Gout Research: 2002-2006
     
Internist (Berl). 2006 May;47(5):509-22.
[Hyperuricemia and gout: diagnosis and therapy.]
[Article in German]
Tausche AK, Unger S, Richter K, Wunderlich C, Grassler J, Roch B, Schroder HE.
Bereich Rheumatologie, Medizinische Klinik und Poliklinik III am Universitatsklinikum Carl Gustav Carus der TU Dresden, .

In our modern society hyperuricemia is one of the most frequent metabolism disturbances. So far, every fourth man and every tenth woman suffer from an asymptomatic or a symptomatic hyperuricemia named gout. Mostly, over nutrition and malnutrition as well as other secondary factors with a genetically determined renal secretion disturbance of uric acid lead to an increase of serum uric acid. By deposition of uric acid crystals in tissues with intermittent immunologic activation of inflammation cells a manifestation of gout can be seen. The clinical image of gout varies widely. It may manifest as acute or chronic arthritis, tophi on the skin, subcutaneous tissue and the skeletal system as well as urate nephropathy. To eliminate the consequences of hyperuricemia in the long term, apart from a thorough anamnesis of nutritional habits a general examination of metabolic parameters is necessary to exclude a metabolic syndrome and other causes for a secondarily caused hyperuricemia. As gout is very often primarily caused by a renal secretion disturbance of uric acid special diagnostics should be done. Basing on literature research and inclusion of experts opinions this article represents the therapeutically options in treatment of hyperuricemia and gout with their resulting side effects and contraindications.

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Rheumatology (Oxford). 2006 Apr 21; [Epub ahead of print]
Effectiveness of interventions for the treatment of acute and prevention of recurrent gout--a systematic review.
Sutaria S, Katbamna R, Underwood M.
Barts and The London, Queen Mary, University of London, Institute of Health Sciences, London, UK.

Objective. To determine the evidence for the effectiveness of treatments for acute gout and the prevention of recurrent gout. Method. Seven electronic databases were searched for randomized controlled trials of treatments for gout from their inception to the end of 2004. No language restrictions were applied. All randomized controlled trials of treatments routinely available for the treatment of gout were included. Trials of the prevention of recurrence were included only if patients who had had gout and had at least 6 months of follow-up were studied. Results. We found 13 randomized controlled trials of treatment for acute gout, two of which were placebo controlled. Colchicine was found to be effective in one study; however, the entire colchicine group developed toxicity. The only robust conclusion from studies of non-steroidal anti-inflammatory drugs is that pain relief from indometacin and etoricoxib are equivalent. We found one randomized controlled trial, reported only as a conference abstract, of recurrent gout prevention. Conclusion. The shortage of robust data to inform the management of a common problem such as gout is surprising. All of the drugs used to treat gout can have serious side effects. The incidence of gout is highest in the elderly population. It is in this group, who are at a high risk of serious adverse events, that we are using drugs of known toxicity. The balance of risks and benefits for the drug treatment of gout needs to be reassessed.

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Curr Opin Rheumatol. 2006 Mar;18(2):193-8.
Recent developments in diet and gout.
Lee SJ, Terkeltaub RA, Kavanaugh A.
Center for Innovative Therapy, University of San Diego, La Jolla, California 92037, USA. s2lee@ucsd.edu

PURPOSE OF REVIEW: Gout is the most common inflammatory arthritis in men, affecting approximately 1-2% of adult men in Western countries. United States gout prevalence has approximately doubled over the past two decades. In recent years, key prospective epidemiological and open-labeled dietary studies, coupled with recent advances in molecular biology elucidating proximal tubular urate transport, have provided novel insights into roles of diet and alcohol in hyperuricemia and gout. This review focuses on recent developments and their implications for clinical practice, including how we advise patients on appropriate diets and alcoholic beverage consumption. RECENT FINDINGS: Studies have observed an increased risk of gout among those who consumed the highest quintile of meat, seafood and alcohol. Although limited by confounding variables, low-fat dairy products, ascorbic acid and wine consumption appeared to be protective for the development of gout. SUMMARY: The most effective forms of dietary regimen for both hyperuricemia and gout flares remains to be unidentified. Until confirmed by a large, controlled study, it is prudent to advise patients to consume meat, seafood and alcoholic beverages in moderation, with special attention to food portion size and content of non-complex carbohydrates which are essential for weight loss and improved insulin sensitivity.

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Rheum Dis Clin North Am. 2006 Feb;32(1):235-44, xii.
Newer therapeutic approaches: gout.
Schumacher HR Jr, Chen LX.
Division of Rheumatology, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA. schumacr@mail.med.upenn.edu

Newer approaches to the treatment of gout have included modifications and further attention to aspects of current therapies, and development of interesting new therapies. Colchicine prophylaxis appears to be needed longer than previously recognized after introduction of a urate-lowering agent. Diet has received attention, though most dietary effects are small. New agents under investigation include pegylated formulations of uricase and a new potent xanthine oxidase inhibitor, febuxostat. Some cardiovascular drugs have been shown to be uricosuric.

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Drugs. 2005;65(18):2593-611.
Gout in solid organ transplantation: a challenging clinical problem.
Stamp L, Searle M, O'Donnell J, Chapman P.
Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz

Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor.Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined.Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with renal failure, solid organ transplant or tophaceous/polyarticular gout. Monitoring for hepatotoxicty is essential for patients taking benzbromarone.Physicians should carefully consider therapeutic options for the management of hypertension and hyperlipidaemia, which are common in transplant recipients. While loop and thiazide diuretics increase serum urate, amlodipine and losartan have the same antihypertensive effect with the additional benefit of lowering serum urate. Atorvastatin, but not simvastatin, may lower uric acid, and while fenofibrate may reduce serum urate it has been associated with a decline in renal function.Gout in solid organ transplantation is an increasing and challenging clinical problem; it impacts adversely on patients' quality of life. Recognition and, if possible, alleviation of risk factors, prompt treatment of acute attacks and early introduction of hypouricaemic therapy with careful monitoring are the keys to successful management.

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Curr Pharm Des. 2005;11(32):4117-24.
Overview of hyperuricaemia and gout.
Masseoud D, Rott K, Liu-Bryan R, Agudelo C.
Division of Rheumatology, Emory University School of Medicine/The Emory Clinic, 1365A Clifton Rd NE, 4th floor, Atlanta, GA 30322, USA.

In most mammals purine degradation ultimately leads to the formation of allantoin. Humans lack the enzyme uricase, which catalyzes the conversion of uric acid to allantoin. The resulting higher level of uric acid has been hypothesized to play a role as an antioxidant. Hyperuricaemia is usually an asymptomatic condition which is hypothesized to play a role in cardiovascular disease and hypertension. Some hyperuricaemic individuals develop gout, an inflammatory arthritis caused by the deposition of monosodium urate crystals in joints. Over time, acute intermittent gouty arthritis can develop into a chronic condition with deposits of monosodium urate (MSU) crystals in joints and as tophi. The mechanisms by which MSU crystals lead to an acute inflammatory arthritis are under investigation and current knowledge is reviewed here. Treatment of gout includes management of acute flares with anti-inflammatory medications such as non-steroidal anti-inflammatory drugs or corticosteroids and long term management with urate-lowering therapy when indicated. Future directions in the treatment of gout, in part guided by a better understanding of pathophysiology, are discussed.

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J Rheumatol. 2006 Jan;33(1):104-9. Epub 2005 Nov 1.
Frequency and predictors of inappropriate management of recurrent gout attacks in a longitudinal study.
Neogi T, Hunter DJ, Chaisson CE, Allensworth-Davies D, Zhang Y.
Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts 02118, USA. tneogi@bu.edu

OBJECTIVE: To evaluate the patterns and determinants of medication use during recurrent gout attacks. METHODS: We followed participants with documented gout in an online prospective case-crossover study. During an attack, subjects were asked if they had consulted a physician for the attack and what medications they were using. Definitely inappropriate therapy was defined as use of allopurinol or a uricosuric agent acutely without having used it as a prophylactic. Potentially inappropriate therapy was defined as use of analgesics alone, alternative remedies, or no medications. We estimated the risk of having >or= 1 attack in 1 year using life table methods. We examined the relation of various risk factors to the risk of inappropriate therapy using Poisson regression. RESULTS: Among 232 participants (mean age 52 yrs, 81% male) with documented gout, the risk of having >or= 1 attack in a year was 69%. One hundred ten participants consulted a physician for each attack, 49 did so for only some attacks, while 43 never consulted a physician for any attack. Fifty-three participants had definitely (n = 10) or potentially (n = 43) inappropriate therapy for their recurrent attacks. Physician consultation for an attack was associated with increased risk of inappropriate therapy (risk ratio, RR, 2.5, p = 0.006), whereas an increasing number of gout attacks was associated with lower risk of inappropriate therapy (RR 0.8, p = 0.01). CONCLUSION: Given the high risk of recurrent attacks and the substantial number of persons whose attacks are not appropriately managed, further education about management of gout attacks for both patients and physicians may be warranted.

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N Engl J Med. 2005 Dec 8;353(23):2450-61.
Febuxostat compared with allopurinol in patients with hyperuricemia and gout.
Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, Streit J, Joseph-Ridge N.
University of Chicago Pritzker School of Medicine, Chicago, USA. mbecker@medicine.bsd.uchicago.edu

BACKGROUND: Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout. METHODS: We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8. The primary end point was a serum urate concentration of less than 6.0 mg per deciliter (360 micromol per liter) at the last three monthly measurements. The secondary end points included reduction in the incidence of gout flares and in tophus area. RESULTS: The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the comparison of each febuxostat group with the allopurinol group). Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups: 64 percent of patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the low-dose febuxostat group discontinued the study. Four of the 507 patients in the two febuxostat groups (0.8 percent) and none of the 253 patients in the allopurinol group died; all deaths were from causes that the investigators (while still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group). CONCLUSIONS: Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate. Similar reductions in gout flares and tophus area occurred in all treatment groups. Copyright 2005 Massachusetts Medical Society.

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Drugs. 2005;65(18):2593-611.
Gout in solid organ transplantation: a challenging clinical problem.
Stamp L, Searle M, O'Donnell J, Chapman P.
Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz

Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor.Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined.Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with renal failure, solid organ transplant or tophaceous/polyarticular gout. Monitoring for hepatotoxicty is essential for patients taking benzbromarone.Physicians should carefully consider therapeutic options for the management of hypertension and hyperlipidaemia, which are common in transplant recipients. While loop and thiazide diuretics increase serum urate, amlodipine and losartan have the same antihypertensive effect with the additional benefit of lowering serum urate. Atorvastatin, but not simvastatin, may lower uric acid, and while fenofibrate may reduce serum urate it has been associated with a decline in renal function.Gout in solid organ transplantation is an increasing and challenging clinical problem; it impacts adversely on patients' quality of life. Recognition and, if possible, alleviation of risk factors, prompt treatment of acute attacks and early introduction of hypouricaemic therapy with careful monitoring are the keys to successful management.

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Curr Pharm Des. 2005;11(32):4133-8.
Dietary factors and hyperuricaemia.
Schlesinger N.
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903-0019, USA. schlesna@umdnj.edu

The connection of gout and hyperuricaemia with gluttony, overindulgence in food and alcohol and obesity dates from ancient times. Studies from different parts of the world suggest that the incidence and severity of hyperuricaemia and gout may be increasing. Uric acid (urate) is the end product of purine degradation. Although most uric acid is derived from the metabolism of endogenous purine, eating foods rich in purines contributes to the total pool of uric acid. Sustained hyperuricaemia is a risk factor for acute gouty arthritis, chronic tophaceous gout, renal stones and possibly cardiovascular events and mortality. Before starting lifelong urate-lowering drug therapy, it is important to identify and treat underlying disorders that may be contributing to hyperuricaemia. It is relevant to recognize the strong association of the insulin resistance syndrome (IRS) (abdominal obesity, dyslipidaemia, hypertension, raised serum insulin levels and glucose intolerance) with hyperuricaemia. Consumption of meat, seafood and alcoholic beverages in moderation and attention to food portion size is important. Moderation in the consumption of not only beer but also other forms of alcohol is essential. In the obese, controlled weight management has the potential to lower serum urate in a quantitatively similar way to relatively unpalatable "low purine" diets. Non-fat milk and low-fat yogurt have a variety of health benefits and dairy products may have clinically meaningful antihyperuricaemic effects. In addition, fruits, such as cherries and high intakes of vegetable protein diet may reduce serum urate levels.

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Am J Manag Care. 2005 Nov;11(15 Suppl):S451-8.
Understanding treatments for gout.
Cannella AC, Mikuls TR.
Section of Rheumatology and Immunology; Nebraska Medical Center; Emile at 42nd Street; Omaha, NE 68198.

Gout is one of the most readily manageable of the rheumatic diseases. This article reviews basic pathways in purine metabolism, uric acid handling, and the pathogenic mechanism of clinical gout, as well as the areas in those pathways amenable to intervention. Attention is also given to associated comorbidities, such as hyperuricemia and obesity, hypertension, hyperinsulinemia, and coronary artery disease. The significance of lifestyle modifications, such as weight loss and alcohol reduction, is discussed as an important adjunct to pharmacotherapy in gout. Current and investigational agents used in gout management are also reviewed. Finally, treatment recommendations for acute and chronic gout are suggested.

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J Rheumatol. 2005 Nov;32(11):2186-8.
Female gout: clinical and laboratory features.
De Souza AW, Fernandes V, Ferrari AJ.
Rheumatology Division, Universidade Federal de Sao Paulo, Sao Paulo-SP, Brazil.

OBJECTIVE: To evaluate and compare clinical and laboratory features of gout in men and women. METHODS: Twenty-seven women and 31 men with gout underwent clinical and laboratory evaluation and review of medical records. RESULTS: Disease onset in women was a mean of 7 years later than in men. There were no differences between women and men regarding systemic hypertension, diabetes mellitus, hyperlipidemia, chronic renal failure, renal stones, ischemic heart disease, or heavy alcohol consumption. Tophaceous gout was similar in both groups, although female gender seemed to be protective against risk of developing tophi (odds ratio: 0.449; 95% confidence interval: 0.151-1.330). Podagra was more common in men, and women showed a higher frequency of upper limb joint involvement. Most patients had low urate excretion rates. Achieving disease control was similar in women and men. Of the 8 women who were premenopausal at disease onset, 7 had secondary causes for gout; 5 of the 8 had high serum urate despite treatment. CONCLUSION: Gout in women had a later onset and higher frequency of upper limb joint involvement in comparison to men. Those with premenopausal onset tended to be refractory to standard therapy.

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Rev Med Suisse. 2005 Sep 14;1(32):2072-4, 2077-9.
[Hyperuricemia in hypertension: any clinical implication?]
[Article in French]
Deleaval P, Burnier M.
Service de Nephrologie et Consultation d'hypertension CHUV, 1011 Lausanne.

Twenty-five percent of untreated hypertensive patients are hyperuricemic. The causal role of uric acid in the pathogenesis of hypertension has not been clearly demonstrated in humans. An elevated serum uric acid appears to be predictive of the development of hypertension. Serum uric acid has also been considered as a cardiovascular risk factor but this issue is controversial. A high serum uric acid is associated with an increased cardiovascular morbidity and mortality in men. Thus, hyperuricemia in hypertensive patients should be considered as a sign of increased risk leading to a more intensive management of all other risk factors. When managing hypertensive patients with hyperuricemia, physicians should know the impact of antihypertensive drugs on serum uric acid to prevent a further increase in uric acid and the development of gout.

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J Hand Surg [Br]. 2005 Oct 20; [Epub ahead of print]
Management of tophaceous gout of the distal interphalangeal joint.
Mudgal CS.
>From the Orthopaedic Hand Service, Massachusetts General Hospital, Yawkey Center, Suite 2100, 55 Fruit Street, Boston, MA 02114, USA.

Surgical management of acute tophaceous gout of the distal interphalangeal joint is often associated with delayed wound healing. Aspiration through neighbouring uninvolved skin is a safe method of treating these tophi. For persistently symptomatic, unstable DIP joints, arthrodesis should be considered.

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MMW Fortschr Med. 2005 Aug 4;147(31-32):28-30.
[The efficacy of selective Cox-2-inhibitors in comparison with conventional NSAIDs]
[Article in German]
Kruger K.
Rheumazentrum Munchen und Praxiszentrum St. Bonifatius. Klaus.Krueger@med.uni-muenchen.de

The currently approved coxibs celecoxib and etoricoxib, have an equivalent effect in comparison with conventional NSAIDs.This has been established both in comparative studies and by several years of practical application. While celecoxib is approved only for the symptomatic treatment of arthrosis and rheumatoid arthritis, etoricoxib can also be employed in the treatment of acute attacks of gout.

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Geriatrics. 2005 Jul;60(7):24-31.
Gouty arthritis. A primer on late-onset gout.
Ene-Stroescu D, Gorbien MJ.
Internal Medicine Northwest, Tacoma, Washington, USA.

Gouty arthritis, a common source of pain and disability, is the most common form of inflammatory arthritis affecting older people. The authors review the epidemiology and pathogenesis of hyperuricemia and gout, as well as the clinical forms of gouty arthritis. Gout is part of a clinical spectrum of conditions (obesity, diabetes mellitus, hyperlipidemia, coronary artery disease) and need for better patient education on management of these associated conditions is emphasized. The general algorithm of gout management is presented. Clinical particularities of gout presentation in older patients (increased incidence in women, polyarticular onset with hand involvement, earlier development of tophi, association with use of diuretics) are reviewed. Barriers against an optimal control of gout include lack of patient education, presence of comorbid conditions, particularly renal impairment, use of multiple drugs such as diuretics, and cognitive decline. Gout management in older adults remains unsatisfactory.

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Expert Opin Investig Drugs. 2005 Jul;14(7):893-903.
Febuxostat: a non-purine, selective inhibitor of xanthine oxidase for the management of hyperuricaemia in patients with gout.
Schumacher HR Jr.
University of Pennsylvania, VA Medical Center, Philadelphia, Pennsylvania, USA. schumacr@mail.med.upenn.edu

Febuxostat is a non-purine, selective inhibitor of xanthine oxidase being developed for the management of hyperuricaemia in patients with gout. With febuxostat 10-120 mg, the pharmacokinetics are linear. No dose adjustment appears to be necessary in those with renal insufficiency or mild-to-moderate hepatic impairment. Febuxostat 10-120 mg/day rapidly and sustainably reduces serum uric acid by 25-70% in uric acid underexcretors and overproducers. Prophylaxis with colchicine or a non-steroidal anti-inflammatory drug can mitigate the gout-flare risk from the rapid urate lowering after febuxostat initiation. Febuxostat is well tolerated, the majority of treatment-related adverse events are transient and mild-to-moderate in severity. Febuxostat can broaden the therapeutic options for urate-lowering therapy in those with gout.

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Geriatrics. 2005 Jul;60(7):24-31.
Gouty arthritis. A primer on late-onset gout.
Ene-Stroescu D, Gorbien MJ.
Internal Medicine Northwest, Tacoma, Washington, USA.

Gouty arthritis, a common source of pain and disability, is the most common form of inflammatory arthritis affecting older people. The authors review the epidemiology and pathogenesis of hyperuricemia and gout, as well as the clinical forms of gouty arthritis. Gout is part of a clinical spectrum of conditions (obesity, diabetes mellitus, hyperlipidemia, coronary artery disease) and need for better patient education on management of these associated conditions is emphasized. The general algorithm of gout management is presented. Clinical particularities of gout presentation in older patients (increased incidence in women, polyarticular onset with hand involvement, earlier development of tophi, association with use of diuretics) are reviewed. Barriers against an optimal control of gout include lack of patient education, presence of comorbid conditions, particularly renal impairment, use of multiple drugs such as diuretics, and cognitive decline. Gout management in older adults remains unsatisfactory.

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Arthritis Rheum. 2005 Jun;52(6):1843-7.
The effects of vitamin C supplementation on serum concentrations of uric acid: results of a randomized controlled trial.
Huang HY, Appel LJ, Choi MJ, Gelber AC, Charleston J, Norkus EP, Miller ER 3rd.
Johns Hopkins University, Baltimore, Maryland 21205, USA. hyhuang@jhsph.edu

OBJECTIVE: Reductions in serum uric acid levels are clinically relevant. Previous studies have suggested a uricosuric effect of vitamin C. Whether vitamin C reduces serum uric acid is unknown. We undertook this study to determine the effects of vitamin C supplementation on serum uric acid concentrations. METHODS: The study was a double-blinded placebo-controlled randomized trial conducted in research units affiliated with an academic institution. Study participants were 184 nonsmokers, randomized to take either placebo or vitamin C supplements (500 mg/day) for 2 months. RESULTS: At the end of the study period, serum uric acid levels were significantly reduced in the vitamin C group (mean change -0.5 mg/dl [95% confidence interval -0.6, -0.3]), but not in the placebo group (mean change 0.09 mg/dl [95% confidence interval -0.05, 0.2]) (P < 0.0001). The same pattern of results was evident in subgroups defined by age, sex, race, body mass index, chronic illness, diuretic use, and quartiles of baseline serum ascorbic acid levels. In the subgroups, from the lowest to the highest quartile of baseline serum uric acid, net mean changes (95% confidence intervals) in serum uric acid with vitamin C supplementation were -0.4 (-0.8, 0.01), -0.5 (-0.9, -0.2), -0.5 (-0.8, -0.2), and -1.0 (-1.6, -0.4) mg/dl (P = 0.06, 0.005, 0.003, and 0.002, respectively). Compared with placebo, vitamin C increased the estimated glomerular filtration rate. CONCLUSION: Supplementation with 500 mg/day of vitamin C for 2 months reduces serum uric acid, suggesting that vitamin C might be beneficial in the prevention and management of gout and other urate-related diseases.

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Curr Opin Rheumatol. 2005 May;17(3):341-345.
Gout: epidemiology and lifestyle choices.
Choi HK, Curhan G.
aRheumatology Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, and bRenal Division and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

PURPOSE OF REVIEW: Recent scientific data serve to illuminate the links between dietary and other factors and the incidence of gout. This review summarizes recent literature about the prevalence and incidence of gout as well as risk factors for gout. RECENT FINDINGS: Epidemiologic studies suggest that the overall disease burden of gout is substantial and growing. Gout seems to be relatively common not only in men but also in older women. A recent large prospective study investigated several purported dietary factors for gout and confirmed some of the long-standing suspicions (red meats, seafood, beer, and liquor), exonerated others (total protein, wine, and purine-rich vegetables), and also identified potentially new protective factors (dairy products). A study based on the Third National Health and Nutrition Examination Survey suggested that these factors affect serum uric acid levels parallel to the direction of risk of gout. In addition, adiposity, weight gain, hypertension, and diuretics were all found to be independent risk factors for incident gout, whereas weight loss was found to be protective. SUMMARY: The disease burden of gout remains substantial and may be increasing. Some of the recently confirmed lifestyle factors may explain the increasing incidence of gout. The public health implications of dietary and lifestyle recommendations should take into account other associated health benefits and risks, because many of these factors have health effects beyond their influence on gout.

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Curr Opin Rheumatol. 2005 May;17(3):319-24.
Recent advances in the management of gout and hyperuricemia.
Wortmann RL.
Department of Internal Medicine, University of Oklahoma College of Medicine, Tulsa, Oklahoma, USA.

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.

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Ann Pharmacother. 2005 May;39(5):854-62. Epub 2005 Apr 12.
Etoricoxib: A Highly Selective COX-2 Inhibitor.
Martina SD, Vesta KS, Ripley TL.
College of Pharmacy, University of Oklahoma, Oklahoma City, OK.

OBJECTIVE: To review the available literature evaluating the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of etoricoxib, a highly selective cyclooxygenase-2 (COX-2) inhibitor that is not currently approved for use in the US. DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-December 2004), Current Contents (1998-December 2004), and Cochrane Library (4th quarter 2004). References from retrieved articles, information from the manufacturer, and abstracts from the American College of Rheumatology and Annual European Congress of Rheumatology meetings were searched. STUDY SELECTION AND DATA EXTRACTION: All clinical trials published in English evaluating etoricoxib were included in this review. An abstract was excluded if it presented preliminary data from trials that are now published, analyzed data previously reported in a published clinical trial, or compared etoricoxib with placebo for an indication with published active-comparator controlled trials. DATA SYNTHESIS: Twelve clinical trials evaluating efficacy were reviewed. Efficacy for acute pain has been evaluated in acute gout, primary dysmenorrhea, and dental surgery and for chronic pain in rheumatoid arthritis, osteoarthritis, and chronic lower back pain. For safety, 3 clinical trials and 6 retrospective analyses of gastrointestinal, renovascular, or cardiovascular adverse effects were reviewed. CONCLUSIONS: Available studies demonstrate the efficacy of etoricoxib compared with nonsteroidal antiinflammatory drugs, but no published studies to date have compared etoricoxib with other selective COX-2 inhibitors. While these agents have demonstrated a significant reduction in gastrointestinal adverse effects, the cardiovascular adverse effects of selective COX-2 inhibition are not well defined. Further study is necessary to delineate the benefits and risks of etoricoxib compared with alternative treatment regimens.

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J Bone Joint Surg Br. 2005 Apr;87(4):513-7.
Crystal arthropathy of the lumbar spine: a series  of six cases and a review of the literature.
Mahmud T, Basu D, Dyson PH.
Trauma Unit, The John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.

There have been very few reports in the literature of gout and pseudogout of the spine. We describe six patients who presented with acute sciatica attributable to spinal stenosis with cyst formation in the facet joints. Cytopathological studies confirmed the diagnosis of crystal arthropathy in each case.Specific formation of a synovial cyst was identified pre-operatively by MRI in five patients. In the sixth, the diagnosis was made incidentally during decompressive surgery. Surgical decompression alone was undertaken in four patients. In one with an associated degenerative spondylolisthesis, an additional intertransverse fusion was performed. Another patient had previously undergone a spinal fusion adjacent to the involved spinal segment, and spinal stabilisation was undertaken as well as a decompression.In addition to standard histological examination material was sent for examination under polarised light which revealed deposition of urate or calcium pyrophosphate dihydrate crystals in all cases.It is not possible to diagnose gout and pseudogout of the spine by standard examination of a fixed specimen. However, examining dry specimens under polarised light suggests that crystal arthropathy is a significant aetiological factor in the development of symptomatic spinal stenosis associated with cyst formation in a facet joint.

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Arthritis Rheum. 2005 Mar;52(3):916-23.
Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout.
Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Palo WA, Eustace D, Vernillet L, Joseph-Ridge N.
Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA. mbecker@medicine.bsd.uchicago.edu

OBJECTIVE: Gout affects approximately 1-2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (>or=8.0 mg/dl). METHODS: We conducted a phase II, randomized, double-blind, placebo-controlled trial in 153 patients (ages 23-80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28. RESULTS: Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40-mg, 44% in the 80-mg, and 59% in the 120-mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40-mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8-13%). Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups. CONCLUSION: Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.

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Arthritis Rheum. 2005 Jan;52(1):283-9.
Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey.
Choi HK, Liu S, Curhan G.
Rheumatology Unit, Bulfinch 165, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. hchoi@partners.org

OBJECTIVE: Various commonly consumed foods have long been suspected of affecting the serum uric acid level, but few data are available to support or refute this impression. Our objective was to evaluate the relationship between dietary factors and serum uric acid levels in a nationally representative sample of men and women in the US. METHODS: Using data from 14,809 participants (6,932 men and 7,877 women) ages 20 years and older in the Third National Health and Nutrition Examination Survey (for the years 1988-1994), we examined the relationship between the intake of purine-rich foods, protein, and dairy products and serum levels of uric acid. Diet was assessed with a food-frequency questionnaire. We used multivariate linear regression to adjust for age, sex, total energy intake, body mass index, use of diuretics, beta-blockers, allopurinol, and uricosuric agents, self-reported hypertension and gout, serum creatinine level, and intake of alcohol. RESULTS: The serum uric acid level increased with increasing total meat or seafood intake and decreased with increasing dairy intake. After adjusting for age, the differences in uric acid levels between the extreme quintiles of intake were 0.48 mg/dl for total meat (95% confidence interval [95% CI] 0.34, 0.61; P < 0.001 for trend), 0.16 mg/dl for seafood (95% CI 0.06, 0.27; P = 0.005 for trend), and -0.21 mg/dl for total dairy intake (95% CI -0.37, -0.04; P = 0.02 for trend). After adjusting for other covariates, the differences between the extreme quintiles were attenuated but remained significant (P < 0.05 for all comparisons). The total protein intake was not associated with the serum uric acid level in multivariate analyses (P = 0.74 for trend). Those who consumed milk 1 or more times per day had a lower serum uric acid level than did those who did not drink milk (multivariate difference -0.25 [95% CI -0.40, -0.09]; P < 0.001 for trend). Similarly, those who consumed yogurt at least once every other day had a lower serum uric acid level than did those who did not consume yogurt (multivariate difference -0.26 [95% CI -0.41, -0.12]; P < 0.001 for trend). CONCLUSION: These findings from a nationally representative sample of adults in the US suggest that higher levels of meat and seafood consumption are associated with higher serum levels of uric acid but that total protein intake is not. Dairy consumption was inversely associated with the serum uric acid level.

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Arthritis Rheum. 2005 Jan;52(1):290-5.
Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial.
Garg JP, Chasan-Taber S, Blair A, Plone M, Bommer J, Raggi P, Chertow GM.
Department of Medicine Research, University of California-San Francisco, UCSF Laurel Heights Suite 430, 3333 California Street, San Francisco, CA 94118-1211, USA.

OBJECTIVE: Gout affects a large fraction of persons with advanced chronic kidney disease, and hyperuricemia may increase the risk of cardiovascular disease. Several hypouricemic agents are contraindicated in patients with end-stage renal disease. Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract. Results of short-term and open-label studies suggest that sevelamer might lower the concentration of uric acid, another organic anion. We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long-term, randomized, clinical trial comparing sevelamer with calcium-based phosphate binders. METHODS: Two hundred subjects undergoing maintenance hemodialysis were randomly assigned to receive either sevelamer or calcium-based phosphorus binders in an international, multicenter, clinical trial. Data on baseline and end-of-study uric acid concentrations were available in 169 subjects (85%); the change in uric acid concentration from baseline to the end of the study was the outcome of interest. RESULTS: Baseline clinical characteristics, including mean uric acid concentrations, were similar in subjects randomly assigned to receive sevelamer and calcium-based phosphate binders. The mean change in uric acid concentration (from baseline to the end of the study) was significantly larger in sevelamer-treated subjects (-0.64 mg/dl versus -0.26 mg/dl; P = 0.03). The adjusted mean change in uric acid concentration was more pronounced when the effects of age, sex, diabetes, vintage (time since initiation of dialysis), dialysis dose, and changes in blood urea nitrogen and bicarbonate concentrations were considered (-0.72 mg/dl versus -0.15 mg/dl; P = 0.001). Twenty-three percent of sevelamer-treated subjects experienced a study-related reduction in the concentration of uric acid equal to -1.5 mg/dl or more, compared with 10% of calcium-treated subjects (P = 0.02). CONCLUSION: In a randomized clinical trial comparing sevelamer and calcium-based phosphate binders, treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations.

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Contrib Nephrol. 2005;147:149-60.
Pharmacological treatment of acute and chronic hyperuricemia in kidney diseased patients.
Bellinghieri G, Santoro D, Savica D.
Department of Medicine and Pharmacology, Division of Nephrology, University of Messina, Messina, Italy.

Several trials argued the possibility that hyperuricemia may have a direct effect on cardiovascular and renal disease. It has been shown that an elevated serum uric acid concentration is a predictor of cardiovascular events such as myocardial infarction. It also predicts the development of hypertension and in hypertensive patients, hyperuricemia is associated with increased cardiovascular morbidity and mortality. Hyperuricemia is a complication often seen in patients with chronic and acute renal disease. The relationship between serum uric acid level and the appearance or progression of renal dysfunction has been debated in the last years. During chemotherapy for hematological malignancies or more rarely for solid tumors, acute renal failure, secondary to a sudden marked increase in uric acid, is not such a rare complication. The therapeutic intervention includes hyper hydration, urinary alkalinization, and the use of uric acid decreasing agents such as allopurinol and rasburicase, a recent recombinant-urate oxidase. In our personal experience, patients with acute renal failure due to hyperuricemia, showed a better renal prognosis with rasburicase than allopurinol. Chronic hyperuricemia is also associated with chronic tubulo-interstitial disease with glomerular sclerosis, and renal dysfunction. Experimental trials showed that uric acid can affect kidneys through different mechanisms at glomerular, tubulo-interstitial and vascular level. Although allopurinol is often the drug of choice, caution must be used to avoid serious side effects. New therapeutic options, for treating hyperuricemia are needed in patients with renal dysfunction for slowing the progression to end stage kidney disease.

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Contrib Nephrol. 2005;147:35-46.
Pharmacology of drugs for hyperuricemia. Mechanisms, kinetics and interactions.
Pea F.
Institute of Clinical Pharmacology & Toxicology, Department of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine, Italy.

The pharmacological profile of drugs for hyperuricemia is reviewed. These agents may reduce the amount of uric acid in blood by means of two different ways: (1) by reducing uric acid production through the inhibition of the enzyme xanthine oxidase (as allopurinol); (2) by increasing uric acid clearance through an inhibition of its renal tubular reabsorption (as probenecid), or through its metabolic conversion to a more soluble compound (as urate oxidase). Allopurinol is rapidly converted in the body to the active metabolite oxypurinol whose total body exposure may be 20-fold greater than that of the parent compound due to a much longer elimination half-life. Allopurinol undergoes several pharmacokinetic interactions with concomitant administered drugs, some of which may be potentially hazardous (especially with mercaptopurine and azathioprine). Probenecid is an uricosuric agent which undergoes extensive hepatic metabolism and whose elimination after high doses may become dose dependent. It may inhibit renal tubular secretion of several coadministered agents, including methotrexate and sulphonylureas. Rasburicase is a recombinant form of the enzyme urate oxidase which catalyzes the conversion of uric acid to the more soluble compound allantoin. Unlike allopurinol, it does not promote accumulation of hypoxanthine and xanthine in plasma, thus preventing the risk of xanthine nephropathy. Rasburicase showed no significant accumulation in children after administration of either 0.15 or 0.20 mg/kg/daily for 5 days. Rasburicase probably undergoes peptide hydrolysis and in in vitro studies was shown neither to inhibit or induce cytochrome P450 isoenzymes nor to interact with several drugs, so that no relevant interaction is expected during cotreatment in patients.

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Clin Orthop. 2004 Dec;(429):157-62.
Arthroscopic intervention in early hip disease.
McCarthy JC, Lee JA.
New England Baptist Hospital, 125 Parker Hill Ave, Boston, MA 02120, USA. jlee1@caregroup.harvard.edu

Advancement in diagnostic and therapeutic applications for hip arthroscopy have dispelled previous myths about early hip disease. Arthroscopic findings have established the following facts: Acetabular labral tears do occur; acetabular chondral lesions do exist; tears are most frequently anterior and often associated with sudden twisting or pivoting motions; and labral tears often occur in association with articular cartilage lesions of the adjacent acetabulum or femoral head, and if present for years, contribute to the progression of delamination process of the chondral cartilage. Magnetic resonance arthrography represents an improvement over conventional magnetic resonance imaging, it does have limitations when compared with direct observation. Although indications for hip arthroscopy are constantly expanding, the most common indications include: labral tears, loose bodies, chondral flap lesions of the acetabular or femoral head, synovial chondromatosis, foreign body removal, and crystalline hip arthropathy (gout, pseudogout, and others). Contraindications include conditions that limit the potential for hip distraction such as joint ankylosis, dense heterotopic bone formation, considerable protrusio, or morbid obesity. Complication rates have been reported between 0.5 and 5%, most often related to distraction and include sciatic or femoral nerve palsy, avascular necrosis, and compartment syndrome. Transient peroneal or pudendal nerve effects and chondral scuffing have been associated with difficult or prolonged distraction. Meticulous consideration to patient positioning, distraction time and portal placement are essential. Judicious patient selection and diagnostic expertise are critical to successful outcomes. Candidates for hip arthroscopy should include only those patients with mechanical symptoms (catching, locking, or buckling) that have failed to respond to conservative therapy. The extent of articular cartilage involvement has the most direct relationship to surgical outcomes. Improvements in technique and instrumentation have made hip arthroscopy an efficacious way to diagnose and treat a variety of intra-articular problems.

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Joint Bone Spine. 2004 Nov;71(6):481-5.
Current management of gout in patients unresponsive or allergic to allopurinol.
Bardin T.
Rheumatology Federation, Lariboisiere Teaching Hospital, 2, rue Ambroise Pare, 75010 Paris, France. thomas.bardin@lrb.ap-hop-paris.fr

The manifestations of gout can be abolished permanently by lifelong urate-lowering therapy maintaining serum urate levels under 360 mmol/l, as this ensures dissolution of pathogenic crystals of monosodium urate monohydrate. Benzbromarone has been withdrawn from the market, leaving allopurinol as the only urate-lowering drug readily available in France. Allopurinol may induce unacceptable side effects, and in patients with dose-limiting renal failure it may not be sufficiently effective. Because allopurinol can induce serious side effects when given concomitantly with purine antimetabolites, it is contraindicated in organ transplant recipients. In patients who cannot tolerate allopurinol, dietary treatment, discontinuation of diuretic agents, and use of losartan or fenofibrate to treat concomitant hypertension or dyslipidemia, respectively, may ensure adequate control of serum urate levels. Desensitization to allopurinol can be attempted in patients with mild cutaneous hypersensitivity reactions but is difficult to perform and rarely used. Uricosuric agents may be helpful in patients with normal or diminished urate excretion. Probenecid is available in France from hospital pharmacies, and benzbromarone can be prescribed via a time-limited authorization procedure. Rasburicase, an Aspergillus urate oxidase produced by genetic engineering, is indicated to prevent acute hyperuricemia induced by chemotherapy for hematological malignancies. Factors that limit the use of rasburicase include the absence of a marketing authorization, the need for parenteral administration, and the absence of validated treatment schedules. Patients with renal failure precluding the use of effective allopurinol dosages are good candidates for benzbromarone therapy. Organ transplant recipients can be given benzbromarone, within the current restrictions to its use; alternatively, mycophenolate mofetil can be substituted for calcineurin inhibitors, which elevate serum urate levels, or for azathioprine, which contraindicates the use of allopurinol.

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J Med Assoc Thai. 2004 Sep;87(9):1087-91.
The efficacy of combined low dose of Allopurinol and benzbromarone compared to standard dose of Allopurinol in hyperuricemia.
Akkasilpa S, Osiri M, Deesomchok U, Avihingsanon Y.
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Thailand.

OBJECTIVE: To compare the efficacy of combined low dose of hypouricemic drugs (Allopurinol 100 mg and benzbromarone 20 mg; Allomaron) and standard dose 300 mg of allopurinol in hyperuricemia. MATERIAL AND METHOD: A prospective, open study of 94 hyperuricemic patients was done at King Chulalongkorn Memorial Hospital. Each group of 47 patients was given a combined low dose of hypouricemic drugs (Allopurinol 100 mg and benzbromarone 20 mg; Allomaron) and a standard dose 300 mg of allopurinol. Serum uric acid was measured before and 4 weeks after receiving the drugs. The efficacy was measured from the difference of the level of serum uric acid before and after receiving the drugs. RESULTS: The patients receiving the combined low dose of hypouricemic drugs and standard dose of allopurinol showed a mean reduction of serum uric acid of 2.5+/-3.4 mg/dl and 4.1+/-2.7 mg/dl consecutively. There was a statistically significant difference between the 2 groups (P = 0.010). CONCLUSION: This study demonstrates that the efficacy of standard dose 300 mg of allopurinol is superior to a combined low dose of allopurinol and benzbromarone in lowering the level of serum uric acid level.

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J Tradit Chin Med. 2004 Sep;24(3):185-7.
Clinical analysis for the acupuncture treatment in 42 cases of gouty renal damage.
Ma X.
Hai'an County Hospital of Traditional Chinese Medicine, Jiangsu Province 226600.

OBJECTIVE: To observe the therapeutic effects of acupuncture on gouty renal damage. METHOD: 72 cases of gouty renal damage were randomly divided into a treatment group of 42 cases and a control group of 30 cases to observe the therapeutic effects and the changes in 24-hour urinary protein content, blood creatinine, uric acid and urea nitrogen in blood before treatment and one month after treatment. RESULTS: The total effective rate in the treatment group reached 95.24%, which was remarkably higher than 63.33% in the control group. After one month of treatment, the indexes were found reduced in both groups, but the reduction rate in the treatment group was obviously superior to that in the control group. CONCLUSION: The patients with repeated attacks of gout may have a higher possibility to suffer from renal damage. Therefore, attention should be paid to its early diagnosis and treatment. Acupuncture may exert good therapeutic effects on early gout complicated with renal damage by adjusting the metabolism and improving the renal function.

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Ther Umsch. 2004 Sep;61(9):579-82.
[Rasburicase (Fasturtec)]
[Article in German]
Vogt B, Gugger M, Frey FJ.
Klinik und Poliklinik fur Nephrologie und Hypertonie, Universitatsspital Bern, Inselspital, Bern. bruno.vogt@insel.ch

Rasburicase (Fasturtec) is an enzyme that transforms uric acid to the more water soluble allantoin to be excreted by the kidneys. Rasburicase fulfills an unmet clinical need in the treatment of hyperuricemia in that it produces a more rapid action of controlling serum uric acid compared with allopurinol. Tumours with high proliferative rate and sensitive to chemotherapy such as hematological malignancies (mainly) solid tumours (occasionally) may lead to a tumor lysis syndrome. In this situation rasburicase can effectively lower serum uric acid concentrations with a secondary improvement in renal function. Hyperuricemia is the hallmark of severe gout with tophi formation. Rasburicase represents an interesting new option in controlling serum uric acid in patients with severe tophaceous gout.

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Ther Umsch. 2004 Sep;61(9):571-4.
[Diagnosis and prevention of uric acid stones]
[Article in German]
Ferrari P, Bonny O.
Department of Nephrology, Fremantle Hospital, University of Western Australia, Perth, Australia. paolo.ferrari@health.wa.gov.au

Uric acid stones occur in 10% of all kidney stones and are the second most-common cause of urinary stones after calcium oxalate and calcium phosphate calculi. The most important risk factor for uric acid crystallization and stone formation is a low urine pH (below 5.5) rather than an increased urinary uric acid excretion. Main causes of low urine pH are tubular disorders (including gout), chronic diarrhea or severe dehydration. Uric acid stone disease can be prevented and these are one of the few urinary tract stones that can be dissolved successfully. The treatment of uric acid stones consists not only of hydration (urine volume above 2000 ml daily), but mainly of urine alkalinization to pH values between 6.2 and 6.8. Urinary alkalization with potassium citrate or sodium bicarbonate is a highly effective treatment, resulting in dissolution of existing stones. Urinary uric acid excretion can be reduced by a low-purine diet. Potassium citrate is the treatment of choice for the prevention of recurrence of uric acid calculi. Allopurinol reduces the frequency of stone formation in hyperuricosuric patients with recurrent uric acid stones and/or gout.

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Drugs. 2004;64(21):2399-416.
Management of Acute and Chronic Gouty Arthritis: Present State-of-the-Art.
Schlesinger N.
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.

There are three stages in the management of gout: (i) treating the acute attack; (ii) lowering excess stores of uric acid to prevent flares of gouty arthritis and to prevent tissue deposition of urate; and (iii) providing prophylaxis to prevent acute flares. It is important to distinguish between therapy to reduce acute inflammation in acute gout and therapy to manage hyperuricaemia in patients with chronic gouty arthritis.During the acute gouty attack nonpharmacological treatments such as topical ice and rest of the inflamed joint are useful. NSAIDs are the preferred treatment in acute gout. The most important determinant of therapeutic success is not which NSAID is chosen, but rather how soon NSAID therapy is initiated. Other treatments include oral and intravenous colchicine, intra-articular and systemic corticosteroids, and intramuscular corticotropin.Optimal treatment of chronic gout requires long-standing reduction in serum uric acid. The urate-lowering drugs used to treat chronic gout are the uricosuric drugs, the uricostatic drugs, which are xanthine oxidase inhibitors, and the uricolytic drugs. Xanthine oxidase inhibitors such as allopurinol, oxipurinol and febuxastat should be used as first-line treatment in patients with renal calculi, renal insufficiency, concomitant diuretic therapy and ciclosporin (cyclosporine) therapy, and urate overproduction. Uricosuric drugs include probenecid, benzbromarone, micronised fenofibrate and losartan. They are the urate-lowering drugs of choice in allopurinol-allergic patients and underexcretors with normal renal function and no history of urolithiasis. The use of recombinant urate oxidase in patients with chronic gout is limited by the need for parenteral administration, the potential antigenicity and production of anti-urate oxidase antibodies, and declining efficacy.The effectiveness of colchicine prophylaxis as an isolated therapy is still to be confirmed by placebo-controlled trials. Another issue is prophylaxis with NSAIDs. There are no comparative studies with colchicine.

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Geriatrics. 2004 Sep;59(9):25-30; quiz 31.
Crystal arthritis. Gout and pseudogout in the geriatric patient.
Cassetta M, Gorevic PD.
Mount Sinai Medical Center, New York, NY, USA.

Gout and pseudogout are inflammatory arthritides due to monosodium urate and calcium pyrophosphate dihydrate crystal formation. Both are prevalent among geriatric patients, and can present as acute mono- or oligoarticular disease, or as a chronic polyarthropathy resembling osteoarthritis or rheumatoid arthritis. Gout in the geriatric patient is a disease affecting women, commonly associated with diuretic usage, often involves the fingers, may be complicated by the development of masses of uric acid crystals (tophi) in soft tissues, and is frequently polyarticular. Pseudogout in the geriatric patient has a variety of clinical presentations, may be acute or chronic, and should be considered in evaluating any patient with osteoarthritis occurring in an atypical distribution. Treatment includes the use of nonsteroidal anti-inflammatory drugs, colchicine, or corticosteroids. Gout may be impacted by dietary factors, weight reduction, and avoidance of certain forms of alcohol; uric acid-lowering agents are effective for refractory or chronic tophaceous disease.

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Hong Kong Med J. 2004 Aug;10(4):261-70.
Gout: a review of its aetiology and treatment.
Li EK.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. edmundli@cuhk.edu.hk

OBJECTIVE: To review the current understanding of the causes and the management of gout. DATA SOURCES: Publications on all peer-review literature from MEDLINE from 1965 to January 2004. STUDY SELECTION: Selected and evaluated by the author. DATA EXTRACTION: Extracted and evaluated by the author. DATA SYNTHESIS: The underlying metabolic disorder in gout is hyperuricaemia. Most patients with hyperuricaemia remain asymptomatic throughout their lifetime. The phase of asymptomatic hyperuricaemia ends with the first attack of gouty arthritis or urolithiasis. The risk of gout and stone formation is increased with the degree and duration of hyperuricaemia. Drugs available for the treatment of acute gouty arthritis, such as non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase 2 inhibitors, systemic corticosteroids, or colchicine, are effective. For periods between attacks, prophylactic therapy, such as low-dose colchicine, is effective. In those with recurrent attacks of more than two to three times yearly, a uric acid-lowering agent as a long-term therapy should be considered to avoid recurrence and the development of tophaceous gout. CONCLUSIONS: Effective management of gout can be achieved through better understanding of the causes of the condition, preventive measures as well as drug treatment.

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J Rheumatol. 2004 Aug;31(8):1575-81.
Compliance with allopurinol therapy among managed care enrollees with gout: a retrospective analysis of administrative claims.
Riedel AA, Nelson M, Joseph-Ridge N, Wallace K, MacDonald P, Becker M.
Ingenix Pharmaceutical Services, Eden Prairie, Minnesota, USA.

OBJECTIVE: Poor compliance with gout medications has been recognized, but seldom studied. We investigated compliance with allopurinol among managed care enrollees suspected to have gout. METHODS: This was a retrospective, administrative claims-based analysis of patients with gout. Compliance with allopurinol was measured using prescription-fill dates and days-supplied amounts. Compliance was defined for each prescription period as the presumed use of allopurinol on at least 80% of the days of that period. RESULTS: Of 9482 patients identified, 65.9% filled at least one prescription for allopurinol during the 24 month followup period; 10.4% of allopurinol users filled one prescription and then discontinued use. Of the remaining patients, 13.7% never achieved compliance with therapy; 18% were compliant throughout the entire followup period. Patients were compliant with therapy for an average of 56% of their treatment periods and noncompliant for an average of 44%. In multivariate analysis, male sex was associated with decreased compliance (p < 0.01), although the effect was mitigated by increasing age. For subjects of both sexes, increasing age was associated with increased compliance (p < 0.05). CONCLUSION: Compliance with allopurinol in this population was low. Because untreated gouty arthritis can lead to serious adverse outcomes (such as recurrent gouty arthritis, chronic gouty arthropathy, tophi, and urolithiasis) that are usually avoidable with antihyperuricemic therapy, efforts to achieve better compliance are warranted.

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Prog Transplant. 2004 Jun;14(2):143-7.
Treating gout in kidney transplant recipients.
Baroletti S, Bencivenga GA, Gabardi S.
Brigham and Women's Hospital, Boston, MA, USA.

OBJECTIVE: To review the etiology, treatment, and preventive strategies of hyperuricemia and gout in kidney transplant recipients. DATA SOURCES: Primary literature was obtained via Medline (1966-June 2003). STUDY SELECTION AND DATA EXTRACTION: Studies evaluating treatment and prevention of hyperuricemia and gout in kidney transplantation were considered for evaluation. English-language studies were selected for inclusion. DATA SYNTHESIS: Approximately 14,000 kidney transplantations were performed in the United States in 2003, and of those transplant recipients, nearly 13% will experience a new onset of gout. The prevalence of hyperuricemia is even greater. There are several mechanisms by which hyperuricemia and gout develop in kidney transplant recipients. Medication-induced hyperuricemia and renal dysfunction are 2 of the more common mechanisms. Prophylactic and treatment options include allopurinol, colchicine, corticosteroids, and, if absolutely necessary, nonsteroidal antiinflammatory drugs. CONCLUSION: It is generally recommended to decide whether the risks of prophylactic therapy and treatment outweigh the benefits. Often, the risk of adverse events associated with agents to treat these ailments tends to outweigh the benefits; therefore, treatment is usually reserved for symptomatic episodes of acute gout. Practitioners must also decide if changes in immunosuppressive regimens may be of benefit on a patient-by-patient basis.

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Metabolism. 2004 Jun;53(6):772-6.
Effect of sauna bathing and beer ingestion on plasma concentrations of purine bases.
Yamamoto T, Moriwaki Y, Ka T, Takahashi S, Tsutsumi Z, Cheng J, Inokuchi T, Yamamoto A, Hada T.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.

To determine whether sauna bathing alone or in combination with beer ingestion increases the plasma concentration of uric acid, 5 healthy subjects were tested. Urine and plasma measurements were performed before and after each took a sauna bath, ingested beer, and ingested beer just after taking a sauna bath, with a 2-week interval between each activity. Sauna bathing alone increased the plasma concentrations of uric acid and oxypurines (hypoxanthine and xanthine), and decreased the urinary and fractional excretion of uric acid, while beer ingestion alone increased the plasma concentrations and urinary excretion of uric acid and oxypurines. A combination of both increased the plasma concentration of uric acid and oxypurines, and decreased the urinary and fractional excretion of uric acid, with an increase in the urinary excretion of oxypurines. The increase in plasma concentration of uric acid with the combination protocol was not synergistic as compared to the sum of the increases by each alone. Body weight, urine volume, and the urinary excretion of sodium and chloride via dehydration were decreased following sauna bathing alone. These results suggest that sauna bathing had a relationship with enhanced purine degradation and a decrease in the urinary excretion of uric acid, leading to an increase in the plasma concentration of uric acid. Further, we concluded that extracellular volume loss may affect the common renal transport pathway of uric acid and xanthine. Therefore, it is recommended that patients with gout refrain from drinking alcoholic beverages, including beer, after taking a sauna bath, since the increase in plasma concentration of uric acid following the combination of sauna bathing and beer ingestion was additive.

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Curr Rheumatol Rep. 2004 Jun;6(3):240-7.
Serum uric acid-lowering therapies: where are we heading in management of hyperuricemia and the potential role of uricase.
Bomalaski JS, Clark MA.
Medical College of Pennsylvania Hospital, Drexel University College of Medicine, 3300 Henry Avenue, Philadelphia, PA 19129, USA. johnsbomalaski@msn.com

Although allopurinol has been available for approximately 50 years, hyperuricemia and its sequelae are not only prevalent, but the incidence and costs associated with this disorder continue to increase. However, several new therapies have been developed. Recombinant urate oxidase has been useful in the treatment of tumor lysis hyperuricemia, and pegylated urate oxidase shows promise in patients with hyperuricemia and gout. Febuxostat and Y-700 are new oral xanthine oxidase inhibitors that are in human clinical trials. Tailoring of antilipid therapy in selected hyperuricemic and hyperlipidemic patients with fenofibrate may be of benefit in lowering blood cholesterol and uric acid levels. Similarly, treatment of selected hyperuricemic patients who also are hypertensive with losartan or amlodipine may be beneficial in lowering blood pressure and hyperuricemia. Despite these advances, new treatments for hyperuricemia are needed.

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Rev Med Liege. 2004 May;59(5):274-80.
[Gout]
[Article in French]
Leclercq P, Malaise MG.
Universite de Liege.

In the presence of a clinical acute monoarthritis, a differential diagnosis has to be made between septic arthritis, gout and diffuse chondrocalcinosis. Gout comes from a purine nucleotide metabolism disorder leading to serum urate level elevation. This hyperuricemia can lead to the deposition of monosodium urate crystals in the joints, causing acute attacks. After long-term evolution, others tissues as the kidneys can be involved: it is chronic gout. The definite diagnosis is based on the presence of monosodium urate crystals in the joint fluid. The diagnosis of gout should prompt a search for associated medical conditions that may affect both urate levels and longevity. These include alcoholism, various nephropathies, myeloproliferative disorders, and hypertension.

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Clin Ther. 2004 Mar;26(3):399-406.
A single-blind, randomized, controlled trial to assess the efficacy and tolerability of rofecoxib, diclofenac sodium, and meloxicam in patients with acute gouty arthritis.
Cheng TT, Lai HM, Chiu CK, Chem YC.
Section of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan, Republic of China. tiantsai@ms2.hinet.net

BACKGROUND: Acute attacks of gouty arthritis are characterized by the rapid onset of severe pain, swelling, and erythema of the affected joint. Nonsteroidal anti-inflammatory drugs are considered the drugs of first choice for treating acute gout. Rofecoxib is a specific cyclooxygenase-2 inhibitor, which has demonstrated analgesic efficacy in the setting of acute pain. Whether it is effective in the treatment of acute gouty arthritis remains to be evaluated. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of rofecoxib compared with diclofenac sodium sustained release (SR) and meloxicam in the treatment of acute gouty arthritis. METHODS: In this single-blind, randomized, controlled, parallel-group study, patients aged > or =18 years with acute gout within 48 hours of onset were randomized to receive oral treatment with 2 tablets of rofecoxib (25 mg), diclofenac (75 mg), or meloxicam (7.5 mg) once daily for 7 days. The primary outcome measures were patients global assessment of response to therapy and investigator assessment of response to therapy on days 3 and 8. Other efficacy measurements included investigator assessment of total inflammatory scores on days 3 and 8 and patient assessment of pain intensity during the first 12 hours of treatment. RESULTS: Sixty-two patients (53 men, 9 women; mean [SD] age, 51.1 [12.1] years) were assigned to receive rofexocib (n = 20), diclofenac (n = 21), or meloxicam (n = 21). For patient global response to therapy on days 3 and 8, rofecoxib was associated with analgesic efficacy in significantly more patients compared with meloxicam (84.2% vs 40.0% of patients [ P=0.005] and 94.7% vs 60.0% of patients [ P=0.02], respectively); no significant differences versus diclofenac were found. Similarly, for investigator global assessment of response to therapy, a greater percentage of responders was found in the rofecoxib group compared with the meloxicam group on day 3 (88.9% vs 40.0% of patients [ P=0.02 ]), but the difference was not significant on day 8. A greater percentage of responders was found in the rofecoxib group compared with the diclofenac group on day 3 (88.9% vs 47.3% [ P=0.007 ]), but the difference was not significant on day 8. Compared with baseline, all regimens showed significant improvement in total inflammatory scores on days 3 and 8 (all P<0.01 ). During the first 12 hours after dosing, pain intensity score was significantly reduced with rofecoxib starting at 0.5 hours ( P<0.05 ), but not with diclofenac or meloxicam. Clinical adverse events (AEs) were reported in 4 (20.0%), 7 (33.3%), and 6 (28.6%) patients in the rofecoxib, diclofenac, and meloxicam groups, respectively; the most common AEs reported were edema in 1 patient each in the rofecoxib (5.0%) and meloxicam (4.8%) groups and 2 patients (9.5%) in the diclofenac group and abdominal (1 [5.0%], 1 [4.8%], and 2 [9.5%], respectively). No significant differences in tolerability were found among the 3 treatment groups. CONCLUSIONS: In this study of patients with acute gouty arthritis, rofecoxib 50 mg once daily provided more effective treatment than diclofenac sodium SR 150 mg and meloxicam 15 mg administered orally once daily for 7 days in > or = 1 efficacy assessment of overall analgesic effect on day 3 or day 8. Rofecoxib achieved a rapid onset of pain relief, demonstrating significant improvement 30 minutes after dosing. All of the regimens appeared well tolerated in the population studied.

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Arthritis Rheum. 2004 Mar;50(3):937-43.
Quality of care indicators for gout management.
Mikuls TR, MacLean CH, Olivieri J, Patino F, Allison JJ, Farrar JT, Bilker WB, Saag KG.
University of Nebraska Medical Center, and Omaha Veterans Administration Medical Center, Omaha, Nebraska 68198-3025, USA. tmikuls@unmc.edu

OBJECTIVE: Despite the significant health impact of gout, there is no consensus on management standards. To guide physician practice, we sought to develop quality of care indicators for gout management. METHODS: A systematic literature review of gout therapy was performed using the Medline database. Two abstractors independently reviewed each of the articles for relevance and satisfaction of minimal inclusion criteria. Based on the review of the literature, 11 preliminary quality indicators were developed and then reviewed and refined by an initial feasibility panel of community and academic rheumatologists. A twelfth indicator was added at the request of the first panel. Using a modification of the RAND/University of California at Los Angeles appropriateness method (bridging teleconference and white-board Internet technology were added), a second expert panel rated each of the proposed indicators for validity using a 9-point scale, in which ratings of 1-3, 4-6, and 7-9 were considered "invalid," "indeterminate," and "highly valid," respectively. Indicators were considered valid if the median panel rating was > or =7 and there was no evidence of panel disagreement (defined to occur when 2 of 6 panelists provided a validity rating of 1-3 and 2 panelists provided a validity rating of 7-9). RESULTS: Ten of the 12 draft indicators were rated to be valid by our second expert panel. Validated indicators pertained to 1) the use of urate-lowering medications in chronic gout, 2) the use of antiinflammatory drugs, and 3) counseling on lifestyle modifications. CONCLUSION: Using a combination of evidence and expert opinion, 10 indicators for quality of gout care were developed. These indicators represent an important initial step in quality improvement initiatives for gout care.

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Z Rheumatol. 2004 Feb;63(1):2-9.
[Gout]
[Article in German]
Grobner W, Zollner N.
Kreisklinik Balingen, Akademisches Lehrkrankenhaus der Universitat Tubingen, Tubinger Str. 30, 72336, Balingen, Germany.

In most cases gout is the clinical manifestation of familial hyperuricemia. Pathogenesis of hyperuricemia, clinical manifestations, diagnosis and differential diagnosis of hyperuricemia and gout are described. Treatment of hyperuricemia consists of dietary measurements and administration of uric acid lowering drugs, such as allopurinol or uricosuric agents. Nonsteroidal antiinflammatory drugs, colchicine and glucocorticosteroids are the treatment of choice for the acute gout attack. Prophylaxis of acute uric acid nephropathy consists of hydration, urine alkalinization and administration of allopurinol or rasburicase. For treatment of acute uric acid nephropathy rasburicase is the drug of choice.

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Radiol Clin North Am. 2004 Jan;42(1):169-84.
Gout: a clinical and radiologic review.
Monu JU, Pope TL Jr.
Department of Musculoskeletal Radiology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 648, Rochester, NY 14642, USA. johnny_monu@urmc.rochester.edu

Gout is a group of diseases characterized by arthritis and results from a disturbance of urate metabolism with the deposition of monosodium urate crystals in the joints and soft tissues. Often, but not invariably, the serum urate levels are elevated as a result of overproduction or underexcretion of uric acid. Clinical manifestations include acute and chronic arthritis, tophaceous deposits, interstitial renal disease, and uric acid nephrolithiasis. The diagnosis is based on the identification of uric acid crystals in joints, tissues, or body fluids. Acute episodes are treated with colchicine, NSAIDs, or steroids. Long-term management includes treatment with uricosuric agents or xanthine oxidase inhibitors.

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Arthritis Rheum. 2004 Feb;50(2):598-606.
Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial.
Rubin BR, Burton R, Navarra S, Antigua J, Londono J, Pryhuber KG, Lund M, Chen E, Najarian DK, Petruschke RA, Ozturk ZE, Geba GP.
University of North Texas, Fort Worth, TX, USA.

OBJECTIVE: To evaluate the efficacy and safety of etoricoxib and indomethacin in the treatment of patients with acute gout. METHODS: A randomized, double-blind, active-comparator study was conducted at 42 sites. A total of 189 men and women (> or =18 years of age) who were experiencing an acute attack (< or =48 hours) of clinically diagnosed gout were treated for 8 days with etoricoxib, 120 mg/day (n = 103), or indomethacin, 50 mg 3 times a day (n = 86). The primary efficacy end point was the patient's assessment of pain in the study joint (0-4-point Likert scale) over days 2-5. Safety was assessed by adverse experiences (AEs) occurring during the trial. RESULTS: Etoricoxib demonstrated clinical efficacy comparable to that of indomethacin in terms of the patient's assessment of pain in the study joint. The difference in the mean change from baseline over days 2-5 was -0.08 (95% confidence interval -0.29, 0.13) (P = 0.46), which fell within the prespecified comparability bounds of -0.5 to 0.5. Secondary end points over the 8-day study, including the onset of efficacy, reduction in signs of inflammation, and patient's and investigator's global assessments of response to therapy, confirmed the comparable efficacy of the two treatments. The etoricoxib-treated patients had a numerically lower incidence of AEs (43.7%) than did the indomethacin-treated patients (57.0%) and a significantly lower incidence of drug-related AEs (16.5% versus 37.2%; P < 0.05). CONCLUSION: Etoricoxib at a dosage of 120 mg once daily was confirmed to be an effective treatment for acute gout. Etoricoxib was comparable in efficacy to indomethacin at a dosage of 50 mg 3 times daily, and it was generally safe and well tolerated.

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Tidsskr Nor Laegeforen. 2003 Oct 23;123(20):2878-80.
[Gout and hyperuricaemia--should both be treated?]
[Article in Norwegian]
Uhlig T.
Nasjonalt revmatologisk rehabiliterings- og kompetansesenter, Revmatologisk avdeling, Diakonhjemmet sykehus, 0319 Oslo. till.uhlig@nrrk.no

Patients with increased levels of uric acid will usually be treated with drugs if symptoms of acute arthritis or kidney stones occur. Drugs for the treatment of acute arthritis attacks include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids systematically or injected into the joint, and colchicine. As prophylactic long-term treatment of recurring attacks, allopurinol, probenicide and colchicine are therapeutic alternatives. There is still no consensus on the treatment of individuals with asymptomatic hyperuricaemia.

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Ann Plast Surg. 2003 Oct;51(4):372-5.
The soft-tissue shaving procedure for deformity management of chronic tophaceous gout.
Lee SS, Lin SD, Lai CS, Lin TM, Chang KP, Yang YL.
Department of Plastic and Reconstructive Surgery, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, and the dagger Department of Surgery, Kaohsiung Municipal HsiaoKang Hospital.

SUMMARY: Gout is a condition characterized by the deposition of monosodium urate crystals in the joints or soft tissue. A gouty tophus occasionally mimics an infectious or neoplastic process. However, the conventional enucleating procedure might cause complications. In severe cases, skin necrosis and tendon or joint exposure can occur after debridements. In this series, the soft-tissue shaver is used for deformity management of the chronic tophaceous patients and the results are encouraging. From November 2000 to August 2002, 17 patients with chronic tophaceous gout were treated by the shaver technique. Suction and irrigation were performed simultaneously while the shaver was operating, and chalky deposits of sodium urate could be removed efficiently. Skin necrosis was minimized by means of proper incision planning. Also, bedside debridements and wound wet dressing were helpful for improving the outcomes. The families and patients were satisfied with the results. In conclusion, severe chronic tophaceous gout can be a surgical challenge. The soft-tissue shaving technique can be useful for cosmetic debulking of large tophi in patients with advanced chronic tophaceous gouty arthritis.

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Ann Pharmacother. 2003 Jul-Aug;37(7-8):1047-54.
Rasburicase for the treatment and prevention of hyperuricemia.
Yim BT, Sims-McCallum RP, Chong PH.
College of Pharmacy, Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA. abtysy@msn.com

OBJECTIVE: To review the information currently available on rasburicase for treatment and prevention of hyperuricemia. DATA SOURCES: MEDLINE (1966-August 2002) was searched for primary and review articles. STUDY SELECTION/DATA EXTRACTION: Studies evaluating rasburicase, including abstracts and proceedings, were considered for inclusion. English-language literature was evaluated for the pharmacology, pharmacodynamics, pharmacokinetics, therapeutic use, and adverse effects of rasburicase. DATA SYNTHESIS: Rasburicase, a recombinant urate oxidase, has been shown to be effective in lowering uric acid and preventing uric acid accumulation in patients with hematologic malignancies who had hyperuricemia or who were at high risk for developing hyperuricemia. It has been approved for pediatric use in the US. CONCLUSIONS: In addition to allopurinol, hydration, and urinary alkalinization, rasburicase is a new alternative for the treatment and prevention of hyperuricemia in patients with hematologic malignancies. Its rapid onset of action and the ability to lower preexisting elevated uric acid levels are the advantages of rasburicase compared with allopurinol. It may allow the patient to receive chemotherapy treatment without delay.

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Clin Rheumatol. 2003 Feb;22(1):73-6.
Long-term remission from gout associated with fenofibrate therapy.
Hepburn AL, Kaye SA, Feher MD.
Rheumatology Section, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. a.hepburn@ic.ac.uk

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.

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Clin Rheumatol. 2003 Feb;22(1):73-6.
Long-term remission from gout associated with fenofibrate therapy.
Hepburn AL, Kaye SA, Feher MD.
Rheumatology Section, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. a.hepburn@ic.ac.uk

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.

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Rheumatology (Oxford). 2003 Feb;42(2):321-5.
Fenofibrate enhances urate reduction in men treated with allopurinol for hyperuricaemia and gout.
Feher MD, Hepburn AL, Hogarth MB, Ball SG, Kaye SA.
Lipid Clinic, London SW10 9NH, UK. m.feher@chelwest.nhs.uk

OBJECTIVE: To assess the short-term urate-lowering effect of fenofibrate in men on long-term allopurinol therapy for hyperuricaemia and gout. METHODS: Ten male patients (38-74 yr) with a history of chronic tophaceous or recurrent acute gout with hyperuricaemia and on established allopurinol at 300-900 mg/day for > or =3 months were studied in an open-crossover study of fenofibrate therapy. Allopurinol at the established dose was continued throughout the study. Clinical and biochemical assessments (serum urate and creatinine, 24-h urinary excretion of urate and creatinine, liver function tests, creatine kinase and fasting serum lipids) were undertaken at: (i) baseline, (ii) after 3 weeks of once-daily therapy with micronized fenofibrate (Lipantil Micro) at 200 mg and (iii) 3 weeks after fenofibrate was withdrawn. RESULTS: Fenofibrate was associated with a 19% reduction in serum urate after 3 weeks of treatment (mean+/-S.E. 0.37+/-0.04 vs 0.30+/-0.02 mM/l; P=0.004). The effect was reversed after a 3-week fenofibrate withdrawal period (0.30+/-0.02 vs 0.38+/-0.03 mM/l). There was a rise in uric acid clearance with fenofibrate treatment of 36% (7.2+/-0.9 vs 11.4+/-1.6 ml/min, normal range 6-11; P=0.006) without a significant change in creatinine clearance. Both total cholesterol and serum triglycerides were also reduced. No patient developed acute gout whilst taking fenofibrate. CONCLUSIONS: Fenofibrate has a rapid and reversible urate-lowering effect in patients with hyperuricaemia and gout on established allopurinol prophylaxis. Fenofibrate may be a potential new treatment for hyperuricaemia and the prevention of gout, particularly in patients with coexisting hyperlipidaemia or those resistant to conventional therapy for hyperuricaemia.

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Clin Ther. 2003 Jun;25(6):1593-617.
A literature review of the epidemiology and treatment of acute gout.
Kim KY, Ralph Schumacher H, Hunsche E, Wertheimer AI, Kong SX.
Temple University, School of Pharmacy, Philadephia, USA.

BACKGROUND: Gout is the most common cause of inflammatory arthritis in men aged >40 years and is frequently encountered in clinical practice. OBJECTIVE: The goal of this article was to review the published literature on the epidemiology, treatment, and estimated burden of illness of acute gout. METHODS: Articles on gout published in English between 1980 and June 2002 were identified through a MEDLINE search. Relevant clinical studies and review articles were found using the text- and keyword-search term gout alone and in combination with epidemiology, prevalence, incidence, complications, outcome, quality of life, economics, cost, prevention or drug therapy. The reference lists of identified articles, especially review articles, were checked for any additional studies that might have been missed in the original MEDLINE search. RESULTS: The epidemiology of gout in various geographic regions has been well documented. Data suggest that environmental, racial, and hereditary factors may influence the development of gout, and that the prevalence of gout appears to be on the rise worldwide. Evidence from well-designed clinical studies evaluating drug therapies for gout is limited. Therapies for acute gout include corticotropin, corticosteroids, colchicine or, more often, nonsteroidal anti-inflammatory drugs (NSAIDs), which have shown comparable efficacy. A recent study suggests that etoricoxib, a new cyclooxygenase-2-selective inhibitor, may be as effective as and better tolerated than traditional NSAIDs in the treatment of gout. Urate-lowering therapy, prophylactic colchicine, and low-dose NSAIDs are used for the long-term prophylaxis of gout. However, all acute and prophylactic therapies are associated with adverse events. Using an economic model for gout, the annual direct burden of illness for new cases of acute gout can be estimated at 27,378,494 US dollars in the United States. CONCLUSIONS: Gout is an increasingly prevalent condition worldwide and creates a heavy economic burden. Available treatments are generally effective; however, they are not devoid of adverse events. Well-designed, long-term, controlled clinical trials evaluating the comparative efficacy and tolerability of treatments for gout are needed.

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Ann Rheum Dis. 2003 Jun;62(6):572-5.
Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism.
Takahashi S, Moriwaki Y, Yamamoto T, Tsutsumi Z, Ka T, Fukuchi M.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo 663-8501, Japan.

OBJECTIVE: To assess the effect of a combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism in hypertriglyceridaemic and/or hypertensive patients with gout. METHODS: Twenty seven patients with gout were included in a fenofibrate plus anti-hyperuricaemic agents combination study, and 25 in a losartan plus anti-hyperuricaemic agents combination study. Serum uric acid concentration, uric acid clearance, and 24 hour urinary uric acid excretion were measured before and two months after the addition of fenofibrate (300 mg once daily) or losartan (50 mg once daily) to anti-hyperuricaemic agents. RESULTS: Combination therapy of fenofibrate or losartan with anti-hyperuricaemic agents, which included benzbromarone (50 mg once daily) or allopurinol (200 mg twice a day), significantly reduced serum uric acid concentrations in accordance with increased uric acid excretion. CONCLUSION: A combination of fenofibrate or losartan with anti-hyperuricaemic agents is a good option for the treatment of gout patients with hypertriglyceridaemia and/or hypertension, though the additional hypouricaemic effect may be modest.

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Curr Rheumatol Rep. 2003 Jun;5(3):227-34.
Hyperuricemia and gout.
Liote F.
Centre Viggo Petersen, INSERUM U349 Hopital Lariboisiere, 2 Rue Ambroise Pare, F75475 Paris, France. frederic.liote@rb.ap-hop-paris.fr

Gout is not a new disease for clinicians; nevertheless, there are still many secrets awaiting discovery for improving knowledge with respect to uric acid metabolism and monosodium urate crystal-induced inflammation. This review of the literature will focus on new insights on the pathogenesis of idiopathic hyperuricemia, and on secondary hyperuricemia and gout. There are also important advances on the pathophysiology of acute gout, especially as a self-limited process (switch from monocyte to macrophage, peroxisome proliferator activated receptor-gamma, and nitric oxide), but also of chronic gouty arthropathy. Armaments for treating hyperuricemia and gout may be already improved by losartan or fenofibrate and, in the future, by urate oxydase-polyethylene glycol 20 and renal handling regulatory molecules. Finally, control of hyperuricemia may also be considered in the prevention and treatment of cardiovascular disease.

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BMJ. 2002 Jun 22;324(7352):1488-92.
Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis.
Schumacher HR Jr, Boice JA, Daikh DI, Mukhopadhyay S, Malmstrom K, Ng J, Tate GA, Molina J.
Division of Rheumatology, University of Pennsylvania School of Medicine and Department of Veterans Affairs Medical Center, Philadelphia, PA 19104, USA.

OBJECTIVE: To assess the safety and efficacy of etoricoxib, a selective cyclo-oxygenase-2 inhibitor, in comparison with indometacin in the treatment of acute gouty arthritis. DESIGN: Randomised, double blind, active comparator controlled trial. SETTING: 43 outpatient study centres in 11 countries. PARTICIPANTS: 142 men and eight women (75 patients per treatment group) aged 18 years or over presenting with clinically diagnosed acute gout within 48 hours of onset. Interventions: Etoricoxib 120 mg administered orally once daily versus indometacin 50 mg administered orally three times daily, both for 8 days. MAIN OUTCOME MEASURES: Patients' assessment of pain in the study joint over days 2 to 5 (primary end point); investigators' and patients' global assessments of response to treatment and tenderness of the study joint (key secondary end points). RESULTS: Etoricoxib showed efficacy comparable to indometacin. Patients' assessment of pain in the study joint (0-4 point Likert scale, "no pain" to "extreme pain") over days 2 to 5 showed a least squares mean change from baseline of -1.72 (95% confidence interval -1.90 to -1.55) for etoricoxib and -1.83 (-2.01 to -1.65) for indometacin. The difference between treatment groups met prespecified comparability criteria. All other efficacy end points, including those reflecting reduction in inflammation and analgesia, provided corroborative evidence of comparable efficacy. Significant pain relief was evident at the first measurement, 4 hours after the first dose of treatment. Prespecified safety analyses revealed that drug related adverse experiences occurred significantly less frequently with etoricoxib (22.7%) than with indometacin (46.7%) (P=0.003), although overall adverse experience rates were similar between the two treatment groups. CONCLUSION: Etoricoxib 120 mg once daily provides rapid and effective treatment for acute gouty arthritis comparable to indometacin 50 mg three times daily. Etoricoxib was generally safe and well tolerated in this study.

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Arthritis Rheum. 2002 Aug15;47(4):356-60.
Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout.
Perez-Ruiz F, Calabozo M, Pijoan JI, Herrero-Beites AM, Ruibal A.
Hospital de Cruces, Pais Vasco, Spain. fperez@hcru.osakidetza.net

OBJECTIVE: The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial. This observational, prospective study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout. METHOD: Sixty-three patients with crystal-confirmed tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues. The tophi targeted for evaluation during followup were the largest in diameter found during physical examination. RESULTS: Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone. The velocity of tophi reduction was linearly related to the mean serum urate level during therapy. The lower the serum urate levels, the faster the velocity of tophi reduction. CONCLUSION: Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout. Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy. Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single-drug therapy.

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Curr Rheumatol Rep. 2002 Jun;4(3):252-6.
Update on colchicine and its mechanism of action.
Molad Y.
Rabin Medical Center, Beilinson Campus, Rheumatology Unit, Petah Tikva 49100, Israel. ymolad@clalit.org.il

Colchicine is a unique anti-inflammatory drug with respect to its limited clinical usefulness and its mode of action. Colchicine is mainly indicated for the treatment and prophylaxis of gout and familial Mediterranean fever. Its mode of action includes modulation of chemokine and prostanoid production and inhibition of neutrophil and endothelial cell adhesion molecules by which it interferes with the initiation and amplification of the joint inflammation. This paper discusses its adverse effects and indications.

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Klin Med (Mosk). 2002;80(2):9-13.
[Gout: current views. Stage oriented treatment]
[Article in Russian]
Fedorova NE, Grigor'eva VD.

Gout is a common disease arising due to abnormal purin metabolism and excessive accumulation of uric acid in the blood (hyperuricemia) and manifesting with attacks of acute gouty arthritis. In long duration of gout uric acids accumulate in the bones and periarticular tissues as tophuses. Repeat attacks lead to development of chronic gouty arthritis. Purins restriction diet is an important component of gout treatment. Treatment of acute arthritis should be started early, in initial pains before the development of the attacks. Gouty arthritis in the presence of continuous hyperuricemia, tophyses and urolithiasis is treated with allopurinol. Its intake should be long and controlled by the blood level of uric acid. Balneotherapy is recommended for patients with chronic gouty arthritis associated with cardiovascular diseases, urolithiasis.

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Ned Tijdschr Geneeskd. 2002 Feb 16;146(7):309-13.
[Summary of the Dutch College of General Practitioners' "Gout" Standard]
[Article in Dutch]
Romeijnders AC, Gorter KJ.
Nederlands Huisartsen Genootschap, afd. Richtlijnontwikkeling en Wetenschap, Postbus 3231, 3502 GE Utrecht.

The typical form of acute gout can be clinically diagnosed. The term 'complicated gout' is used if there are more than three acute attacks of gout per year, tophi or urate stones in the urinary tracts. In the case of recurrent probable acute gout, a diagnostic fine needle aspirate from the joint during an attack is indicated. First choice treatment of acute gout consists of NSAIDs. Colchicine is the second choice treatment and the third choice treatment consists of corticosteroids. Excessive alcohol use should be limited. Treatment of chronic gout depends on the uric acid excretion in the 24-hour urine. If the level of excretion is too low, the first choice should be benzbromarone, and if the uric acid output is too high, allopurinol should be the treatment of first choice. Increased fluid intake is recommended; maintenance treatment with colchicine is not advised. Consultation with or referral to a rheumatologist is indicated in the case of doubt about the diagnosis of 'acute gout' or 'complicated gout', or (suspected) bacterial arthritis and insufficient treatment effect.

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J Rheumatol. 2002 Feb;29(2):331-4
Local ice therapy during bouts of acute gouty arthritis.
Schlesinger N, Detry MA, Holland BK, Baker DG, Beutler AM, Rull M, Hoffman BI, Schumacher HR Jr.
Department of Medicine and New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, USA.

OBJECTIVE: To evaluate the effect of local application of ice on duration and severity of acute gouty arthritis. METHODS: Nineteen patients with acute gout were enrolled and randomized into 2 groups. Group A (n = 10) received topical ice therapy, oral prednisone 30 mg PO tapered to 0 over 6 days and colchicine 0.6 mg/day. Group B was the control group (n = 9), given the same regimen but without the ice therapy. The patients were followed for one week. RESULTS: The mean reduction in pain for those patients treated with ice therapy was 7.75 cm (on 10 cm visual analog scale) with standard deviation +/- 2.58 compared with 4.42 cm (+/- SD 2.96) for the control group. Using a Wilcoxon rank-sum test there was a significant difference (p = 0.021 ) in pain reduction between the ice therapy and control groups. Joint circumference and synovial fluid volume also tended to be more effectively reduced after one week of therapy in the ice group compared with controls, but these did not achieve statistical significance. CONCLUSION: The group treated with ice had a significantly greater reduction in pain compared with the control group. Although the clinical improvement was impressive, due to the small sample size we could not show statistically significant improvement in all the variables that tended to suggest that effect was more than simply analgesic. Cold applications may be a useful adjunct to treatment of acute gouty arthritis.

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Bull Exp Biol Med. 2002 May;133(5):491-3.
Dyshormonal disorders in gout: experimental and clinical studies.
Mukhin IV, Ignatenko GA, Nikolenko VY.
Donetsk State Medical University.

A total of 107 patients with primary gout were examined. The pituitary-gonadal system is imbalanced in male patients with gout, which manifests by hyperproduction of progesterone and suppressed production of testosterone and estradiol. These changes are more pronounced in patients with chronic arthritis and proteinuric nephropathy. Similar dyshormonal changes are experimentally simulated in rats by induction of purine metabolism disorders. Exogenous injection of androgens in experimental hyperuricemia led to normalization of purine metabolism and hormonal homeostasis.

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N Z Med J. 2002 Jul 26;115(1158):U109.
A survey of indications, results and complications of surgery for tophaceous gout.
Kumar S, Gow P.
Department of Rheumatology, Middlemore Hospital, Auckland, New Zealand.

AIMS: To document the indications, results and complications associated with surgery for tophaceous gout in Middlemore Hospital. METHODS: A retrospective study of the notes of all patients who underwent surgery for tophaceous gout at Middlemore Hospital from July 1995 to July 2001 was performed. Serum creatinine and uric acid results were obtained and the use of allopurinol assessed. RESULTS: 45 patients underwent surgery for gouty tophi. 89% were males and 11% females. 16% were Maori, 38% Pacific people, 42% Europeans and 4% were from other ethnic backgrounds. Renal impairment (serum creatinine. >0.11 mmol/L) was the most common associated medical problem (38%), followed by hypertension (27%), ischaemic heart disease and/or congestive heart disease (20%) and diabetes mellitus (18%). 68% of patients had elevated serum urate levels (>0.42 mmol/L) and only 31% had previously been taking allopurinol. Sepsis control in infected or ulcerated tophi was the main indication for surgery (51%), followed by mechanical problems caused by foot, elbow and hand tophi (27%). The diagnosis of soft tissue masses was unclear in 18% of the patients prior to surgery. 4% of patients underwent tophus surgery mainly for pain control. 53% of patients experienced delayed wound healing as a result of complications of surgery with the majority of these patients (16/24, 67%) having infected or ulcerated tophi prior to surgery. Three patients (7%) required digital amputations for ongoing sepsis. 47% of patients did not have any complication of surgery and had complete wound healing within one week. CONCLUSIONS: Surgery for tophaceous gout is associated with a relatively high rate of complication when sepsis is the main indication. Patients with gout in this study population had several associated medical co-morbidities, which contributed to the high complication rate. Gout control was poor as evidenced by a high rate of hyperuricaemia, and less than one third of the study population were on allopurinol. Better control of gout would reduce the risk of tophi formation and the need for surgery.

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Med Hypotheses. 2001 Aug;57(2):241-2.
Self-treatment for gout.
Symons MC.
Bone & Joint Research Unit, St Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, London, UK.

After describing some of the symptoms of gout and considering some causes, such as an excess of ethanol, the source of the pain in the infected joint is discussed. This is known to be from urate crystals formed in the synovial fluid inside the joint. It is suggested herein that the pain is due to grinding from the crystals through the surface film of the joint, and possibly into the bone itself, which is relatively soft. The pain then stems in part from the resulting inflammation. The key hypothesis is that these urate crystals dissolve on warming. Hence, by warming the joint concerned in hot water, and moving the joint around to encourage diffusion, the urate concentration is reduced and crystals no longer form, provided the treatment is continued. Copyright 2001 Harcourt Publishers Ltd.

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