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Febuxostat for prevention of gout attacks.

(1) Febuxostat is a selective inhibitor of xanthine oxidase. Its use in the management of hyperuricemia and gout is being studied. (2) In a 52-week, phase III randomized clinical trial, febuxostat was superior to allopurinol for lowering uric acid levels. Its efficacy in preventing gout attacks was similar to that of allopurinol. Despite a similar rate of adverse effects, individuals on febuxostat were more likely to stop treatment than those on allopurinol. (3) The most commonly observed adverse effects with febuxostat include liver function test abnormalities, diarrhea, headache, nausea, vomiting, abdominal pain, and dizziness. (4) Given that renal dysfunction is a risk factor for hyperuricemia and gout, the safety and efficacy of febuxostat in this population should be considered, but only limited data are available. (5) The diffusion of febuxostat may be limited by its price relative to that of allopurinol, regardless of whether febuxostat proves to have advantages in specific populations.

Allopurinol↗

Use of piroxicam in the treatment of acute gout.

The authors carried out an open noncomparative study to evaluate the anti-inflammatory therapeutic activity of piroxicam in 40 adult patients suffering from acute gout. The patients ranged in age from 28 to 68 years (the average age was 51.6 years) overall, 21 men and 19 women participated in the trial. All of the patients had their disease for more than one year and they were receiving treatment with Benziodarone, 100 mg per day when the drug was discontinued from clinical use in Brazil. All of these patients subsequently experienced aggravation of their disease and had an acute attack of gout. Each patient was given piroxicam, 40 mg, in a single dose on the first day and two divided doses of 20 mg for the following five days. The affected joints were: elbow, knee, ankle and hallux. Severity of pain at rest, severity of pain on movement, tenderness, swelling, redness, heat and restriction of movement were evaluated. By the sixth day of the trial, good or total remission was observed in all patients. Overall evaluation of efficacy showed excellent and good results in 81.6% of the patients. Tolerability was excellent and good in 92.5%. All adverse reactions that occurred during the use of piroxicam therapy were noted. Five patients showed mild side effects, such as pyrosis, nausea and headache, and two patients had severe side effects (skin rash, gastric disturbance) that necessitated withdrawal from therapy. Finally, statistical analysis demonstrates that piroxicam is highly efficacious in the treatment of acute gout.

Acute Disease↗

[Therapy of hyperuricemia and gout].

Therapy of hyperuricemia and gout has to depend on pathogenesis and stage of the disease. Dietary regimen are in the forefront in treatment of asymptomatic hyperuricemia. Uric acid lowering drugs can only be supported in repeated serum-measures from 9 mg/dl up. The therapy of an acute attack of gout primarily is done with non-steroidal antiinflammatory drugs, in rare cases with colchicine or corticoids. Gouty arthritis in intermission, independent of the extent of hyperuricemia, as well as chronic gout are indications for an uric acid lowering pharmacotherapy, usually for life. A special therapeutic challenge arises out of renal complications and the frequent association with the metabolic syndrome.

Acute Disease↗

Clinical presentation and disease associations of gout: a hospital-based study of 100 patients in Singapore.

The aim of this retrospective study was to characterise the clinical presentation and disease associations of Oriental patients with gout seen in our hospital over a six-month period. One hundred patients comprising of 77 males and 23 females [89% Chinese, 7% Malays, 2% Indians and 2% others; mean age was 50.9 years (range 18 to 82 years), mean age at onset of disease was 43.7 years (range 16 to 78 years)] were studied. The disease was familial in 18% and 44% of patients had a history of alcohol ingestion. Co-morbid conditions included hypertension (36%), hyperlipidaemia (25%), renal failure (17%), ischaemic heart disease (13%), diabetes mellitus (4%), systemic lupus erythematosus (3%), psoriasis (2%) and ankylosing spondylitis (1%). The majority of patients (68%) had at least one associated disease. At the onset of disease, the joints commonly involved were the ankles (39%) and knees (27%) whilst the first metatarsophalangeal (MTP) joint was affected in only 26% of cases. Polyarticular onset was uncommon (n = 6). The precipitating factors reported by the patients included food (n = 23), alcohol (n = 12), drugs (n = 4), trauma (n = 3) and surgery (n = 2). Eleven patients had a history of renal calculi and 15% had tophaceous gout. Majority of patients (71%) had been treated with urate-lowering drugs (allopurinol). We concluded that gout in Singapore predominantly affects middle-aged men who often have an accompanying illness.

Adolescent↗

Preliminary criteria for the classification of the acute arthritis of primary gout.

The American Rheumatism Association sub-committe on classification criteria for gout analyzed data from more than 700 patients with gout, pseudogout, rheumatoid arthritis, or septic arthritis. Criteria for classifying a patient as having gout were a) the presence of characteristic urate crystals in the joint fluid, and/or b) a topus proved to contain urate crystals by chemical or polarized light microscopic means, and/or c) the presence of six of the twelve clinical, laboratory, and X-ray phenomena listed in Table 5.

Acute Disease↗

Monosodium urate crystals in the knee joints of patients with asymptomatic nontophaceous gout.

We aspirated synovial fluid from the knees of 50 patients with asymptomatic, nontophaceous gout, in whom synovial fluid monosodium urate (MSU) crystals had previously been documented in the knees or other joints. Fifty-eight percent of these asymptomatic patients had MSU crystals in their knee joints. Serum uric acid levels, serum creatinine levels, volume of synovial fluid aspirated, and cell counts of the aspirated fluid did not differentiate the MSU crystal-positive group from the group without MSU crystals. Clinical factors such as alcohol abuse, coronary heart disease, hypertension, duration of gout, duration of the intercritical period, and drug therapy did not differentiate the 2 groups. Nineteen patients consented to aspiration of their other knee. Seven of these patients (37%) had MSU crystals bilaterally, and 6 patients (32%) had them unilaterally. The implications of the persistence of MSU crystals (including those in intracellular locations) in many patients, despite normalization of serum uric acid levels, should be determined. Knee joint aspiration is a sensitive method for the demonstration of MSU crystals in asymptomatic patients. The procedure might also be useful in documenting these crystals in patients who have had attacks of arthritis with features consistent with a diagnosis of gout, but in whom MSU crystals have not been documented.

Allopurinol↗

Analysis of the genotypes for aldehyde dehydrogenase 2 in Japanese patients with primary gout.

Alcoholic ingestion is one of the major factors for increasing serum uric acid levels. Genotypes of aldehyde dehydrogenase 2 (ALDH2, E.C.1.2.1.3), which regulates the sensitivity of an individual to ethanol, were determined in Japanese patients with gout and control subjects by allele specific oligonucleotide hybridization using PCR amplified gene. The most common allele ALDH2*1 codes for normal ALDH2 activity, while the less common allele ALDH2*2 codes for a lower enzyme activity. The frequency of homozygotes of ALDH2*2 was significantly lower in patients with gout than those with rheumatoid arthritis or a normal population. Plasma and urinary hypoxanthine levels were strikingly increased after ethanol drinking in homozygotes for ALDH2*1 but not in heterozygotes for ALDH2*1/ALDH2*2, indicated extensive purine nucleotide degradation in homozygote for ALDH2*1. These data indicated that alcohol ingestion may not be the requisite factor but is deeply involved in the pathogenesis of gout and hyperuricemia.

Alcohol Drinking↗

Gout disease. Its natural history based on 1,000 observations.

Gout disease in our country as both exogenous factors (dietary habits, professions, etc.) and endogenous factors (sex, inheritance, etc.) play a polygenic role in its incidence. Those conditions resulting in hyperuricemia (diseases, drugs, etc.) facilitate the clinical manifestations. But a genetic determinant in the articular reaction in front of an accumulation of uric acid crystals or in the development of such crystallization is a fundamental factor in the manifestation of the disease. In our series we were able to confirm the high incidence of arterial hypertension, renal lithiasis and renal participation in gout. The role of lead and of certain professions in favouring the hyperuricemia is suggested. A classification of gout, from a functional point of view, must include both the clinical form and the analysis of the whole renal function, and the renal handling of uric acid. This is mandatory not only for the diagnosis and prognosis of the disease but to set the basis of its adequate management.

Calculi↗

Impact of associated medical conditions on clinical features of gout.

In view of the various available drugs, we are now in a very much better situation for treatment of gout, with and without associated medical conditions. When several drugs are employed in one single patient, however, one may run into drug interactions, resulting into exaggerated hyperuricemia or induced acute gouty arthritis. In lieu of the various associated medical conditions, controlled or uncontrolled, the clinical features of gout may be modified. Accordingly, one must treat the patient's gout as well as his various stages of the associated medical conditions, and each patient must be individualized.

Adult↗

Serum lipids and lipoproteins in patients with primary gout.

Serum lipid and lipoprotein values of 32 male patients suffering from gout were quantitated and compared with corresponding values of a random control group which did not differ significantly with regard to age, body weight index and socio-economic status. All patients were on therapy with allopurinol which lasted on average for 6 years. The most striking differences between patients and controls were the increased triglyceride and apo B values and the decreased HDL-cholesterol (HDL-C) and HDL-phospholipid (HDL-PL) values in the patient group. The values of total cholesterol, LDL-cholesterol, apo A-I and Lp (a) were not significantly different between patients and controls. The great differences in the ratios of apo B/LDL-C, apo A-I/HDL-C and apo A-I/HDL-PL values suggest that gout is connected with changes in the chemical composition of the major lipoprotein classes. In three normolipemic individuals who were treated for 3 weeks with allopurinol no changes in lipoproteins and apolipoproteins were apparent. The results are discussed in view of the atherosclerosis risk of patients suffering from gout.

Apolipoproteins A↗

Long-term remission from gout associated with fenofibrate therapy.

Short-term studies with fenofibrate, an established treatment for hyperlipidaemia, have shown that its unique side effect of urate lowering is mediated through enhanced renal urate clearance. The long-term effects of fenofibrate on hyperuricaemia and gout have not previously been reported. We report two patients with hyperlipidaemia in association with hyperuricaemia in whom long-term fenofibrate therapy was associated with a sustained reduction in serum urate and lipid levels, together with remission from recurrent attacks of acute gout. The mechanisms involved in these effects and the potential role for fenofibrate in the management of gout are discussed.

Fenofibrate↗

Recent advances in the epidemiology of gout.

Gout remains among the most common of all inflammatory arthridities with an incidence that appears to have risen. Evidence is accumulating to support lifestyle and dietary factors, such as heavy consumption of beer and liquor as well as diets rich in meats and seafood as important gout risk factors. There is also a renewed interest in important associations between gout and other comorbidities like hypertension and cardiovascular disease. The importance of hyperuricemia on health considerations beyond the musculoskeletal system is an area worthy of even more study.

Global Health↗

The Filipino and gout.

Hyperuricemia and gout has been recognized among the Filipinos in Hawaii, Alaska, and mainland United States for almost two decades. Several studies bearing out this impression have been reviewed. The awareness of these observation prompted an extension to the Filipino in his natural environment. These studies showed a lower mean of serum uric acid values in healthy subjects when using comparative enzymatic spectrophotometric determinations. Aside from genetic factors, Filipino hyperuricemia may become manifest because of environmental stress, including dietary stress, and investigators postulate that some Filipinos possess a renal defect that may lead to hyperuricemia due to renal inability to compensate for an increased purine intake which may occur in the shift from a low-purine Filipino diet to a high-purine Western diet in his new environment, as in the case of the Filipino immigrant. The clinical profile of gout as it exists in the Philippines has been compared and found to be similar generally to that of other series. The control of the hyperuricemia and gout has been satisfactorily accomplished in the Filipino patients with the long-term use of allopurinol, sometimes complemented with colchicine taken daily.

Adolescent↗

Systemic steroid therapy for acute gout: a clinical trial and review of the literature.

Nonsteroidal antiinflammatory drugs are frequently used as initial therapy in acute gout. In select cases, however, colchicine has been recommended as an alternative therapy. A review of the literature raises significant concerns regarding the cost to benefit ratio of using colchicine in this setting. A survey of alternative forms of therapies showed few studies investigating the efficacy and side effects of a short course of oral steroids, and little support for this modality in standard textbooks. Our preliminary study suggests that a short course of oral corticosteroid therapy can be used effectively for acute gout when NSAIDs are contraindicated. The use of prednisone 30 to 50 mg or its equivalent initially, and gradually tapered over 10 days, results in clinical resolution without rebound arthropathy or steroid complications in most patients. As a result, we rarely use colchicine in the management of acute gout in our practice.

Acute Disease↗

The prevalence and prophylaxis of gout in England.

The prevalence of gout in England was reported as having nearly doubled in the 1970s to about 3 per 1000, and it is possible that it has continued to increase. There may also have been some change in the level of prophylactic therapy compared with the 44.8% recorded in 1979. In this study, data were provided from their morbidity registers by 40 volunteer practices with a combined population of over 300,000 patients. Analyses of prevalence by age and sex, and of the extent of prophylaxis were made. The male:female ratio and the increase with age found were in line with earlier work, but overall prevalence was much higher at almost 10 per 1000. There was considerable inter-practice variation: 20% of this could be accounted for by the age and sex structure of the practice populations, but neither economic status nor broad geographical factors appeared to be significant, and it did not appear to be due to variation between practices in the level of special interest in gout. Prophylactic therapy--almost entirely allopurinol--was being prescribed for 48% of the sufferers; though practices varied widely in their propensity to give it, as a group the amount of allopurinol they used was close to the national average. The increase found in the prevalence of gout may be related to an increase in obesity in the population.

Adult↗

An unusual case of tophaceous gout involving the anterior cruciate ligament.

Abstract We describe a very unusual case of a 49-year-old man with tophaceous gout involving and infiltrating the base of the anterior cruciate ligament of the left knee. To our knowledge, such a case has never been reported in the literature, although gout is well known and widely studied. Magnetic resonance imaging findings and differential diagnosis were analyzed before arthroscopy. Tophaceous gout was suspected at arthroscopy and confirmed on pathologic examination. Treatment consisted of partial removal of the tumor by arthroscopy, conserving the anterior cruciate ligament.

Anterior Cruciate Ligament↗

Gout: update on some pathogenic and clinical aspects.

Pathogenesis of gout inflammation remains unknown, but recent advances have been made with respect to initiation, amplification, and self-limitation. Direct crystal-cell membrane contact leads to cell activation, involving membrane-associated molecules. Resolution of acute gout inflammation is a mechanism that is controlled by monocyte-macrophage switch, which results in the loss of cytokine production capability and, conversely, the ability to produce anti-inflammatory molecules. MRI and ultrasound findings provide preliminary data that are not yet used in clinical trials. Diagnosis and management recommendations are missing, but this gap will be filled soon with the upcoming European League Against Rheumatism Task Force's recommendations on gout.

Crystallization↗

Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat gout.

The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and then to uric acid, which plays a crucial role in gout. A total of 122 traditional Chinese medicinal plants, selected according to the clinical efficacy and prescription frequency for the treatment of gout and other hyperuricemia-related disorders, have been evaluated for the enzyme inhibitory activity. Among the 122 methanol extracts derived from these species, 69 were shown to be inhibitory at 100 microg/ml, with 29 having greater than 50% inhibition. As to the equal amount of water extracts, 40 were disclosed to be active at 100 microg/ml, with 13 possessing more than 50% inhibition. At 50 microg/ml, 58 methanol and 24 water extracts exhibited inhibitory activity, with 15 of the former and two of the latter showing greater than 50% inhibition. The most active was the methanol extract of the twig of Cinnamomum cassia (Lauraceae) (IC(50), 18 microg/ml), which was followed immediately by those of the flower of Chrysanthemum indicum (Asteraceae) (IC(50), 22 microg/ml) and the leaves of Lycopus europaeus (Lamiatae) (IC(50), 26 microg/ml). Among the water extracts, the strongest inhibition of the enzyme was observed with that of the rhizome of Polygonum cuspidatum (Polygonaceae) (IC(50), 38 microg/ml). The IC(50) value of allopurinol used as a positive control was 1.06 microg/ml. The study demonstrated that the effects for these medicinal plants used for the gout treatment were based, at least in part, on the xanthine oxidase inhibitory action.

Enzyme Inhibitors↗