Abstract: Hyperuricemia is commonly diagnosed in subjects with abnormal purine metabolism. Prolonged hyperuricemia often associated with gout, which is a vital risk factor for joint dysfunction. The current study was designed to determine the efficacy of vitamin C supplements for treatment of high serum uric acid (UA) among hyperuricemic and gouty patients, and finding-out the effect of supplementation on serum creatinine (Cr) level and glomerular filtration rate (GFR). This intervention study was started in April, 2013, till two months. A convenient sample of 30 adults aged between 24-75 years of both genders was assigned into two study groups: hyperuricemic (n=15) and gouty (n=15) groups. Each participant supplemented with 500 mg/day vitamin C chewable tablets for 2 months. Serum UA, Cr, and GFR were measured before and after treatment. At the end of this study, Cr and GFR enhanced insignificantly in both groups. UA increased insignificantly in gouty group after 2 months by about 0.31 mg/dl. On the other hand, hyperuricemic group showed significant (P ≤0.05) decrease in UA (-0.78 mg/dl) after 2 months duration. In conclusion, supplementation with 500 mg/day vitamin C for 2 months significantly attenuated serum UA for hyperuricemic patients and insignificantly affected serum UA in gouty patients. The uselessness of vitamin C supplements on gouty patients could be associated to a number of possible reasons.

Gout is not only associated with obstructive sleep apnea (OSA), but the intermittent episodes of hypoxia that occur with OSA may also have a role in causing gout. Epidemiological studies have documented a higher incidence and prevalence of gout in individuals diagnosed with OSA than in individuals never diagnosed with OSA. The pathophysiology of OSA’s chronic episodes of hypoxia leading to hyperuricemia and gout involves boththe overproduction and underexcretion of uric acid. Treating OSA may be an additional way to control gout and its life-threatening comorbidities. Clinicians are urged to evaluate their patients with hyperuricemia/gout for OSA as it may lead to alternative ways to control gout with superior outcomes that simply pharmacologic treatment alone.

Hyperuricemia is a risk factor for gout. It has been well observed that a large proportion of hyperuricemia individuals have never had a gout attack(s), while some patients with gout can have a normuricemia. This raises a puzzle of the real role of serum uric acid (SUA) in the occurrence of gout attacks. As the molecule of uric acid has its dual effects in vivo with antioxidant property as well as being an inflammatory promoter, it has been placed in a delicate position in balancing metabolisms. Gout seems to be a multifactorial metabolic disease and its pathogenesis should not rely solely on hyperuricemia or MSU crystal. This critical review aims to unfold the mechanisms of the SUA role participating in gout development. It also discusses some key elements which are prerequisite for the formation of gout in association with the current therapeutic regime. The compilation should be helpful in precisely fighting for a cure of gout clinically and pharmaceutically.

Objective: To evaluate two different DECT postprocessing protocols for detection of MSU deposits in foot tendons of cadavers with verification by polarizing light microscopy as gold standard.Material and Methods: A total of 40 embalmed cadavers (15 male; 25 female; median age, 82 years; mean, 80 years; range, 52 - 99; SD ± 10.9) underwent DECT to assess MSU deposits in foot tendons.Two postprocessing DECT protocols with different Hounsfield unit (HU) thresholds 150/500 (=established) versus 120/500 (= modified) HU were applied to dual source acquisition with 80 kV for tube A and 140 kV for tube B.Six fresh cadavers (4 male; 2 female; median age, 78; mean, 78,5; range 61 - 95 ) were examined by DECT. Tendon dissection of 2/6 fresh cadavers with positive DECT 120 and negative DECT 150 studies were used to verify MSU deposits by polarizing light microscopy.Results: The tibialis anterior tendon was found positive in 57.5%/100% (DECT 150/120), peroneus tendon in 35%/100%, achilles tendon in 25%/90%, flexor halluces longus tendon in 10%/100%, and tibialis posterior tendon in 12.5%/97.5%. DECT 120 resulted in increased tendon MSU deposit detection, when DECT 150 was negative, with an overall agreement between DECT 150 and DECT 120 of 80 % (P = 0.013). Polarizing light microscope confirmed MSU deposits detected only by DECT 120 in tibialis anterior, achilles, flexor halluces longus and peroneal tendons.Conclusion: The DECT 120 protocol showed a higher sensitivity when compared to DECT 150.

Perforating dermatoses are dermatologic disorders with transepidermal elimination (TE) of dermal substances. While TE is typically associated with collagen and elastin, it can also occur as a secondary event in other processes, and it is important to keep a broad differential. We present a case of perforating tophaceous gout, which underscores the need for a thoughtful approach to perforating disorders. An updated review of recent literature is also presented.

Introduction: Individuals with gout are at higher risk of developing chronic conditions, such as diabetes, chronic kidney disease (CKD), and cardiovascular diseases. In this study, the association between urate-lowering therapy (ULT) use and the prevalence of these conditions was evaluated. Methods: This observational, cross-sectional pharmacoepidemiologic study used the 2013-2018 biannual cycles of the National Health and Nutrition Examination Survey. The inclusion criteria were adults 30 years of age and older with a diagnosis of gout. The association between ULT treatment status and dyslipidemia, coronary heart disease, heart failure, hypertension, and chronic kidney disease was evaluated, as well as associations with select clinical laboratory biomarkers. Results: Use of ULT was 28.9% (95%CI 24.3%-33.9%). There was no significant association between ULT use and the prevalence of heart failure, coronary heart disease, hypertension, or dyslipidemia (p>0.05). Those on ULT had a lower mean eGFR compared to those not on treatment (68.03 versus 74.74 mL/min/1.73m², p=0.014). LDL- and HDL- and total cholesterol were significantly lower among those receiving ULT treatment (p<0.05). Conclusion: ULT use continues to be low among those with gout. Those on ULT were more likely to be diagnosed with CKD, college graduates and above, older males, and obese. Clinical guidelines conditionally recommend ULTs in co-morbid kidney disease; while our results may reflect guidelines recommendation for ULT use in CKD patients, worsening kidney function while taking ULT is unlikely. Further research is necessary to determine the long-term impact of ULTs on kidney function and cardiovascular biomarkers.

Gout is the most common form of inflammatory arthritis. Hyperuricaemia is the pre-requisite for gout and is influenced by variable modifiable and non-modifiable risk factors. Clinical features unique for gout are due to deposition of monosodium urate (MSU) crystal in articular and extra articular tissues. Among various treating agents, anti-inflammatory drugs and urate lowering therapies (ULT) are used widely and successfully, however, non-medicinal means are also effective in the disorder. In their updated guidelines, ACR (2012) and EULAR (2016) recommended both medicinal and non-medicinal approaches that could be used in treating gout, though some of the recommendations are based on lower level of evidence. Moreover, researchers’ continued effort in finding new gout managing agents appear promising, for example, role of Lesinurad in gout management (CLEAR1, CLEAR2). In this new synthesis the author is aimed to provide updated information on gout management based on a systematic review including published work within last ten years between 2008 and 2018 and for this purpose, using ‘clinical trials in gout management’ string, published worked searched in PubMed database from 1st September 2018 to 30 October 2018. Besides the recent ACR and EULAR evidence based management guidelines, the author reviewed another 91 (total 93) articles to make this new draft – 39 articles describe role of pharmacological agents and 54 describe different gout risks, pharmacokinetics/pharmacodynamics of ULT, association between raised sUA level and renal impairment, efficacy of non-pharmacological agents in reducing sUA. According to published work, anti-inflammatory agent is the most appropriate drug group in mitigating inflammatory symptoms of gout, though they often adversely affect over other vital 2 organs with impaired function. Besides ULT, uricase analogues are also found useful in non refractory gout. Since anti-inflammatory agents and ULT contraindicate in some clinical conditions, intra-articular steroid and or adrenocorticotropic hormone (ACTH) are appropriate alternatives instead. However, head-to-head comparison between different NSAIDs, NSAID and prednisolone, NSAID and colchicine are yet to perform. Use of combined anti-inflammatory preparations in gout is also based on lower level of evidence. Regarding effective maximum dose and long-standing impact of ULT on vital organs we are yet to reach a conclusion. Likewise, non-medicinal approaches are widely using in achieving target sUA level, though some of them are based on biased study outcomes and or study with inadequate power, requiring further analysis. Among non-pharmacological approaches, life-style modification, restriction of purine rich diets, avoidance of gout inciting agents are important, but inconclusive. Educating patients’ about diseases, risk factors, available treatment options and side effects from them are also important in terms of achieving sUA level, nevertheless too much counseling sometimes could be worthless.

The accumulation of loss of function mutations in the uricase gene well explains the high urate levels in hominoids (apes and humans) compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in the antioxidant role of urate and the role of the uricase gene in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase gene in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy.

Gout is at least 3 times more prevalent in men than in women. However, concurrent with rising total gout prevalence, complex factors, including comorbidities, diet and lifestyle, and aging, have promoted higher gout prevalence in females. This narrative review focuses on summarizing recent developments in the landscape of gout in women, and mechanisms involved. New knowledge on sex hormone effects on both urate-excreting and urate-reabsorbing transporters, and higher hypertension and chronic kidney disease prevalence in women compared to men, may help explain why gout incidence rises robustly after menopause in women to approach that in men. Racial and ethnic factors, risk profiles based on heritable genetic polymorphisms of urate transporters, and diet, body mass index, and lifestyle factors differ according to sex. In addition, sex differences in clinical phenotypes and outcomes of gout and non-gout illnesses include more frequent comorbidities, more pain and disability during gout flare, different perceptions of disease burden, and more frequent severe cutaneous hypersensitivity reaction to allopurinol in women. Significantly, women with gout also have poorer COVID-19 outcomes than do men. Collectively, such findings support the potential clinical benefits of tailoring gout and hyperuricemia treatment according to sex.

Introduction. A needle is inserted into a joint for arthrocentesis or injection of a therapeutic medication(s), commonly a corticosteroid. The aim of this paper is to discuss the first theme identified from a scoping review of corticosteroid injections for the pathology of the first metatarsophalangeal joint. Pathology. The two most common pathologies affecting the first metatarsophalangeal joint are osteoarthritis and bunions. An arthritic joint is regularly injected with a corticosteroid, but bunions are not. Other pathologies that may receive an injection include rheumatoid arthritis, gout, sesamoiditis and post-operative arthrofibrosis. Discussion. Most available evidence discusses corticosteroid injections for osteoarthritis, but there is a paucity of high-quality evidence, especially for corticosteroid use in other pathological conditions. Conclusion. Whilst the evidence base suggests that corticosteroid injections are safe short- and mid-term treatment options for a range of soft tissue and joint pathology, the specific indications, and short/long-term outcomes in the first metatarsophalangeal joint pathologies are not clear and warrant further study.

Pharmacogenomics (PGx) is the study of how variations of the patient genetic makeup could influence the selection and dosing of medications, including urate-lowering therapies (ULTs). Patients with gout present with several comorbidities, warranting the use of several long-term medications that increase their pill burden and the risk of adverse drug events. PGx testing can identify individuals who are more or less likely to benefit from a given treatment and ultimately improve adherence and reduce polypharmacy. Gout management involves using various ULTs associated with specific genetic variations that could modulate medication safety and efficacy. Individuals carrying the HLA-B*58:01 variant are at a higher risk of serious and life-threatening skin reactions from taking allopurinol. Besides, racial disparities in HLA-B distribution warrant testing for its status in high-risk populations, specifically some Asian subgroups and African Americans. G6PD-deficient individuals are prone to develop hemolytic anemia and methemoglobinemia with pegloticase and probenecid use. Patients with the less active form of the drug-metabolizing CYP2C9 are at higher risk for NSAID-related upper gastrointestinal (GI) bleeding. The drug-gene pair interactions among various gout therapies were also reviewed. Allopurinol-related genes included AOX, ABCG2, and SLC22A12. Febuxostat-related genes included UGT1A1. Benzbromarone- and probenecid- related genes included SLC22A12 and ABCB1. Colchicine-related genes included CYP2D6, ABCB1, rs6916345 G>A, and SEPHS1. Finally, the corticosteroid-related gene included HCG22; and the anakinra-related gene included IL1RA. This review synthesizes the most contemporary level of evidence for using PGx in gout pharmacotherapy, as referenced in the CPIC guidelines, FDA, PharmGKB, and current literature.

High fructose and sugar-sweetened soft drink (SSSD) intakes are associated with elevated blood uric acid concentrations and increased risk of gout and cardiovascular disease. Fruits are naturally high in fructose but their effect on cardiometabolic risk is unknown. We examined the effect on serum uric acid and cardiometabolic risk factors of consuming fructose from either fruit or SSSD in overweight adults. 48 healthy, overweight (BMI≥ 28 kg/m²) men (n=21) and women (n=20) were randomised to either a fruit (n = 19) or SSSSD (n = 22) intervention for 4 weeks. The fruit group received 6 items of fresh and dried fruit per day and the SSSD group received 955ml of SSSD per day with treatments matched for energy and fructose content. Serum uric acid concentrations were significantly reduced in men in the fruit group compared to the SSSD group (difference 57.2 μmol/L [95% CI: 16.4, 98.0], p= 0.008) but there was no difference amongst women (1.3 μmol/L [95%CI: -9.5, 6.9], p= 0.295). There differences in weight change or other cardiometabolic risk factors. These findings suggest no need to restrict fruit intake in individuals with elevated serum uric acid concentrations, such as those with gout.

Vitamin D plays an important role in maintaining healthy mineralized skeleton. It is also consid-ered an immunomodulatory agent that regulate the innate and adaptive immune systems. Multi-ple observational studies have demonstrated the association between low level of serum 25-hydroxyvitamin D [25(OH)D] and presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies and oste-oarthritis (OA). Nevertheless, the specific benefits of vitamin D supplement for treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for improvement of disease ac-tivity of RA, SLE and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently from others since inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain serum 25(OH)D level at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis and fracture, and possibly 40 – 60 ng/mL (100 – 150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.