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Gout: HELP
Articles from University of Lausanne
Based on 31 articles published since 2008

These are the 31 published articles about Gout that originated from University of Lausanne during 2008-2019.
+ 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 The role of IL-1 in gout: from bench to bedside. 2018

So, Alexander / Dumusc, Alexandre / Nasi, Sonia. ·Service de Rhumatologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. ·Rheumatology (Oxford) · Pubmed #29272514.

ABSTRACT: The translation of our knowledge of the biology of MSU crystal-induced IL-1 secretion gives rise to new targets and therapeutic strategies in the treatment of acute gout. The NACHT, LRR and PYD domains-containing protein 3 inflammasome is key to this, and is the subject of intense research. Novel pathways that modulate inflammasome activation, reactive oxygen species generation and extracellular processing of IL-1 have been described and show promise in in vitro and animal studies. Meanwhile, blocking IL-1 by various IL-1 inhibitors has shown the validity of this concept. Patients with acute gout treated with these inhibitors showed positive clinical and biological responses. More work needs to be performed to assess the risk/benefit profile of anti-IL-1 therapies as well as to identify those who will benefit the most from this novel approach to the treatment of gout.

3 Review Inflammation in gout: mechanisms and therapeutic targets. 2017

So, Alexander K / Martinon, Fabio. ·Service of Rheumatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Avenue Pierre Decker 4, 1011 Lausanne, Switzerland. · Department of Biochemistry, University of Lausanne, 155 Chemin des Boveresses, 1066 Epalinges, Switzerland. ·Nat Rev Rheumatol · Pubmed #28959043.

ABSTRACT: The acute symptoms of gout are triggered by the inflammatory response to monosodium urate crystals, mediated principally by macrophages and neutrophils. Innate immune pathways are of key importance in the pathogenesis of gout, in particular the activation of the NLRP3 inflammasome, which leads to the release of IL-1β and other pro-inflammatory cytokines. The orchestration of this pro-inflammatory cascade involves multiple intracellular and extracellular receptors and enzymes interacting with environmental influences that modulate the inflammatory state. Furthermore, the resolution of inflammation in gout is becoming better understood. This Review highlights recent advances in our understanding of both positive and negative regulatory pathways, as well as the genetic and environmental factors that modulate the inflammatory response. Some of these pathways can be manipulated and present novel therapeutic opportunities for the treatment of acute gout attacks.

4 Review Discordant American College of Physicians and international rheumatology guidelines for gout management: consensus statement of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN). 2017

Dalbeth, Nicola / Bardin, Thomas / Doherty, Michael / Lioté, Frédéric / Richette, Pascal / Saag, Kenneth G / So, Alexander K / Stamp, Lisa K / Choi, Hyon K / Terkeltaub, Robert. ·Department of Medicine, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand. · University Paris Diderot Cité Sorbonne, Service de Rhumatologie, Centre Viggo Petersen, Lariboisière Hospital, INSERM U1132, Paris, France. · Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham (UAB), 820 Faculty Office Tower, 510 20th Street, Birmingham, Alabama 35294-3408, USA. · Service of Rheumatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Avenue Pierre Decker 4, 1011 Lausanne, Switzerland. · Department of Medicine, University of Otago, Christchurch, P.O. BOX 4345, Christchurch 8140, New Zealand. · Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit Street, Harvard Medical School, Boston, Massachusetts 02114, USA. · VA San Diego Healthcare System, 111K, 3350 La Jolla Village Drive, San Diego, California 92161, USA. ·Nat Rev Rheumatol · Pubmed #28794514.

ABSTRACT: In November 2016, the American College of Physicians (ACP) published a clinical practice guideline on the management of acute and recurrent gout. This guideline differs substantially from the latest guidelines generated by the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) and 3e (Evidence, Expertise, Exchange) Initiative, despite reviewing largely the same body of evidence. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) convened an expert panel to review the methodology and conclusions of these four sets of guidelines and examine possible reasons for discordance between them. The G-CAN position, presented here, is that the fundamental pathophysiological knowledge underlying gout care, and evidence from clinical experience and clinical trials, supports a treat-to-target approach for gout aimed at lowering serum urate levels to below the saturation threshold at which monosodium urate crystals form. This practice, which is truly evidence-based and promotes the steady reduction in tissue urate crystal deposits, is promoted by the ACR, EULAR and 3e Initiative recommendations. By contrast, the ACP does not provide a clear recommendation for urate-lowering therapy (ULT) for patients with frequent, recurrent flares or those with tophi, nor does it recommend monitoring serum urate levels of patients prescribed ULT. Results from emerging clinical trials that have gout symptoms as the primary end point are expected to resolve this debate for all clinicians in the near term future.

5 Review Imaging in Gout and Other Crystal-Related Arthropathies. 2016

Omoumi, Patrick / Zufferey, Pascal / Malghem, Jacques / So, Alexander. ·Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, Rue du Bugnon 46, Lausanne 1011, Switzerland. Electronic address: patrick.omoumi@chuv.ch. · Department of Rheumatology, Lausanne University Hospital, Av Pierre Decker 5, Lausanne 1011, Switzerland. · Department of Radiology, Saint Luc University Hospital, UC Louvain, Av Hippocrate 10, Brussels 1200, Belgium. ·Rheum Dis Clin North Am · Pubmed #27742018.

ABSTRACT: In this article, the authors consider the manifestations of intraarticular and periarticular crystal deposits. Most cases of crystal deposits are asymptomatic and represent incidental findings at imaging. In symptomatic arthropathies, imaging can play an important role in the diagnosis and assessment of disease progression and the extent of crystal deposits. Conventional radiography is the most common imaging modality. But ultrasound, conventional computerized tomography (CT), dual-energy CT, and MRI play an increasing role. The authors review typical radiographic features of crystal-induced arthropathies and findings that help to differentiate them. The authors also emphasize the increasing role of complementary imaging techniques.

6 Review Why better treatment of gout is needed. 2016

So, Alexander K. ·Service de Rhumatologie, CHUV and University of Lausanne, Switzerland. alexanderkai-lik.so@chuv.ch. ·Clin Exp Rheumatol · Pubmed #27586807.

ABSTRACT: The treatment of gout is thought to be simple, but in reality we are confronted regularly with patients who do not adhere to treatment and patients who have other medical conditions that render the choice of therapy difficult. A treat-to-target approach is essential in order to manage hyperuricaemia effectively and this, combined with a better use of existing treatments, offers the best way forward.

7 Review Interleukin-1 as a therapeutic target in gout. 2015

Dumusc, Alexandre / So, Alexander. ·Department of Rheumatology, Lausanne University Hospital, CHUV, Lausanne, Switzerland. ·Curr Opin Rheumatol · Pubmed #25633244.

ABSTRACT: PURPOSE OF REVIEW: To give an overview of current evidence for interleukin (IL)-1 blockade in the management of gout. RECENT FINDINGS: Three IL-1 blockers are currently available for clinical use: anakinra, rilonacept and canakinumab. Recent studies have focused on drugs with a long half-life: rilonacept and canakinumab. For treatment of acute gouty arthritis, three randomized controlled trials (RCTs) showed efficacy of canakinumab with some safety concerns and one RCT failed to show efficacy of rilonacept. For prevention of gout flare when starting uric acid lowering therapy (ULT), four RCTs showed efficacy of rilonacept and one RCT showed efficacy of canakinumab. SUMMARY: There is sufficient evidence supporting the use of IL-1 blockers for treatment of acute gouty arthritis or for prevention of gout flares when starting ULT in selected patients, with contraindications or intolerance to conventional therapy. More data are needed to assess safety and to specify their use in routine practice.

8 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.

9 Review The concept of the inflammasome and its rheumatologic implications. 2014

So, Alexander / Busso, Nathalie. ·Service de rhumatologie, université de Lausanne, CHU Vaudois, avenue Pierre-Decker 4, 1011 Lausanne, Suisse. Electronic address: alexanderkai-lik.so@chuv.ch. · Service de rhumatologie, université de Lausanne, CHU Vaudois, avenue Pierre-Decker 4, 1011 Lausanne, Suisse. ·Joint Bone Spine · Pubmed #24703401.

ABSTRACT: The inflammasome is a proteolytic complex that regulates IL1β and IL-18 secretion in macrophages and dendritic cells. Its plays a vital role in the control of the inflammatory and cellular responses to infectious and danger signals and is an essential part of the innate immune system. Four different inflammasomes have been identified so far, and the NLRP3-inflammasome has been the best-studied in relation to human disease. Activation of the NLRP3-inflammasome by microcrystals, such as monosodium urate (MSU) and basic calcium phosphate (BCP) crystals, leads to IL1β release, which in turn triggers local inflammation. Dysfunction of the NLRP3-inflammasome due to mutations of the NLRP3 gene is the cause of the auto-inflammatory syndrome CAPS. The symptoms and signs of inflammation in both conditions respond to IL1 blockade. IL1 inhibitors have also been used successfully in other idiopathic inflammatory diseases, suggesting that dysregulated inflammasome activity contributes to the pathogenesis of multiple diseases, but the precise underlying mechanisms remain to be identified.

10 Review Emerging therapies for gout. 2014

Edwards, N Lawrence / So, Alexander. ·Department of Medicine, University of Florida College of Medicine, 1600 South West Archer Road, Gainesville, FL 32610-0277, USA. Electronic address: edwarnl@medicine.ufl.edu. · Service de Rhumatologie, CHUV, Avenue Pierre Decker, Lausanne 1011, Switzerland. ·Rheum Dis Clin North Am · Pubmed #24703353.

ABSTRACT: Over the past decade much has been learned about the mechanisms of crystal-induced inflammation and renal excretion of uric acid, which has led to more specific targeting of gout therapies and a more potent approach to future management of gout. This article outlines agents being developed for more aggressive lowering of urate and more specific anti-inflammatory activity. The emerging urate-lowering therapies include lesinurad, arhalofenate, ulodesine, and levotofisopam. Novel gout-specific anti-inflammatories include the interleukin-1β inhibitors anakinra, canakinumab, and rilonacept, the melanocortins, and caspase inhibitors. The historic shortcomings of current gout treatment may, in part, be overcome by these novel approaches.

11 Review Recommendations for the use of ultrasound in rheumatoid arthritis: literature review and SONAR score experience. 2013

Zufferey, Pascal / Tamborrini, Giorgio / Gabay, Cem / Krebs, Andreas / Kyburz, Diego / Michel, Beat / Moser, Urs / Villiger, Peter M / So, Alexander / Ziswiler, Hans Rudolf. ·CHUV, av Pirre decker 4, 1005, Lausanne (vd), SWITZERLAND; pascal.zufferey@chuv.ch. ·Swiss Med Wkly · Pubmed #24363082.

ABSTRACT: Ultrasound (US) has become a useful tool in the detection of early disease, differential diagnosis, guidance of treatment decisions and treatment monitoring of rheumatoid arthritis (RA). In 2008, the Swiss Sonography in Arthritis and Rheumatism (SONAR) group was established to promote the use of US in inflammatory arthritis in clinical practice. A scoring system was developed and taught to a large number of Swiss rheumatologists who already contributed to the Swiss Clinical Quality Management (SCQM) database, a national patient register. This paper intends to give a Swiss consensus about best clinical practice recommendations for the use of US in RA on the basis of the current literature knowledge and experience with the Swiss SONAR score. Literature research was performed to collect data on current evidence. The results were discussed among specialists of the Swiss university centres and private practice, following a structured procedure. Musculoskelatal US was found to be very helpful in establishing the diagnosis and monitoring the evolution of RA, and to be a reliable tool if used by experienced examiners. It influences treatment decisions such as continuing, intensifying or stepping down therapy. The definite modalities of integrating US into the diagnosis and monitoring of RA treatments will be defined within a few years. There are, however, strong arguments to use US findings as of today in daily clinical care. Some practical recommendations about the use of US in RA, focusing on the diagnosis and the use of the SONAR score, are proposed.

12 Review Update on gout 2012. 2012

So, Alexander / Busso, Nathalie. ·Service de Rhumatologie, Département de l'Appareil Locomoteur, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. alexanderkai-lik.so@chuv.ch ·Joint Bone Spine · Pubmed #23165182.

ABSTRACT: Significant scientific advances have been made over the last five years in the pathogenesis of hyperuricemia and understanding how monosodium urate (MSU) crystals provoke gout. New detection methods using ultrasound (US) have been evaluated and may become part of our routine diagnostic approach in a patient presenting with gout. This review will concentrate on the latest developments in the field, and discuss how these data may impact on clinical practice. Finally, a brief review of the therapeutic implications and new therapies that have become available will be presented.

13 Review [The etiology and management of gout]. 2012

Pazár Maldonado, B / So, A. ·Department of Rheumatology, Centre Hospitalier Universitaire Vaudois, 1011, Lausanne, Suisse. ·Z Rheumatol · Pubmed #22370804.

ABSTRACT: Gout is an inflammatory arthritis caused by monosodium urate (MSU) crystal deposits in and around the joint. The formation of urinary calculi can also occur in gout, but are less common than arthritis. Gout usually presents with recurrent episodes of joint inflammation, which over time lead to tophus formation and joint destruction. In the last decade, significant advances have been made regarding not only the epidemiology and genetics of gout and hyperuricemia but also the mechanisms of inflammation and treatment of gout. In addition, knowledge concerning the key role of interleukin 1 (IL-1) has provided new therapeutic perspectives. However, the current management of gout is often suboptimal, with many Patienten either not receiving adequate treatment or being unable to tolerate existing treatments. New therapeutic agents provide interesting new options for Patienten with difficult-to-treat gouty arthritis.The English full-text version of this is available at SpringerLink (under "Supplemental").

14 Review The mechanisms of inflammation in gout and pseudogout (CPP-induced arthritis). 2012

Busso, N / Ea, H-K. ·DAL, Service de Rhumatologie, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. Nathalie.Busso@chuv.ch ·Reumatismo · Pubmed #22303529.

ABSTRACT: Recent advances have stimulated new interest in the area of crystal arthritis, as microcrystals can be considered to be endogenous "danger signals" and are potent stimulators of immune as well as non-immune cells. The best known microcrystals include urate (MSU), and calcium pyrophosphate (CPP) crystals, associated with gout and pseudogout, respectively. Acute inflammation is the hallmark of the acute tissue reaction to crystals in both gout and pseudogout. The mechanisms leading to joint inflammation in these diseases involve first crystal formation and subsequent coating with serum proteins. Crystals can then interact with plasma cell membrane, either directly or via membrane receptors, leading to NLRP3 activation, proteolytic cleavage and maturation of pro-interleukin-1β (pro-IL1β) and secretion of mature IL1β. Once released, this cytokine orchestrates a series of events leading to endothelial cell activation and neutrophil recruitment. Ultimately, gout resolution involves several mechanisms including monocyte differentiation into macrophage, clearance of apoptotic neutrophils by macrophages, production of Transforming Growth Factor (TGF-β) and modification of protein coating on the crystal surface. This review will examine these different steps.

15 Review The NLRP3 inflammasome in health and disease: the good, the bad and the ugly. 2011

Menu, P / Vince, J E. ·Department of Biochemistry, University of Lausanne, Epalinges, Switzerland. philippe.menu@unil.ch ·Clin Exp Immunol · Pubmed #21762124.

ABSTRACT: While interleukin (IL)-1β plays an important role in combating the invading pathogen as part of the innate immune response, its dysregulation is responsible for a number of autoinflammatory disorders. Large IL-1β activating platforms, known as inflammasomes, can assemble in response to the detection of endogenous host and pathogen-associated danger molecules. Formation of these protein complexes results in the autocatalysis and activation of caspase-1, which processes precursor IL-1β into its secreted biologically active form. Inflammasome and IL-1β activity is required to efficiently control viral, bacterial and fungal pathogen infections. Conversely, excess IL-1β activity contributes to human disease, and its inhibition has proved therapeutically beneficial in the treatment of a spectrum of serious, yet relatively rare, heritable inflammasomopathies. Recently, inflammasome function has been implicated in more common human conditions, such as gout, type II diabetes and cancer. This raises the possibility that anti-IL-1 therapeutics may have broader applications than anticipated previously, and may be utilized across diverse disease states that are linked insidiously through unwanted or heightened inflammasome activity.

16 Review Uric acid transport and disease. 2010

So, Alexander / Thorens, Bernard. ·Service de Rhumatologie, Department of Musculoskeletal Medicine, University of Lausanne, Lausanne, Switzerland. ·J Clin Invest · Pubmed #20516647.

ABSTRACT: Uric acid is the metabolic end product of purine metabolism in humans. It has antioxidant properties that may be protective but can also be pro-oxidant, depending on its chemical microenvironment. Hyperuricemia predisposes to disease through the formation of urate crystals that cause gout, but hyperuricemia, independent of crystal formation, has also been linked with hypertension, atherosclerosis, insulin resistance, and diabetes. We discuss here the biology of urate metabolism and its role in disease. We also cover the genetics of urate transport, including URAT1, and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development.

17 Review Mechanisms of inflammation in gout. 2010

Busso, Nathalie / So, Alexander. ·Service de Rheumatologie, Centre Hospitalier Universitaire Vaudois, Université de Lausanne, Avenue Pierre Decker, 1011 Lausanne, Suisse. ·Arthritis Res Ther · Pubmed #20441605.

ABSTRACT: An acute attack of gout is a paradigm of acute sterile inflammation, as opposed to pyogenic inflammation. Recent studies suggest that the triggering of IL-1beta release from leucocytes lies at the heart of a cascade of processes that involves multiple cytokines and mediators. The NLRP3 inflammasome appears to have a specific role in this regard, but the biochemical events leading to its activation are still not well understood. We review the known mechanisms that underlie the inflammatory process triggered by urate crystals and suggest areas that require further research.

18 Review The NLRP3 inflammasome: a sensor for metabolic danger? 2010

Schroder, Kate / Zhou, Rongbin / Tschopp, Jurg. ·Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland. ·Science · Pubmed #20075245.

ABSTRACT: Interleukin-1beta (IL-1beta), reactive oxygen species (ROS), and thioredoxin-interacting protein (TXNIP) are all implicated in the pathogenesis of type 2 diabetes mellitus (T2DM). Here we review mechanisms directing IL-1beta production and its pathogenic role in islet dysfunction during chronic hyperglycemia. In doing so, we integrate previously disparate disease-driving mechanisms for IL-1beta, ROS, and TXNIP in T2DM into one unifying model in which the NLRP3 inflammasome plays a central role. The NLRP3 inflammasome also drives IL-1beta maturation and secretion in another disease of metabolic dysregulation, gout. Thus, we propose that the NLRP3 inflammasome contributes to the pathogenesis of T2DM and gout by functioning as a sensor for metabolic stress.

19 Review Developments in the scientific and clinical understanding of gout. 2008

So, Alexander. ·Service de Rhumatologie, Departement de Médecine, CHU Vaudois, University of Lausanne, Ave Pierre Decker, 1011 Lausanne, Switzerland. alexanderkai-lik.so@chuv.ch ·Arthritis Res Ther · Pubmed #18947374.

ABSTRACT: Gout is the most common form of inflammatory arthritis in the elderly. In the last two decades, both hyperuricemia and gout have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies provide new insights into the transporters that handle uric acid in the kidney as well as possible links between these transporters, hyperuricemia, and hypertension. The treatment of established hyperuricemia has also seen new developments. Febuxostat and PEG-uricase are two novel treatments that have been evaluated and shown to be highly effective in the management of hyperuricemia, thus enlarging the therapeutic options available to lower uric acid levels. Monosodium urate (MSU) crystals are potent inducers of inflammation. Within the joint, they trigger a local inflammatory reaction, neutrophil recruitment, and the production of pro-inflammatory cytokines as well as other inflammatory mediators. Experimentally, the uptake of MSU crystals by monocytes involves interactions with components of the innate immune system, namely Toll-like receptor (TLR)-2, TLR-4, and CD14. Intracellularly, MSU crystals activate multiple processes that lead to the formation of the NALP-3 (NACHT, LRR, and pyrin domain-containing-3) inflammasome complex that in turn processes pro-interleukin (IL)-1 to yield mature IL-1 beta, which is then secreted. The inflammatory effects of MSU are IL-1-dependent and can be blocked by IL-1 inhibitors. These advances in the understanding of hyperuricemia and gout provide new therapeutic targets for the future.

20 Clinical Trial Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). 2017

Bardin, Thomas / Keenan, Robert T / Khanna, Puja P / Kopicko, Jeff / Fung, Maple / Bhakta, Nihar / Adler, Scott / Storgard, Chris / Baumgartner, Scott / So, Alexander. ·Rhumatologie, Lariboisière Hospital, and Université Paris Diderot Sorbonne Cité, Paris, France. · Division of Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA. · Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA. · Biometrics, Ardea Biosciences, Inc., San Diego, California, USA. · Research & Development, Ardea Biosciences, Inc., San Diego, California, USA. · Research & Development, AstraZeneca Pharmaceuticals, Gaithersburg, Maryland, USA. · Medical Affairs, Ardea Biosciences, Inc., San Diego, California, USA. · Service de rhumatologie, Université de Lausanne, Lausanne, Switzerland. ·Ann Rheum Dis · Pubmed #27821644.

ABSTRACT: OBJECTIVES: Determine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial. METHODS: Patients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data. RESULTS: Patients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively. CONCLUSION: Lesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy. TRIAL REGISTRATION NUMBER: NCT01493531.

21 Clinical Trial Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. 2010

So, Alexander / De Meulemeester, Marc / Pikhlak, Andrey / Yücel, A Eftal / Richard, Dominik / Murphy, Valda / Arulmani, Udayasankar / Sallstig, Peter / Schlesinger, Naomi. ·University Hospital of Lausanne, Lausanne, Switzerland. AlexanderKai-Lik.So@chuv.ch ·Arthritis Rheum · Pubmed #20533546.

ABSTRACT: OBJECTIVE: To assess the efficacy and tolerability of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, for the treatment of acute gouty arthritis. METHODS: In this 8-week, single-blind, double-dummy, dose-ranging study, patients with acute gouty arthritis whose disease was refractory to or who had contraindications to nonsteroidal antiinflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg; n = 143) or an intramuscular dose of triamcinolone acetonide (40 mg; n = 57). Patients assessed pain using a 100-mm visual analog scale. RESULTS: Seventy-two hours after treatment, a statistically significant dose response was observed for canakinumab. All canakinumab doses were associated with numerically less pain than triamcinolone acetonide; thus, a dose with equivalent efficacy to triamcinolone acetonide 72 hours after treatment could not be determined. The reduction from baseline in pain intensity with canakinumab 150 mg was greater than with triamcinolone acetonide 24, 48, and 72 hours after treatment (differences of -11.5 mm [P = 0.04], -18.2 mm [P = 0.002], and -19.2 mm [P < 0.001], respectively), and 4, 5, and 7 days after treatment (all P < 0.05). Canakinumab significantly reduced the risk of recurrent flares versus triamcinolone acetonide (P ≤ 0.01 for all doses) (relative risk reduction 94% for canakinumab 150 mg versus triamcinolone acetonide). The overall incidence of adverse events was similar for canakinumab (41%) and triamcinolone acetonide (42%); most were mild or moderate in severity. CONCLUSION: Our findings indicate that canakinumab 150 mg provides rapid and sustained pain relief in patients with acute gouty arthritis, and significantly reduces the risk of recurrent flares compared with triamcinolone acetonide.

22 Article An unusual location of gouty panniculitis: A case report. 2017

Martin, David / Joliat, Gaëtan-Romain / Fournier, Pierre / Brunel, Christophe / Demartines, Nicolas / Gié, Olivier. ·aDepartment of Visceral Surgery bInstitute of Pathology, University Hospital CHUV, Lausanne, Switzerland. ·Medicine (Baltimore) · Pubmed #28422890.

ABSTRACT: RATIONALE: Gouty panniculitis, characterised by the deposition of monosodium urate crystals in subcutaneous tissue, is a rare clinical manifestation of gout. PATIENT CONCERNS: The case of a 67-year-old man is reported, who presented an erythematous nodule on the upper part of the right buttock suspicious for an abscess. This was in the context of chemotherapy for non-Hodgkin's lymphoma. DIAGNOSES: Histopathologic examination demonstrated gouty panniculitis. INTERVENTIONS: Because infection was suspected, an incision was performed. The lesion was found to be densely calcified and friable, without purulent discharge. Therefore, a surgical en-bloc resection was performed. OUTCOMES: The wound healed slowly initially due to a combination of malnutrition, chemotherapy and infection. A wound infection with Enterococcus faecium was treated with antibiotic therapy (carbapenem for seven days) and local therapy. At 6-week follow up the wound showed good granulation tissue and was healing well by secondary intention. The patient was instructed to continue anti-hyperuricaemic treatment. LESSONS SUBSECTIONS: In patients known to have long-standing hyperuricaemia and gout with nonspecific subcutaneous erythematous nodules, gouty panniculitis should be considered.

23 Article Treat-to-target (T2T) recommendations for gout. 2017

Kiltz, U / Smolen, J / Bardin, T / Cohen Solal, A / Dalbeth, N / Doherty, M / Engel, B / Flader, C / Kay, J / Matsuoka, M / Perez-Ruiz, F / da Rocha Castelar-Pinheiro, G / Saag, K / So, A / Vazquez Mellado, J / Weisman, M / Westhoff, T H / Yamanaka, H / Braun, J. ·Rheumazentrum Ruhrgebiet, and Ruhr University Bochum, Herne, Germany. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · Assisitance Publique Hôpitaux de Paris Rheumatology Department, Lariboisière Hospital, University Paris Diderot, Sorbonne Paris-Cité and INSERM, UMR 1132, Paris, France. · Research Medical Unit INSERM, Université Paris VII-Denis Diderot Assistance Publique-Hôpitaux de Paris, Service de Cardiologie, Hôpital Lariboisière, Paris, France. · University of Auckland and Auckland District Health Board, Auckland, New Zealand. · University of Nottingham, Nottingham, UK. · Medical Faculty, Institute of General Practice and Family Medicine, University Bonn, Bonn, Germany. · UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, Massachusetts, USA. · Carnegie Mellon University, Pittsburgh, Pennsylvania, USA. · Rheumatology Division, Hospital de Cruces, Baracaldo, Vizcaya, Spain. · Discipline of Rheumatology, Rio de Janeiro State University, Rio de Janeiro, Brazil. · University of Alabama at Birmingham, Birmingham, Alabama, USA. · Service de Rhumatologie, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. · Servicio de Reumatología, Hospital General de México, México City, México. · Division of Rheumatology, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, USA. · Medical Department I, Marien Hospital Herne, Ruhr-University of Bochum, Herne, Germany. · Tokyo Women's Medical University, Tokyo, Japan. ·Ann Rheum Dis · Pubmed #27658678.

ABSTRACT: OBJECTIVES: The treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout. METHODS: A committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived. RESULTS: Although no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance. CONCLUSIONS: This is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon.

24 Article Guidelines for the treatment of gout: a Swiss perspective. 2016

Wüthrich, Heloise / Alromaih, Fahad / So, Alexander. ·Service de Rhumatologie, CHUV, Lausanne, Switzerland. ·Swiss Med Wkly · Pubmed #27585109.

ABSTRACT: Gout is a common condition and its management is suboptimal. A number of guidelines on the management of gout have been published in the last decade by professional societies with the aim of informing the physician of the recommended therapeutic strategies and the treatment options. We have tried to synthesize the current recommendations and to highlight some challenges that still need to be resolved in clinical practice in Switzerland.

25 Article Replication of association of the apolipoprotein A1-C3-A4 gene cluster with the risk of gout. 2016

Rasheed, Humaira / Phipps-Green, Amanda J / Topless, Ruth / Smith, Malcolm D / Hill, Catherine / Lester, Susan / Rischmueller, Maureen / Janssen, Matthijs / Jansen, Timothy L / Joosten, Leo A / Radstake, Timothy R / Riches, Philip L / Tausche, Anne-Kathrin / Lioté, Frederic / So, Alexander / van Rij, Andre / Jones, Gregory T / McCormick, Sally P / Harrison, Andrew A / Stamp, Lisa K / Dalbeth, Nicola / Merriman, Tony R. ·Department of Biochemistry, University of Otago, Dunedin, New Zealand Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide. · Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, SA, Australia. · Department of Rheumatology, Rijnstate Hospital, Arnhem. · Department of IQ HealthCare, VieCuri Medical Centre, Venlo. · Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands. · Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Department of Rheumatology, University Clinic Carl-Gustav-Carus, Dresden, Germany. · INSERM, UMR-S 1132, Hospital Lariboisière University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris, F-75205, France. · DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé 05-5029, Lausanne, Switzerland. · Department of Surgery, University of Otago, Dunedin. · Department of Medicine, University of Otago, Wellington. · Department of Medicine, University of Otago, Christchurch. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Biochemistry, University of Otago, Dunedin, New Zealand tony.merriman@otago.ac.nz. ·Rheumatology (Oxford) · Pubmed #27094595.

ABSTRACT: OBJECTIVE: Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout. METHODS: We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C). RESULTS: In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10). CONCLUSION: Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.