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Background/purpose: Taiwan Drug-Injury Relief System (TDRS) has been implemented since 1999. More than 60% of the approved applications were associated with severe cutaneous adverse reactions (SCARs). Studies assessing SCARs using real-world evidence are very limited. TDRS offers abundant case information as a source of real-world evidence to investigate the characteristics of SCARs in Taiwan. The purpose of this study is to understand the trends and characteristics of SCARs in Taiwan.Methods: Applications from Drug-Injury Relief Database (TDRD) from 1999 to 2016 were retrospectively analyzed.Results: A declining trend in SCARs application was noticed after 2012, and 952 applications of SCARs were identified. The most common subtypes of SCARs were SJS/TEN (n = 455/206), DRESS (n = 228), GBFDE (n = 34) and AGEP (n = 18). The most common culprit drugs were allopurinol, carbamazepine, phenytoin, diclofenac and lamotrigine for SJS/TEN; allopurinol, phenytoin, co-trimoxazole, carbamazepine and phenobarbital for DRESS; mefenamic acid for GBFDE; non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibacterials for AGEP. The proportions of mortality cases were 28.9% for SJS/TEN; 36% for DRESS; 11.8% for GBFDE and 5.6% for AGEP. The mean latent period of SJS/TEN, DRESS, GBFDE and AGEP were 21.8 days, 29.2 days, 3.3 days and 6.7 days, respectively.Conclusion: The approved drug-injury relief applications associated with SCARs were mainly SJS, TEN and DRESS. The most common culprit drugs were antiepileptics, antibacterials, antigout agents, and NSAIDs. The latent periods showed some distinct features for different types of SCARs. In light of the high mortality rate, public awareness and vigilance of SCARs are crucial for the patient safety. [ABSTRACT FROM AUTHOR]

Gout is the most common form of inflammatory arthritis in men, yet both patients and the public often do not recognise gout as a form of arthritis. Instead, due to historical misconceptions, gout is typically seen as a lifestyle disease caused by poor diet. In reality, there are a number of risk factors that contribute to gout, including genetic factors. Views of gout as precipitated by lifestyle alone can lead to stigma, and maladaptive beliefs that it should be treated primarily through dietary changes. This is thought to contribute to poor uptake of, and adherence to, effective pharmaceutical treatments. Gout has some of the poorest medication adherence rates of any chronic disease, contributing to suboptimal health outcomes for patients. Recent research suggests that when gout is referred to as 'urate crystal arthritis' (a rarely used name for gout), the perception of the disease by members of the public was more accurate. It was viewed as being less under personal control (i.e. less appropriately managed by behaviours such as dietary intake), and more appropriately managed by long-term medical treatment. This finding raises the possibility that patients themselves might also benefit from gout being explicitly labelled as arthritis. Indeed, parallels can be drawn between this case and other diseases that have recently had their names changed to improve outcomes, namely primary biliary cirrhosis and schizophrenia. A movement away from the term gout may benefit those living with the disease by changing illness perceptions and increasing uptake of, and adherence to, guideline-recommended treatment(s). [ABSTRACT FROM AUTHOR]

Gout, a debilitating inflammatory arthritis, currently affects more than 9 million Americans. Hyperuricemia, the laboratory abnormality associated with the development of gout, also occurs in a significant number of patients with chronic kidney disease (CKD), a condition that affects approximately 14% of the US population. Several recent studies have attempted to provide a definitive link between the presence of hyperuricemia and progression of CKD; however, the treatment of asymptomatic hyperuricemia in CKD is not supported by recent randomized controlled trials. The pharmacology of acute gout flares and urate lowering is complicated in patients who also have evidence of CKD, primarily because of an increased risk of medication toxicity. Recipients of kidney transplants are particularly at risk of debilitating gout and medication toxicity. We review the available data linking CKD, gout, and hyperuricemia, providing practice guidelines on managing gout in CKD patients and kidney transplant recipients. We advocate for much greater involvement of nephrologists in the management of gout in renal patients. [ABSTRACT FROM AUTHOR]

Background/purpose: Previous studies have reported that the indication and starting dose of allopurinol may be associated with the incidence of hypersensitive reactions. As allopurinol-related severe cutaneous adverse reactions (SCARs) constitute a significant proportion of drug injury relief applications in Taiwan, this study sought to examine allopurinol use and related adverse reactions through an analysis of recent drug injury relief applications.Methods: Allopurinol-related drug injury relief applications from 1999 to 2016 were collected, and descriptive statistical methods were used to analyze recent applications dating from 2011 to 2016.Results: A total of 174 allopurinol-related drug injury relief applications were submitted between 2011 and 2016, with the majority involving cases over the age of 65 (75.3%; mean age of all cases was 69.2). Most allopurinol-related drug injuries concerned the skin (173 out of 174 cases, 99.4%). The majority of cases had other co-morbidities such as cardiovascular disease/hypertension (86.2%), chronic kidney disease (58.6%), or diabetes (46.6%). Over 70% of cases initiated allopurinol at a dose of 100 mg/day or less. Analysis revealed that the greatest number of cases (44.6%) occurred in those with an estimated glomerular filtration rate (eGFR) between 15 and 60 mL/min/1.73 m2 and who initiated allopurinol at a dose of 100 mg/day.Conclusion: Old age and renal dysfunction are key risk factors for allopurinol hypersensitivity. When considering allopurinol for elderly patients with impaired kidney function, a full risk-benefit assessment, dosage adjustments, and careful monitoring may be warranted. [ABSTRACT FROM AUTHOR]

A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30 mg/kg), allopurinol (20 mg/kg) or benzbromarone (20 mg/kg) were orally administered to mice for 7 days. On the 7th day, uric acid and creatinine in serum and urine, blood urea nitrogen (BUN), malondialdehyde (MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin (H&E) staining. Hepatic XOD, renal urate transporter 1 (URAT1), glucose transporter type 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP-binding cassette transporter G2 (ABCG2) were detected by Western blot and real time polymerase chain reaction (PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid (FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent. [ABSTRACT FROM AUTHOR]

Gout is a progressive, painful, debilitating form of inflammatory arthritis. It is caused by factors that elevate the concentration of serum uric acid (sUA), leading to hyperuricemia (sUA >6.8 mg/dL). Continued elevated sUA can result in monosodium urate (MSU) crystal deposition in joints and soft tissues, and can cause acute and chronic inflammation. The prevalence of hyperuricemia and gout has increased over the last few decades, likely due to an aging population, changes in lifestyles and diet, and an increase in gout-associated comorbidities. Untreated or improperly treated gout can lead to chronic manifestation of the disease, including persistent inflammation, increased number of flares, development of tophi, and structural joint damage. Data show that even when patients are asymptomatic, ongoing inflammation and subsequent damage occurs locally at the joint and systemically. The aim of long-term treatment of gout is to reduce sUA levels to <6 mg/dL, which is below the saturation point of MSU (6.8 mg/dL), to inhibit formation of new crystals and to promote dissolution of existing crystals. Gout treatment should improve disease outcomes by eliminating gout flares, inducing long-term resolution of tophi, and more effectively managing comorbidities, many of which are associated with hyperuricemia. A number of studies have demonstrated that treating to the target of <6 mg/dL, by using effective therapies to lower sUA, results in reduction in the incidence of gout flares as well as shrinkage and eventual disappearance of tophi. Gout is often poorly managed due to a number of factors including lack of physician and patient adherence to treatment guidelines. Patients need to be educated about their diagnosis and management of the disease, such as the influence of diet and the importance of compliance with long-term treatment. With treatment, regular sUA monitoring, and patient adherence, gout is a curable disease. [ABSTRACT FROM PUBLISHER]

Background: Gout continues to be underdiagnosed and poorly managed despite the potential for cure. US and European management guidelines recommend treating to target serum urate (sUA) levels of <6 mg/dL (or <5 mg/dL to durably improve severe symptoms), with use of regular sUA monitoring, but studies suggest relatively poor adherence to these recommendations. This study investigates the real-world state of gout management in the United States by describing the characteristics of a large patient population treated in primary care and rheumatology settings.Methods: A retrospective chart audit, conducted among 124 primary care physicians and 125 rheumatologists, included 1245 patients with gout. Physicians completed structured case report forms capturing 12 months of sUA laboratory values, flare counts, comorbidities, types and doses of treatment, treatment duration, diagnosis date, physician specialty and socio-demographic factors. Focusing on the xanthine oxidase inhibitors (n = 858), descriptive statistics and multivariate models characterized relationships between patient characteristics, disease control, and treatment.Results: Only 83 (11%) patients achieved disease control, defined as a 12-month average sUA ≤6 mg/dL, no flares, and no tophi. Patients with greatest disease severity (defined as sUA >6 mg/dL, ≥2 flares per year, and tophi) were more likely to have kidney disease and other comorbidities. In a multivariate model, predictors of more severe gout were rheumatologist (vs primary care) management, febuxostat (vs allopurinol) use and presence of comorbid conditions.Conclusion: Our findings confirm the inadequacy of gout management in the real-world setting. Regular monitoring, including sUA measurement as recommended in guidelines, is important to assess gout control. Our analyses also demonstrate that patients with more severe gout are more likely to have comorbid conditions, be treated by a specialist and use newer therapies. [ABSTRACT FROM AUTHOR]

Gout is a common crystal-induced inflammatory arthritis, the prevalence and clinical complexity of which is increasing in the face of a growing aged population with multiple co-morbidities. Recent epidemiological studies emphasise that lifestyle factors strongly influence the development of hyperuricaemia and gout. Moreover, there is growing evidence that gout is an independent risk factor for cardiovascular disease. Acute attacks of gout are extremely painful and disabling, and if repeated attacks go untreated, chronic deforming arthritis ensues. Early diagnosis and appropriate therapy is essential to reduce long-term disability. Identification of monosodium urate crystals on synovial fluid analysis is the gold standard in gout diagnosis. Nonsteroidal anti-inflammatory drugs and oral or intra-articular corticosteroids remain central to the treatment of acute attacks. Prophylactic colchicine use, during the intercritical period, reduces gout flares, a common complication on initiation of urate-lowering therapy (ULT). Allopurinol is the treatment of choice when ULT is indicated. Gout management is suboptimal in many patients because of non-adherence to treatment and underutilisation of available treatments. Treating to target: a serum uric acid level < 0.35mmol/l, prevents crystal deposition in joints and soft tissues, thereby preventing acute attacks and ongoing inflammation, as well as decreasing the size and number of tophi. Treatment strategies should include attention to cardiovascular risk. The family practitioner is paramount to gout management which should be individualised. Emphasis should be placed on ongoing education and prevention. [ABSTRACT FROM AUTHOR]

Summary: Behçet''s disease is a systemic vasculitic disease characterized mainly by recurrent oral and genital aphthous ulcers, uveitis and skin findings. Central nervous system involvement is a serious manifestation. A case of acute meningeal syndrome secondary to Behçet''s disease is presented. Behçet''s disease should always be considered in differential diagnosis of acute meningeal syndrome without signs of viral infection, particularly in the context of multisystem manifestations. [Copyright &y& Elsevier]

Objectives: Results from a recent study showed that the risk of cardiovascular and all-cause mortality was higher in patients who received febuxostat, a potent urate-lowering agent, than that in patients who received allopurinol. Therefore, we hypothesized that an abrupt change in serum urate levels caused by urate-lowering agents would influence the risk of cardiovascular events.Methods: We included patients with a history of cardiovascular disease (CVD) who received allopurinol or febuxostat. Cardiovascular events were defined as follows: nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, and cardiovascular death. The change in serum urate levels was determined by the difference or reduction rate in urate within 6 months after exposure to allopurinol or febuxostat. The factors associated with cardiovascular events were evaluated by Cox regression analysis.Results: In total, 207 patients with CVD who were exposed to allopurinol or febuxostat were included. Cardiovascular events occurred in 38 patients (18.4%). In univariate analysis, age, diabetes mellitus, baseline urate levels, difference in mean urate levels between baseline and post-exposure (Δuratemean), and reduction rate in urate to the lowest post-exposure levels (Δuratelowest/day) were associated with cardiovascular events. Further, results from the multivariate analysis revealed that age [hazard ratio (HR) 1.036, 95% confidence interval (CI), 1.001-1.072, p = 0.042], Δuratemean (HR 1.188, CI, 1.033-1.366, p = 0.015), and Δuratelowest/day (HR 6.963, CI, 2.215-21.886, p = 0.001) were associated with cardiovascular events.Conclusion: Rapid reduction in serum urate levels was associated with a higher risk of cardiovascular events. Thus, careful attention should be paid to abruptly changing serum urate levels after treating urate-lowering agent in high-risk CVD patients. [ABSTRACT FROM AUTHOR]