[Gout; chronic gout, complicated gout and crenotherapy of gout].
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OBJECTIVE: Mechanisms underlying the adolescent-onset and early-onset gout are unclear. This study aimed to discover variants associated with early-onset gout. METHODS: We conducted whole-genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12 to 19 years) to discover common and low-frequency single-nucleotide variants (SNVs) associated with gout. Candidate common SNVs were genotyped in an early-onset gout cohort of 2,834 individuals (gout onset ≤30 years old), and meta-analysis was performed with the discovery and replication cohorts to identify loci associated with early-onset gout. Transcriptome and epigenomic analyses, quantitative real-time polymerase chain reaction and RNA sequencing in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated the regulation and function of candidate gene RCOR1. RESULTS: In addition to ABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified two novel loci (Pmeta < 5.0 × 10-8): rs12887440 (RCOR1) and rs35213808 (FSTL5-MIR4454). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low-frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte messenger RNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. CONCLUSION: This is the first comprehensive genetic characterization of adolescent-onset gout. The identified risk loci of early-onset gout mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent-onset gout.
We examined whether the age at onset, gender, arthritic manifestations, and tophus formation in familial gout are different from those in nonfamilial gout, and we also examined the contributory effect of genetic association to the concurrence of hypertriglyceridemia, hypercholesterolemia, type 2 diabetes mellitus (DM), hypertension, obesity, and renal insufficiency with gout in Taiwan. A total of 21,373 gout patients' data from Ho-Ping Gout database were analyzed in this study retrospectively. The clinical and laboratory data were compared between familial and nonfamilial gout. Mean age at onset of gout in familial subjects was significantly 7.5 years lower than that of nonfamilial subjects (40.9 +/- 13.4 v 48.4 +/- 14.2 years, P =.0001), while gender, arthritic severity, and tophus formation were not significantly different between these 2 groups. Familial gout had lower serum triglyceride (TG), total cholesterol (TC), and percentage of hypertension than nonfamilial gout (182.4 +/- 125.3 v 195.9 +/- 135.8 mg/dL, P =.0001; 207.5 +/- 42.5 v 210.4 +/- 48.8 mg/dL, P =.0003; and 19.57% v 22.56%, P <.0001, respectively). Their serum creatinine, body mass index (BMI), and percentage of type 2 DM were not significantly different. Our results demonstrate that familial gout is associated with precocious onset. Furthermore, the contributory effect of genetic association to the concurrence of hyperlipidemia and hypertension with gout is less than that of environmental factors, while the effect of genetic association to the concurrence of obesity, type 2 DM, and renal insufficiency with gout is equivalent to that of environmental factors.
OBJECTIVE: To determine if lowering of serum uric acid (SUA) concentrations below 6 mg/dl or longer duration of lowered SUA will result in depletion of urate crystals from the knee joints and prevent further attacks of gout. METHODS: A prospective study was initiated 10 years ago at Philadelphia VA Medical Center to attempt to maintain SUA levels of patients with crystal proven gout at < 6.0 mg/dl. We recalled all 57 patients who were available during 1999. Patients were divided into 2 groups: Group A, with SUA still > 6 mg/dl, and Group B, with SUA < or = 6 mg/dl. A knee joint aspirate was requested from all asymptomatic Group B patients and many in Group A. Aspirates were examined by polarized light microscopy for identification of crystals. RESULTS: There were no differences between the groups in age, sex, duration of gout, or serum creatinine. Group A (n = 38) had a mean of 6 attacks of gout for the recent year, those with tophi having the most frequent attacks. Among the 16 patients in this group who agreed to knee aspiration, monosodium urate (MSU) crystals were found in 14, although they were asymptomatic at the time. Nineteen patients (Group B) were able to maintain serum urate levels < or = 6 mg/dl for > 12 months. Nearly half of them had no attack of gout for 2 or more years, with a mean of 1 attack in the last year for the whole group. Three patients in whom tophi were found did not have major flares of gout within the past year. Knee joint aspiration was done on 16 asymptomatic patients. Seven (44%) still had MSU crystals present in their knees. Patients in this group who were taking prophylactic colchicine did not differ with respect to the character of synovial fluid from those who had discontinued it for up to several years, although the frequency of attacks was less in those who continued colchicine. CONCLUSION: A majority of patients were able to deplete urate crystal stores in their knee joint fluids when their SUA levels were kept to < or = 6 mg/dl for several years. The mechanisms for persistence in some patients, and whether such crystals have clinical implications, are not known. Patients with chronic gout need serum urate concentrations to be kept low to prevent further attacks.
Subcutaneous tophaceous deposits of monosodium urate, in the absence of arthritis, may occasionally occur as the initial manifestation of gout. In this report, we describe a 35-year-old man who presented with a 6-year history of multiple subcutaneous nodules and no history of previous articular complaints. Needle aspirations of the nodules proved them to be deposits of monosodium urate. A literature search revealed 28 other cases with a similar presentation. We propose the term "gout nodulosis" as a clinical entity at one end of the spectrum of gout to describe this group of patients.
This report describes the case of a 63-year-old obese and alcoholic butcher who suffered two episodes of distal oligoarthritis. These episodes were attributed to gout on the basis of response to colchicine and demonstration of hyperuricemia. Given the presence of hepatomegaly, splenomegaly and hyperleukocytosis, a sternal puncture and myelogram were performed and led to diagnosis of chronic myelogenous leukemia. In addition to the classic predisposing factors for gout, sickle cell anemia could be implicated in Black Africa. Longer life expectancy for patients with sickle cell anemia could increase the incidence of gout in Black Africa.
A number of patients with aseptic necroses of bone and hyperlipoproteinemia of types II and IV after Fredrickson are reported on. More than one half of them had hyperuricemia without symptoms of gout. The relationship between fat-, purine- and carbohydrate-metabolism are discussed. The clinical pictures of hyperuricemia, gout and hyperlipoproteinemia are shown to resemble each other. Differential diagnosis, particularly as related to aseptic necroses of bone, is discussed in detail.
Tophaceous deposits are frequently noted within articular cartilage, synovium, tendons, tendon sheaths, pinnae and the soft tissue on the extensor surface of the forearms, feet, and bursae in patients with a history of chronic gout. The authors describe an unusual case of severe chronic tophaceous gout without prior diagnostic history or presence of acute attacks. They describe the procedure for the excision of these masses as well as the radiographic and pathological findings.
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Explore the source record for details and available documents.
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Explore the source record for details and available documents.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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A subglottic tophaceous deposition of urate crystals is a rare finding. We report on a case of a male Caucasian who had a moderate dysphonia without any further laryngeal symptoms. The laryngoscopy revealed a hemispheric lesion on the left subglottic region. An excision biopsy was performed, and the histopathological examination of the dissected specimen showed a tophus. Diagnostic and therapeutic strategies are discussed.