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Gout: HELP
Articles from Basel
Based on 52 articles published since 2008
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These are the 52 published articles about Gout that originated from Basel during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
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 [Uric acid, kidney disease and nephrolithiasis]. 2016

Kim, Min Jeong / Hopfer, Helmut / Mayr, Michael. ·1 Klinik für Ambulante Innere Medizin und Medizinische Poliklinik, Universitätsspital Basel. ·Ther Umsch · Pubmed #27008449.

ABSTRACT: Different types of kidney disease are known to be associated with hyperuricemia. The underlying pathophysiologic mechanisms strongly vary, and different ways of therapeutic approach are therefore required. In tumor lysis syndrome, a rapid, excessive increase of serum uric acid level can cause an acute renal failure. For chronic urate nephropathy, on the other hand, constantly elevated serum uric acid level for a longer period seems to be important. Being still controversial as a disease entity however, the aetiology for putative chronic urate nephropathy might be in fact chronic lead intoxication, as suggested by quite an amount of association data. In terms of uric acid nephrolithiasis, the major risk factor is a urinary acidification defect with persistently acidic urine pH, and not necessarily hyperuricemia or hyperuricosuria. Evidence suggests that metabolic diseases with increased insulin resistance are strongly associated with urinary acidification defect. Patients with uric acid kidney stones should therefore be thoroughly evaluated for such metabolic diseases and in a positive case adequately treated.

8 Review [Nutritional therapy of gout]. 2016

Nickolai, Beate / Kiss, Caroline. ·1 Ernährungsberatung, Universitätsspital Basel. ·Ther Umsch · Pubmed #27008448.

ABSTRACT: Nutrition and nutritional behaviours have been found to play a major role in the development of gout. Studies show that body mass index (BMI), as well as excessive intake of alcoholic beverages, meat, soft drinks and fruit juices increase the risk of developing gout. Similarly, dairy products and coffee have been seen to decrease the risk of hyperuricemia and gout, as they increase the excretion of uric acid. Flares of gout are often caused by large meals and high alcohol consumption. Each additional intake of meat portion per day increases the risk of gout by 21 %. Taking total alcohol consumption into account, the risk of gout increases after one to two standard drinks. In contrast to previous assumptions purine-rich plant foods like legumes and vegetables do not increase the risk of gout. The current dietary guidelines take into account nutritional factors, which not only consider purine intake, but also their endogenous production and their influence on renal excretion. A balanced diet based on the Swiss healthy eating guideline pyramid as well as the Mediterranean diet is appropriate for this patient population. The treatment of gout is multi-faceted, since this patient population presents other comorbidities such as obesity, diabetes mellitus, dyslipidemia and hypertension. Collectively, these risk factors are diet dependent and require a treatment strategy that is centered on modifying one's nutrition and nutritional behaviours. The aim of such therapy is to educate the patient as well as treat the accompanying comorbidities with the goal of decreasing serum uric acid values. Motivated patients require consultation and follow-up care in order to be able to actively decrease the serum uric acid.

9 Review [Causes, mechanisms and possible therapeutic targets of gout]. 2016

Manigold, Tobias. ·1 Abteilung für Rheumatologie, Universitätsspital Basel. ·Ther Umsch · Pubmed #27008447.

ABSTRACT: Gout is the most frequent arthritis worldwide with increasing prevalence in industrialized countries and massive socioeconomic consequences. The knowledge regarding the pathomechanisms which lead to arthritis has substantially increased during the last decade. Consistently, new therapeutic approaches and substances appear at the horizon. This review covers aspects of clinical presentation, diagnosis and current treatment. The pathomechanisms leading to NLRP3 inflammasome activation and IL-1beta secretion are reviewed in detail. Finally, selected new therapeutic targets and substances are discussed.

10 Review [Hyperuricemia, gout and cardiovascular diseases]. 2016

Murray, Karsten / Burkard, Thilo. ·1 Abteilung für Kardiologie, Universitätsspital Basel. · 2 Klinik für Ambulante Innere Medizin und Medizinische Poliklinik, Universitätsspital Basel. ·Ther Umsch · Pubmed #27008446.

ABSTRACT: Hyperuricemia, gout as well as arterial hypertension and metabolic syndrom are highly prevalent and clinicians are frequently confronted with both conditions in the same patient. Hyperuricemia and gout are associated with cardiovascular comorbidities and a high cardiovascular risk. Despite coherent pathophysiological concepts, it remains to be determined, if this association is independent and causal. In daily clinical practice, cardiovascular risk factors should be thoroughly identified and consequently treated in all patients with hyperuricemia and gout. If preventive treatment of asymptomatic hyperuricemia with urate-lowering agents may improve cardiovascular risk and outcomes remains to be determined and is recommended only in special situations like young patients with severe hyperuricemia.

11 Review [Histopathophysiology of Gout]. 2016

Hügle, Thomas / Krenn, Veit. ·1 Abteilung Rheumatologie, Universitätsspital Basel. · 2 MVZ-Zentrum für Histologie, Zytologie und Molekulare Diagnostik, Trier, Deutschland. ·Ther Umsch · Pubmed #27008445.

ABSTRACT: Despite being a frequent cause of arthritis and bone erosions, the underlying cellular and subcellular reaction in gout is insufficiently understood. The inflammasome as intracellular sensor for crystals plays an important role, notably resulting in interleukin (IL)-1 production. Morphologically, hyperplasia of the synovial membrane with joint effusion, along with fibrinogen deposition and influx of neutrophils and lymphocytes are observed. Extracellular NET formation by neutrophils is involved in the regulation of inflammatory tissue reaction. Furthermore, the release of IL-10 and tumor necrosis factor (TNF)-receptors along with lymphocyte proliferation induce the natural resolution of acute gouty arthritis which typically occurs after several days. In contrast to acute gout, tophi consisting of urate crystals are surrounded by histiocytes and multinucleated cells, resembling a foreign body reaction. The deposition of extracellular matrix by fibrocytes is usually observed around tophi. This fibrotic reaction is likely enhanced by Th2-lymphocytes. Bone erosions in gout occur around tophi and are triggered by osteoclast activation through RANK-ligand expression by lymphocytes. In conclusion, understanding the orchestration of inflammation in gout might help to identify new therapeutic targets.

12 Review [Imaging findings of cristal deposit disorders]. 2016

Hirschmann, Anna / Studler, Ueli. ·1 Klinik für Radiologie und Nuklearmedizin, Universitätsspital Basel. · 2 Röntgeninstitut Imamed Radiologie Nordwest. ·Ther Umsch · Pubmed #27008444.

ABSTRACT: Cristal deposit disorders are characterised by cristal deposits in hyaline and fibrocartilage, in synovium, capsule, ligaments and tendons and periarticular soft tissue. Calciumpyrophosphatedihydrate (CPPD), hydroxyapatite (calcific tendinitis) and uric acid arthropathies are the most common cristal deposit diseases. Radiography is still the number one image modality for initial imaging and the identification of cristal-induced inflammatory arthropathies. Differentiation between the entities of cristal deposit arthropathies can be challenging. Clincial and radiological findings may overlap in different cristal deposit arthropathies, owing a certain diagnosis difficult.

13 Review [Current epidemiology of gout]. 2016

Ankli, Barbara. ·1 Klinik für Rheumatologie, Universitätsspital Basel. · 2 Klinik für Rheumatologie, Bethesda-Spital Basel. ·Ther Umsch · Pubmed #27008443.

ABSTRACT: Gout is the most common inflammatory arthritis in adults nowadays. Prevalence has risen over the last decades. Patients over 65 years are disproportionally affected. A male/female ratio of 4:1 is diminishing after menopause (still 3:1). The relative risk of developing gout increases in a linear progression with the serum uric acid level. Other risk factors beside hyperuricemia are genetic predisposition, age, male gender, adipositas, lifestyle modification, chronic kidney disease and intake of diuretics. Many gout patients suffer from comorbidities. The metabolic syndrome is associated with gout. Two fifths of patients with gout had also chronic kidney disease. Reasons for the rise in prevalence are longevity, dietary habits and the high prevalence of patients with chronic kidney disease in the general population.

14 Review [Gout management: an update]. 2016

Ankli, Barbara / Krähenbühl, Stephan. ·1 Klinik für Rheumatologie, Universitätsspital Basel. · 2 Klinik für Rheumatologie, Bethesda-Spital Basel. · 3 Klinik für Pharmakologie, Universitätsspital Basel. ·Ther Umsch · Pubmed #27008442.

ABSTRACT: Gout is the most frequent arthritis worldwide. Despite progress in therapeutic options the majority of gout patients are still insufficiently treated. International guidelines (ACR, EULAR, 3e initiative) clearly specify treatment targets: keep the patient flare-free and maintain a low urate serum level (< 360 µmol/l). The treat to target strategy includes therapy of flares, urate lowering treatment (ULT) and prophylaxis of flares. Evolution of gout guidelines over several years shows a broader indication for ULT, mandatory prophylaxis of flares during the initiation of ULT over several months and an earlier start of ULT in patients with flares as soon as symptoms have diminished. Colchicine is the preferred specific flare treatment, Caution has to be taken especially in patients with kidney disease, patients with hepatic dysfunction or in patients with interacting comedication. Low dose oral colchicine is nowadays the standard flare treatment. NSAIDs and prednisone are valuable alternatives. Interleukin-1 blockers offer a quick resolution of flares and may be an option in patients with chronic gout and severe kidney disease. Xanthinoxidase inhibitors (XOI) are the mainstay of ULT, with allopurinol still being the preferred XOI. The recently approved XOI febuxostat is eliminated mostly by the liver and can induce a faster lowering of urate. Uricosuric drugs such as probenecid are recommended in patients with sufficient renal function in whom the treatment goals cannot be reached with XOI. In Switzerland, only the two gout-lowering drugs allopurinol and probenecid are available, which reduces the therapeutic possibilities. Treatment success is often hampered by malcompliance. Recent guidelines stress the importance of patient education to ameliorate compliance. Comorbidities such as metabolic syndrome, cardiovascular and kidney disease are often found in gout patients. Patients with severe kidney disease are the most difficult to treat: the choice of antiinflammatory treatment is narrowed, ULT has to be uptitrated very carefully and patients often suffer from repeated flares. Another factor associated with treatment failure is the low physician’s adherence towards the guidelines. Therapeutic failure can lead to chronic and refractory gout (polyarticular gout, uncontrolled flare activity, chronic synovitis, destructive tophi) which makes the further management very difficult. Most gout patients are treated in primary care settings. Patients with chronic gout or at high risk for development of chronic gout (in particular patients with severe kidney disease or patients transplanted) should be additionally treated by a rheumatologist.

15 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.

16 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.

17 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.

18 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.

19 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.

20 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.

21 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").

22 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.

23 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.

24 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.

25 Clinical Trial Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis. 2013

Chakraborty, Abhijit / Van, Linh M / Skerjanec, Andrej / Floch, David / Klein, Ulf R / Krammer, Gerhard / Sunkara, Gangadhar / Howard, Dan. ·Clinical Pharmacology, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. ·J Clin Pharmacol · Pubmed #24122883.

ABSTRACT: Pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1β monoclonal antibody, canakinumab, in gouty arthritis patients from three studies are reported. Canakinumab has low serum clearance (0.214 L/day), low steady-state volume of distribution (7.44 L), a 25.8-day half-life, and approximately 60% subcutaneous absolute bioavailability in a typical 93-kg patient. Creatinine clearance had a small positive impact on serum canakinumab clearance that is not likely to be clinically relevant. Binding to circulating IL-1β was demonstrated by increases in total serum IL-1β following canakinumab dosing. Total IL-1β kinetics and canakinumab pharmacokinetics were characterized by a population-based pharmacokinetic-binding model, where the estimated apparent in vivo dissociation constant (signifying binding affinity of canakinumab to circulating IL-1β) was 0.99 nmol/L in gouty arthritis patients. Canakinumab treatment provided rapid, sustained decreases in C-reactive protein and serum amyloid A, provided superior pain relief to triamcinolone acetonide, and increased time to first recurrent attack (P ≤ 0.01 favoring all canakinumab doses vs. triamcinolone acetonide).

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