Acute Gout Attack Research Articles

Quantitative proteomics by iTRAQ-PRM based reveals the new characterization for gout

BackgroundGout is a common and complex form of immunoreactive arthritis based on hyperuricemia, while the symptoms would turn to remission or even got worse. So, it is hard to early identify whether an asymptomatic hyperuricemia (AHU) patient will be susceptible to get acute gout attack and it is also hard to predict the process of gout remission to flare. Here, we report that the plasma proteins profile can distinguish among acute gout (AG), remission of gout (RG), AHU patients, and healthy controls.MethodsWe established an isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM) based method to measure the plasma proteins for AG group (n = 8), RG group (n = 7), AHU group (n = 7) and healthy controls (n = 8).ResultsEleven differentially expressed proteins such as Histone H2A, Histone H2B, Thrombospondin-1 (THBS1), Myeloperoxidase (MPO), Complement C2, Complement component C8 beta chain (C8B), Alpha-1-acid glycoprotein 1 (ORM1), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Carbonic anhydrase 1 (CA1), Serum albumin (ALB) and Multimerin-1 (MMRN1) were identified. Histone H2A, Histone H2B and THBS1 might be the strongest influential regulator to maintain the balance and stability of the gout process. The complement and coagulation cascades is one of the main functional pathways in the mechanism of gout process.ConclusionsHistone H2A, Histone H2B and THBS1 are potential candidate genes for novel biomarkers in discriminating gout attack from AHU or RG, providing new theoretical insights for the prognosis, treatment, and management of gout process.Trial registrationThis study is not a clinical trial.

Anti-inflammatory drugs as new inhibitors to xanthine oxidase: In vitro and in silico approach

The two important targets to treat gout disease are (1) control the hyperuricemia by the inhibition of Xanthine Oxidase (XO) and (2) treatment of acute attacks of gout by the use of anti-inflammatory drugs. It is important to distinguish between therapy to manage hyperuricemia and to reduce acute inflammation. While reducing hyperuricemia is resolved very slowly with available drugs, gout symptoms like pain and inflammation may become persistent. The objective of this study is to find a relevant treatment with a beneficial double effect. (1) As an anti-inflammatory, analgesic, and antipyretic effect and (2) as XO inhibitory effect, which is the main objective of this study. We investigated the effect of five non-steroidal anti-inflammatory drugs (NSAIDs) against human and bovine milk xanthine oxidases (HXO and BXO) using the double enzyme detection method (DED) and molecular docking with the Autodock vina program. in vitro results show that the NSAIDs give an important inhibition to HXO and BXO with an IC50 of 2.04 ± 0.13 μg/ml, 2.75 ± 0.23 μg/ml, 1.45 ± 0.19 μg/ml, 0.31 ± 0.13 μg/ml and 1.27 ± 0.11 μg/ml, for HXO, and 2.96 ± 0.27 μg/ml, 9.46 ± 0.13 μg/ml, 6.21 ± 1.17 μg/ml, 0.83 ± 0.11 μg/ml, and 3.48 ± 0.13 μg/ml, for BXO, for respectively, Naproxen, Ibuprofen, Diclofenac, Indomethacin, and Celecoxib. Testing the inhibitory activity of these drugs on both XOs shows an important inhibition, especially from Indomethacin, which could be a promising lead compound for reducing acute inflammation and at the same time controlling hyperuricemia.

β-Caryophyllene Ameliorates MSU-Induced Gouty Arthritis and Inflammation Through Inhibiting NLRP3 and NF-κB Signal Pathway: In Silico and In Vivo.

Gouty arthritis serves as an acute reaction initiated by the deposition of monosodium urate (MSU) crystals around the joints. In this study, the anti-inflammatory effects of phytochemical β-caryophyllene on MSU crystal-induced acute gouty arthritis in vivo and in silico were explored. Through bioinformatics methods and molecular docking, it screened the specific influence pathway of β-caryophyllene on gout. Certain methods including enzyme-linked immunosorbent assay, western blotting, and immunohistochemical staining were adopted to quantify. β-caryophyllene significantly reduced inflammation and function of ankle joints in MSU Crystals-induced gouty arthritis rats, while decreasing serum cytokine levels. Furthermore, it inhibited the expressions of NLRP3, Caspase-1, ASC, TLR4, MyD88, p65, and IL-1β in the synovial tissue so as to reduce inflammation and protect ankle joints’ function. A new research approach in which β-caryophyllene treatment to acute attacks of gout is provided through the research results.

Role of Vitamin C in Prophylaxis and Treatment of Gout-A Literature Review.

Gout, known as “the disease of the kings”, is the most frequent type of arthritis. It results from sustained hyperuricemia that leads to monosodium urate crystal deposition in joint structures and soft tissue. Environmental factors such as diet affect the incidence of gout; there is a known relationship between the occurrence of an acute attack of gout and the consumption of alcohol and meat; and a low purine diet is a widely recognized nonpharmacological method of supplementing the treatment and preventing recurrence of arthritis. This review aims to summarize the current knowledge about the role of vitamin C in prevention and treatment of gout. A PubMed/Medline database search on the role of vitamin C in purine metabolism was done. Reports from in vitro and animal studies seem to be promising and to allow explanation of the physiological relationship between vitamin C and uric acid. Most epidemiological studies indicate a significant correlation between high vitamin C intake and lower serum uric acid levels. Despite promising observations, there are few observational and interventional studies, and their results do not clearly define the benefits of a high daily intake of vitamin C in preventing the development and recurrence of gout.

Обзор эффективности и безопасности нестероидных противовоспалительных препаратов для лечения острого приступа подагрического артрита

Gout is one of the most common forms of inflammatory arthritis. Medical care for gout includes non-steroidal anti-inflammatory drugs (NSAIDs). This paper reviews the efficacy and safety of NSAIDs prescribed for the acute attack of gout, in particular, AMBENIUM® parenteral. It was demonstrated that phenylbutazone is a powerful NSAID that provides significant analgesic and anti-inflammatory effects. Considering a broad spectrum of adverse reactions of NSAIDs, these agents should be prescribed and used under in-depth analysis of patient’s condition, comorbidities and the level of their decompensation, and potential drug interactions. In addition, optimal dosages and duration of NSAID treatment are of particular importance. The authors conclude that AMBENIUM® parenteral is an effective and safe therapeutic modality for gout. Its profile and risk/benefit ratio are regarded as “favorable” compared to other NSAIDs. KEYWORDS: gout, arthritis, pain, non-steroidal anti-inflammatory drugs, parenteral, efficacy, safety. FOR CITATION: Vasilyuk V.B., Syraeva G.I., Faraponova M.V. Efficacy and safety of non-steroidal anti-inflammatory drugs for acute attack of gout. Russian Medical Inquiry. 2021;5(2):96–101. DOI: 10.32364/2587-6821-2021-5-2-96-101.

Characteristics, Comorbidities, and Potential Consequences of Uncontrolled Gout: An Insurance-Claims Database Study.

IntroductionGout is a common, progressive, systemic inflammatory arthritis caused by hyperuricemia. Current guidelines recommend that serum uric acid (sUA) levels be maintained below 6.0 mg/dl to minimize acute gout attacks, tophi development, and long-term joint and organ damage. This study examined the influence of uncontrolled gout on post-diagnosis comorbidities and medication use.MethodsThe Humana Research Database (2007–2016, commercial insurance and Medicare) was searched (PearlDiver tool) for patients who had a gout diagnosis code, claims data for at least 6 months before and after diagnosis, and at least 90 days of continuous urate-lowering therapy within 1 year of diagnosis. Patients with controlled (all sUA measurements < 6.0 mg/dl) and uncontrolled (all sUA measurements ≥ 8.0 mg/dl) gout were further examined and compared to better understand the influence of uncontrolled gout on post-diagnosis comorbidities, medication use, and reasons for seeking medical care.ResultsA total of 5473 and 1358 patients met inclusion and classification criteria for the controlled and uncontrolled groups, respectively. Identified comorbidities in both groups included hypertension, hyperlipidemia, diabetes, cardiovascular disease, and chronic kidney disease (CKD). However, the uncontrolled group was more likely to have diabetes, CKD, and cardiovascular disease (including heart failure and atrial fibrillation). Additionally, CKD tended to be more advanced in the uncontrolled gout population (Stage 4–5: 34.6 vs. 22.2%). Overall opioid use was higher in uncontrolled patients.ConclusionsThe current study identified differences between controlled and uncontrolled gout patients, including usage of medication, severity of CKD, and prevalence of CKD, diabetes, and heart disease.

Experience sharing on treatment of an acute colchicine poisoning patient

Colchicine is mainly used in the treatment of acute gout attack, acute attack of chronic gout and other diseases in clinic. But the drug has high toxicity (highly toxic), the therapeutic dose is very close to the toxic dose, and there is no special effect after poisoning drug detoxification. The clinical manifestations of early patients after poisoning are not specific, which brings some difficulties and challenges in clinical diagnosis and treatment, and virtually increases the probability of death from drug poisoning. The drug poisoning is still sporadic reports. On September 1, 2020, a patient with acute colchicine poisoning was admitted to People's Hospital of Songtao Miao Autonomous County. This patient is the one with the longest poisoning time that can be retrieved by authoritative medical journals. After treatment, the patient was cured and discharged. This article reported the experience of diagnosis and treatment.

Asymptomatic hyperuricemia: are we passing the problem?

Hyperuricemia is a laboratory phenomenon of persistent increase in serum uric acid concentration (above 420 μmol/l). This condition precedes gout, but only in every 5 cases does hyperuricemia develop into gout. The main pathogenic factor in this disease is not uric acid, but the enzyme xanthine oxidase. In treatment, it is important to block it as a source of free radicals, and then we can improve the prognosis in patients. Today, there is no doubt about the association of hyperuricemia with obesity, metabolic syndrome, diabetes, heart failure, hyperlipidemia and hypertension. For example, hypertension in healthy patients occurs with a frequency of 6.39 %, with hyperuricemia, this figure increases to almost 50 %, and in patients with gout – up to 73.9 %. Asymptomatic hyperuricemia is not considered treatable, although ultrasound studies have shown that sodium monourate crystals (MUN) are deposited in soft tissues and joints. Their presence is a marker of asymptomatic hyperuricemia. Therefore, experts have recently begun to talk about a new stage of gout. If earlier we listed asymptomatic hyperuricemia, acute gout attack, intermittent gout and chronic tofus gout, now we are talking about an additional second stage - asymptomatic hyperuricemia with the deposition of MUN crystals. The path from hyperuricemia to chronic gout can take up to 11 years, but after 4 years can develop kidney damage and decreased glomerular filtration rate, after 6 years - hypertension, and after 10 years – heart failure. So is it worth waiting for the development of chronic gout or perhaps you should start treatment for hyperuricemia earlier?

The effect of bariatric surgery on purine metabolism and gout

Gout is an auto-inflammatory tophaceous disease characterized by the deposition of crystals of monosodium urate and developing in connection with this inflammation in people with hyperuricemia (HU). Except to genetic factors, risk factors for the development of HU and gout are many modifiable factors, including metabolic syndrome and obesity, and their correction is the most important component of successful disease control. Obesity can change the clinical picture of gout, characterized by an earlier onset, a large number of affected joints. Weight loss helps reduce uric acid (UA) serum levels. Bariatric / metabolic surgery significantly reduces the incidence of comorbid obesity and mortality, and is by far the most effective way to combat obesity. In addition to improving health, an important goal of bariatric surgery is to improve the quality of life. Bariatric surgery can prevent the development of HU in subjects with an initially normal level of serum UA before surgery. The dynamics of the concentration of UA in serum can be a predictor of successful bariatric surgery and help in predicting the severity of postoperative weight loss. The decrease in body weight after bariatric surgery leads to a decrease in UA in the long-term postoperative period, however, there is a high frequency of acute gout attacks in the early postoperative period. Thus, bariatric surgery has a significant effect on HU and gout and can be an effective treatment for this disease.

Are intra-articular steroids as effective as oral steroids for treating acute gout attacks?

Are intra-articular steroids as effective as oral steroids for treating acute gout attacks?

Interdisciplinary approach to the management of patients with chronic gout

Gout, one of the most common forms of inflammatory arthritis, is characterized by severe joint pain, which often interferes with daily activities. In recent years, further research on its causes and on improving diagnosis, treatment and prevention has been ongoing. It is known that gout usually occurs due to the accumulation of sodium monourate crystals in joints due to high levels of serum uric acid. In 2019, the Annals of the Rheumatic Diseases journal published new data on imaging and clinical diagnostics methods based on the principles of evidence-based medicine. Formulated by experts, they were adopted as a consensus of the European League Against Rheumatism (EULAR). The American College of Rheumatology (ACR) has now developed new strategies to treat and prevent gout. On May 11, 2020, the Arthritis &amp; Rheumatology Journal presented guidelines for the management of gout patients, including the treatment of acute gout attack, indications for urate-lowering therapy and instructions for its optimal use, as well as recommendations on lifestyle and drugs that are often prescribed to patients with comorbidity. The purpose of this review is to summarize current knowledge with a focus on recent advances in the algorithm for managing acute and chronic gout patients.

Interdisciplinary approach to the management of patients with chronic gout

Gout, one of the most common forms of inflammatory arthritis, is characterized by severe joint pain, which often interferes with daily activities. In recent years, further research on its causes and on improving diagnosis, treatment and prevention has been ongoing. It is known that gout usually occurs due to the accumulation of sodium monourate crystals in joints due to high levels of serum uric acid. In 2019, the Annals of the Rheumatic Diseases journal published new data on imaging and clinical diagnostics methods based on the principles of evidence-based medicine. Formulated by experts, they were adopted as a consensus of the European League Against Rheumatism (EULAR). The American College of Rheumatology (ACR) has now developed new strategies to treat and prevent gout. On May 11, 2020, the Arthritis &amp; Rheumatology Journal presented guidelines for the management of gout patients, including the treatment of acute gout attack, indications for urate-lowering therapy and instructions for its optimal use, as well as recommendations on lifestyle and drugs that are often prescribed to patients with comorbidity. The purpose of this review is to summarize current knowledge with a focus on recent advances in the algorithm for managing acute and chronic gout patients.

Rare Location and Clinical Presentation of Gout Disease: Distal Ulna Localized Gout Disease and Acute Gout Attack of the Wrist

Gout is one of the most common inflammatory arthritis in adults. This disorder is caused by the accumulation of monosodium urate crystals insoft tissues and joints because of the hyperuricemia. One of the lower extremity joint especially the first metatarsophalangeal joint is affectedby more than 75% of the gout attacks. In this study, we reported a rare presentation of gout disease, the acute gout attack of the wrist, in awoman, 72 years aged, who has not been diagnosed before. Gout which occurs with the involvement of the wrist is very rare and no other caseswith distal ulna localization have been reported according to our knowledge. We reported the first case of gout disease which started from distalulna. The patient was operated because the symptoms did not recover with conservative treatments.

The clinical efficacy of urate-lowering therapy in acute gout: a meta-analysis of randomized controlled trials.

Gout is a common chronic disease with a high recurrence rate. To date, the debate continues about the best time for using urate lowering therapy (ULT) during an acute gout attack. This updated meta-analysis is designed to assess the clinical efficacy of ULT in the management of acute exacerbations of gout. Through the results, we hope to determine whether uric acid lowering agents should be used to manage acute exacerbations of gout. A comprehensive search of six databases without language restrictions includes PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, and WanFang data. The literature used was published before October 2019. Six randomized controlled trials (RCTs) with 557 patients met the inclusion criteria. Standardized mean difference (SMD), weighted mean difference (WMD), risk ratio (RR), and 95% confidence interval (CI) were used for estimating the clinical efficacy of ULT in acute gout. Data results showed no statistical difference in the pain visual analogue score (VAS) by day 3 (weighted mean difference (WMD), 0.06; 95% CI, - 0.13 to 0.25; I2 0%; P = 0.55), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between the group using uric acid lowering agents and the group that was not using such agents. Moreover, the patients using ULT agents had lower serum uric acid level (standardized mean difference (SMD), - 0.73; 95% CI, -0.92 to -0.54; I2 23%; P < 0.00001) and showed better adherence to medication (risk ratio (RR), 1.40; 95% CI, 1.18 to 1.65; I2 0%; P < 0.0001) as compared with the patients not that were not using such agents. However, there was no substantial difference in the recurrence rate of acute gout attacks (RR, 0.84; 95% CI, 0.59 to 1.19; I2 0%; P = 0.33).The evidence for this is, however, very moderate. Our finding shows that it is beneficial in many aspects to use uric-acid-lowering drugs at the initial stage of an acute gout attack. However, larger sample size studies are still needed to prove our results. Registration number: PROSPERO (CRD42020153924). Key Points • This is a first meta-analysis about the clinical efficacy of urate-lowering therapy (ULT) in acute gout without language restrictions. • ULT in acute gout may not aggravate the pain (WMD, 0.06; 95% CI, - 0.13 to 0.25). • ULT at the initial stage of an acute gout attack can reduce serum uric acid level (SMD, -0.73; 95% CI, - 0.92 to - 0.54) and improve medication compliance in patients (RR, 1.40; 95% CI, 1.18 to 1.65). • ULT in acute gout is not associated with the risk of gout flares (RR, 0.84; 95% CI, 0.59 to 1.19).

OP0168 CARDIOVASCULAR EVENT ASSOCIATED WITH INITIATING ALLOPURINOL AND FEBUXOSTAT - ACUTE GOUT ATTACK AND CARDIOVASCULAR GOUT ATTACK

Background:When serum uric acid rapidly increases or decreases due to such as alcohol consumption or fasting, free urate crystals are formed, which induce an acute joint inflammation referred to as an acute gout attack. In 86.4% of patients with gout, dual energy computed tomography demonstrated the deposition of urate crystals in vasculature, and urate crystals have been observed in coronary arteries and various tissues in 10.9% of patients with a heart transplant. However, whether hyperuricemia and urate crystal directly cause cardiovascular disease is not well known. We previously reanalyzed the CARES trial to calculate the mortality rates based on the median duration of exposure to study drugs and the median follow-up duration. A sharp increase in mortality was observed after allopurinol and febuxostat were discontinued. Even in view of the Sick-Stopper Effect, for about 40-fold increase in mortality following drug discontinuation, we postulated that the sharp increase in mortality may be associated with rapid changes in uric acid level (rebound hyperuricemia), and that withdrawal of hypouricemic agent leads to an acute inflammatory response due to an abrupt increase in serum uric acid level with subsequent free urate crystal formation in the cardiovascular system (cardiovascular gout attack)(1).Objectives:Based on this hypothesis that some cardiovascular events may be cardiovascular gout attacks, we investigated the association between the cardiovascular event and initiation of hypouricemic agent, when is accompanied by acute gout attack and/or fluctuation of uric acid, in gout patients.Methods:Using the Korean National Health Insurance Service (KNHIS) database, which covers the entire Korean population, we conducted a population-based cohort study among gout patients who initiated allopurinol or febuxostat between 2012 and 2018. The initiators were defined as those who had no prior dispensing of any urate-lowering therapy for at least 60 months before the first dispensing date (i.e. index date) of either allopurinol or febuxostat. We excluded patients with a diagnosis of cancer and patients treated with benzbromarone. We investgated a composite cardiovascular event of hospitalized myocardial infarction, ischemic stroke, and cerebral hemorrhage.Results:We identified hospitalizations for cardiovascular event (acute myocardial infarction (n = 3538), cerebral infarction (n = 5127), and cerebral hemorrhage (n = 1593)) that occurred within 2 year before and 2 year after initiation of allopurinol or febuxostat. Of these, 4333 cardiovascular event (0.014 per person-time, 95% confidence interval [CI], 0.014 to 0.015) occurred in 2 years before initiation of allopurinol or febuxostat, 1032 cardiovascular event (0.081 per person-time, 95% confidence interval [CI], 0.076 to 0.086) occurred in 30 days before initiation of allopurinol or febuxostat. And, 83 cardiovascular event (0.030 per person-time, 95% CI, 0.024 to 0.037) occurred in 7 days after initiation of allopurinol or febuxostat. (Figure)Figure 1Conclusion:Initiation of febuxostat and allopurinol was significantly associated with acute myocardial infarction, cerebral infarction, and cerebral hemorrhage. Considering that allopurinol and febuxostat usually are initiated a few weeks after a acute gout attack. Acute gout attack and/or fluctuation of uric acid level might be significantly associated with cardiovascular event. Some of cardiovascular events might be cardiovascular gout attack.

AB0057 THE ROLE OF NON-INFLAMMATORY MACROPHAGES INITIATING AND RESOLVING THE INFLAMMATORY RESPONSE OF MONOSODIUM URATE IN MICE

Background:Gout is the most common chronic inflammatory arthritis around the world which is associated with many conditions that affect longevity and well-being, such as metabolic syndrome, cardiovascular diseases, and renal diseases. [1]Objectives:Gout is the most common inflammatory arthritis around the world. Innate immunity has been implicated in gout inflammation in recent years. However, the phenomena of maintenance of ‘asymptomatic’ hyperuricemia, the spontaneous resolution of acute gouty arthritis and non-inflammatory tophus and its association with immune regulation are still elusive. We propose that resident macrophages may be a key player in the suppression of gouty inflammation. To address this hypothesis, we used non-inflammatory macrophages to explore the role played in initiating or resolving the inflammatory response.Methods:Bone marrow-derived macrophages (BMDM) were stimulated with monosodium rate (MSU), then analyzed the expression of RNA and protein of inflammatory cytokines, including IL-1β, IL-18 and TNF-α. In addition, we also observe the ability of macrophage to phagocyte and hydrolyze MSU crystal.Results:Our results indicate that MSU alone could not induce IL-1β, IL-18, and TNF-α mRNA expression and protein production. However, when macrophages were pre-stimulated with lipopolysaccharide (LPS) or MSU, as well as in combination the production of IL-1β and IL-18 were significantly increased. Furthermore, MSU maybe amplifies LPS-induced protein production of IL-1β and IL-18 but not in TNF-α. A temporal delay in the correlation between mRNA expression and protein production was shown. The results also indicated that macrophages could not only phagocytize MSU crystals but may also hydrolyze MSU crystals.Conclusion:These data indicate that MSU crystal alone is insufficient to induce pro-inflammatory cytokines production, however, when exposed to an infectious source of infection, it will amplify the inflammatory response and there is a synergistic effect between MSU and LPS. This may explain the diverse clinic phenomena of ‘asymptomatic’ hyperuricemia, non-inflammatory tophus and acute gouty arthritis. The high efficiency of phagocytosis and hydrolyzed MSU crystals of macrophages may explain the spontaneous regression of acute gouty arthritis. These findings may provide a new therapy for the prevention and treatment of acute gout attacks.

SO079ASYMPTOMATIC HYPERURICEMIA, A REGULATOR OF INNATE IMMUNITY IN CHRONIC KIDNEY DISEASE

Abstract Background and Aims Asymptomatic hyperuricemia (HU) is common among patients with chronic kidney disease (CKD) but the causative role of HU on CKD progression remains controversial. Two large multi-center randomized controlled trials (RCTs), the CKD-FIX and the PERL study, have now disproven a causal relation. On the other hand, a causative role of persistent HU exists with gouty arthritis but a rapid correction of HU with urate lowering therapy can also elicit acute gout attacks. This suggests a more complex role of HU in this context. Hence, we hypothesized that soluble uric acid (sUA) has immunomodulatory effects on leukocyte function during the immune response to monosodium urate (MSU) crystals. Method Alb-creERT2;Glut9lox/lox and Glut9lox/lox control mice were injected with tamoxifen and placed either on a chow or high-fat diet with inosine to induce HU with or without CKD. After two weeks, MSU crystals or vehicle were injected into air pouches or postcapillary venules in the cremaster muscle of transgenic mice. Leukocyte infiltration and the extent of inflammation were assessed by flow cytometry, intravital microscopy, ELISA, and colorimetric assays. Human blood neutrophils and CD14+ monocytes were isolated from CKD stage G2-4 (n=10) and CKD stage G5 (n=18) patients or healthy individuals (n=15). Neutrophil transwell migration assays were performed and the number of migrated human neutrophils towards chemoattractants determined by flow cytometry. Human blood CD14+ monocytes were treated with MSU crystals or lipopolysaccharide ex vivo, and the expression of inflammatory mediators determined by RT-PCR and flow cytometry. Results We found that the presence of HU impaired leukocyte recruitment into MSU crystal-injected air pouches of mice with or without CKD. Intravital microscopy revealed that HU specifically reduced leukocyte adhesion, extravasation, and leukocyte-related tissue inflammation. The CKD-mediated attenuation of MSU crystal-induced inflammation was fully reversible by treating HU with urate lowering therapy such as rasburicase. In blood neutrophils isolated from healthy individuals, sUA diminished β2 integrin activation and expression, and hence impaired neutrophil migration ex vivo. An impaired migratory capability was also observed in neutrophils from CKD stage G2-4 or G5D patients. Moreover, sUA attenuated Toll-like and TNFα receptor-induced human monocyte activation, a process depending on the intracellular uptake of sUA via the urate transporter SLC2A9 (GLUT9), the only urate transporter expressed by these immune cells. Conclusion We identify sUA as an endogenous modulator of innate immunity. HU modulates neutrophil migration by altering efficient β2 integrin activation and suppresses pattern recognition receptor-driven monocyte activation via SLC2A9 in gouty arthritis related or unrelated to CKD (see Figure). This process provides a molecular explanation for several previously unexplained clinical phenomena in the context of gouty arthritis and renal failure.

Current Gout Management Guidelines

Only 20 % of patients have hyperuricemia implemented in gout as a clinically defined disease. In Madrid, at the Congress of the European League Against Rheumatism (EULAR) in 2013, it was concluded that gout is two different diseases, one of which is metabolic and manifests as hyperuricemia (also called “chemical gout”), and the other the gout component is actually a typical inflammation of the joints of the favorite localization due to the deposition of sodium monourate crystals in the tissues. That is, gout is always hyperuricemia, but hyperuricemia is not always gout.The main principles of gout management are the treatment of acute gout attack with colchicine, non-steroidal anti-inflammatory drugs, glucocorticosteroids, and combinations thereof; further prevention of acute attack with minimal doses of the aforementioned drugs; long-term lifesaving therapy. A non-purine selective xanthine oxidase inhibitor with potent hypouricemic action and evidence-based febuxostat is thought to be 2–3 times more effective than allopurinol.

Evaluation of febuxostat initiation during an acute gout attack: A prospective, randomized clinical trial.

Urate-lowering treatment (ULT) is recommended in gout management. However, initiation of ULT during an acute gout flare is still inconclusive. This study aimed to evaluate the efficacy and safety of the ULT febuxostat administered at initiation of an acute gout attack. A prospective randomized controlled clinical trial was conducted for 12 weeks in primary gout patients who were admitted with acute gout attacks. Subjects were randomly assigned to the febuxostat group in which febuxostat, 40mg daily, was administered in the primary care setting for attacks, or to the control group in which febuxostat, 40mg daily, was administered after the attacks. All patients received adequate anti-inflammatory and analgesic therapies. Serum urate (SU) levels were monitored throughout the study. Pain, measured using a visual analogue scale (VAS), and gout recurrence rate were used as primary outcomes. Flare-related inflammation biomarkers were selected as secondary outcomes. Fifty-two patients completed the study (febuxostat group: n=28; control group: n=24). No significant differences were detected in VAS scores between the two groups over the first 14-day observation period (P>0.05). Administration of febuxostat decreased SU levels significantly during the first 2-week period. However, the gout recurrent rate or gout flare-related inflammation indicators did not change in the febuxostat or control groups. Treatment-related adverse events were mild and similar between groups. Initiation of the urate-lowering drug febuxostat during an acute gout attack caused no significant difference in daily pain, recurrent flares, or adverse effects. The treatment significantly decreased SU levels in the early stage and might have potential long-term benefits in these patients.

Gout and Its Management in Clinical Practice

Gout and Its Management in Clinical Practice Abstract. Resolution of an acute attack is usually the prime objective in routine clinical management of gout. Crystal identification in synovial fluid by polarised light microscopy is considered the diagnostic gold standard. Imaging procedures such as high-resolution ultrasonography are also useful. Non-steroidal anti-inflammatory drugs, steroids and colchicine (not approved in Switzerland, available from pharmacies) are used to treat an acute gout attack. Just as important as the diagnosis and treatment of an acute attack is the long-term management of hyperuricaemia in order to prevent further gout attacks as well as possible renal, cardiac or metabolic complications. Therefore, patients with a confirmed diagnosis of gout should, apart from non-pharmacologic interventions, receive hypouricaemic therapy with a target uric acid level of <360 µmol/l (<6 mg/dl). Drugs of first choice are xanthine oxidase inhibitors. Achievement of the therapeutic objective should be periodically reviewed, adjusting therapy as necessary.