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Background Lowering plasma urate in subjects with gout is associated with an increase in flares because of an altered equilibrium between soluble urate and uric acid crystals.1 Details of the relationship between plasma urate lowering and gout flares have not been fully delineated. Pegloticase is a mammalian recombinant uricase conjugated to polyethylene glycol approved for the treatment of chronic gout refractory to conventional oral urate lowering therapy.2–4 Results from the two 6 month randomised clinical trials (RCTs) of pegloticase showed that during months 1–3, there was an increase in pegloticase-treated subjects experiencing gout flares vs those receiving placebo. However, the reported analysis did not separate results for subjects who did and did not respond to pegloticase with a sustained reduction in plasma urate levels or relate flares to plasma urate levels. Objectives To determine factors associated with the occurrence of flares in subjects who did and did not respond to pegloticase in the two RCTs for this therapy. Methods This analysis used results from 2 pivotal RCTs2 of pegloticase (8 mg every 2 weeks [q2] or every 4 weeks [q4]) vs placebo in subjects with chronic refractory gout. A responder was defined as a subject with plasma urate Results There were increases in the frequency of subjects experiencing flares and the mean flare frequency in the pegloticase group vs placebo during the first 3 months of the trial (figure 1A). In contrast, there were marked reductions in both outcomes during months 3–6 (figure 1B). The increase in flares in the first 3 months was most evident (p=0.0006) and the decrease during the second 3 months was least marked (p=0.0006) in subjects receiving q4 pegloticase. Previous analysis indicated that q2 pegloticase caused persistently lowered plasma urate in responders, whereas q4 administration resulted in a more saw tooth pattern.5 Multivariate linear regression analysis indicated that the only variable associated with flares in the treated subjects was the absolute change in plasma urate prior to these events. Assessment of plasma urate at both 2 weeks and immediately before flares indicated that larger differences between these two values were associated with increased flare occurrence (p=0.002). Conclusions Flares associated with pegloticase treatment in subjects with chronic refractory gout were increased most markedly in responders to monthly administration and were significantly associated with fluctuations in plasma urate levels. Such fluctuations are much more common with monthly administration of pegloticase vs the recommended biweekly treatment regimen. References [1] Wortmann RL, et al. Clin Ther2010;32:2386. [2] Sundy JS, et al. JAMA2011;306:711. [3] Mandell BF, et al. Arthritis Rheumatol2016;68(suppl 10):212. [4] Mandell BF, et al. Arthritis Rheumatol2017; 69(suppl 10):2054. [5] Lipsky PE, et al. Arthritis Res Ther2014;16:R60. Disclosure of Interest L. Calabrese: None declared, T. Fields Consultant for: Horizon Pharma, Takeda, Ironwood, Speakers bureau: Horizon Pharma, Takeda, Ironwood, A. Yeo Consultant for: Horizon Pharma, P. Lipsky Consultant for: Horizon Pharma

Background In 2016 EULAR evidence based clinical guidelines on Gout treatment have been updated.1 Objectives to assess current daily practice physicians’ approach to management of chronic gout patients Methods a cross-sectional anonymous survey had been offered to hospital and outpatient departments physicians dealing with gout patients resulting in 97 back-feed replies yielded. This publication deals with chronic gout treatment practice. Results all survey participants were divided into 3 groups. Group 1 consisted of 18 rheumatologists (professional experience median 19.6 years, range 1 to 43), group 2 included 60 general practitioners (GP, professional experience 27; 4–47), group 3 included other specialists (cardiologists, surgeons etc.) who reported frequent contacts with gout patients (professional experience 16.5; 1–44). Rheumatologists reported to contact median 15 (range 2–40) gouty subjects per month, while group 2 reported to see 31 – 10 and group 3 consults 41 – 12 patients per month. All rheumatologists and 45 GPs reported initiation of allopurinol or febuxostat after gouty arthritis resolution, while 11 general practitioners did not start antihyperuricemic drugs in subjects with kidney and/or cardiovascular comorbidities. In Group 3 only 6 responders had experience of antihyperuricemic drugs administration, but 3 of them reported allopurinol initiation during gout flare. Only 2 rheumatologists and 2 GPs were aware of gout flare low dose colchicin prophylaxis during allopurinol dose adjustment. Administration of maximal allopurinol daily maintenance doses over 300 mg was reported only by 7 rheumatologists and 7 GPs. Other specialists did not have any personal experience of allopurinol dose adjustment. By responders’ assessment every 2–3 patient continues to experience gout flares in spite of prescribed treatmen Conclusions intensive educational intervention is urgently required to change current practice of chronic gout treatment in Russia. Reference [1] Richette P, et al. 2016updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis2017;76:29–42 Disclosure of Interest None declared

Background in everyday practice chronic gout patients are frequently consulted by general practitioners, surgeons, cardiologists and other specialists. In general, chronic gout patients have been reported to be quite incompliant, but it remains unclear whether low compliance depends on the specialty of the prescribing physician.1 Objectives to compare the clinical course of gout in patients consulted by different specialists and to identify factors of low patients’ compliance in Russia. Methods cross-sectional study included 56 chronic gout patients aged 31 to 82 (median 54 years). Average gout symptoms duration was 6.8 years, average attacks frequency was 6.4 per year. Tofi were present in 21.4% of patients. All subjects were divided into three groups: Group 1 consisted of treatment naive patients at primary rheumatologist visit, Group 2 and Group 3 included patients who had previously been treated. Group 2 subjects were visiting both non-rheumatologists and rheumatologists. Group 3 were managed by rheumatologists strictly according to the EULAR evidence-based recommendations.2 Results Group 1 primary consulted rheumatologists at the age of 47.3±14.5, Group 2 patients were assessed at the age of 58.4±15.2, and Group 3 were aged 51.2±13.5. Disease symptoms duration was maximal in Group 2 (10.6±10.6 years) while 5 years in Groups 1 and Group 3. Flares frequency was the lowest in Group 3 (2.2±1.8 per year), while in Group 2 it was extremely high – (10,58±10,56 per year). The incidence of tofi and urolithiasis was lowest in the Group 3 whereas every third treatment naive patient had tophi or/and urolythiasis. To relieve gouty arthritis vast majority of patients used NSAIDs, though at 50% strength of the recommended dose. Only 9%–14% of flares were controlled by colchicine in Groups 2 and 3. Colchicine prevention of flares was prescribed only in 45% of cases by rheumatologists. The most frequent urate-lowering therapy (ULT) was allopurinol, it was taken only by 63% of patients of the third group and 35.7% in the second group. While patients in the third group took the drug daily, the other patients did not follow the administration scheme. Serum creatinine level was the lowest (87.5±16.8 μmol/L) in Group 3, being the highest in treatment of naive patients (102.7±30.0 μmol/L). Serum uric acid target level was achieved only in the compliant Group 3 patients (343 μmol/L), while Group 2 levels varied between 462–546 μmol/L, being the highest (625 μmol/L) in treatment naive Group 1. Low compliance risk factors were: age under 45, absence of comorbidity and long term multiple drugs consumption. Conclusions chronic gout patients’ compliance and quality of patient management can be assessed as alarmingly low. Rheumatologists adhering to EULAR evidence-based approach to gout management can actually achieve recommended treatment targets. Both general practitioners and other specialists are in need of consistent educational program on gout management. Younger and comorbidity-free gout patients should be encouraged to follow attending physician’s recommendations. Reference [1] Burrell A, Wong P, Ollendorf D, et al. Defining compliance/adherence and persistence: ISPOR Special Interest Working Group. Value Health2005; 8:A194–5. Disclosure of Interest None declared

Gout is the most common inflammatory arthritis in adults. Given the increasing prevalence of gout and associated comorbidities, there is a growing need for better therapeutic options. While current treatment options satisfactorily control the disease in some patients, many patients, especially those with associated comorbidities, have contraindications to current treatments and need more treatment options. New drugs are needed to further improve our treatment, especially in patients with associated comorbidities. The duration of therapy for acute and chronic gout as well as combination of therapies, recommended by the American College of Rheumatology (ACR) guidelines, need to be further studied. The past decade has been an exciting time for gout research with significant advances in our understanding of disease pathogenesis and its treatment. The new ACR guidelines have improved gout visibility and will improve gout awareness and treatment in the future. With growing treatment options, gout is becoming a disease that can be cured.

Objective Comorbidity is an important concern for chronic gout patients. We evaluated the relationship between comorbidity profiles and gout in Taiwan aborigines and Taiwanese Han. Methods We used the claims data from the Taiwan national health insurance database for 2004 to 2006. Physician-diagnosed gout and comorbidities were coded using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Total sampling from Pingtung County of southern Taiwan included 37,482 aborigines (gout cases, n = 3906 and controls, n = 33,576) and 37,451 Han (gout cases, n = 1115 and controls, n = 36,336). Results In 2006, the gout prevalences were 10.42% and 2.98% (prevalence ratio [PR] = 3.50) in the aborigines and Han general populations, respectively. The prevalences of uric acid nephrolithiasis and tophi were higher in aborigines (0.42% and 0.30%, respectively) than in Han (0.09% and 0.04%, respectively). When stratified by comorbidity status, the prevalences of gout were 4.49% and 27.34% in aborigines and 1.52% and 9.44% in Han (approximate PR = 3.00). Similarly, the prevalence ratios of gout in the comorbidity group, compared with the non-comorbidity group, were 6.09 in aborigines and 6.23 in Han. Multivariate odds ratios [ORs] showed that hypercholesterolemia, hyperglyceridemia, essential hypertension and renal insufficiency were the common comorbidities of gout (OR ≥ 1.63); heart failure exerted a significant effect only in aborigines (OR = 1.55). For five comorbidity factors, patients with multiple comorbidities had higher gout prevalence (maximum OR = 12.90). Conclusion Gout prevalence was higher in aborigines, both with and without comorbidities, than in Han. The comorbid diseases and comorbidity aggregations showed a substantial association with gout occurrence in both ethnicities.

Objectives Acute gout is a common arthritis that may eventually develop into chronic tophaceous gout (CTG). CTG usually is manifested by recurrent gout attacks. The diagnosis and treatment of CTG is challenging. Although the emergence of CTG without previous gout attacks is uncommon, it is important to recognize this unusual gout presentation. Methods Herein, we present two cases of CTG, occurring in elderly patients with chronic kidney disease (CKD) on diuretics, who presented without a prior history of acute gout attacks. We also searched PUBMED, Ovid MEDLINE, and Google scholar (1970–2017), for “tophi as the initial manifestation of gout” and “chronic gout without previous attacks”, and extracted relevant data. Results The search disclosed one retrospective study and several case reports and case series describing 96 patients. Clinical and laboratory data was extracted from 34 patients. We found that a specific group of patients, e.g., elderly patients, most often female patients, suffering from CKD, and treated with diuretics, are specifically reported in the English medical literature to present with CTG as their first manifestation of gout. Conclusion The two cases and our literature review try to emphasize the many faces of chronic gout, in particular, its presentation without previous gout attacks.

Background Ultrasonography (US), magnetic resonance imaging (MRI), computed tomography (CT), and X-ray are the alternative diagnostic modalities used to identify affected joints and surrounding tissues (tophi, erosions and synovitis) in gout patients, but the potential of each method for sequential assessment of disease regression in pts receiving urate-lowering therapy is not sufficiently studied [1] Objectives Comparison of US, CT, X-ray and MRI efficacy for sequential assessment of affected joints in pts treated with urate-lowering agents. Methods The open prospective study was conducted in 2013–2015 yy at V.A. Nasonova Research Institute of Rheumatology. 22 pts with crystal-verified gout (4 (15%) f and 18 (85%) m), mean age – 54,5±12,7 years, were included. The dose of allopurinol administered in all pts was adjusted by titration starting from 100 mg/day. Instrumental diagnostic examination (US, MRI, CT and plain X-ray of knee joints) was performed at baseline and after one year of follow up. US of knee joints was performed using multi-frequency linear array transducer, at 7 to 17 MHz frequencies; for MRI examination “Esaote Artrosan 0.25TI” was used, GE “Light Speed” - for CT scans, and Stephanix – for plain X-ray examination. Applied descriptive statistics STATISTICA 10.0 (StatSoft/Inc., USA) package was used for statistical analysis. Results Mean serum level of uric acid decreased from 568±115 μmol/l to 302±135 μmol/l. The target level ( Conclusions MRI and US, as for synovitis, erosions and tophi dynamics, are comparable, at that for erosions MRI is more accurate. CT is the most informative approach to monitor intraosseous tohhi regression. X-ray is low- informative modality for sequential assessment of gout. References Grainger R, Dalbeth N, Keen H, et al. Imaging as an outcome measure in gout studies: report from the OMERACT gout working group. J Rheumatol 2015; 42(12):2460e4. Disclosure of Interest None declared

Objectives To evaluate the prevalence of ultrasonographic gout specific signs of foot joints. Methods This is a cross-sectional study which includes 15 patients with chronic gout, defined according to the American College of Rheumatology criteria (ACR 1977). Ultrasound (US) examination was performed using a high-frequency linear probe (Toshiba Xario®, frequency (8–14 MHz)) in B mode. 330 articular sites were studied at their dorsal surface. The ultrasound has objectified the presence of two signs: hyperechoic band over the superficial margin of the articular cartilage described as a double contour (DC) and tophaceous deposits at the joint cavity. Results The mean age at onset was 54.7±12,6 years, and the median diagnosis duration was 0 (0.3) years). The results of the US examination are summarized in Table 1. Conclusions This study showed a predilection for the gout specific ultrasound signs (DC and tophaceous deposits) in the tarsometatarsal and metatarsophalangeal joints, especially in the first MTP. The contribution of musculoskeletal ultrasound seems to be very interesting to objectify the presence of gout specific signs of the foot joints. Disclosure of Interest None declared

Objectives To compare the prevalence of ultrasonographic gout specific signs at the dorsal and plantar surfaces of the metatarsophalangeal joints (MTP). Methods This is a cross-sectional study which includes 15 patients with chronic gout, defined according to the American College of Rheumatology criteria (ACR 1977). Ultrasound (US) examination was performed using a high-frequency linear probe (Toshiba Xario®, frequency (8–14 MHz)) in B mode. 150 articular sites were studied at their dorsal and plantar surfaces. The ultrasound has objectified the presence of two signs: hyperechoic band over the superficial margin of the articular cartilage described as a double contour (DC) and the tophaceous deposits at the joint cavity. We compared the prevalence of the two signs between the dorsal and palmar surfaces at each site studied. Results The mean age at onset was 54.7±12,6 years, and the median diagnosis duration was 0 (0.3) years). The results of the US examination are summarized in Table 1. Conclusions Our study suggests that globally, DC predilect significatily in dorsal than in plantar surfaces of MTP joints. These results should be verified on a larger population. Disclosure of Interest None declared

Objectives To compare the prevalence of ultrasonographic gout specific sign double contour between the dorsal and palmar surfaces of the hand joints. Methods This is a cross-sectional study which includes 15 patients with chronic gout, defined according to the American College of Rheumatology criteria (ACR 1977). Ultrasound (US) examination was performed using a high-frequency linear probe (Toshiba Xario®, frequency (8–14 MHz)) in B and Doppler modes. 560 articular sites were studied at their dorsal and palmar surfaces. We compared the prevalence of the hyperechoic band over the superficial margin of the articular cartilage described as a double contour (DC) between the dorsal and palmar surfaces at each site studied. Results The mean age at onset was 54.7±12,6 years, and the median diagnosis duration was 0 (0.3) years). The results of the US examination are summarized in Table 1 Conclusions Our study suggests that globally, DC predilect significatily in dorsal than in palmar surfaces of hand joints. These results should be verified on a larger population. Disclosure of Interest None declared

Objectives To evaluate the prevalence of ultrasonographic gout specific signs of hand and fingers joints. Methods This is a cross-sectional study which includes 15 patients with chronic gout, defined according to the American College of Rheumatology criteria (ACR 1977). Ultrasound (US) examination was performed using a high-frequency linear probe (Toshiba Xario®, frequency (8–14 MHz)) in B mode. 540 articular sites were studied at their dorsal surface. The ultrasound has objectified the presence of two signs: hyperechoic band over the superficial margin of the articular cartilage described as a double contour (DC) and the tophaceous deposits at the joint cavity. Results The mean age at onset was 54.7±12,6 years, and the median diagnosis duration was 0 (0.3) years). The results of the US examination are summarized in Table 1. Conclusions This study showed a predilection for the gout specific ultrasound signs (DC and tophaceous deposits) of the wrist and MCP joints. The contribution of musculoskeletal ultrasound seems to be very interesting to objectify the presence of gout specific signs in the hand and fingers joints. Disclosure of Interest None declared

Objective. The aim of this study was to systematically review outcome domains and measurement tools used in gout trials and their accordance with the preliminary OMERACT gout recommendations published in 2005. Methods. Randomized controlled trials (RCTs) and quasi-RCTs investigating any intervention for gout published up to February 2013 were included. Recruitment start dates and all measured outcomes were extracted. Risk of bias (RoB) was assessed with the Cochrane Collaboration tool. Numbers of OMERACT domains were compared for trials at low vs unclear/high RoB and for recruitment start date before 2005 or 2005 and later. Results. Of 9784 articles screened, 38 acute and 30 chronic gout trials were included. Mean (s.d.) number of OMERACT outcomes was 2.9 (1.1) (out of 5) and 2.5 (1.2) (out of 9) for acute and chronic gout trials, respectively. Health-related quality of life, participation and joint damage imaging were not assessed in any trial. Tools used to measure individual domains varied widely. There were no differences in the number of OMERACT outcomes reported in acute or chronic gout trials recruiting before 2005 vs 2005 or later [mean (s.d.): 3.0 (1.1) vs 3.5 (1.3), P = 0.859 and 2.7 (1.1) vs 2.8 (1.4), P = 0.960, respectively]. While both acute and chronic trials at low RoB reported more OMERACT domains than trials at unclear/high RoB, these differences were not significant. Industry-funded trials and trials performed by OMERACT investigators reported more OMERACT outcome domains. Conclusion. We found no appreciable impact of the OMERACT recommendations for gout trials to date

Gout is a common disorder with clinical signs and symptoms resulting from inflammatory responses to monosodium urate crystals deposited in tissues from extracellular fluids saturated for urate. Long-term management of gout focuses on nonpharmacologic and pharmacologic means to achieve and maintain serum urate levels in a subsaturating range. Despite a firm understanding of gout pathophysiology, means to achieve certain diagnosis, and a variety of effective therapies, treatment outcomes remain suboptimal. In this review, available nonpharmacologic and pharmacologic therapies for chronic gout are discussed and a framework is provided for successful achievement and maintenance of goal-range serum urate levels.

Objective: To assess the urate-lowering efficacy and safety of Febuxostat versusAllopurinol in subjects with hyperuricemia and gout. Study design: Randomized controlled trial.Place and duration of study: Department of Orthopaedic and Trauma Surgery Mardan MedicalComplex Teaching Hospital Bacha khan Medical College Mardan from February 2012 to March2013. Material and Methods: Fifty patients of chronic gout and hyperuricemia fulfilling theinclusion criteria were divided into two equal groups by random method having 25 patients eachand received either a fixed dose(80 mg) of Febuxostat (Group A) or Allopurinol (Group B) 300mgonce daily for 16 weeks. The primary end point was the percentage of patients reaching serumurate level

Joint Bone Spine - In Press.Proof corrected by the author Available online since lundi 20 mars 2017

Objective To determine patient-derived weights or prioritization for core outcome domains in chronic gout clinical studies. Methods Three patient groups participated in a conjoint decision-making exercise using 1000Minds software, which asked participants to make repeated judgments regarding which of 2 hypothetical patients with gout represented the best response to treatment. Each scenario compared 2 patients on the basis of change in 2 of 5 core outcome domains at a time. Agreement of 80% of the group was required to answer each scenario. Re-voting was performed once after discussion in instances of disagreement. Results The relative importance accorded to each outcome domain was different across the 3 groups of patients. There was some consistency that tophi was the least or second to least important outcome domain for every group and pain between attacks was ranked in the bottom third of priority for all groups. Gout attacks were ranked as the second or third most important domain in each group. However, the relative importance of serum urate (SUA) and activity limitations was quite different among the 3 groups, with 1 group ranking SUA as the most important outcome and 1 group ranking it as the second to least important outcome. Conclusion Despite some consistency in the relative value of some outcome domains for chronic gout studies, there is sufficient disagreement in the relative importance of other domains of outcome to challenge the validity of constructing a composite index of response that would be applicable to most gout patients.

Intravenous pegloticase (KRYSTEXXA®), a recombinant polyethylene glycol-conjugated form of uricase (a uric acid-specific enzyme lacking in humans), is a novel approach to treating chronic gout refractory to conventional therapy. Pegloticase 8 mg every 2 weeks provides sustained reductions in plasma uric acid levels to less than the therapeutic target of 6 mg/dL (360 μmol/L) in a substantial proportion of patients with chronic refractory gout. The risk of infusion-related reactions can be minimized by following the recommended precautions, which include monitoring of serum uric acid levels.

Gout is one of the most common inflammatory arthritides that predominantly affects the first metatarsophalangeal joint. The underlying inflammatory process is elicited by the deposition of monosodium urate (MSU) crystals in the affected joint that are termed tophi and which may in the course of chronic gout progress into subcutaneous depositions of tophi. In this case report, we present a patient (PID: 6925981) who was seen in our outpatient department with a first episode of tophaceous gout in the finger, an infrequently seen condition that mostly affects older men with long-term gout. We discuss the case in view of the current literature on diagnosis and treatment of tophaceous gout.

This aimed to compare the three radiographic methods of digital tomosynthesis (DT), plain radiography, and computed tomography (CT) for evaluating changes in feet of patients with chronic gouty arthritis. Two independent radiologists read the plain radiography, DT, and CT images of 30 male patients with gout. The degrees of erosion and joint space narrowing were scored using the Sharp–van der Heijde scoring method in 18 foot joints, which consisted of four proximal interphalangeal and one interphalangeal joint of the first toe, five metatarsophalangeal, five tarsometatarsal, and three naviculo-cuneiform joints of the foot. DT showed high reproducibility [0.929 for intraobserver intraclass correlation coefficient (ICC) and 0.838 for interobserver ICC]. DT showed similar results to those of CT and superior results to those of plain radiography for evaluating radiographic damage [mean total score, 8.5 ± 14.6 (±standard deviation) for plain radiography, 12.9 ± 12.4 for DT, and 12.6 ± 11.2 for CT]. This study showed that DT is a good method for evaluating radiographic changes in patients with gout. Further research is needed to apply DT to actual clinical settings.

Aim To review the assessment and management of gout by general practitioners (GPs) and medical officers (MOs) within the Illawarra Network, Australia. Method A survey was sent to GPs and MOs within the Illawarra Network. Results Of 110 GPs, 45 responded. Of 129 MOs, 42 responded. The overall response was 32.6%. On analysis, 65.1% felt their knowledge of gout to be adequate and 61.6% thought they had been educated well. In acute assessment, 59.1% of GPs responded that the diagnosis of gout best be confirmed with a joint aspiration and 36.4% clinical suspicion. Differing, 85.7% of MOs chose a joint aspiration. In acute management, if colchicine were used, 59.1% of GPs would give 1 mg followed by 0.5 mg an hour later, then 0.5 mg twice daily, compared to 9.5% of MOs, while 20.5% of GPs would use 1 mg twice daily. Chronic management was answered poorly. After an acute attack, urate lowering therapy (ULT) would be started 14 days after by 47.7% of GPs, compared to 69.0% of MOs. GPs were more likely to start ULT within 7 days (52.3% vs. 31.0%). With dosing of ULT, 45.3% would treat to target, while 46.5% would dose to the creatinine clearance. Prophylactic therapy with ULT would be started by 81.8%, although only 17.4% would continue it for 3–6 months. Conclusion There is poor adherence to recommended practice for dosing of colchicine in acute gout. Also in the management of chronic gout, in particular, the timing of starting ULT and the use of prophylaxis when initiating ULT.

Although pharmacologic therapies for hyperuricemia in patients with gout have been well established and are reasonably effective, a small proportion of patients are refractory to treatment and/or present with articular disease so severe as to render standard treatments inadequate. Pegloticase, a PEGylated mammalian urate oxidase with a novel mechanism of action, was recently approved in the USA for the treatment of chronic gout in adult patients refractory to conventional therapy. This paper outlines the development of this unique agent and provides details of the Phase III clinical trial program. A discussion of patient selection, treatment considerations, and risk management for infused pegloticase follows. As a new class of biologic agent offering documented and dramatic effects on lowering serum uric acid and remarkably rapid outcomes in resolving tophi, pegloticase can provide safe and effective management of hyperuricemia and gout for many patients, particularly those who have a high disease burden ...

Purpose of review Gout is a true crystal deposition disease, extremely painful and bone and tissue damaging if untreated. It is the only curable form of arthritis. Although we have many treatments to cure gout, it is a disease that is consistently undertreated/mismanaged and perceived by clinicians and the lay public as a 'laughable condition' with the patients' lifestyle often held erroneously to account. This article would give you a good understanding of modern and established pharmacological and nonpharmacological treatments used in the management of acute and chronic gout and how to 'treat to target' to cure the disease. Recent findings Many of the drugs we use to manage patients with gouty arthritis have been in existence since the 1970s and 1980s. In the past few years, because of the improved physiological understanding of gout, new innovative treatments such as anti-IL inhibitors, a nonxanthine oxidase inhibitor and the uricase enzymes have been developed adding to our armamentarium of drugs. Summary With the introduction of new research, we have been able to explore how to also use established treatments more effectively, raising the profile of gout and its best management and introducing the principle of treating the patient to urate target.

Gout and hyperuricemia are among the most common inflammatory–metabolic disorders of mankind. Evidence gathered in recent years clearly identifies monosodium urate crystals as exerting a powerful inflammatory stimulus through activation of the inflammasome. Dysregulation of inflammasome function has been implicated in the pathogenesis of a variety of autoinflammatory disorders – so-called inflammasomopathies, including gout, Type 2 diabetes and cancer. Activation of the inflammasome results in the release of proinflammatory cytokines, particularly IL-1, which has been shown to significantly contribute to human disease, and its inhibition has proven of benefit for certain autoinflammatory disorders. The potential therapeutic benefit of inflammasome inhibition with the use of biologic agents used alone or in combination for the therapy of gout is discussed.

The paper presents the results of a trial of the efficacy and safety of the nonsteroidal anti-inflammatory drug Amelotex® (meloxicam) used to prevent episodes of arthritis in patients with gout during initiation of allopurinol therapy. The study has demonstrated that one-month therapy with Amelotex® can minimize the risk of arthritis exacerbations when allopurinol is used. Amelotex® shows a good tolerability and causes the low rates of side effects

Once described as the disease of kings, gout has developed a much greater incidence and prevalence. The incidence of gout is on the rise predominantly in the elderly. There appears to be a greater risk of developing gout with hyperuricemia, hypertension, and renal disease. High fructose drinks, red meat, organ meats, fatty seafood, and beer or liquor also appear to increase the risk of developing gout. Gout can lead to inflammation and damage to cartilage, bone, bursa, tendons, heart, or kidneys. Patients with gout will have many years of asymptomatic hyperuricemia followed by episodes of acute gouty inflammation and asymptomatic periods. Some people with gout will progress to chronic gout with tophi deposits, pain, deformity, and bone and cartilage destruction.

Despite the recognition that tophus regression is an important outcome measure in clinical trials of chronic gout, there is no agreed method of tophus measurement. A number of methods have been used in clinical trials of chronic gout, from simple physical measurement techniques to complex advanced imaging methods. This paper summarises the methods of tophus measurement that have been used and discusses the properties of these methods. Physical measurement using Vernier calipers fulfils most aspects of the Outcomes Measures in Rheumatology (OMERACT) filter. Rigorous testing of the complex methods, particularly with respect to reliability and sensitivity to change is needed, to determine the appropriate use of these methods. Further information is also required regarding which method of physical measurement is best for use in future clinical trials. The need to develop and test a patient reported measure of tophus burden is also highlighted.

Objective.To summarize the endorsement of measures of patient-reported outcome (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10).Methods.During the OMERACT 10 gout workshop, validation data were presented for key PRO domains including pain [pain by visual analog scale (VAS)], patient global (patient global VAS), activity limitation [Health Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.0). Data were presented on all 3 aspects of the OMERACT filters of truth, discrimination, and feasibility. One PRO, health-related quality of life measurement with the Medical Outcomes Study Short-form 36 (SF-36), was previously endorsed at OMERACT 9.Results.One measure for each of the 3 PRO of pain, patient global, and activity limitation was endorsed by > 70% of the OMERACT delegates to have appropriate validation data. Specifically, pain measurement by VAS was endorsed by 85%, patient global assessment by VAS by 73%, and activity limitation by HAQ-DI by 71%. GAQ v2.0 received 30% vote and was not endorsed due to several concerns including low internal consistency and lack of familiarity with the measure. More validation studies are needed for this measure.Conclusion.With the endorsement of one measure each for pain, patient global, SF-36, and activity limitation, all 4 PRO for chronic gout have been endorsed. Future validation studies are needed for the disease-specific measure, GAQ v2.0. Validation for PRO for acute gout will be the focus of the next validation exercise for the OMERACT gout group.

Gout is a painful and disabling inflammatory arthritis of increasing prevalence associated with hyperuricemia and the deposition of monosodium urate crystals in soft tissues and joints. Diagnosed gout cases have been estimated at 2.13% of the 2009 US population. The highest incidence occurs in the 65+ year age group, with males more than twice as likely to be afflicted as females.To present the epidemiology of chronic gout and to discuss its disease burden.This commentary is based on expert opinion and supplemented with published/presented information identified through PubMed and rheumatology associations.The steady rise of diagnosed gout cases can generally be linked to an aging population with multiple comorbidities, the use of certain prescription medications, and changes in diet and lifestyle. Progression to chronic gout has numerous causes such as poor compliance with, ineffectiveness of, or inability to tolerate prescribed regimens. Despite the availability of urate-lowering therapies (ULT), patients may either have contraindications to them or may not adequately respond. Patients with high flare frequency, tophi, and the inability to maintain serum urate levels below 6 mg/dL with ULT can be categorized as having chronic gout that is refractory, with a substantial disease burden. Based on lack of therapeutic options for urate-lowering for patients with chronic gout refractory to conventional therapy, the economic burden of this small but substantial population contributes disproportionately to the overall economic burden of chronic gout. Recent availability of gout-specific ICD-9-CM codes capturing the cost intense and impactful aspects of the disease - flares and tophi - is likely contribute to understanding the full health economic burden in gout.The impact of chronic gout, especially if refractory to treatment, on functionality, productivity, quality of life and health care costs can be substantial and is deserving of future research.

The rising prevalence of gout has led the pharmaceutical industry to rediscover what it had considered a forgotten disease. In April 2009, the Food and Drug Administration (FDA) approved febuxostat (Takeda Pharmaceuticals; Deerfield, IL), the first new urate-lowering gout drug in more than 40 years. In August 2009, the FDA approved colchicine for the treatment of acute gout. Several other pharmaceutical companies are also conducting clinical trials to test new drugs for acute and chronic gout. This article reviews new drugs and drugs in development in the management of acute and chronic gout.

Gout is a disorder of purine metabolism, usually associated with recurrent bouts of arthritis in the joints of the lower limbs, affecting men 40 to 50 years of age, which leads to the development of subcutaneous tophi in patients with long-lasting disease. Cases of patients with chronic gouty arthritis mimicking rheumatoid arthritis, and vice-versa, are rare. This report describes the case of a 56-year old male with symmetric, deforming, and polyarticular arthritis affecting, specially, the joints of the hands and wrists, with diffuse subcutaneous nodules throughout his body, atypical radiographic findings, and urolithiasis. Following clinical evaluation and additional tests, this patient received a diagnosis of chronic tophaceous gout mimicking mutilating rheumatoid arthritis.

Great strides have been made in understanding gout as a disease over the centuries. Despite these advances, reports suggest that the management of gout is relatively suboptimal at the primary care level. This article reviews important considerations in the management of gout and provides an evidence-based approach for the management of acute and chronic gouty arthritis at the primary care level. Recurrent monoarticular pain and swelling should raise the suspicion of gout and the demonstration of urate crystals in synovial fluid during a clinical episode confirms the diagnosis. Acute gouty attacks should be managed with appropriate doses of non-steroidal anti-inflammatory drugs (NSAIDs) or colchicines or steroids. Recurrent attacks of gout, presence of tophi and urate stones necessitate urate-lowering drugs. Prophylactic anti-inflammatory agents for up to six months should be added at initiation of urate-lowering therapy to reduce flares of acute attacks. Gout management requires lifelong commitmen...

Objective. To compare efficacy of different glucocorticoid (GC) medication forms in protracted and chronic gout arthritis. Material and methods. 59 pts with tophaceous gout (crystal-verified diagnosis) and arthritis of three and more joints lasting more than a months in spite of treatment with sufficient doses of nonsteroidal anti-inflammatory drugs were included. Median age of pts was 56 [48;63], median disease duration — 15,2 years [7,4;20], median swollen joint count at the examination — 8 [5; 11]. The patients were randomized into 2 groups. Methylprednisolone (MP) 500 mg/day iv during 2 days and placebo im once was administered in one of them, betamethasone (BM) 7 mg im once and placebo iv twice — in the other. Results. Number of pts with full resolution of arthritis, recurrent exacerbation, insufficient arthritis resolution or clinically insignificant response was comparable in both groups. More rapid decrease of pain at moving was achieved during the first 2-3 days after GC administration in pts with full resolution of arthritis (p=0,03) in group receiving MP in comparison with BM. At day 14 joint damage measures did not differ between groups. Conclusion. Efficacy of short-term glucocorticoid administration does not depend on mode of administration and GC medication form (methylprednisolone 500 mg/day iv during 2 days or betamethasone 7 mg im once.

PURPOSE OF REVIEW Novel therapies for gout have recently been developed which has prompted considerable efforts in defining the relevant outcomes for measurement in intervention trials of gout. This review summarizes the consensus exercises refining domains for measurement and the work of individual groups in assessment of the validity of measurement tools for these domains. RECENT FINDINGS Recent publications have focused on the consensus exercises and validation studies of measurement tools, particularly in relation to tophus size and imaging. SUMMARY Consensus on potential outcome domains has been achieved, but measuring these domains requires further validation in observational studies and confirmation of relevance from people with gout. Further work is also required in refining measurements of tophus size and imaging scores. The role of a response criteria measure is also yet to be defined, especially in relation to reduction in flare frequency, or whether composite criteria are necessary.

Objective To identify a valid method to measure radiographic damage in patients with chronic gout. Methods The scoring method that best represented radiographic damage in individual joints was analyzed by comparing a gold standard rheumatologist consensus global score with recognized scoring methods, including the Sharp/van der Heijde erosion and narrowing scores, Ratingen destruction score, and Steinbrocker score. Ninety-five proximal interphalangeal joints from 12 patients with gout were included in this analysis. Scoring of hand and feet radiographs from an additional 35 patients with gout was used to analyze the sites to be included in a scoring system and the additional features to be recorded. Results For individual joints, the combination of the Sharp/van der Heijde erosion and narrowing scores correlated best with the consensus global score. In addition, the limits of agreement were narrowest for the combined Sharp/van der Heijde erosion and narrowing score. All joint areas in the Sharp/van der Heijde rheumatoid arthritis score and the distal interphalangeal joints were affected by chronic gout and contributed to the total score. Additional features (extraarticular erosions, joint space widening, and ankylosis) occurred infrequently, and scoring of these features did not increase the reliability of the total score. The reliability of the total score was high: intraclass correlation coefficient for intraobserver reproducibility was 0.993–0.998 and for interobserver reproducibility was 0.963–0.966. The modified Sharp/van der Heijde score was able to discriminate between early and advanced disease. Conclusion A modified Sharp/van der Heijde system accurately and reliably represents radiographic joint damage in chronic gout.

This review presents research published over the last year examining use of urate-lowering therapy (ULT) as well as trends over time in adherence to this class of agents. Additionally, it explores factors associated with nonadherence to ULTs for chronic gout and interventions to improve chronic gout management.New literature suggests prescriptions of ULTs for prevalent and incident gout patients remains lower than expected based on the burden of the disease in the population. Overall ULT adherence remains suboptimal, in part related to inadequate patient education and copayment costs; although one study demonstrated improvement in adherence over a 15-year study period. Finally, interventions that include patient education and medication titration based on laboratory results successfully lowered serum urate levels to less than 6 mg/dl in the majority of patients.Gout remains a prevalent disease that is poorly managed despite effective treatments. Recent research suggests that ULTs are underutilized and even when prescribed are not well adhered to. Patient-centered interventions that focus on education about pharmacologic therapy and lifestyle modifications with medication titration have resulted in a greater proportion of patients achieving recommended serum urate levels.

Paracoccidioidomycosis is an endemic South American systemic mycosis caused by the dimorphic fungusParacoccidioides brasiliensis(P. brasiliensis). The main clinical form of disease is pulmonary, but all organs may be involved. We report a case of overinfection byP. brasiliensisin chronic gouty arthritis affecting the proximal phalanx of the right hallux. The patient required proximal amputation and long-term antifungal therapy.

Gout is the most common form of inflammatory arthritis in men over 40. Although the pattern of disease is becoming increasingly severe, promising new therapies are emerging for both acute and chronic gout. Copyright © 2011 Wiley Interface Ltd

Gout is an acute and chronic inflammatory disorder associated with high morbidity and impaired quality of life. There has been a substantial increase in the prevalence and incidence of gout in recent years. Novel diagnostic and therapeutic options have provided new insights into the pathogenesis and management of hyperuricemia and gout in the last decade. This clinical review aims to summarize the diagnostic process and management of acute and chronic gout.

Gout has been academically considered to be a step-up disease consisting of different stages: acute gout, intercritical gout, and chronic gout. This simple approach may lead to misinterpretation and misdiagnosis. In clinical practice, we should consider gout as a single disease with either or both acute (most commonly, episodes of acute inflammation) and persistent clinical manifestations, but not restricted to chronic synovitis. In this article, an innovative, practical, and rational approach to the clinical manifestations and diagnosis of gout is presented, which may be supportive for clinicians involved in everyday care and management of patients with gout.

У роботі представлено патоморфологічне дослідження операційного матеріалу, видаленого під час хірургічного лікування суглобів верхніх і нижніх кінцівок 32 хворих (31 чоловік і 1 жінка) з первинною тофусною подагрою, середній вік 56,1 років. У результаті вперше встановлено динаміку морфологічних змін у суглобовій капсулі за подагри, уточнено стадійність розвитку патоморфологічних змін у тканинах суглоба та їх залежність від тяжкості клінічного перебігу захворювання. Зауважено на необхідності профілактики частоти загострень., В работе представлено патоморфологическое исследование операционного материала, взятого во время хирургического лечения суставов верхних и нижних конечностей 32 больных (31 мужчина и 1 женщина), страдающих первичной тофусной подагрой, средний возраст 56,1 лет. В результате впервые установлена динамика морфологических изменений в суставной капсуле при подагре, уточнена стадийность развития патоморфологических изменений в тканях сустава и их зависимость от тяжести клинического течения заболевания. Указано на необходимость профилактики частоты обострения., Gout is a chronic disease which is accompanied by a primary violation of the uric acid (purine) metabolism, increased value of uric acid (hyperuricemia) in blood and urates’ deposition in tissues (crystals of the sodium salt of the uric acid). The incidence of gout is increasing in recent years. Men suffer from this pathology in the USA in 0.84% cases, in the Western Europe from 0.1 to 2 % cases, and in persons over 55 years old is about 6 % ones. Prevalence of gouty arthritis in Ukraine is 64.7 per 100 000 of population.Objective: to clarify the morphological changes in the tissues joints and periarticular structures in patients with primary tophaceous gout course.Methods: morphological study of the surgical specimens taken during surgery for removal of gouty tophi and correction of deformations performed in 32 patients with chronic gout (31 men and 1 woman), aged from 39 to 78 years (mean age - 56,1 ± 3,5 years).Results: during the first 1-3 years of tophi form rarely. Just in case of severe pathological process their formation directly depends on value of uremia. With increasing of the disease structural and functional organization changes of the joint capsule progressed. Necrotic and destructive processes predominated. In severe cases of the clinical course of gout accompanied with high content of uric acid in blood serum, frequent (4-5 times a year) and continuous attacks of gout, which intakes 3 to 4 or more joints, bright distinct degenerative and necrotic changes not just in the joint capsule but also in paraarticular tissues, primarily joint cartilage and subchondral bone came out. They firstly characterized with activation of endochondral ossification or dystrophic and necrotic lesions of the articular cartilage and subchondral bone.Conclusions: gouty arthritis is one of the variants of chronic inflammation, which is determined by the deposition of urates of the uric acid into the joint capsule and characterized by active fibroblastic proliferation of cellular elements with the formation of fibrous connective tissue on early stages, and in cases of severe course it characterized by actively progressing degenerative and destructive lesions of all joint tissues leading to disability. The basis of the inflammatory cell infiltrate is combination of macrophages, lymphocytes, cellular elements of the connective tissue (fibroblasts) and giant cell formation. Defined by us pathomorphologic vicissitude of pathologic changes in the joint tissues allows to clarify the therapeutic approach to tophaceous gout. Direct dependence of the severity of pathological changes in the joint tissues on the severity of the clinical course of gout requires active prevention and reduction of the frequency of exacerbations of the pathologic process.

The treatment of gout with chronic clinical manifestations comprises three aspects, in the following order of clinical importance: (1) reducing serum urate to the therapeutic range to dissolve monosodium urate crystals (MSUCs) formed in tissues, using urate-lowering therapy (ULT); (2) preventing or reducing the risk of episodes of acute inflammation (EAIs) that appear and even increase in frequency during the initiation of ULT (prophylaxis); (3) promptly, safely, and effectively treating any EAIs that may appear until proper and stable serum urate levels are achieved.