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OBJECTIVE: Determine the proportion of patients achieving target serum urate (SU), defined as < 6 mg/dl for patients with non-severe gout and < 5 mg/dl for patients with severe gout, as well as the proportion of patients achieving remission after 5 years of followup. METHODS: Patients from the Gout Study Group (GRESGO) cohort were evaluated at 6-month intervals. Demographic and clinical data were obtained at baseline. Visits included assessments of serum urate, flares, tophus burden, health-related quality of life using the EQ-5D, activity limitations using the Health Assessment Questionnaire adapted for gout, and pain level and patient's global assessment using visual analog scales. Treatment for gout and associated diseases was prescribed according to guidelines and available drugs. RESULTS: Of 500 patients studied, 221 had severe gout (44%) and 279 had non-severe gout (56%) at baseline. No significant differences were observed across the study in percentages of severe gout versus non-severe gout patients achieving SU 6 mg/dl or 5 mg/dl. The highest proportion of patients achieving target SU (50-70%) and remission (39%) were found after 3-4 years of followup. In the fifth year, these proportions decreased and 28% of the patients were in remission, but only 40 patients remained in the study. None of the patients with severe gout achieved remission. CONCLUSION: In patients with severe gout, target SU was hard to achieve and remission was not possible. The main obstacles for target SU and gout remission include poor medication adherence, persistent tophi, and loss to followup.
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Supressores da Gota/uso terapêutico , Gota/sangue , Gota/tratamento farmacológico , Índice de Gravidade de Doença , Ácido Úrico/sangue , Adulto , Feminino , Seguimentos , Gota/epidemiologia , Inquéritos Epidemiológicos , Humanos , Estudos Longitudinais , Masculino , Adesão à Medicação , México/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Indução de Remissão , Resultado do Tratamento , Escala Visual Analógica , Adulto JovemRESUMO
OMERACT proposed a set of mandatory and discretionary domains to evaluate the effect of treatment in patients with gout. To determine the percentage of improvement and the effect size 6 and 12 months after starting a proper treatment in patients with gout from our cohort (GRESGO) based on the OMERACT proposal for chronic gout. GRESGO is a cohort of consecutive, new patients with gout attending either of two dedicated clinics. This report includes 141 patients evaluated at baseline and 6 months plus 101 of them completing a 12-month follow-up in 2012. Clinical data including the OMERACT domains for chronic gout were collected at baseline and every 6 months. Treatment was prescribed by their attending physician with the purpose of getting < 6 mg/dL of seric uric acid (sUA). Most patients were males (96%) with inappropriate treatment (95%); 66% had tophi, 30% metabolic syndrome, and 32% low renal function. Mean dose of allopurinol at baseline and throughout the study went from 344 ± 168 mg/day to 453 ± 198 at 12 months. Most OMERACT domains and renal function improved significantly; 73% improved > 20% from 6 to 12 months. Greater improvement was observed in the domains: flares, index tophus size, pain, general health assessment, and HAQ score, all of them associated to lower sUA values. Chronic gout patients improve significantly in most OMERACT domains when conventional and regular treatment is indicated. sUA < 6 mg/dL is associated with greater improvement.
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Gota/tratamento farmacológico , Rim/efeitos dos fármacos , Adulto , Alopurinol/administração & dosagem , Feminino , Seguimentos , Gota/sangue , Gota/fisiopatologia , Supressores da Gota/administração & dosagem , Humanos , Rim/fisiopatologia , Masculino , México , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Ácido Úrico/sangueRESUMO
OBJECTIVE: To assess potential associations among serum cytokines and microRNA (miR) levels with ultrasound (US) findings suggestive of urate deposits in chronic asymptomatic hyperuricemia and gout. METHODS: All participants underwent musculoskeletal US and measurements of serum interleukin-1ß (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, interferon-γ, tumor necrosis factor, monocyte chemoattractant protein 1, and epithelial neutrophil-activating peptide 78, as well as miR-146a, miR-155, and miR-223 levels. RESULTS: Thirty individuals with asymptomatic hyperuricemia, 31 normouricemic controls, and 30 patients with gout were included. The frequency of synovitis and double contour sign using US was similar between asymptomatic hyperuricemia (67% and 27%, respectively) and patients with gout (77% and 27%, respectively), and each had a higher frequency than controls (45% and 0%, respectively). Serum IL-6 and IL-8 levels were similar between patients with asymptomatic hyperuricemia (mean ± SD 69.7 ± 73.4 and 18.5 ± 25.6 pg/ml, respectively) and gout (mean ± SD 75.8 ± 47.6 and 24.4 ± 31.7 pg/ml, respectively), and higher than controls (mean ± SD 28.2 ± 17.6 and 7.4 ± 6.0 pg/ml, respectively). A similar distribution was observed for miR-155 levels in asymptomatic hyperuricemia, patients with gout, and controls (mean ± SD 0.22 ± 0.18, 0.20 ± 0.14, and 0.08 ± 0.04, respectively). Associations between morphostructural abnormalities suggestive of urate deposits (regardless of clinical diagnosis) and serum markers were assessed. Subjects with urate deposits had higher IL-6 (257.2 versus 47.0 pg/ml; P = 0.005), IL-8 (73.2 versus 12.0 pg/ml; P = 0.026), and miR-155 (0.21 versus 0.16; P = 0.015) levels than those without deposition findings. CONCLUSION: In individuals with chronic asymptomatic hyperuricemia, the presence of synovitis and double contour sign by US may represent a subclinical manifestation of monosodium urate crystal nucleation, capable of triggering inflammatory pathways (IL-6 and IL-8) and mechanisms of intercellular communication (miR-155), similar to what is observed in patients with gout.
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MicroRNA Circulante/sangue , Citocinas/sangue , Gota/sangue , Gota/diagnóstico por imagem , Hiperuricemia/sangue , Hiperuricemia/diagnóstico por imagem , Articulações/diagnóstico por imagem , Ultrassonografia Doppler , Adulto , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Crônica , Estudos Transversais , Cristalização , Feminino , Gota/etiologia , Humanos , Hiperuricemia/complicações , Hiperuricemia/diagnóstico , Articulações/química , Masculino , México , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sinovite/sangue , Sinovite/diagnóstico por imagem , Sinovite/etiologia , Ácido Úrico/análiseAssuntos
Humanos , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Ácido Úrico/sangue , Literatura de Revisão como Assunto , Anti-Inflamatórios não Esteroides/uso terapêutico , Educação de Pacientes como Assunto , Técnica Delphi , Interleucina-1/antagonistas & inibidores , Guias de Prática Clínica como Assunto , Corticosteroides/uso terapêutico , Medicina Baseada em Evidências , Aconselhamento Diretivo , Exacerbação dos Sintomas , Revisões Sistemáticas como Assunto , Gota/sangue , Gota/terapia , Estilo de VidaRESUMO
ABSTRACT Gout is considered the most common form of inflammatory arthritis in men over 40 years. The authors present a brief review of the current treatment of gout and discuss the existing pharmacological limitations in Brazil for the treatment of this disease. Although allopurinol is still the main drug administered for decreasing serum levels of uric acid in gout patients in this country, the authors also present data that show a great opportunity for the Brazilian drug market for the treatment of hyperuricemia and gout and especially for patients using private and public (SUS) health care systems.
RESUMO A gota é considerada a forma mais comum de artrite inflamatória em homens acima de 40 anos. Os autores apresentam uma breve revisão sobre o tratamento atual da gota e discutem as limitações farmacológicas existentes no Brasil para o tratamento dessa enfermidade. Apesar de o alopurinol ainda ser a principal medicação para a redução dos níveis de uricemia de pacientes com gota no país, os autores também apresentam dados que apontam para uma grande oportunidade para o mercado farmacológico brasileiro em relação ao tratamento da hiperuricemia e da artrite gotosa e especialmente para pacientes usuários de sistemas privados de saúde e do SUS (Sistema Único de Saúde).
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Humanos , Ácido Úrico/sangue , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Gota/tratamento farmacológico , Brasil/epidemiologia , Incidência , Aprovação de Drogas , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Gota/sangue , Gota/epidemiologiaRESUMO
Gout is considered the most common form of inflammatory arthritis in men over 40 years. The authors present a brief review of the current treatment of gout and discuss the existing pharmacological limitations in Brazil for the treatment of this disease. Although allopurinol is still the main drug administered for decreasing serum levels of uric acid in gout patients in this country, the authors also present data that show a great opportunity for the Brazilian drug market for the treatment of hyperuricemia and gout and especially for patients using private and public (SUS) health care systems.
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Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Hiperuricemia/tratamento farmacológico , Ácido Úrico/sangue , Brasil/epidemiologia , Aprovação de Drogas , Gota/sangue , Gota/epidemiologia , Humanos , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , IncidênciaRESUMO
Gout is the most common form of inflammatory arthritis affecting men, and current evidence suggests that genetic factors contribute to its progression. As a previous study identified that WD40 repeat protein 1 (WDR1) is associated with gout in populations of European descent, we sought to investigate its relationship with this disease in the Han Chinese population. We genotyped six WDR1 single nucleotide polymorphisms in 143 gout cases and 310 controls using Sequenom MassARRAY technology. The SPSS 16.0 software was used to perform statistical analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression, with adjustments for age and gender. In an analysis using an allelic model, we identified that the minor alleles of rs3756230 (OR = 0.64, 95%CI = 0.450-0.911, P = 0.013) and rs12498927 (OR = 1.377, 95%CI = 1.037-1.831, P = 0.027) were associated with gout risk. In addition, we found that the "A/A" genotype of rs12498927 was associated with increased risk of gout under codominant (OR = 2.22, 95%CI = 1.12- 4.40, P = 0.042) and recessive models (OR = 2.24, 95%CI = 1.20-4.17, P = 0.012). We also determined the "A/G" genotype of rs12498927 to be significantly associated with higher urea levels in gout patients (P = 0.017). Our data shed new light on the association between genetic variations in the WDR1 gene and gout susceptibility in the Han Chinese population.
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Gota/genética , Proteínas dos Microfilamentos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , China , Feminino , Gota/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Ureia/sangueRESUMO
INTRODUCTION: Gout is considered to be an autoinflammatory disease and the presence of monosodium urate (MSU) crystals stimulates activation of NPRL3 inflammasome and subsequently caspase-1, generating production of active IL-1ß and IL-18. However, the association between serum cytokines levels and clinical manifestations of the disease is not yet well understood. We evaluated the serum profile of proinflammatory cytokines (IL-1ß, IL-6, IL-8, IL-17A, IL-18, IL-22, and IL-23) and described their relationship with clinical and laboratory data. METHODOLOGY: Thirty-nine male patients with gout (GG) were assessed for clinical and laboratory variables and cytokine levels were measured by ELISA. For the purposes of comparison, 34 males with no previous history of arthritis were also included in the study (CG). RESULTS: Seventeen participants (43%) exhibited active arthritis on evaluation. Levels of IL-18 were significantly higher in patients in relation to the CG (p = 0.0013). No statistically significant differences were found between the GG and CG for the other measured cytokines. There was a moderate correlation between IL-18 and ESR (R = 0.43, p = 0.0073), CRP (R = 0.47, p = 0.0025), and serum levels of IL-6 (R = 0.36, p = 0.023). An association was observed between serum levels of IL-6 and the presence of tophi (p = 0.005) and deformities (p = 0.0008), as well as a correlation between this cytokine and ESR (R = 0.41, p = 0.011) and CRP (R = 0.48, p = 0.02). CONCLUSIONS: IL-18 is associated with inflammatory activity in gout, as well as with IL-6 levels, while IL-6 is associated with clinical and laboratory activity, the presence of tophi and articular deformities, and may be a prognostic marker of this pathology.
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Gota/sangue , Interleucina-18/sangue , Interleucina-6/sangue , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Estudos de Casos e Controles , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Previous studies have shown that the PDK2 and ABCG2 genes play important roles in many aspects of gout development in European populations. However, a detailed genotype-phenotype analysis was not performed. The aim of the present study was to investigate the potential association between variants in these two genes and metabolism-related quantitative phenotypes relevant to gout in a Chinese Tibetan population. In total, 316 Chinese Tibetan gout patients were recruited from rheumatology outpatient clinics and 6 single nucleotide polymorphisms in PDK2 and ABCG2 were genotyped, which were possible etiologic variants as identified in the HapMap Chinese Han Beijing population. A significant difference in blood glucose levels was detected between different genotypes of rs2728109 (P = 0.005) in the PDK2 gene. We also detected a significant difference in the mean serum uric levels between different genotypes of rs3114018 (P = 0.004) in the ABCG2 gene. All P values remained significant after Bonferroni's correction for multiple testing. Our data demonstrate potential roles for PDK2 and ABCG2 polymorphisms in the metabolic phenotypes of Tibetan gout patients, which may provide new insights into the etiology of gout. Further studies are required to confirm these findings.
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Transportadores de Cassetes de Ligação de ATP/genética , Glicemia/metabolismo , Predisposição Genética para Doença , Gota/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Ácido Úrico/sangue , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Povo Asiático , Feminino , Expressão Gênica , Gota/sangue , Gota/etnologia , Gota/patologia , Projeto HapMap , Humanos , Masculino , Proteínas de Neoplasias/metabolismo , Fenótipo , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Análise de Sequência de DNA , TibetRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Leaves infusion of Pimenta pseudocaryophyllus (Gomes) Landrum is used in Brazilian folk medicine to treat the predisposition to arthritical and gouty affections of the joints, fever and other diseases. A refreshing drink prepared with the specie is also used due to its diuretic, sedative and aphrodisiac actions. AIM OF THE STUDY: The study was undertaken to investigate the mechanisms of anti-hyperuricemic effect and anti-inflammatory activity of P. pseudocaryophyllus extracts. MATERIALS AND METHODS: Anti-hyperuricemic effect was investigated using xanthine oxidase assay and uricosuric studies with rats in which hyperuricemia was induced by potassium oxonate and uric acid. Anti-inflammatory activity was investigated on MSU crystal-induced paw edema model. Ethyl acetate extracts of the leaves (EAL) and branches (EAB), ethanolic extracts of leaves (EEL) and branches (EEB) and aqueous extracts of leaves (AL) and branches (AB) were evaluated. RESULTS: The extracts of P. pseudocaryophyllus evaluated showed expressive results regarding the inhibition of xanthine oxidase enzyme in vitro and they were also able to reduce serum uric acid levels in hyperuricemic rats. The investigation of the mechanism of action, it was found that EAL, EAB, EEB, AB (125 and 250 mg/kg) and AL (250 mg/kg) promoted an increase on the urinary excretion of uric acid and EEL, EEB, AB (125 and 250 mg/kg) and EAB (250 mg/kg) were capable to inhibit liver xanthine oxidase. Treatments with EEL (125 and 250 mg/kg) and EEB (250 mg/kg) were able to reduce edema at 48 th h. EAL and EAB (125 and 250 mg/kg) showed significant anti-inflammatory activity on monosodium urate crystal-induced paw edema model at all evaluated times. CONCLUSIONS: The specie P. pseudocaryophyllus showed remarkable anti-hyperuricemic effects through uricosuric effects and inhibition of xanthine oxidase and therefore can be considered as a promise in the treatment of diseases related to hyperuricemia. Moreover, ethyl acetate extracts had significant anti-inflammatory activity.