Treatment of hyperuricemia, gout and other crystalline arthritidies

Gout is a very common joint disease which is due to chronic hyperuricemia and its related articular involvements. Yet it can be cured when appropriately managed. Comprehensive management of gout involves correct identification and addressing all causes of hyperuricemia, treating and preventing attacks of gouty inflammation (using colchicine NSAIDs, and/or steroids), and lowering serum urate (SUA) to an appropriate target level indefinitely. The ideal SUA target is, at a minimum, less than 6 mg/dL (60 mg/L or 360 μmol/L), or even less than 5 mg/dL in patients with tophi. The SUA target should remain at less than 6 mg/dL for long in all gout patients, especially until tophi have resolved. Patient education and adherence to therapy are key point to the optimal management of gout, aspects which are often neglected. Adherence can be monitored in part by continuing, regular assessment of the SUA level. More difficult cases of gout often need a combination of urate lowering therapy (ULT) for both refractory hyperuricemia and chronic tophaceous arthritis. Chronic tophaceous gouty arthropathy which do not respond adequately to optimized oral ULT might benefit from the use of pegloticase, when this is available in, for example, Italy and other European countries. By contrast, in calcium pyrophosphate (CPP) crystal deposition disease (CPPD), as evidenced by pseudo gout attacks or chronic polyarthritis, similar anti-inflammatory strategies have been recommended, but there have as yet been no controlled trials. Of note, there is no treatment for the underlying metabolic disorders able to control the CPPD. Management of crystal-induced arthropathies (CIA) depends not only on clinical expression, namely acute attacks or chronic arthropathy, but also on the underlying metabolic disorder. We will mainly focus on gout as an archetype of CIA.     

Predictors of poor response to urate-lowering therapy in patients with gout and hyperuricemia: a post-hoc analysis of a multicenter randomized trial

Clinical Rheumatology - Clinical guidelines have recommended a target of serum uric acid (SUA) level below 6.0 mg/dL for the urate-lowering therapy (ULT) of gout patients, but there are...     

Relationship of medication adherence,serum uric acid level and diet to recurrent attacks of gout

Aim of the workTo evaluate the relationship between medication adherence, serum uric acid (SUA) levels, and diet, with recurrent gout attacks.Patients and methodsThis study included 89 patients being followed up for gouty arthritis. A self-administered, structured questionnaire was used to collect socio-demographic data, gout attacks frequency, history of acute intake of purine rich foods prior to the gouty attack, and adherence to urate-lowering therapies (ULT).Results89 patients were studied, 84 males and 5 females with a mean age of 55.4 ± 13.7 years, disease duration 12.22 ± 9.2 years and body mass index 24.67 ± 5.01. 71.9% were Malays, 20.2% Chinese, 6.7% Indians and 1.1% others. 61.8% had at least one episode of gout flare in the past 6 months. Of the 86 taking ULT, 65 (75.6%) were adherent. There was no difference in clinical characteristics between those who had high versus low adherence. High adherence to ULT was not associated with lower SUA or not having recurrent gout attacks. Having a high SUA level [OR = 2.86 (95%CI:1.52–5.39)], acute intake of purine-rich foods [OR = 2.01 (95%CI:1.09–3.73)] and obesity [OR = 1.58 (95%CI:1.09–2.32)] were significantly associated with recurrent gout attacks.ConclusionsAlthough three-quarters of patients were adherent to their ULT, it was not associated with a reduction in recurrent gout attacks or lower SUA levels. Recurrent gout attacks were associated with a high SUA and an acute intake of purine-rich foods. To reduce the burden of recurrent gout attacks, ULT may need to be intensified even in adherent patients, as well as avoiding dietary indiscretions.     

Concordance of the management of chronic gout in a UK primary-care population with the EULAR gout recommendations

OBJECTIVES: To assess concordance of the management of chronic gout in UK primary care with the European League Against Rheumatism (EULAR) gout recommendations. METHODS: A postal questionnaire was sent to all adults aged >30 years registered with two general practices. Patients with possible gout attended for clinical assessment, at which the diagnosis was verified clinically. Aspects of chronic gout management, including provision of lifestyle modification advice, use of urate-lowering therapies (ULT) including dose titration to serum urate (SUA) level, prophylaxis against acute attacks, and diuretic cessation were assessed in accordance with the EULAR recommendations. RESULTS: Of 4249 (32%) completed questionnaires returned, 488 reported gout or acute attacks and were invited for clinical assessment. Of 359 attendees, 164 clinically confirmed cases of gout were identified. Advice regarding alcohol consumption was recalled by 59 (41%), weight loss by 36 (25%) and diet by 42 (29%). Allopurinol was the only ULT used and was taken by 44 (30%); 31 (70%) were taking 300 mg daily. Mean SUA was lower in allopurinol users than non-users (318 vs 434 micromol/l) and was less often >360 micromol/l in allopurinol users (23% vs 75%). Eight patients had recently commenced allopurinol; two of these also were taking prophylactic colchicine or non-steroidal anti-inflammatory drugs. Of 25 patients with diuretic-induced gout, 16 (64%) were still taking a diuretic. CONCLUSION: Treatment of chronic gout is often suboptimal and poorly concordant with EULAR recommendations. Lifestyle advice is infrequently offered, and allopurinol is restricted to a minority. Persistent hyperuricaemia was often seen in allopurinol non-users, but was also in allopurinol users, suggesting that doses >300 mg are often necessary.     

CaseBook Challenges: Managing Gout,Hyperuricemia and Comorbidities—Dialogue with the Experts

The prevalence of gout and hyperuricemia are on the rise in the United States corresponding with an increase in risk factors for these conditions, such as obesity, metabolic syndrome, and the use of diuretics. A progressive disorder, untreated gout can be debilitating and result in tophi, chronic arthropathy, and recurrent kidney stones. Although joint aspiration is needed for a definitive diagnosis, the majority of patients are diagnosed presumptively based on medical history and presentation with characteristic signs and symptoms. Patients with gout also often have multiple comorbidities, and there is an increasing body of evidence that shows hyperuricemia is associated with incidence hypertension, diabetes, chronic kidney disease, and heart failure. Clinical strategies for the management of gout and hyperuricemia must include considerations for these and other common cardiometabolic and renal conditions. In addition to acute flare therapy and prophylaxis, the treatment of gout involves lowering serum uric acid (SUA) levels with the urate-lowering therapies (ULTs) allopurinol or febuxostat. Once begun, treatment with ULT is lifelong. However, inadequate dosing and patient nonadherence or intolerance to therapy often lead to treatment failure. Recent guidelines from the American College of Rheumatology stress tailoring therapy and target SUA level (traditionally <6 mg/dL, but lower levels may be needed for certain patients) based on gout severity and the presence of comorbid conditions. Because painful acute gout flares may result in trips to the emergency department and because the majority of gout cases are managed in primary care, it is important for clinicians practicing in these settings to be able to diagnose and treat this condition and communicate with patients to improve their understanding of the disease process and adherence to treatment.     

Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan

Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long‐term urate‐lowering treatment. Urate‐lowering drugs should be used during the inter‐critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate‐lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia.     

Temporal evolution of urate crystal deposition over articular cartilage after successful urate-lowering therapy in patients with gout: An ultrasonographic perspective

Objective: To detect evolution of ultrasonographic signs of deposition of monosodium urate crystals (MSUC) in gouty joints by serial ultrasonography after initiation of urate-lowering therapy (ULT).

Methods: Adult gout patients were examined by serial ultrasonography after initiation of ULT with target serum uric acid (SUA) Results: Thirty-eight male patients with gout with mean age of 50?±?11?years, median disease duration of 48 months and baseline mean SUA level of 8.8?±?1.5?mg/dL were recruited. Ultrasonographic evidence of MSUC deposition was detected in 89.74% of first metatarsophalangeal (MTP) joints and 27.63% of knee joints. Double contour sign (DCS), tophi, and hyperechoic spots (HES) were detected in 77.63%, 43.42%, and 19.74% of first MTPs, respectively. SUA level normalizes and plateaus after fourth month of follow-up. DCS thickness reduced significantly throughout the follow-up period. Overall, 86.25% DCS and 100% HES disappeared with median time of 6 months and 5.7 months, respectively. SUA normalization was the only significant predictor of DCS disappearance.

Conclusions: Serial ultrasonographic determination of DCS, tophi, or HES during hypouricemic therapy is a noninvasive, effective method to detect the lowering of burden of urate load in gouty joints.     

As compared to allopurinol, urate-lowering therapy with febuxostat has superior effects on oxidative stress and pulse wave velocity in patients with severe chronic tophaceous gout

We prospectively evaluated whether an effective 12-month uric acid-lowering therapy (ULT) with the available xanthine oxidase (XO) inhibitors allopurinol and febuxostat in patients with chronic tophaceous gout has an impact on oxidative stress and/or vascular function. Patients with chronic tophaceous gout who did not receive active ULT were included. After clinical evaluation, serum uric acid levels (SUA) and markers of oxidative stress were measured, and carotid–femoral pulse wave velocity (cfPWV) was assessed. Patients were then treated with allopurinol (n = 9) or with febuxostat (n = 8) to target a SUA level ≤360 μmol/L. After 1 year treatment, the SUA levels, markers of oxidative stress and the cfPWV were measured again. Baseline characteristics of both groups showed no significant differences except a higher prevalence of moderate impairment of renal function (estimated glomerular filtration rate <60 ml/min) in the febuxostat group. Uric acid lowering with either inhibitors of XO resulted in almost equally effective reduction in SUA levels. The both treatment groups did not differ in their baseline cfPWV (allopurinol group: 14.1 ± 3.4 m/s, febuxostat group: 13.7 ± 2.7 m/s, p = 0.80). However, after 1 year of therapy, we observed a significant cfPWV increase in the allopurinol group (16.8 ± 4.3 m/s, p = 0.001 as compared to baseline), but not in the febuxostat patients (13.3 ± 2.3 m/s, p = 0.55). Both febuxostat and allopurinol effectively lower SUA levels in patients with severe gout. However, we observed that febuxostat also appeared to be beneficial in preventing further arterial stiffening. Since cardiovascular events are an important issue in treating patients with gout, this unexpected finding may have important implications and should be further investigated in randomized controlled trials.     

Gout in the heart transplant recipient: physiologic puzzle and therapeutic challenge

PURPOSE: Hyperuricemia and gouty arthritis have been associated with cyclosporine use in renal transplant recipients. Patients requiring heart or heart-lung transplantation may have additional risk factors for the development of gout, yet it has not previously been described in this population. We share herein our clinical experience with gouty arthritis in six heart transplant recipients. PATIENTS AND METHODS: During a one-year period, six hospitalized male heart transplant patients were seen in consultation for gouty arthritis. Five were subsequently followed for gout as outpatients; the sixth died within six months. Management included trials of nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, allopurinol, and intra-articular steroid injections, as well as attempts to minimize cyclosporine nephrotoxicity. RESULTS: Three patients had gout in remission at time of transplant surgery, and three others developed gout for the first time two to 45 months after transplantation. Following transplant surgery, both pre-existing and new-onset gout appeared to exhibit an accelerated course, with unusually rapid development of chronic polyarticular disease and tophi in four of the five patients followed for more than six months. Peak serum uric acid levels ranged from 11.0 mg/dL to 16.5 mg/dL. NSAIDs produced reversible renal insufficiency in four patients. Gout-related infections occurred in three patients, one of whom died. CONCLUSION: Acute gouty arthritis may occur in the heart transplant recipient despite concomitant use of immunosuppressive drugs. Cyclosporine, with its attendant hypertension and nephrotoxicity, appears to be the major risk factor for hyperuricemia in this setting, leading to the accelerated development of tophi and chronic polyarthritis. Management is complicated by the patients' renal insufficiency and propensity to infection, as well as by interaction with transplant-related medications. Prevention of hyperuricemia by minimizing cyclosporine nephrotoxicity appears to be the best management strategy, with judicious use of allopurinol for those patients in whom this preventive approach fails.     

Gout and Organ Transplantation

Acute and chronic gout are common complications following organ transplantation. Risk factors include those shared with the general population (eg, diuretic use) and transplant-specific risk factors (eg, cyclosporine). Clinical features of gout are similar to those seen in the general population, although tophi may be more common. A definitive diagnosis requires demonstration of monosodium urate crystals within synovial fluid or tophi. Treatment is often empiric, although a poor response should prompt joint aspiration to exclude septic arthritis. Corticosteroids are commonly used to treat acute gout due to the adverse profile and drug interactions with NSAIDs and colchicine. Sustained reduction of serum urate (≤6 mg/dL) is critical in long-term management. Allopurinol is the most commonly used agent, although vigilant monitoring is required if combined with azathioprine. Other options include febuxostat and benzbromarone. The role of newer agents such as interleukin-1 inhibitors and uricases remains to be determined. General measures should include minimizing diuretic use.     

Gout:A clinical overview and its association with cardiovascular diseases

Gout is a common disease caused by the deposition of monosodium urate(MSU) crystals in patients with hyperuricemia, and characterized by very painful recurrent acute attacks of arthritis. The gold standard for diagnosing gout is the identification of MSU crystals in synovial fluid by polarization light microscopy. Arthritis attacks can be treated with anti-inflammatory medications, such as non-steroidal anti-inflammatory drugs, colchicine, oral prednisone, or intra-articular or intramuscular glucocorticoids. To prevent gout uric acid lowering therapy with for example allopurinol can be prescribed. When gout is adequately treated, the prognosis is good. Unfortunately, the management of gout patients is often insufficient. Gout is associated with dietary factors, the use of diuretics, and several genetic factors. Comorbidities as hypertension, chronic kidney disease, cardiovascular diseases, the metabolic syndrome, diabetes, obesity, hyperlipidemia, and early menopause are associated with a higher prevalence of gout. Xanthine oxidase and chronic systemic inflammation seem to play an important role in the pathophysiology of the association between gout and cardiovascular diseases. To prevent cardiovascular diseases goutpatients must be early screened for cardiovascular risk factors.     

Prophylaxis of acute flares when initiating febuxostat for chronic gouty arthritis in a real-world clinical setting

Objective: Flare prophylaxis is recommended during urate-lowering therapy (ULT) despite lack of proven benefit especially when initiating febuxostat. We investigated if colchicine or steroids administration during initiation of febuxostat for chronic gouty arthritis reduces the frequency and/or severity of acute gout flares.

Methods: Patients with confirmed diagnosis of gout starting febuxostat were retrospectively studied. Frequency, severity, and length of flares were analyzed. Assessment of severity based on a visual analog scale (VAS).

Results: Two hundred and seventy-three patients were studied. The mean dose of colchicine and steroids was 0.53?±?0.15?mg PO QD and 7.55?±?1.30?mg prednisone equivalent PO QD; while the duration was 6.13?±?1.14 and 6.20?±?1.36 months, respectively. Subjects treated with colchicine and steroids suffered fewer total flares (0.30, 0.96 vs 2.47, p?=?.000), fewer flares from 0 to 3 months (0.26, 0.71 vs 1.72, p?=?.000), less severe flares assessed by VAS than those without prophylactic therapy (3.65, 3.49 vs 5.54, p?=?.000). Both total flares (p?=?.003) and flares from 0 to 3 months (p?=?.008) of the colchicine group were fewer than the steroids group. There were no significant differences in length of flares among groups (p?=?.815). Both colchicine and steroids were well tolerated.

Conclusion: The use of colchicine or steroids prophylaxis reduces the frequency and severity of acute gout flares during initiation of febuxostat for chronic gouty arthritis. Colchicine is superior to steroids in flares prophylaxis. Prophylactic therapy with colchicine 0.5?mg PO QD or steroids 7.5?mg prednisone equivalent PO QD for 6 months is suggested.     

Managing Gout in the Primary Care Setting: What You and Your Patients Need to Know

The US prevalence of gout, a rapidly progressive inflammatory arthritic condition linked to serum uric acid levels, has grown in recent years, in part due to the increasing prevalence and incidence of predisposing factors in the population, such as metabolic syndrome, obesity, and the use of diuretics. Left untreated, gout can be debilitating and cause deformity. Although a definitive diagnosis requires joint aspiration, only ∼11% of patients with suspected gout undergo this procedure, and a presumptive diagnosis based on patient medical history and presentation with characteristic symptoms and comorbidities is a reasonable guidelines-based approach that has utility in the primary care setting, where approximately 70% of all cases and nearly 3,000,000 visits occur. The therapeutic standard for patients with recurrent gout flares is urate-lowering therapy (ULT), including allopurinol and the recently introduced febuxostat, the first new treatment for gout in 40 years. Although ULT must be taken consistently to sustain benefits, inadequate dosing and patient nonadherence or intolerance to therapy often lead to treatment failure. It is important that primary care clinicians understand gout diagnosis and therapeutic approaches and can communicate effectively with patients to improve treatment adherence.

Online Access

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Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout?

OBJECTIVE: To determine if lowering of serum uric acid (SUA) concentrations below 6 mg/dl or longer duration of lowered SUA will result in depletion of urate crystals from the knee joints and prevent further attacks of gout. METHODS: A prospective study was initiated 10 years ago at Philadelphia VA Medical Center to attempt to maintain SUA levels of patients with crystal proven gout at < 6.0 mg/dl. We recalled all 57 patients who were available during 1999. Patients were divided into 2 groups: Group A, with SUA still > 6 mg/dl, and Group B, with SUA < or = 6 mg/dl. A knee joint aspirate was requested from all asymptomatic Group B patients and many in Group A. Aspirates were examined by polarized light microscopy for identification of crystals. RESULTS: There were no differences between the groups in age, sex, duration of gout, or serum creatinine. Group A (n = 38) had a mean of 6 attacks of gout for the recent year, those with tophi having the most frequent attacks. Among the 16 patients in this group who agreed to knee aspiration, monosodium urate (MSU) crystals were found in 14, although they were asymptomatic at the time. Nineteen patients (Group B) were able to maintain serum urate levels < or = 6 mg/dl for > 12 months. Nearly half of them had no attack of gout for 2 or more years, with a mean of 1 attack in the last year for the whole group. Three patients in whom tophi were found did not have major flares of gout within the past year. Knee joint aspiration was done on 16 asymptomatic patients. Seven (44%) still had MSU crystals present in their knees. Patients in this group who were taking prophylactic colchicine did not differ with respect to the character of synovial fluid from those who had discontinued it for up to several years, although the frequency of attacks was less in those who continued colchicine. CONCLUSION: A majority of patients were able to deplete urate crystal stores in their knee joint fluids when their SUA levels were kept to < or = 6 mg/dl for several years. The mechanisms for persistence in some patients, and whether such crystals have clinical implications, are not known. Patients with chronic gout need serum urate concentrations to be kept low to prevent further attacks.     

Dyslipidemia,Alcohol Consumption,and Obesity as Main Factors Associated With Poor Control of Urate Levels in Patients Receiving Urate‐Lowering Therapy

Objective

In real life, in a substantial proportion of gouty patients receiving urate‐lowering therapy (ULT), urate levels are not maintained below the target of 6.0 mg/dl. We aimed to search for factors associated with poor control of serum uric acid (UA) levels in a large population of patients with gout receiving ULT.

Methods

This cross‐sectional study involved adults with gout in primary care who were receiving ULT. Demographics, gout history, comorbidities, lifestyle, clinical factors, concomitant treatments, and laboratory data were compared in well‐controlled gout (serum UA ≤6.0 mg/dl) versus poorly controlled gout (serum UA >6.0 mg/dl) on univariate and multivariate analyses.

Results

Among the 1,995 patients receiving ULT, only 445 (22.3%) had reached the target of 6.0 mg/dl serum UA. Such patients had a lower rate of gout flares within the previous year than patients without the target (mean ± SD 1.7 ± 1.4 versus 2.1 ± 1.4; P < 0.0001). The main factors associated with poor serum UA level control in multivariate analysis were low high‐density lipoprotein cholesterol level (adjusted odds ratio [OR] 0.5 [95% confidence interval (95% CI) 0.26–0.96]; P = 0.04), high total cholesterol level (OR 1.83 [95% CI 1.29–2.60]; P = 0.0007), increased waist circumference (OR 1.55 [95% CI 1.11–2.13]; P = 0.008), and alcohol consumption (OR 1.52 [95% CI 1.15–2.00]; P = 0.003).

Conclusion

Dyslipidemia, abdominal obesity, and alcohol consumption are the main factors associated with a poor response to ULT. Knowledge of these factors might help physicians identify cases of gout that may be less likely to achieve target urate level.

     

Colchicine-induced rhabdomyolysis

A case of colchicine-induced rhabdomyolysis is reported. A 79-year-old man with ischemic heart disease, chronic atrial fibrillation, chronic renal failure, hypothyroidism, and gout arthritis was hospitalized because of fatigue, myalgia, and leg weakness, shortly after starting treatment with colchicine. Investigation confirmed the diagnosis of rhabdomyolysis, and discontinuation of colchicine resulted in resolution of clinical and biochemical features of rhabdomylysis. Colchicine-induced rhabdomyolysis is a rare complication, and the postulated mechanisms and risk factors for this severe complication are discussed.     

PSEUDOPODAGRA: Differential Diagnosis of Gout

Several conditions may give rise to diagnostic difficulty by mimicking the painful swollen big toe which is so characteristic of gout. They include soft-tissue infection, pyrophosphate arthropathy, acute calcific periarthritis, palindromic rheumatism, ankylosing spondylitis, Reiter's disease and other post-infective arthropathies, psoriatic arthropathy, sarcoidosis, osteoarthrosis and mechanical problems, infective arthritis, arthritis of pancreatic disorders, non-disease, and psychogenic rheumatism. The diagnosis of gout should be based on identification of urate crystals, since raised serum-uric-acid levels and response to colchicine are unreliable tests.     

La maladie goutteuse

Gout is a chronic disease due to the deposition of monosodium urate microcrystals in joints and tissues. Its incidence and prevalence are increasing worldwide in close relation with the epidemic of obesity and metabolic syndrome. Gout is related to chronic hyperuricemia that should be treated to ensure the reduction or even the disappearance of acute attacks (“gout flares”) and to reduce the size and number of tophi. If arthritis of the first metatarsophalangeal joint is the most typical form, other joints may be affected, including the spine. Demonstration of urate microcrystals arthritis allows diagnosis of gout but, in the absence of possibility of performing joint puncture, imaging may be useful for providing complementary diagnostic elements. Appropriate care is essential to reduce the number of flares and the evolution towards gouty arthropathy but also in terms of public health in order to reduce costs related to this pathology.     

An update on gout

Gout is the most common cause of inflammatory arthritis in men aged more than 50, affecting approximately 1–2% of adult men in the Western world. The incidence and prevalence of gout is on the rise. Increasing longevity, dietary trends, obesity, metabolic syndrome, hypertension, increased use of low-dose aspirin, major organ transplantation and increased survival from coronary artery disease and end-stage renal disease have been implicated as the possible contributory factors. By far, the commonest cause of hyperuricaemia (that accounts for 90% of patients with gout) is decreased renal clearance. Patients with gout should avoid excess of alcohol (beer and spirits, particularly), red-meat and sea-food. Vegetarian food and dairy products reduce the risk of gouty arthritis. For the treatment of acute gout, options include non-steroidal antirheumatic drugs (NSAIDs), steroids (systemic or intra-articular) and colchicine. High dose of colchicine often results in diarrhoea and should be best avoided. Most patients respond within 18 hours to a dose of 0.5 mg twice daily. Colchicine is contraindicated if creatinine clearance is lower than 30 ml/min. Optimal treatment of chronic gout requires long-term reduction of serum urate to the lower half of the normal uric acid reference range. Prevention of attacks requires modification of lifestyle factors such as weight loss, moderation in the consumption of alcohol and meat and withdrawal of drugs known to cause elevated uric acid levels. Drugs used for chronic gout can be divided in three categories: (a) Uricostatic (xanthine oxidase inhibitor), e.g. allopurinol, oxipurinol, febuxostat, (b) Uricosuric, e.g. benzbromarone, sulfinpyrazone, probenecid, losartan, fenofibrate and (c) Uricolytic, e.g. uricozyme, rasburicase. Febuxostat is a new oral xanthine oxidase inhibitor, which has been shown to be more powerful in lowering uric acid levels compared to allopurinol. The drug is mainly metabolised by the liver and can be used in renal and hepatic insufficiency with no dose adjustment. Benzbromarone is an excellent uricosuric agent. Pegylated uricase is currently under development.