Gout: Pascual E

Zhang W, Doherty M, Pascual E, Bardin T, Barskova V, Conaghan P, Gerster J, Jacobs J, Leeb B, Lioté F, McCarthy G, Netter P, Nuki G, Perez-Ruiz F, Pignone A, Pimentão J, Punzi L, Roddy E, Uhlig T, Zimmermann-Gòrska I, Anonymous00035. · Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Ann Rheum Dis. · Pubmed #16707533 No free full text.

Abstract: OBJECTIVE: To develop evidence based recommendations for the diagnosis of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert, representing 13 European countries. Ten key propositions regarding diagnosis were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Wherever possible the sensitivity, specificity, likelihood ratio (LR), and incremental cost-effectiveness ratio were calculated for diagnostic tests. Relative risk and odds ratios were estimated for risk factors and co-morbidities associated with gout. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 10 key propositions were generated though three Delphi rounds including diagnostic topics in clinical manifestations, urate crystal identification, biochemical tests, radiographs, and risk factors/co-morbidities. Urate crystal identification varies according to symptoms and observer skill but is very likely to be positive in symptomatic gout (LR = 567 (95% confidence interval (CI), 35.5 to 9053)). Classic podagra and presence of tophi have the highest clinical diagnostic value for gout (LR = 30.64 (95% CI, 20.51 to 45.77), and LR = 39.95 (21.06 to 75.79), respectively). Hyperuricaemia is a major risk factor for gout and may be a useful diagnostic marker when defined by the normal range of the local population (LR = 9.74 (7.45 to 12.72)), although some gouty patients may have normal serum uric acid concentrations at the time of investigation. Radiographs have little role in diagnosis, though in late or severe gout radiographic changes of asymmetrical swelling (LR = 4.13 (2.97 to 5.74)) and subcortical cysts without erosion (LR = 6.39 (3.00 to 13.57)) may be useful to differentiate chronic gout from other joint conditions. In addition, risk factors (sex, diuretics, purine-rich foods, alcohol, lead) and co-morbidities (cardiovascular diseases, hypertension, diabetes, obesity, and chronic renal failure) are associated with gout. SOR for each proposition varied according to both the research evidence and expert opinion. CONCLUSIONS: 10 key recommendations for diagnosis of gout were developed using a combination of research based evidence and expert consensus. The evidence for diagnostic tests, risk factors, and co-morbidities was evaluated and the strength of recommendation was provided.

Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan P, Gerster J, Jacobs J, Leeb B, Lioté F, McCarthy G, Netter P, Nuki G, Perez-Ruiz F, Pignone A, Pimentão J, Punzi L, Roddy E, Uhlig T, Zimmermann-Gòrska I, Anonymous00034. · Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Ann Rheum Dis. · Pubmed #16707532 No free full text.

Abstract: OBJECTIVE: To develop evidence based recommendations for the management of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert representing 13 European countries. Key propositions on management were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Where possible, effect size (ES), number needed to treat, relative risk, odds ratio, and incremental cost-effectiveness ratio were calculated. The quality of evidence was categorised according to the level of evidence. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 12 key propositions were generated after three Delphi rounds. Propositions included both non-pharmacological and pharmacological treatments and addressed symptomatic control of acute gout, urate lowering therapy (ULT), and prophylaxis of acute attacks. The importance of patient education, modification of adverse lifestyle (weight loss if obese; reduced alcohol consumption; low animal purine diet) and treatment of associated comorbidity and risk factors were emphasised. Recommended drugs for acute attacks were oral non-steroidal anti-inflammatory drugs (NSAIDs), oral colchicine (ES = 0.87 (95% confidence interval, 0.25 to 1.50)), or joint aspiration and injection of corticosteroid. ULT is indicated in patients with recurrent acute attacks, arthropathy, tophi, or radiographic changes of gout. Allopurinol was confirmed as effective long term ULT (ES = 1.39 (0.78 to 2.01)). If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors, allopurinol desensitisation, or a uricosuric. The uricosuric benzbromarone is more effective than allopurinol (ES = 1.50 (0.76 to 2.24)) and can be used in patients with mild to moderate renal insufficiency but may be hepatotoxic. When gout is associated with the use of diuretics, the diuretic should be stopped if possible. For prophylaxis against acute attacks, either colchicine 0.5-1 mg daily or an NSAID (with gastroprotection if indicated) are recommended. CONCLUSIONS: 12 key recommendations for management of gout were developed, using a combination of research based evidence and expert consensus. The evidence was evaluated and the SOR provided for each proposition.

Pascual E, Sivera F. · No affiliation provided · Ann Rheum Dis. · Pubmed #17881662 No free full text.

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Pascual E, Perdiguero M. · No affiliation provided · Ann Rheum Dis. · Pubmed #16837492 No free full text.

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Pascual E, Doherty M. · Professor M Doherty, Academic Rheumatology, Clinical Sciences Building, City Hospital, Nottingham, NG5 1PB, UK. · Ann Rheum Dis. · Pubmed #18385278 No free full text.

Abstract: Although joint aspiration is a basic clinical skill, aspiration of normal joints, or asymptomatic clinically quiescent joints, is only rarely undertaken. There are two main indications for this procedure. Firstly, for definitive diagnosis of crystal-associated arthritis (gout and pseudogout) during the intercritical period and for subsequent monitoring of treatment success of gout; and secondly, to obtain normal synovial fluid for biomarker research. The justification for these indications, the success rate and the technical aspects related to this procedure are presented in this article.

Pascual E, Sivera F. · Rheumatology Section, Hospital General Universitario de Alicante, Alicante, Spain. · Curr Opin Rheumatol. · Pubmed #17278926 No free full text.

Abstract: PURPOSE OF REVIEW: The purpose of this review is to highlight the recent developments in the management of gout. RECENT FINDINGS: Guidelines for the diagnosis and management of gout from EULAR, quality of care indicators, and outcome measures for clinical trials have been published. The standards of gout diagnosis and management are very low. Allopurinol remains the mainstay for serum uric acid lowering therapy. In an important percentage of patients receiving allopurinol, serum uric acid levels are insufficient to promote crystal dissolution. Febuxostat, a new serum uric acid lowering drug, has shown good results. Information on uricase continues to appear. For treatment of gouty inflammation, etoricoxib (a new cyclooxygenase 2 inhibitor) has been shown to be as effective as indomethacin. Finally, the association of gout with the metabolic syndrome and its comorbidities, and the newly described association of gout with myocardial infarction, bring lifestyle and dietary modifications to the front in the management of gout. SUMMARY: Proper gout management requires changes to the physician's attitude towards the disease; essentially: (1) an unequivocal diagnosis based in urate crystal identification, (2) a clearly settled aim of the treatment: crystal elimination from the joints and elsewhere, and (3) proper use of the available therapeutic alternatives. Promoting a proper lifestyle appears to be especially important.

Grassi W, Meenagh G, Pascual E, Filippucci E. · Cattedra di Reumatologia, Università Politecnica delle Marche, Ancona, Italy. · Semin Arthritis Rheum. · Pubmed #17011611 No free full text.

Abstract: OBJECTIVES: To date, high-resolution ultrasound (US) has not been fully exploited in the field of crystalline arthropathy. Both gout and calcium pyrophosphate deposition (CPPD) disease are significant diseases within the purview of the rheumatologist. The aim of this pictorial review was to present the principal findings in patients with crystal deposition in gout and CPPD. METHODS: US pictures were obtained from 60 consecutive patients, 34 with CPPD disease and 26 with gout, whose diagnosis was confirmed by synovial fluid analysis. The US examinations were performed using the following US systems: Diasus (Dynamic Imaging, Livingstone, UK) and Logiq 9 (General Electric Medical Systems, Milwaukee, WI). RESULTS: Pictorial evidence of the principal US findings in gout includes monosodium urate (MSU) deposition on the surface of articular cartilage, various patterns within synovial fluid ranging from completely anechoic fluid to collections filled with aggregates of variable shape and echogenicity, microdeposition within tendons, and tophus formation. In CPPD, the hallmark US features include crystal deposition within articular cartilage, calcification of fibrocartilage, together with focal crystal deposition within tendons. CONCLUSION: US is an impressive imaging modality in crystalline arthropathy. The anatomical location of the crystal deposits, clearly depictable by US, allows differentiation between MSU and CPPD aggregates.

Pascual E, Jovaní V. · Rheumatology Section, Hospital General Universitario de Alicante, Calle Maestro Alonso 109, Alicante 03010, Spain. · Best Pract Res Clin Rheumatol. · Pubmed #15939364 No free full text.

Abstract: Synovial fluid (SF) accumulates in the joint cavity in different conditions; this review outlines the data from those analyses that help in their differential and definitive diagnosis. The gross appearance of the fluid can provide a quick bedside orientation with regard to the amount of inflammation present in the joint: totally transparent SF originates in non-inflammatory conditions--of which osteoarthritis is the most common--and the amount of turbidity grossly relates to the amount of inflammation. Most turbid to purulent fluids usually come from infected joints, but exceptions are not uncommon. The white cell count offers quantitative information, but the boundaries between non-inflammatory and inflammatory SF and between this and septic fluid are very hazy and figures have to be interpreted in the clinical setting. Detection and identification of monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals allow a precise diagnosis of gout and CPPD crystal-related arthropathy. Only one in five CPPD crystals have sufficient birefringence for easy detection and they are easily missed if searched for only using a polarised microscope. Instructions for beginners are given. Proper microbiological studies of the SF is the key to the diagnosis of infectious conditions.

Pascual E, Pedraz T. · Sección de Reumatología, Hospital General Universitario de Alicante, Maestro Alonso 109, 03010 Alicante, Spain. · Curr Opin Rheumatol. · Pubmed #15103259 No free full text.

Abstract: PURPOSE OF THE REVIEW: We have reviewed the latest publications on epidemiology of gout; also there have been new insights into the regulation of the inflammation resulting from the regular interaction occurring between MSU crystals and cells in both asymptomatic and symptomatic gouty joints. Finally we review different publications of clinical interest. RECENT FINDINGS: The incidence of gout has been found to be increasing, and the disease starts at an earlier age; this likely relates to changes in dietary habits that lead to the development of the insulin resistance syndrome to which hyperuricemia, and thus gout, relates. Dietary modifications to correct the insulin resistance syndrome and reduce uricemia by increasing renal clearance of urate have heath consequences that go far beyond their beneficial effect on gout. Monosodium urate crystals and cells interact in the asymptomatic joints of gouty patients. The mechanisms that trigger a gouty attack with this background and those responsible for the self-limitation of gouty attacks are not understood. The degree of maturation of the monocytes-macrophages present in the fluid appears to modulate the consequences of the crystal-cell interaction and gives a hint of how from the crystal-cell interaction may result in such divergent consequences as intense inflammation or the absence of symptoms. Interest in gout treatment continues, as shown by the number of papers on the subject reviewed. In most cases, gout is an easy disease to treat, but we do not have enough information about how to handle those few patients with "difficult" disease, and what we refer colloquially to as difficult gout has not been properly defined yet. SUMMARY: Gout incidence and severity appear to be increasing likely in relation to dietary habits. Switching the pattern of secretion of inflammatory mediators with maturating macrophages which contain MSU crystals may be the key to self limitation of gouty attacks. We must define better which gout is a "difficult" one.

Pascual E. · Hospital General Universitario de Alicante, Spain. · Curr Opin Rheumatol. · Pubmed #10803751 No free full text.

Abstract: Reviews and opinion articles stressing the need for better reproducibility of crystal identification in synovial fluid continue to be published. The possibility of definitive diagnosis of gout by crystal identification during intercritical periods appears now established. The problems associated with the use of allopurinol have also received some attention, as well as the strategies of dealing with allopurinol hypersensitivity. Gout in transplanted patients is reviewed, with special attention to the difficulties related to its treatment; various therapeutic options for this group are reviewed. The use of benzbromarone to reduce uricemia appears to be especially appropriate for this group of patients, in whom allopurinol is problematic. Finally, the pathogenetic mechanisms of the disease, and the relation between urate crystals and inflammation are reviewed.

Fernández C, Noguera R, González JA, Pascual E. · No affiliation provided · J Rheumatol. · Pubmed #10529162 No free full text.

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Sivera F, Aragon R, Pascual E. · Rheumatology Unit, Hospital General Universitario de Alicante, Universidad Miguel Hernándes, Spain. · Ann Rheum Dis. · Pubmed #17557892 No free full text.

Abstract: OBJECTIVES: To asses the clinical feasibility of aspirating symptomatic and asymptomatic first metatarsophalangeal (MTP) joints with a 29-gauge needle in order to obtain a synovial fluid (SF) sample. METHODS: All consecutive aspirations of first MTP joints performed within our department were prospectively recorded. The procedure was considered successful if SF volume was enough to perform a crystal search. Crystals were identified using a polarised light microscope (magnification x400) with a first order red compensator. Pain was recorded on a 10-cm visual analogue scale (VAS). RESULTS: Aspirations were attempted in 33 first MTP joints in 31 patients. SF was drawn from 30 of the joints (91%), with little difference between asymptomatic (89%) and inflamed joints (93%). The technique was well tolerated (mean VAS 1.74). Urate monosodium crystals were identified in 22 samples (73%) and another sample contained calcium pyrophosphate dihydrate crystals. CONCLUSIONS: A 29-gauge needle allows easy aspiration of the first MTP joint with only modest discomfort for the patients, and generally yields a SF sample of sufficient volume for crystal detection and identification.

Pascual E, Sivera F. · Catedrático de Medicina (Reumatología), Hospital General Universitario de Alicante, Maestro Alonso 109, 03010 Alicante, Spain. · Ann Rheum Dis. · Pubmed #17223663 No free full text.

Abstract: OBJECTIVES: To determine whether hypouricaemic treatment results in the disappearance of urate crystals from gouty joints and to define the time required. METHODS: In 18 patients with monosodium urate (MSU) crystal proven gout, and after the initiation of successful serum uric acid (SUA)-lowering treatment, an arthrocentesis of the asymptomatic signal joint (11 knees, 7 first metatarsophalangeal joints) was performed every 3 months to obtain a synovial fluid (SF) sample. The sample was then analysed for the presence of MSU crystals, and the number of crystals/400x field was noted. SUA levels and the duration of gout were also noted. RESULTS: MSU crystals disappeared from the SF of all 18 joints after reduction of SUA to normal levels. The time required for disappearance ranged from 3 to 33 months; disappearance time correlated with the duration of gout (r(s) = 0.71; p<0.01). The median number of MSU crystals in the SF samples before urate-lowering treatment was 7.5 (2.5-11) crystals/400x field, reducing to 3 (1-6.5) crystals/400x field (p<0.05) at 3 months. Crystal counts continued to decrease after 3 months. CONCLUSIONS: In gout, reduction of SUA to normal levels results in disappearance of urate crystals from SF, requiring a longer time in those patients with gout of longer duration. This indicates that urate crystal deposition in joints is reversible. Normalisation of SUA levels results in a decrease in the concentration of MSU crystals in SF in the asymptomatic gouty joints. This may partially explain the reduced frequency of gouty attacks when a patient has been treated with SUA-lowering drugs.

Oliviero F, Pascual E, Punzi L. · Cattedra e Unità Operativa Complessa di Reumatologia, Università di Padova, Via Giustiniani, 2 - 35128 Padova. · Reumatismo. · Pubmed #16258607 links to  free full text

Abstract: Synovial fluid analysis for crystals represents one of the most important laboratory test for the evaluation of rheumatic diseases. The identification of monosodium urate and calcium pyrophosphate dihydrate crystals allows the prompt diagnosis of gout and pyrophosphate crystal-related arthropaties. Crystals are identified based on their shape and birefringence through a polarized light microscope equipped with a first order red compensator. Due to its simple execution and high diagnostic value, this examine should be always performed to complete synovial fluid analysis.

Lumbreras B, Pascual E, Frasquet J, González-Salinas J, Rodríguez E, Hernández-Aguado I. · Department of Clinical Analysis, Hospital General Universitario de Alicante, Spain. · Ann Rheum Dis. · Pubmed #15769916 links to  free full text

Abstract: BACKGROUND: Identification of monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPPD) crystals in synovial fluid samples is diagnostic of gout and CPPD crystal related arthropathy. Various studies have shown poor consistency in results of crystal analysis. OBJECTIVE: To determine whether training of the analysts increases the consistency. METHODS: An expert rheumatologist gave a course on crystal detection and identification. The four trained observers then blindly and independently examined synovial fluid samples previously classified by the expert which had been obtained from patients with both crystal arthropathies and other non-crystal related inflammatory joint conditions. RESULTS: 194 observations were made on 64 synovial fluid samples: 96 without crystals (49.4%), 55 with CPPD crystal (28.4%), and 43 with MSU crystals (22.2%). For crystal detection (presence or absence of crystals), sensitivity was 95.9% and specificity 86.5%. For identification of MSU crystals, sensitivity was 95.3% and specificity 97.2%. For identification of CPPD crystals, sensitivity was 92.7% and specificity 92.1%. The kappa index of agreement with the reference standard between the observers was 0.84 for any crystal detection, 0.93 for MSU crystal sample identification, and 0.79 for CPPD crystal sample identification. CONCLUSIONS: For trained observers, the detection and identification of crystals in synovial fluid is a consistent procedure.

Pascual E, Batlle-Gualda E, Martínez A, Rosas J, Vela P. · Hospital General Universitario de Alicante, Spain. · Ann Intern Med. · Pubmed #10577299 links to  free full text

Abstract: BACKGROUND: The diagnosis of gout in the intercritical phase can be difficult. OBJECTIVE: To determine whether synovial fluid analysis allows the diagnosis of intercritical gout. DESIGN: Cross-sectional study. SETTING: Outpatient rheumatology clinics. PATIENTS: 101 patients with gout. INTERVENTION: Arthrocentesis of 80 knees and 21 first metatarsophalangeal joints (each joint from a different patient) that had been inflamed but were currently asymptomatic. MEASUREMENTS: Frequency with which arthrocentesis yielded synovial fluid; presence of monosodium urate crystals in the synovial fluid sample; and, for synovial fluid with crystals, the number of microscope fields that had to be scanned before crystals were found. RESULTS: Synovial fluid was obtained from 91 of 101 joints. The fluid from all 43 patients not receiving hypouricemic agents contained monosodium urate crystals. These crystals were found in the synovial fluid of only 34 of 48 patients receiving hypouricemic agents. In 90% of the synovial fluid samples that contained crystals, crystals were seen in the first five microscope fields examined. CONCLUSIONS: Arthrocentesis of asymptomatic knees and first metatarsophalangeal joints and synovial fluid analysis are simple procedures that facilitate the diagnosis of gout during intercritical periods.

Ivorra J, Rosas J, Pascual E. · Sección de Reumatología, Hospital General Universitario de Alicante, and Universidad Miguel Hernández, Alicante, Spain. · Ann Rheum Dis. · Pubmed #10460193 links to  free full text

Abstract: OBJECTIVE: To determine the proportion of calcium pyrophosphate dihydrate (CPPD) crystals that appear as non-birefringent when observed under the polarised light microscope. METHODS: Two observers examined independently 10 synovial fluid samples obtained during an episode of arthritis attributable to CPPD crystals. Ten synovial fluid samples from patients with acute gout were used as a reference. The examination was performed after placing a fluid sample in a Niebauer haemocytometric chamber; a crystal count was done first under ordinary light, then in the area corresponding to a 0.1 ml, under polarised light RESULTS: The percentages of birefringence appreciated for CPPD were 18% (confidence intervals (CI) 12, 24) for observer 1, and 17% (CI 10, 24) for observer 2 (difference NS). The percentages of birefringence for monosodium urate were 127% (CI 103, 151) for observer 1 and 107% (CI 100, 114) for observer 2 (difference NS). Percentages above 100% indicate that crystals missed under ordinary light became apparent under polarised light. CONCLUSION: Only about one fifth of all CPPD crystals identified by bright field microscopy show birefringence when the same synovial fluid sample is observed under polarised light. If a search for CPPD crystals is conducted under polarised light, the majority of the crystals will be missed. Ordinary light allows a better rate of CPPD crystal detection but observation under polarised light of crystals showing birefringence is required for definitive CPPD crystal identification.

Pascual E, Sivera F, Yasothan U, Kirkpatrick P. · No affiliation provided · Nat Rev Drug Discov. · Pubmed #19247302 No free full text.

Abstract: In May 2008, febuxostat (Adenuric; Ipsen), an inhibitor of xanthine oxidase, was granted marketing authorization by the European Commission for the treatment of chronic hyperuricaemia in conditions in which urate deposition has occurred, such as gouty arthritis.

Doherty M, Bardin T, Pascual E. · No affiliation provided · Ann Rheum Dis. · Pubmed #17998219 No free full text.

This publication has no abstract.