunn-Horng / Slot, Ole / Lazovskis, Juris / White, Douglas / Cimmino, Marco A / Uhlig, Till / Dalbeth, Nicola. ·University of Pennsylvania, Philadelphia. · University of Otago, Wellington, New Zealand. · Boston University School of Medicine, Boston, Massachusetts. · VieCuri Medical Centre, Venlo, The Netherlands, and Scientific IQ HealthCare, Radboud University Medical Center, Nijmegen, The Netherlands. · Chiang Mai University, Chiang Mai, Thailand. · Hospital General de México, Mexico City, Mexico. · Nasonova Research Institute of Rheumatology of Russia, Moscow, Russia. · University College Dublin and Mater Misericordiae University Hospital, Dublin, Ireland. · University of Otago Christchurch, Christchurch, New Zealand. · Hospital Universitario Cruces, BioCruces Health Research Institute, and Basque Country University, Barakaldo, Spain. · Hospital General Universitario de Elda, Alicante, Spain. · Université Paris Diderot, INSERM UMR 1132 and Service de Rhumatologie, Hôpital Lariboisière, AP-HP, Paris, France. · Westfries Gasthuis, Hoorn, The Netherlands. · University of Pavia and IRCCS Policlinico San Matteo Foundation, Pavia, Italy, and Skane University Hospital Malmö/Lund, Lund, Sweden. · University of Pavia and IRCCS Policlinico San Matteo Foundation, Pavia, Italy. · Taichung Veterans' General Hospital, Taichung, Taiwan, Republic of China. · University Hospital Carl Gustav Carus, Dresden, Germany. · Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. · Rijnstate Hospital, Arnhem, The Netherlands. · China Medical University Hospital, Taichung, Taiwan, Republic of China. · Copenhagen University Hospital Glostrup, Glostrup, Denmark. · Riverside Professional Centre, Sydney, Nova Scotia, Canada. · Waikato District Health Board and Waikato Clinical School, Hamilton, New Zealand. · University of Genoa, Genoa, Italy. · Diakonhjemmet Hospital, Oslo, Norway. · University of Auckland, Auckland, New Zealand. ·Arthritis Rheumatol · Pubmed #27748084.

ABSTRACT: OBJECTIVE: To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard. METHODS: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout. RESULTS: US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23-10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68-8.17]), and serum urate level (OR 1.31 [95% CI 1.06-1.62]). CONCLUSION: US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi.