Hyperuricemia, urine uric excretion, and associated complications in thalassemia patients.

Thalassemia patients have a high cell turnover rate due to chronic hemolysis and ineffective erythropoiesis; therefore, hyperuricemia is anticipated. This study aimed to identify the prevalence of hyperuricemia, gout and nephrolithiasis, conditions associated with serum uric acid (SUA), and urine uric acid excretion (UUA) in thalassemia patients. This was a cross-sectional study in patients aged 15 years or older at Chiang Mai University Hospital. All patients had blood and 24-h urine collection test. We enrolled 112 thalassemia patients in which 67.0% were female, 64.3% had beta thalassemia/Hb E, 76.8% were transfusion dependent, and 59.8% were post splenectomy. The median age was 29 (16-58) years. Mean SUA was 6.7 ± 2.0 mg/dl and hyperuricemia (SUA > 6.8 mg/dl) was found in 47 cases (45.2%). Intact spleen (ORs 4.3, 95%CI 1.55-12.50, p = 0.01) and lower FEuric (ORs 2.08, 95%CI 1.35-3.33, p < 0.01) were associated with hyperuricemia significantly. Seven (6.3%) had gouty arthritis and nine (8%) had microscopic hematuria, one case being confirmed nephrolithiasis. The mean UUA excretion was 981.3 ± 335.0 mg/day and UUA hyperexcretion (> 700 mg/24 h) was found in 83.3%. UUA hyperexcretion patients had renal hyperfiltration 46%, glomerular dysfunction 84%, and tubular dysfunction 7.7%. From our study, hyperuricemia was found in approximately 40% of thalassemia patients but gouty arthritis occurred only in few patients (6%). This may be explained by urinary uric hyperexcretion which is found in over 80%. The significant risk factors for hyperuricemia were intact spleen and lower fraction excretion of uric acid.

Clinical manifestations and molecular aspects of phosphoribosylpyrophosphate synthetase superactivity in females.

Objectives: Phosphoribosylpyrophosphate synthetase (PRPS1) superactivity is an X-linked disorder characterized by urate overproduction Online Mendelian Inheritance in Man (OMIM) gene reference 300661. This condition is thought to rarely affect women, and when it does, the clinical presentation is mild. We describe a 16-year-old African American female who developed progressive tophi, nephrolithiasis and acute kidney failure due to urate overproduction. Family history included a mother with tophaceous gout who developed end-stage kidney disease due to nephrolithiasis and an affected sister with polyarticular gout. The main aim of this study was to describe the clinical manifestations of PRPS1 superactivity in women. Methods: Whole exome sequencing was performed in affected females and their fathers. Results: Mutational analysis revealed a new c.520 G > A (p.G174R) mutation in the PRPS1 gene. The mutation resulted in decreased PRPS1 inhibition by ADP. Conclusion: Clinical findings in previously reported females with PRPS1 superactivity showed a high clinical penetrance of this disorder with a mean serum urate level of 8.5 (4.1) mg/dl [506 (247) µmol/l] and a high prevalence of gout. These findings indicate that all women in families with PRPS1 superactivity should be genetically screened for a mutation (for clinical management and genetic counselling). In addition, women with tophaceous gout, gout presenting in childhood, or a strong family history of severe gout should be considered for PRPS1 mutational analysis.

Joint Clinical Consensus Statement of the American College of Foot and Ankle Surgeons® and the American Association of Nurse Practitioners®: Etiology, Diagnosis, and Treatment Consensus for Gouty Arthritis of the Foot and Ankle.

Gout is a condition that commonly affects the foot and ankle, and practitioners who treat these structures should be aware of the methods to diagnose and treat this form of arthritis. Practitioners also need to recognize extra-articular manifestations of the disease. Although the acutely red, hot, swollen joint is a common presentation, chronic tophaceous gout can be associated with pain, nodule formation, and cutaneous compromise. Since the underlying causes that lead to excessive monosodium urate deposition may be treatable, early and accurate diagnosis can be very beneficial and may even prevent articular degeneration.

[A case of gout secondary to primary myelofibrosis].

A 52-year-old man was referred to our department with a 2-year history of polyarthritis. He was diagnosed as gout due to acute arthritis of bilateral feet dorsum 2 years ago,but he didn't receive any standard treatment. 1 year ago,there were more and more joints evolved during the gout attack, and many subcutaneous nodules occurred. When he presented to our clinic 1 month ago,the urate acid level was as high as 715 µmol/L. Moreover, we could find bone erosion in the X rays of his hand and foot,as well as synovitis,double contour sign and tophus on the ultrasound examination. The diagnosis of gout was clearly and definitely. However, he had leukocytosis and thrombocytosis for 4 years in the past history, and the urate acid level was only 400 µmol/L at that time. He also had well-controlled hypertension. The family history was unremarkable. Furthermore, we found megalosplenia on his physical examination. The bone marrow examination showed myelofibrosis and JAK2 V617F gene was positive. He was diagnosed as primary myelofibrosis and treated with interferon-α, together with urate acid-lowing therapy (febuxostat 60 mg once daily). Following-up for 1 year,the dosage of febuxostat decreased to 40 mg once daily, and the patient didn't have gout attack again, some of the tophus diminished, and the urate acid level ranged from 400 to 500 µmol/L. Gout is a common disease in clinical practice,usually combined with metabolic syndrome,chronic renal failure and specific drugs using (diuretic and calcineurin inhibitors). However,it is relatively rare to see gout associated with myeloproliferative diseases, including polycythemia vera, primary thrombocythemia, primary myelofibrosis and chronic myelocytic leukemia. In these diseases, the turnover of nucleic acids is greatly augmented, and an excess of purine metabolites, including uric acid, is released. In the natural course of gout, the appearance of tophus from the first onset of arthritis usually takes several years. This patient only had one traditional risk factor, but his urate acid level was remarkably high and he developed tophus in a short term. After treatment of primary myelofibrosis, the symptom of gout partially alleviated. Careful physical examination and medical history taking lead to the diagnosis of secondary gout, which should be reminded in the daily practice.

[Evidence-based recommendations for diagnostics and treatment of gouty arthritis in the specialist sector : S2e guidelines of the German Society of Rheumatology in cooperation with the AWMF]. / Evidenzbasierte Empfehlung zur Diagnostik und Therapie der Gichtarthritis im fachärztlichen Sektor : S2e-Leitlinie der Deutschen Gesellschaft für Rheumatologie (DGRh) in Kooperation mit der AWMF.

Due to the increasing prevalence of gout, particularly in old age, the disease is becoming of increasing importance in Germany. Gout is one of the most common forms of recurrent inflammatory arthritis and is induced by the deposition of monosodium urate crystals in synovial fluid and other tissues. The principal goals of therapy in chronic gout are the symptomatic treatment of the acute joint inflammation and the causal treatment of the underlying metabolic cause, the hyperuricemia. Only a consistent and permanent reduction of the serum uric acid level ultimately results in an efficient avoidance of further gout attacks and therefore the prevention of structural damage. Due to an often inadequate treatment of gout, the target of healing the disease is often not achieved. A correct and timely diagnosis and adequate assessment of comorbidities associated with gout are, however, of substantial importance for patient and physician to achieve remission of the disease. In order to create a solid basis for a timely and effective treatment of affected patients, in 2016 the German Society of Rheumatology (DGRh) initiated the development of S2e guidelines on gouty arthritis for specialists. This article summarizes these S2e guidelines on the management of gouty arthritis in the specialist sector.

[Causes, mechanisms and possible therapeutic targets of gout]. / Ursachen, Mechanismen und mögliche therapeutische Ziele der Gicht.

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.

Effect of sodium alginate addition to resveratrol on acute gouty arthritis.

OBJECTIVE: Resveratrol has been shown to exert anti-inflammatory and antioxidant effects, while sodium alginate is a common pharmaceutic adjuvant with antioxidative and immunomodulatory properties. We performed an animal study to investigate the effect of sodium alginate addition to resveratrol on acute gouty arthritis. METHODS: Twenty-four SPF Wistar mice were randomized to four groups receiving the combination of sodium alginate and resveratrol, resveratrol alone, colchicine, and placebo, respectively. Acute gouty arthritis was induced by injection of 0.05 ml monosodium urate (MSU) solution (25g/mL) into ankle joint cavity. IL-1ß, CCR5, and CXCL10 levels in both serum and synovial fluid were measured using ELISA. NLRP3 expression in the synovial tissues was measured using western plot. RESULTS: The combination of sodium alginate and resveratrol significantly reduced synovial levels of IL-1ß, CCR5, and CXCL10 when compared with colchicines, and all P values were less than 0.0001. The combination of sodium alginate and resveratrol was also superior to resveratrol in terms of both serum levels and synovial levels of IL-1ß, CCR5, and CXCL10. In addition, resveratrol, with or without sodium alginate, could reduce NLRP3 expression obviously in the synovial tissues. CONCLUSION: The combination of sodium alginate and resveratrol has better effect over colchicines in treating MSU-induced acute gouty arthritis.

Pathogenesis and Clinical Management of Gouty Arthritis.

Gout, the most common of the crystal arthritides is a result of disturbed uric acid metabolism and precipitation of urate crystals in extra cellular space of joints, periarticular tissue, bones and other organs. In the West, gout affects around 1% of adult men over 45 years of age. The estimated incidence being 0.6 to 2.1 per 1000 per year, with a prevalence of 9.5 to 13.5 per 1000 persons of all ages.1 The incidence of gout has been on rise globally; potentially attributable to recent shifts in diet, lifestyle, medical care, and increased longevity.2 Gout is three to four times more common in males than in pre-menopausal females; incidence in women increases after menopause and after the age of 60, approaches that in men.3 This update aims to highlight recent developments in understanding pathogenesis of gout along with current management strategies.

Inflammatory gout: observations over a half-century.

This is a discussion of acute gouty arthritis, seen for over 50 years of engagement. It addresses the evolution of our current understanding of the interaction between urate crystals and key cellular components of the gouty inflammatory paroxysm, with new material on pathogenesis.

[The etiology and management of gout]. / Ätiologie und Management der Gicht.

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").

The last defence? Surgical aspects of gouty arthritis of hand and wrist.

OBJECTIVE: To review the epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment of gouty arthritis of the hand and wrist, with a focus on the surgical aspects. DATA SOURCES AND EXTRACTION: Electronic databases including MEDLINE, PubMed, and the Cochrane library were searched with the key words of "gouty arthritis", "hand", "wrist", and "surgical". STUDY SELECTION: A total of 55 articles were selected for inclusion in this review. DATA SYNTHESIS: There is no existing study for the overall prevalence of gout in Asia, though one study showed that it was 3.1% in Taiwan. Its pathophysiology entails hyperuricaemia, trauma, lower temperatures, and previous diseases. Gouty arthritis of hand and wrist presents as acute wrist pain, subcutaneous or peritendinous tophi, tenosynovitis, entrapment neuropathy, tendon rupture, or even bone destruction. Demonstration of negatively birefringent crystals in the absence of organisms and a normal white cell count in synovial fluid confirm the diagnosis. Medical treatment including non-steroidal anti-inflammatory drugs, colchicines, allopurinol, uricosuric agents, and lifestyle modifications remain the mainstay of treatment. Surgical treatment options for tophaceous gout involve decompression by aspiration, incision and drainage, tenosynovectomy, shaving procedures, and complex surgical approach. CONCLUSION. While medical treatment remains the mainstay of treatment for gouty arthritis of the hand and wrist, 5% of patients may not respond. In this group, surgery is often performed in advanced stages, but yields less-than-satisfactory outcomes. Gouty arthritis is difficult to treat when it starts to cause stiffness and deformities. Although more studies are needed to evaluate the outcomes, the authors suggest that one possible solution is pre-emptive surgery.

Establishment of a clinical diagnostic model for gouty arthritis based on the serum biochemical profile: A case-control study.

ABSTRACT: The disease progression of gouty arthritis (GA) is relatively clear, with the 4 stages of hyperuricemia (HUA), acute gouty arthritis (AGA), gouty arthritis during the intermittent period (GIP), and chronic gouty arthritis (CGA). This paper attempts to construct a clinical diagnostic model based on blood routine test data, in order to avoid the need for bursa fluid examination and other tedious steps, and at the same time to predict the development direction of GA.Serum samples from 579 subjects were collected within 3 years in this study and were divided into a training set (n = 379) and validation set (n = 200). After a series of multivariate statistical analyses, the serum biochemical profile was obtained, which could effectively distinguish different stages of GA. A clinical diagnosis model based on the biochemical index of the training set was established to maximize the probability of the stage as a diagnosis, and the serum biochemical data from 200 patients were used for validation.The total area under the curve (AUC) of the clinical diagnostic model was 0.9534, and the AUCs of the 5 models were 0.9814 (Control), 0.9288 (HUA), 0.9752 (AGA), 0.9056 (GIP), and 0.9759 (CGA). The kappa coefficient of the clinical diagnostic model was 0.80.This clinical diagnostic model could be applied clinically and in research to improve the accuracy of the identification of the different stages of GA. Meanwhile, the serum biochemical profile revealed by this study could be used to assist the clinical diagnosis and prediction of GA.

NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice.

Gouty arthritis is a common inflammatory disease characterized by monosodium urate (MSU) crystal-induced nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation with upregulated caspase 1 protease and IL-1ß in macrophages. Cucurbitacin B (CuB) is a tetracyclic triterpene that possesses a potential anti-inflammatory activity. However, the immunomodulatory and anti-inflammatory effects of CuB on gout have not been well characterized. Therefore, the purpose of the present study was to determine whether CuB exhibits anti-inflammatory effects on gout and to analyze the underlying molecular mechanism. We examined the effects of CuB on various stimuli-activated bone marrow-derived macrophages (BMDMs) and in a mouse model with MSU-induced acute gouty arthritis. Our results demonstrated that CuB effectively suppressed multiple stimuli-activated IL-1ß secretion by interrupting NLRP3 inflammasome complex formation, inhibiting NLRP3 inflammasome activation and suppressing key enzymes of glycolysis in macrophages. Consistent with this, CuB pretreatment also ameliorated MSU-induced arthritis in vivo models of gout arthritis, manifested by reduced foot swelling and inflammatory cell infiltration. Taken together, our data provide the evidence that CuB is an NLRP3 inflammasome inhibitor with therapeutic potential for treating NLRP3 inflammasome-mediated diseases, especially gouty arthritis.

Gout in pediatric renal transplant recipients.

Clinical gout has rarely been described after pediatric renal transplantation (RTx), although asymptomatic hyperuricemia is common in these patients. We describe three male pediatric patients who presented with gouty arthritis 7-8.5 years following RTx. Since receiving allopurinol, all patients had been free of gouty symptoms. To prevent severe bone marrow depletion, the dosage of azathioprine, an immunosupressant drug, was reduced by 50% to prevent interaction with allopurinol. Because atypical presentation of gout can occur, a high index of suspicion is needed to allow appropriate diagnosis of this disease in patients with skeletal pain after RTx.

Refractory polyarticular gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome.

Immune reconstitution inflammatory syndrome (IRIS) describes the initial clinical deterioration some patients manifest upon initiation of effective antiretroviral therapy (ART) for HIV infection. In this report we describe a case of IRIS manifesting as polyarticular gout, a previously unreported rheumatological manifestation of IRIS. A 53-year-old HIV-infected man with a history of intermittent attacks of gout and an initial CD4 count of 112 cells/microL and a viral load of >100,000 copies/mL presented to our institution with severe, refractory, polyarticular gout approximately 4 weeks after initiating ART. At this point, the patient demonstrated significant gains in his CD4 counts (103 cells/microL) and a greater than 3 log decline in his HIV-1- viral load. This episode was prolonged lasting for approximately 10 weeks and required hospitalization for the management of pain and control of inflammation. The temporal associations of this attack with the initiation of ART and the observed immunologic reconstitution make IRIS a clinical possibility.Monosodium urate crystals through their interactions with interleukin 1- beta, and neutrophilic synovitis play a critical role in the pathophysiology of gout. Defects in both neutrophil and macrophage function and imbalances in the cytokine milieu are documented in HIV infected patients. The introduction of ART results in restoration of neutrophil and macrophage function, declines in levels of the anti-inflammatory cytokine IL-10, and increases in levels of proinflammatory cytokines including IL-1 beta, which may provide the necessary milieu for the precipitation of attacks of severe polyarticular gout in the context of ART initiation.

[Gout arthritis: Pathogenesis, diagnostics and treatment]. / Die Gichtarthritis: Pathogenese, Diagnostik und Behandlung.

The initial presentation of gouty arthritis can be a dramatic event. Chronic gout may lead to the destruction of joints, invalidity and increased mortality. The incidence of this disorder is high, despite effective therapeutic measures. The treatment of refractory cases may be a challenge to the general practitioner and the specialist alike. The article presented here summarizes the current state of diagnostics and treatment of acute and chronic gout.

Role of T cells in the pathogenesis and treatment of gout.

Though macrophages and neutrophils are considered to be the principal immune cells involved in gout inflammation, recent studies highlight an emerging role of T cell subsets in the pathogenesis of gout. Some studies found that abnormal functions of several T cell subsets and aberrant expressions of their signature cytokines existed in gouty arthritis. Additionally, recent studies also suggested that therapeutic strategies by targeting pro-inflammatory T cell subsets or their related cytokines could ameliorate monosodium urate (MSU) crystals-induced arthritis in mice. The important role of T cells in gouty arthritis may provide some explanation for the absence of acute gout attacks among individuals with severe hyperuricemia or clinical evidence of MSU crystals deposition. Nevertheless, the molecular mechanisms underlying the role of those T cell subsets in gouty arthritis and their role in the initiation, progression and resolution of gouty arthritis are largely elusive, which need to be elaborated in future research. Uncovering the role of those T cell subsets in gout may transform our understanding of gout and facilitate new promising preventive or therapeutic strategies for gouty arthritis.

Imaging of gout: findings and pitfalls. A pictorial review.

Gout is the most common crystal arthropathy, accounting for up to 5% of all arthritis. The hallmark of the disease is hyperuricemia with the subsequent deposition of monosodium urate (MSU) crystals in the intra- and extra-articular soft tissues and bones, leading to inflammation of these tissues. Recurrent intermittent flares can result in chronic gouty arthritis leading to cartilage and bone destruction. The most sensitive and specific imaging methods for diagnosing acute gout are ultrasound and dual energy computed tomography (DECT). In the chronic or tophaceous gout, imaging may depict tophi and their local destructive effect on surrounding tissues with characteristic findings on radiographs. In this pictorial review the imaging features of acute and chronic gout on radiographs, ultrasound, and DECT are presented, as well as imaging pitfalls that one needs to be aware.

Gouty arthritis in acute cerebrovascular disease.

BACKGROUND: Gouty arthritis is a metabolic disorder associated with several medical diseases and is considered as a high-risk factor of acute myocardial infarction and cardiovascular mortality. Since no study has assessed the frequency of gout attack in acute-stroke patients, a retrospective analysis of gouty arthritis in stroke patients was performed to identify the frequency and characteristics of gouty arthritis in hospitalized stroke patients. METHODS: We reviewed the data of 920 patients admitted to the neurology ward of the Chiayi Chang Gung Memorial Hospital between 2002 and 2005 with ischemic stroke. The frequency of gouty arthritis in these patients was evaluated. The severity of the risk factors was compared between the patients with gout and those without. RESULTS: The frequency of gouty arthritis in the stroke patients was 6.5%. Most patients had an attack of gout within 9 days of admission. History of gout, uric acid level and hypercholesterolemia were independent risk factors of gout attack during acute stroke. The duration of acute-ward stay was longer in patients with gout than in those without (17.17 vs. 14.01 days, p = 0.016). CONCLUSIONS: Our retrospective study demonstrated that gout attack is not uncommon in acute-stroke patients and may result in longer duration of acute-ward stay.