Urate lowering therapy in this country has mainly been achieved by the use of allopurinol and probenecid. A new xanthine oxidase inhibitor called febuxostat has been approved in 2009 for treatment of hyperuricaemia in gout. In this report, we describe the management of a patient with chronic tophaceous gout using febuxostat. The reduction in serum uric acid to target levels was rapid, and the tophi size had also reduced significantly while on therapy. There was no unwanted side effect observed during the therapy. Therefore, febuxostat would be a useful alternative drug in the treatment of hyperuricaemia in gout patients who have contraindications to allopurinol and probenecid.
Study site: Rheumatology clinic, Selayang Hospital, Kuala Lumpur, Malaysia
Introduction: Febuxostat is a non-purine-selective oral xanthine oxidase inhibitor drug, and is an alternative to Allopurinol to lower serum uric acid in gout patients. It is probably more effective than Allopurinol, however, its use is limited because of its cost and availability. Allopurinol has been the mainstay treatment for gout for about 50 years. However, its use has been associated with allergic reactions especially in patients with renal impairment.The objective of this study was to describe HTAA Rheumatology Unit experiences with Febuxostat in the management of gout.
Materials and method: Case records belonging to 6 patients who had been started on Febuxostat between January 2012 and January 2017 were analysed.
Results: The majority of patients on Febuxostat were males (83.3%) as well as Malays (83.3%). About 66.7% of patients had already developed mild to moderate chronic kidney disease (GFR between 30-89 mL/min) due to multifactorial causes by the time they were started on Febuxostat. Also 33% of patients had mild liver impairment (ALT & AST < 1.5 ULN) due to fatty liver prior to Febuxostat. All patients had been started on Febuxostat due to allergic reactions to Allopurinol. All patients were on Febuxostat 40 mg once a day. Following Febuxostat, a significant decrease in the uric acid levels much closer to the target level i.e. less than 360 µmol/L were achieved in all patients. Only 1 patient (16.7%) developed a side effect i.e. ALT > 1.5 ULN while the rest tolerated the drug very well.
Conclusion: Although the number of patients analysed was small, Febuxostat was shown to be very effective and safe for use in patients with gout even with concomitant mild to moderate renal impairment. Serum uric acid levels reduced significantly while on the lowest dose of 40 mg once a day.
Malaysia has a rich diversity of medicinal plants and some of them inhibit xanthine oxidase (XO), which can be introduced as new natural sources of gout medication and a substitute for synthetic xanthine oxidase inhibitors (XOI). The degree of XO inhibitory activity was determined by measuring the absorbance spectrophotometrically at 295 nm, which is associated with uric acid formation. Our preliminary screening study had employed the use of distilled water, 70% methanol and absolute ethanol to extract XOI from twenty parts of five plant species, namely, Averrhoa carambola, Carica papaya, Dimocarpus longan malesianus, Manilkara zapota and Salacca zalacca. These plants were selected based on their frequent medicinal usages by local folks. The results have shown that an aqueous extract of Carica papaya mature leaves has promising activity to inhibit XO up to 75.68 ± 0.1%. Statistical experimental design were employed to optimize the selected sample (dried Carica papaya leaves: distilled water) on extraction of XOI and the maximum XOI percentage of 86.93 ± 1.9% was obtained, which exhibited only 6.76% less than the activity exhibited by allopurinol (93.69 ± 0.2%), a commercial XOI. The comparison was made between allopurinol and optimized extract on the basis of IC50concentrations. Allopurinol showed IC50 value of 3.74 μg/ml that is considerably lower as compared to the optimized sample (4.33 μg/ml).
Tumoral calcinosis is an uncommon condition which has been described to exist in primary and secondary forms. A lack of awareness of this entity can lead to unnecessary procedures and incorrect management. We report a case of a patient on peritoneal dialysis who presented with multiple painful joint swellings to the orthopaedic department. An initial diagnosis of septic arthritis was made, then revised to chronic tophaceous gout and referred to the rheumatology unit.
INTRODUCTION: Hyperuricemia has been identified as an independent risk factor for coronary artery disease (CAD). Uric acid lowering therapy could potentially lower the risk of CAD. Conventional treatments have been effective in treating acute gout flares in most patients, but certain options, like NSAIDs could increase the risk of CAD. Area covered: This review covers the aspect of cardiac safety with traditional and new medications used in treating both acute flares and chronic gout according to the most recent international guidelines. Expert opinion: All NSAIDs, not just selective Cox 2 inhibitors, have associated with them different degrees of cardiac risk; therefore, NSAIDs should be avoided when treating patients with underlying CAD. Interleukin-1 inhibitors appear to be safe alternatives for treating cardiac patients who are contraindicated to conventional treatment. Presently, there is a paucity of evidence concerning whether treatment of hyperuricemia could lower the risk of CAD and this must be explored further. It is also important to explore the cardiac safety of plegloticase to better ascertain its safety in CAD patients.
INTRODUCTION: Cardiovascular disease is a major cause of morbidity and mortality. Primary care doctors as general practitioners (GPs) play a central role in prevention, as they are in contact with a large number of patients in the community through provision of first contact, comprehensive and continuing care. This study aims to assess the adequacy of cardiovascular disease preventive care in general practice through a medical audit.
METHODS: Nine GPs in Malaysia did a retrospective audit on the records of patients, aged 45 years and above, who attended the clinics in June 2005. The adequacy of cardiovascular disease preventive care was assessed using agreed criteria and standards.
RESULTS: Standards achieved included blood pressure recording (92.4 percent), blood sugar screening (72.7 percent) and attaining the latest blood pressure of equal or less than 140/90 mmHg in hypertensive patients (71.3 percent). Achieved standards ranged from 11.1 percent to 66.7 percent in the maintenance of hypertension and diabetic registries, recording of smoking status, height and weight, screening of lipid profile and attaining target blood sugar levels in diabetics.
CONCLUSIONS: In the nine general practice clinics audited, targets were achieved in three out of ten indicators of cardiovascular preventive care. There were vast differences among individual clinics.
Matched MeSH terms: Gout Suppressants/therapeutic use
ETHNOPHARMACOLOGICAL RELEVANCE: Lippia nodiflora has been traditionally used in the Ayurvedic, Unani, and Sidha systems, as well as Traditional Chinese Medicine (TCM) for the treatment of knee joint pain, lithiasis, diuresis, urinary disorder and swelling.
AIM OF THE STUDY: The present study aims to investigate the antihyperuricemic effect of the L. nodiflora methanol extract, fractions, and chemical constituents and their mechanism of action in the rat model.
MATERIALS AND METHODS: The mechanisms were investigated by performing xanthine oxidase inhibitory, uricosuric, and liver xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitory studies in potassium oxonate- and hypoxanthine-induced hyperuricemic rats. The plant safety profile was determined using acute toxicity study. The molecular docking of the active compound to the xanthine oxidase was simulated using computer aided molecular modeling analysis.
RESULTS: Oral administration of methanol extract showed a dose-dependent reduction effect on the serum uric acid level of hyperuricemic rats. F3 was the most potent fraction in lowering the serum uric acid level of hyperuricemic rats. Bioactivity-guided purification of F3 afforded two phenylethanoid glycosides, arenarioside (1) and verbascoside (2) and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4), and nodifloretin (5). The highest serum uric acid reduction effect was exhibited by 3 (66.94%) in hyperuricemic rats, followed by 5 (55.97%), 4 (49.16%), 2 (29.03%), and 1 (22.08%) at 0.2 mmol/kg. Dose-response investigation on 3 at doses of 0.05, 0.1, and 0.3 mmol/kg produced a significant dose-dependent reduction on the serum uric acid level of hyperuricemic rats. Repeated administration of F3 or 3 to the hyperuricemic rats for 10 continuous days resulted in a significant and progressive serum uric acid lowering effect in hyperuricemic rats. In contrast, methanol extract and F3 did not reduce serum uric acid level of normoruricemic rats. In addition, F4 significantly increased the uric acid excretion of hyperuricemic rats at 200mg/kg. No toxic effect was observed in rats administered with 5000 mg/kg of methanol extract or F3.
CONCLUSION: The potential application of L. nodiflora against hyperuricemia in the animal in accordance with its traditional uses has been demonstrated in the present study for the first time. The antihyperuricemic effect possessed by L. nodiflora was contributed mainly by liver XOD/XDH inhibitory activities and partially by uricosuric effect. Flavonoids mainly accountable for the uric acid lowering effect of L. nodiflora through the inhibition of XOD/XDH activities.
KEYWORDS: Antihyperuricemic; Hypoxanthine-induced hyperuricemic rat; Lippia nodiflora; Liver xanthine oxidase and xanthine dehydrogenase; Serum uric acid; Uric acid excretion
OBJECTIVE: Studies found a strong association between allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and the HLA-B*58:01 allele. HLA-B*58:01 screening-guided therapy may mitigate the risk of allopurinol-induced SJS/TEN. This study aimed to evaluate the cost-effectiveness of HLA-B*58:01 screening before allopurinol therapy initiation compared with the current practice of no screening for Malaysian patients with chronic gout in whom a hypouricemic agent is indicated.
METHODS: This cost-effectiveness analysis adopted a societal perspective with a lifetime horizon. A decision tree model coupled with Markov models were developed to estimate the costs and outcomes, represented by quality-adjusted life years (QALYs) gained, of three treatment strategies: (a) current practice (allopurinol initiation without HLA-B*58:01 screening); (b) HLA-B*58:01 screening before allopurinol initiation; and (c) alternative treatment (probenecid) without HLA-B*58:01 screening. The model was populated with data from literature review, meta-analysis, and published government documents. Cost values were adjusted for the year 2016, with costs and health outcomes discounted at 3% per annum. A series of sensitivity analysis including probabilistic sensitivity analysis were carried out to determine the robustness of the findings.
RESULTS: Both HLA-B*58:01 screening and probenecid prescribing were dominated by current practice. Compared with current practice, HLA-B*58:01 screening resulted in 0.252 QALYs loss per patient at an additional cost of USD 322, whereas probenecid prescribing resulted in 1.928 QALYs loss per patient at an additional cost of USD 2203. One SJS/TEN case would be avoided for every 556 patients screened. At the cost-effectiveness threshold of USD 8695 per QALY, the probability of current practice being the best choice is 99.9%, in contrast with 0.1 and 0% in HLA-B*58:01 screening and probenecid prescribing, respectively. This is because of the low incidence of allopurinol-induced SJS/TEN in Malaysia and the lower efficacy of probenecid compared with allopurinol in gout control.
CONCLUSION: This analysis showed that HLA-B*58:01 genetic testing before allopurinol initiation is unlikely to be a cost-effective intervention in Malaysia.
BACKGROUND: The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR) vary among the different populations previously studied.
AIM: To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms (DRESS) in our population.
METHODS: We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010.
RESULTS: A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases) followed by SJS/TEN (110 cases) and DRESS (34 cases). Antibiotics was the most commonly implicated drug group (146 cases) followed by anticonvulsants (81 cases) and antigout drugs (50 cases). The most frequently implicated drug was allopurinol (50 cases). Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases). Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively.
CONCLUSIONS: The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.
Study site: department of dermatology in Hospital Sultanah Aminah
An off-the-shelf Raman Spectrometer (RS) was used to noninvasively determine the presence of monosodium urate (MSU) crystals on the metatarsophalangeal joint (MTPJ) of a single gout sufferer. The spectrum sourced from the clinically diagnosed gout sufferer was compared to that sourced from an age-matched healthy subject scanned using the same protocol. Minimal signal processing was conducted on both spectra. Peaks characteristic of MSU crystals were evident on the spectrum sourced from the gout sufferer and not on the spectrum from the healthy control.
OBJECTIVE: We describe a 10 year observation of the effect of control of hyperuricemia compared with self-medication alone in patients with chronic gout.
METHODS: We studied 299 consecutively self-referred Malayo-Polynesian men with chronic gout, mean age 35 +/- 14.3 SD years. Subjects comprised 228 cases with chronic gout without tophi or urolithiasis (Group 1) and 71 with those complications (Group 2). Attacks of acute gouty arthritis were treated with nonsteroidal antiinflammatory drugs (NSAID) and/or corticosteroids. After acute arthritis had settled, urate-lowering drugs were instituted in both groups combined with low dose colchicine and/or low dose NSAID for at least 0.5-2 years. Urate levels were maintained longterm at a mean of < 5 mg/dl. After 10 years, the dropouts were traced and evaluated for comparison with baseline and those who remained in the study. In Group 2 the urate-lowering drugs were continued.
RESULTS: Control of gout and hyperuricemia was achieved in all patients who remained under control: 91.6% of the 299 patients for at least 2 years (short-term), up to 5 years in 87.5% (medium term), and up to 10 years in 79.6% (longterm). In Group 1 (chronic gout without complication) only 36.8% had no attacks during 8 years, after they had tapered urate-lowering drug after the first 2 years of the study. In the 61 dropouts the intermittent symptomatic treatment and/or self-medication without longterm control of hyperuricemia resulted after 1 decade in chronic gout with more complications and associated conditions leading to increased morbidity, disability, and comorbidity, and 3 early mortalities.
CONCLUSION: By controlling hyperuricemia, improvement of the prognosis of chronic gout, comorbidity, and early death was achieved compared with self-medication alone. Self-medication in a developing country if continued unchecked may become a public health problem in a population with a high prevalence rate of gout.
AIM: The main objective of this study is to elucidate the clinical significance of the SLC2A9/GLUT9 rs11722228 polymorphism among male gout patients.
METHOD: We consecutively recruited all newly diagnosed male gout patients who were treatment-naive from the rheumatology outpatient clinics of two Malaysian hospitals. Age-matched healthy male adults were employed as controls. All subjects were tested for the SLC2A9/GLUT9 rs11722228 genotypes, serum uric acid (SUA), urine uric acid and creatinine levels. All gout subjects were examined for the presence of tophi and sonographically screened for renal calculi.
RESULTS: A total of 73 male gout patients and 73 age-matched healthy male adults were recruited in this study. The genotypic frequencies of SLC2A9/GLUT9 rs1172228 did not differ significantly between the gout cases and the healthy controls. The gout subjects with the CC genotype had significantly higher SUA levels (P = 0.002), family history of gout (P < 0.050) and the occurrence of renal calculi (P = 0.026). The SUA-adjusted odds ratios (OR) of the occurrence of renal calculi in the CC genotype (OR = 1 [reference]) was significantly higher than the CT genotype (OR = 0.338, 95%CI: 0.141-0.813) and the TT genotype (OR = 0.271, 95%CI: 0.086-0.854).
CONCLUSIONS: The genotypic distribution of SLC2A9/GLUT9 rs1172228 in male gout patients did not differ significantly from that of healthy male controls. However, the CC genotype in gout had significant associations with higher levels of SUA, renal calculi and a positive family history of gout.
Study site: Rheumatology clinic, Tuanku Jaafar Hospital, Malaysia and Putrajaya Hospital, Malaysia