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PubMed2006

Proteomic analysis of Down's syndrome patients with gout.

BACKGROUND: In this study, the expression of hypoxanthine-guanine phosphoribosyl transferase (HPRT) in Down's syndrome patients with gout (DS/G) was determined, and possible underlying mechanisms of gout were characterized using proteomic tools. METHODS: Serum was obtained from DS/G, healthy controls and gout patients (without DS), recruited from the rheumatology clinic. Baseline enzyme assays were recorded and RT-PCR used to identify HPRT gene expression. 2-D electrophoresis and mass spectrometry were utilized to determine a plausible explanation concerning the mechanisms leading to increased uric acid levels in DS patients. RESULTS: Two DS patients were diagnosed with gouty arthritis. Their HPRT enzyme activity was slightly lower than that of normal controls. HPRT expression was also slightly decreased in DS/G patients compared with controls. Serum protein profiles of these two DS/G patients revealed that haptoglobin alpha chain and apolipoprotein A1 (ApoA1) were both significantly down-regulated. Protein expression was validated by immunoblot. CONCLUSION: Our results revealed that low levels of haptoglobin in the two DS/G patients were related to renal dysfunction may have affected uric acid excretion and caused gout. However, decreased ApoA1 revealed a positive correlation between defective lipid metabolism and gouty arthritis in DS/G patients.

Adult↗
PubMed2006

"Crystal clear"-sonographic assessment of gout and calcium pyrophosphate deposition disease.

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.

Arthritis, Gouty↗
PubMed2006

Spinal gout in a renal transplant patient: a case report and literature review.

BACKGROUND: Gout in the axial spine is rare. We present a case report on a renal transplant patient who developed fever and acute back pain at the L5 through S1 level secondary to sodium urate deposits. We review the literature on this rare disease and propose a management algorithm based on a resulting analysis. CASE DESCRIPTION: A 37-year-old man with a history of gout and a renal transplant for IgA nephropathy presented with acute back pain and fever without evidence of neurological deficits. Magnetic resonance imaging revealed a uniformly contrast-enhancing infiltrative process involving the right pedicle, lamina, and inferior facet of the L5 vertebra. Computed tomography-guided needle biopsy revealed a friable white tissue consistent with sodium urate crystals. Conservative treatment with steroids and narcotics was used with good symptomatic relief. CONCLUSION: Although few cases of gout involving the spine have been reported, its prevalence is likely grossly underestimated. Most patients have a history of gout and have elevated levels of serum urate level on presentation. The disease most commonly involves the lumbar spine. Patients usually have neurological deficits on presentation, and surgical decompression produces favorable outcomes. However, conservative medical management is appropriate for those with back pain only. Aggressive control of hyperuricemia is essential regardless of the method of treatment.

Adult↗
PubMed1975

The radiology of gout. Review article.

The radiological features of gout are presented on the basis of a consecutive series of 64 in-patients and a review of the literature. Gout is a painful and potentially crippling disorder. Since fewer patients are referred with a classical acute attack due to the advent of more effective drug therapy, the radiologist may be presented with unusual or atypical cases. It is confirmed that there are no specific radiological features of gout. Provided a high index of suspicion be mai-tained, particularly in those groups of patients in whom secondary gout is common, a combination of signs may allow the diagnosis to be correctly inferred, leading to biochemical confirmation.

Acute Disease↗
PubMed1997

Incidence of diabetes and gout in hypertensive patients during 8 years of follow-up. The General Practice Hypertension Study Group.

Hypertension has been shown to be closely associated with metabolic disorders such as diabetes mellitus and gout. The aim of this study was to establish the incidence of both these diseases in hypertensive patients and their age-matched controls and to assess the risk associated with diuretic treatment. The results refer to the data base of 2295 hypertensive and 2280 controls from the General Practice Hypertension Study Group who were screened for hypertension. The rescreened hypertensive subjects (n = 1190) and their controls (n = 938) were followed for an average of 8 years. The diagnosis of diabetes and gout was made by their general practitioners. After 8 years of follow-up, diabetes mellitus was diagnosed in 5.0% of hypertensive and 1.5% normotensive subjects. The diagnosis of gout was made in 3.1% and 0.9%, respectively. Moreover, diabetes mellitus occurred more frequently in both hypertensive men and women, with diuretic treatment and without (respectively, men given diuretic: relative risk (RR) = 2.74, 95% confidence interval (CI): 0.99, 7.5; and men not given diuretic: RR = 2.25, 95% CI: 1.0, 5.3: women RR = 4.03 95% CI: 1.5, 10.8, and RR = 3.47, 95% CI: 1.4, 8.9) in comparison with their age-matched controls. For gout the excess was confirmed in hypertensive men with and without diuretic treatment (RR = 6.25 (95% CI: 2.4, 16.7) vs 3.93 (95% CI: 1.6, 9.7)).

Diabetes Mellitus↗
PubMedDate not supplied

Gout: not just for the rich and famous! Everyman's disease.

Gout is a painful form of arthritis that affects more than a million Americans annually. Using a case study, a discussion of the clinical onset, signs and symptoms, diagnosis, and treatment of acute and chronic gout is presented. The incidence and etiology of gout is presented, along with current diagnostic criteria and the most common differential diagnoses to consider. The current trends in diagnosing and treating the acute and chronic forms of gout are also addressed as well as some of the controversies and concerns about treatment options. The treatment plan and follow-up for the patient in the case presentation conclude the discussion.

Acute Disease↗
PubMed2005

Recent advances in the management of gout and hyperuricemia.

PURPOSE OF REVIEW: To review the recent advances in the management of gout and hyperuricemia. RECENT FINDINGS: The first quality indicators for gout management have been proposed. Selective COX II inhibitors, as well as traditional NSAIDs, are effective in acute gout. A new xanthine oxidase inhibitor, febuxostat, and pegylated uricases are in clinical trials. SUMMARY: The therapeutic aims in gout include termination of the acute attack as promptly and gently as possible, prevention of future attacks, prevention or reversal of complications of the, and prevention or reversal of associated features such as obesity, hypertriglyceridemia, hypertension, or alcoholism.

Gout↗
PubMed1991

Misdiagnosis of rheumatoid arthritis in an elderly woman with gout.

Polyarticular gout may be misdiagnosed in the elderly. This reflects the confusing clinical presentation of "diuretic gout" in the elderly, characterized by polyarticular onset, subacute symptoms, hand involvement, and early development of tophi. A misdiagnosis of rheumatoid arthritis can lead to poor treatment of gout, failure to recognize underlying renal insufficiency, and associated cardiac risks. Hyperuricemia may reflect systemic ATP depletion in acutely ill patients and thus represents a predictor for mortality. Medical treatment of polyarticular gout in elderly patients with compromised cardiac and renal function requires recognition of the clinical profile and consideration of the increased toxicity from standard therapies.

Aged↗
PubMed1982

Family study of lipid and purine levels in gout patients.

A family study was performed to determine whether the hypertriglyceridaemia associated with gout is present in families of gout patients or due to the life style of the patient himself. The study revealed the expected hypertriglyceridaemia in gout patients; this was reflected by elevated serum levels of prebetalipoproteins and with reduction in the proportion of beta-lipoprotein. None of these abnormalities were seen in the first-degree relatives. Furthermore, the proportion of high-density lipoproteins was not significantly raised in gout patients.

Female↗
PubMed1983

Acute polyarticular gout.

We report here on 41 male patients with acute polyarticular gout seen in 3 years. Acute polyarticular gout continues to masquerade as other commoner rheumatological disorders such as septic arthritis, rheumatoid arthritis, degenerative joint disease, and even hemiparesis. Almost all of these patients had clues to the diagnosis of acute gout in their medical history. These clues included a past history of intermittent acute gout, prior attacks of polyarticular arthritis, previous hyperuricaemia, and/or obvious tophi. The patients all responded promptly to nonsteroidal anti-inflammatory drugs. We observed serious toxic drug reactions in 8 patients.

Acute Disease↗
PubMed1983

A controlled study of diet in patients with gout.

To determine whether patients with gout have a diet which is distinctive in quality or quantity a careful dietary questionnaire was posed over 7 days to 61 men with gout and 52 control subjects. The average daily intake of most nutrients, including total purine nitrogen, was similar except that the patients with gout drank significantly more alcohol. Beer was the most popular beverage, and 25 (41%) of those with gout consumed more than 60 g alcohol daily (equivalent to 2 . 5 litres of beer). The heavy drinkers had a significantly higher intake of purine nitrogen, half of which was derived from beer. Though the effect of ingested purine on the blood uric acid is difficult to estimate, it probably was sufficient to have a clinical effect, augmenting the hyperuricaemic effect of alcohol itself.

Alcoholic Beverages↗
PubMed2000

Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study.

OBJECTIVES: Insulin resistance (IR) has been increasingly implicated in the pathogenesis of gout. The lipoprotein abnormalities described in hyperuricaemic subjects are similar to those associated with IR, and insulin influences renal urate excretion. In this study it was investigated whether dietary measures, reported to be beneficial in IR, have serum uric acid (SU) and lipid lowering effects in gout. METHODS: Thirteen non-diabetic men (median age 50, range 38-62) were enrolled. Each patient had had at least two gouty attacks during the four months before enrollment. Dietary recommendations consisted of calorie restriction to 6690 kJ (1600 kcal) a day with 40% derived from carbohydrate, 30% from protein, and 30% from fat; replacement of refined carbohydrates with complex ones and saturated fats with mono- and polyunsaturated ones. At onset and after 16 weeks, fasting blood samples were taken for determination of SU, serum cholesterol (C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Results were expressed as median (SD). RESULTS: At onset, the body mass index (BMI) was 30.5 (8.1) kg/m(2). Dietary measures resulted in weight loss of 7.7 (5.4) kg (p=0.002) and a decrease in the frequency of monthly attacks from 2.1 (0.8) to 0.6 (0.7) (p=0.002). The SU decreased from 0.57 (0.10) to 0.47 (0.09) mmol/l (p=0.001) and normalised in 7 (58%) of the 12 patients with an initially raised level. Serum cholesterol decreased from 6.0 (1.7) to 4.7 (0. 9) mmol/l (p=0.002), LDL-C from 3.5 (1.2) to 2.7 (0.8) mmol/l (p=0. 004), TGs from 4.7 (4.2) to 1.9 (1.0) mmol/l (p=0.001), and C:HDL-C ratios from 6.7 (1.7) to 5.2 (1.0) (p=0.002). HDL-C levels increased insignificantly. High baseline SU, frequency of attacks, total cholesterol, LDL-C and TG levels, and total C:HDL-C ratios correlated with higher decreases in the respective variables upon dietary intervention (p<0.05). CONCLUSION: The results suggest that weight reduction associated with a change in proportional macronutrient intake, as recently recommended in IR, is beneficial, reducing the SU levels and dyslipidaemia in gout. Current dietary recommendations for gout may need re-evaluation.

Adult↗
PubMed1985

The measurement of high density lipoprotein subfractions in patients with primary gout using a simple precipitation method.

We have evaluated a simple dextran sulphate precipitation method for measuring high density lipoprotein cholesterol (HDL) subfractions and have used this method to measure plasma HDL2 and HDL3 in a group of 28 patients with primary gout. These patients were found to have significantly lower levels of plasma HDL and HDL2 than a group of healthy controls, matched for age and sex and of similar body mass index (BMI); no significant difference in mean levels of the HDL3 subfraction was found however. We have confirmed the high prevalence of hypertriglyceridaemia in subjects with gout compared to controls and the mean serum triglyceride levels were significantly higher (P less than 0.01) in the gout group than in controls. We have also shown that subjects with high serum triglyceride levels tend to have low plasma HDL2 concentrations, a finding which is consistent with an inverse relationship between these two parameters. These lipid abnormalities may partly explain the high prevalence of premature atherosclerosis in patients with primary gout.

Chemical Precipitation↗
PubMed2006

Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase.

PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single subcutaneous injections of PEG-uricase (4 to 24 mg) were administered to 13 such subjects (11 had tophaceous gout), whose plasma uric acid concentration (pUAc) was 11.3 +/- 2.1 mg/dl (mean +/- SD). By day seven after injection of PEG-uricase, pUAc had declined by an average of 7.9 mg/dl and had normalized in 11 subjects, whose mean pUAc decreased to 2.8 +/- 2.2 mg/dl. At doses of 8, 12, and 24 mg, the mean pUAc at 21 days after injection remained no more than 6 mg/dl. In eight subjects, plasma uricase activity was still measurable at 21 days after injection (half-life 10.5 to 19.9 days). In the other five subjects, plasma uricase activity could not be detected beyond ten days after injection; this was associated with the appearance of relatively low-titer IgM and IgG antibodies against PEG-uricase. Unexpectedly, these antibodies were directed against PEG itself rather than the uricase protein. Three PEG antibody-positive subjects had injection-site reactions at 8 to 9 days after injection. Gout flares in six subjects were the only other significant adverse reactions, and PEG-uricase was otherwise well tolerated. A prolonged circulating life and the ability to normalize plasma uric acid in markedly hyperuricemic subjects suggest that PEG-uricase could be effective in depleting expanded tissue stores of uric acid in subjects with chronic or tophaceous gout. The development of anti-PEG antibodies, which may limit efficacy in some patients, is contrary to the general assumption that PEG is non-immunogenic. PEG immunogenicity deserves further investigation, because it has potential implications for other PEGylated therapeutic agents in clinical use.

Adult↗
PubMed2003

[Management of hyperuricemia in occupational health: with reference to "guidelines for the management of hyperuricemia and gout"].

In 1996, the need for the clinical guidelines for the management of hyperuricemia and gout was proposed of the consensus conference held at the 29th annual meeting of the Japanese Society of Purine and Pyrimidine Metabolism (president Yuji Matsuzawa). At the consensus conference, the following announcement was made. 1. Because the majority of patients with hyperuricemia are in the condition of multiple risk factor clustering syndrome, hyperuricemia per se should be counted as one of the typical lifestyle related diseases. 2. Medical management should be directed independently for the treatment of gouty arthritis and for control of the serum uric acid level. 3. The serum uric acid level should be taken into account as a possible cardiovascular risk factor. 4. Urine alkalization should be started if there is no symptom indicating hyperuricemia for the prophylaxis of urinary stones and renal dysfunction. 5. All the medical management should be considered under the consensus of the many expert physicians dealing with hyperuricemia and gout. This principal announcement was made by the consensus conference and the simple management recommendation of a 6-7-8 rule was proposed through the consensus of expert physicians. Recently, a guideline committee was organized in the Japanese Society of Gout and Nucleic Acid Metabolism (previous by the Japanese Society of Purine and Pyrimidine Metabolism) and the Guidelines for the Management of Hyperuricemia and Gout were prereleased in February and published in August 2002. In the new guidelines, the above policy was introduced and evidence was collected to give the guidelines contemporary clinical usefulness and value. It will help in the proper management of hyperuricemia in apparently healthy persons in occupational health, having multiple risk factors.

Arteriosclerosis↗
PubMed1997

MR imaging of tophaceous gout.

OBJECTIVE: MR imaging is not routinely used for evaluation of tophaceous gout. However, gout may present clinically in an atypical, unusual, or confusing manner. A gouty tophus occasionally mimics an infectious or neoplastic process, and MR imaging may be obtained under these circumstances. The purpose of this study was to determine the MR imaging characteristics of intraosseous and soft-tissue tophi. MATERIALS AND METHODS: We identified 13 MR imaging examinations performed during a 27-month period on nine patients with gouty arthritis. All were men 42-70 years old. T1-, proton density-, and T2-weighted spin-echo MR images were obtained for all the examinations. Nine examinations included contrast-enhanced MR images. The findings were then evaluated, as were the corresponding radiographs. RESULTS: Five patients presented with articular involvement, three patients with an isolated soft-tissue mass, and one patient with persistent soft-tissue swelling. The duration of symptoms ranged from 3 months to more than 20 years. Nearly all the tophi were of intermediate signal intensity on T1-weighted images. On T2-weighted images, three sites revealed an overall increase in the signal intensity of the tophi, whereas 10 studies showed a heterogeneous decrease in signal intensity. All but one tophus showed homogeneous enhancement. Erosion of adjacent bone, synovial pannus, joint effusion, soft-tissue edema, and bone marrow edema were common associated findings. CONCLUSION: The MR appearance of tophi in patients with tophaceous gout is constant on T1- but quite variable on T2-weighted images. This variability in signal intensity could be related to calcium within a tophus. Tophaceous gout should be considered in the differential diagnosis when a mass reveals heterogeneously low to intermediate signal intensity, particularly if the adjacent bone shows typical erosive changes or if other joints are involved. When faced with this situation, radiologists may find it helpful to obtain a further clinical history and recommend evaluating the patient's serum urate level.

Adult↗
PubMed1996

Unusual presentations of gout. Tips for accurate diagnosis.

In cases of unusual presentations, such as the three cases described here, gout or gouty arthritis may be misdiagnosed as rheumatoid arthritis, septic arthritis, or other rheumatic conditions and thus inappropriately treated. Microscopic analysis using compensated polarized light and culture of synovial fluid helps distinguish gouty arthritis from other arthropathies, and the presence of monosodium urate crystals establishes the diagnosis of gout. When gout is suspected, yet the initial examination does not reveal the telltale crystals, reexamination of synovial fluid is warranted. It is important for physicians to remember, though, that diagnosis of gout does not rule out the possibility of concurrent arthritic conditions.

Adult↗
PubMedDate not supplied

"Like a virgin": Absence of rheumatoid arthritis and treponematosis, good sanitation and only rare gout in Italy prior to the 15th century.

OBJECTIVES: This study was conducted to test several hypotheses: 1. That rheumatoid arthritis and syphilis were New World diseases, only transmitted to the Old World subsequent to the passages of Christopher Columbus; 2. To indirectly test the hypothesis that lead poisoning was prevalent in Roman Italy by looking for its byproduct, gout; 3. To test the hypothesis of compromised sanitation in ancient Italy, on the basis of spondyloarthropathy frequency; and 4. To assess variation of trauma frequencies in ancient Italy, by examining frequency of focal periosteal reaction. METHODS: Skeletons from sites ranging from the Bronze Age to the Black Plague epidemic of 1485-1486 were macroscopically evaluated for focal periosteal reaction and for the cardinal signs of rheumatoid arthritis, treponemal disease, gout and spondyloarthropathy. RESULTS: Examination of 688 individuals revealed low frequency of focally distributed periosteal reaction (bumps) in sites dated from the 3400-700 years before present, sharply increasing in the 15th century. Diffuse periosteal reaction was present only as isolated occurrences secondary to hypertrophic osteoarthropathy and sabre shin reaction was notably absent. Erosive disease was uncommon and always oligoarticular in distribution. No marginal erosions were present, with the exception of an isolated metatarsal with classic overhanging edge sign of gout. Subchondral erosions, peripheral joint fusion and axial skeletal involvement identified spondyloarthropathy frequencies of 1-3%, independent of the antiquity of the site. CONCLUSIONS: Italy, prior to Columbus was like a virgin. Rheumatoid arthritis and treponemal disease (specifically syphilis) were not present, further supporting the contention that they are New World-derived diseases. Periosteal signs of minor trauma were rare prior to fifteenth century plague times. This suggests a potential role of domestic (as opposed to outside environment activities) in is development. The hypothesis for a role of lead poisoning in the demise of the Roman Empire is falsified by the rarity of gout. The frequency of spondyloarthropathy was significantly below that found in sanitarily challenged populations, suggesting high standards of hygiene in ancient Italy.

Arthritis, Rheumatoid↗