Sonographic Tophi and Inflammation Are Associated With Carotid Atheroma Plaques in Gout

Objective: Gout and cardiovascular disease are closely related, but the mechanism connecting them remains unknown. This study aims to explore whether urate crystal deposits and inflammation (assessed by ultrasound) are associated with carotid atherosclerosis.Methods: We included consecutive patients with crystal-proven gout newly presenting to a tertiary rheumatology unit. Patients under urate-lowering treatment were excluded. Ultrasound assessment was performed during intercritical periods. Musculoskeletal scans evaluated six joints and four tendons for urate crystal deposits (double contour, aggregates, and tophi), and power Doppler (PD) signal (graded 0–3) as a marker of local inflammation. The sum of locations showing deposits or a positive PD signal (≥1) was registered. Carotids were scanned for increased intima-media thickness (IMT) and atheroma plaques, according to the Mannheim consensus. Associations were analyzed using logistic regression.Results: The study included 103 patients showing sonographic crystal deposits at the examined locations (mean sum 9.9, minimum 2); tophi were the most frequent. Two-thirds of participants presented a positive PD signal (30.1% grade 2–3). In the carotid scans, 59.2% of participants showed atheroma plaques, and 33.0% increased IMT. Tophi (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.03–1.50) and a positive PD signal (OR 1.67; 95% CI 1.09–2.56) were significantly associated with atheroma plaques, while an increased IMT showed no sonographic association.Conclusion: Sonographic crystal deposits and subclinical inflammation were consistently observed in patients with intercritical gout. Tophi and a positive PD signal were linked to carotid atherosclerosis. Our findings may contribute to understanding the complex relationship between gout and atherosclerosis.

SUCCESSFUL CORRECTION OF HYPERURICEMIA AND FOLLOWING ARTHROSCOPIC INTERVENTION IN A YOUNG GOUT PATIENT: CASE STUDY

Patient G., male, 32 years old was admitted to Chengdu Rheumatism hospital with the complains of pain and ulceration at the site of big tophaceous stone of fourth finger joint on the right hand as well as the pain and restricted movements in other right hand joints (elbow, wrist, fingers). Patient was first diagnosed with the gout approximately 10 years prior; by his own choice did not receive any urate-lowering treatment, only using oral analgesics during gout attacks. After surgery and following urate lowering therapy patient has noted functional improvement and reduction of pain. Decrease in serum urate levels from 586.7 to 469.3 μmol/L was reported. Wounds healing took from 1 to 1.5 weeks, with the wound on fourth metacarpophalangeal joint of the right hand being the last one to heal due to the wide ulceration defect. The longer follow-up period is needed to fully evaluate functional outcome (6-month follow-up examinations were scheduled).

Reasons for discontinuing urate lowering treatment in community dwelling adults with gout: results of a primary care-based cross-sectional study

Objectives To examine the prevalence of urate lowering treatment (ULT) in community dwelling adults with gout and the reasons for drug discontinuation. Method Adults with gout living in East Midlands, UK, were mailed a postal questionnaire by their general practice surgery. It enquired about demographic details, co-morbidities, number of gout flares in the previous 12-months, current ULT and reasons for discontinuing ULT if applicable. N (%), median (inter-quartile range (IQR)) and mean (standard deviation (SD)) were used for descriptive purposes. Mann–Whitney U test and chi-square test were used for univariate analyses. Stata v16 was used for data analysis. Statistical significance was set at p < 0.05. Results Data for 634 gout patients (89.3% men, mean (SD) age 64.77 (12.74) years)) were included. 59.8% of the respondents self-reported taking ULT currently, with the vast majority (95.6%) taking Allopurinol. Participants self-reporting current ULT experienced fewer gout flares in the previous 12 months than those who did not self-report current ULT (median (IQR) 0 (0–2) and 1 (0–3)) respectively, p < 0.05). 16.9% (107) participants self-reported ULT discontinuation previously. The most-commonly cited reasons for this were side-effects (29.7%), being fed-up of taking tablets (19.8%), and no benefit from treatment or ULT induced gout flares (19.8%). Treatment stopped by the GP without clear reason known to participant (15.8%) was another common reason. Conclusion This study identified patient, physician and treatment related barriers to long-term ULT. These should be addressed when initiating ULT and during regular review. Further research is required to confirm these findings in other populations.

12-month results from the real-life observational treat-to-target and tight-control therapy NOR-Gout study: achievements of the urate target levels and predictors of obtaining this target

ObjectivesGout is often not adequately treated, and we aimed to apply urate lowering treatment (ULT) combined with individual information to achieve target serum urate (sUA) in clinical practice, and to identify predictors of achievement of this sUA target.MethodsPatients with a recent gout flare and sUA >360 µmol/L (>6 mg/dL) were consecutively included in a single-centre study and managed with a treat-to-target approach combining nurse-led information about gout with ULT. All patients were assessed with tight controls at baseline, 1, 2, 3, 6, 9 and 12 months including clinical examination, information on demographics, lifestyle, self-efficacy and beliefs about medicines. The treatment target was sUA <360 µmol/L and multivariable logistic regression was used to identify predictors of target attainment with ORs and 95% CIs.ResultsOf 211 patients (mean age 56.4 years, disease duration 7.8 years, 95% males), 186 completed the 12-month study. Mean sUA levels decreased from baseline mean 500 to 311 µmol/L at 12 months with 85.5% achieving the treatment target. Alcohol consumption at least weekly versus less frequently (OR 0.14; 95% CI 0.04 to 0.55) as well as beliefs in overuse of medicines (OR per unit 0.77; 95 CI 0.62 to 0.94) decreased the chance of reaching the treatment target, while higher self-efficacy for arthritis symptoms (OR 1.49 per 10 units; 95% CI 1.09 to 2.05) increased the likelihood.ConclusionsThis study shows that target sUA can be achieved with ULT in most patients. Less self-reported alcohol consumption, low beliefs in overuse of medicines and higher self-efficacy are associated with treatment success.

Treating Hyperuricemia: The Last Word Hasn’t Been Said Yet

Gout as well as asymptomatic hyperuricemia have been associated with several traditional cardiovascular risk factors and chronic kidney disease. Both in vitro studies and animal models support a role for uric acid mediating both hemodynamic and tissue toxicity leading to glomerular and tubule-interstitial damage, respectively. Nevertheless, two recent well designed and carried out trials failed to show the benefit of allopurinol treatment on kidney outcomes, casting doubts on expectations of renal protection by the use of urate lowering treatment. With the aim of providing possible explanations for the lack of effect of urate lowering treatment on chronic kidney disease progression, we will critically review results from all available randomized controlled trials comparing a urate-lowering agent with placebo or no study medication for at least 12 months and report renal clinical outcomes.

Controlling pain and hyperuricemia in patients with tophaceous gout after joints surgery

The primary treatment of tophaceous gout is to control the disease by pharmacological therapy. Additional surgical intervention is used to correct cosmetic deformation in joints or disabling functional disorder; however, one of its reported complications is hyperuricemia and recurrent attacks of pain. Objectives: to access the effectiveness of Low Intensity Laser therapy as addition to urate lowering treatment in patients with tophaceous gout, who underwent joints surgery in the Chengdu Rheumatism Hospital, in comparison to those patients who received only nonsurgical treatment. Subjects and methods. The effectiveness of Low Intensity Laser therapy (LILT) and urate lowering treatment in patients with tophaceous gout was investigated in 63 male patients of Chengdu Rheumatism hospital with tophaceous gout who underwent joints surgery. Control group was formed of 63 gout patients comparable in age and pre-treatment uric acid, who received non-surgical treatment.Results. Patients underwent surgery in one or two sessions, the most common lesion site being foot joints: toes (49.41%), ankle (39.68%) and knee (34.92%), with restricted mobility in the mentioned joints. Levels of CRP before the treatment were elevated in almost all patients (median 3.74 (0.2, 48.75) mg/L), regardless of the other comorbidities. Urate lowering therapy notably reduced the levels of CRP to 2.44 (0, 33.27) mg/L in study group and to 1.3 (0.13, 31.72) mg/L in controls. After surgery and following urate lowering therapy all patients noted functional improvement and reduction of pain. Decrease in serum urate levels were reported in 96.83% of patients in study group and in 93.65% of controls. There was no significant difference in serum UA between patients who underwent joint surgery and who didn’t. Patients, who in addition to surgery received Low-Level Laser Therapy therapy, had a lowest mean serum UA after treatment (280.93 ± 97.05 μmol/L), but due to wide range of variation, difference to other groups wasn’t statistically significant. Addition of laser therapy also helped to reduce the pain almost twice (0.56±0.56 compared to 1.04 ± 0.91). However, we haven’t registered notable anti-inflammatory influence of LILT. There was a weak direct link established between levels of serum UA and CRP after treatment, but in patients receiving laser therapy, CRP was elevated more often, compared to those who weren’t prescribed with LILT or controls. Conclusion. Arthroscopic shaving and other surgical approaches focused on joints often doesn’t affect system hyperuricemia in any way and can’t be viewed as a substitute to urate lowering therapy. However, our experience confirms that timely performed surgery contribute to functional improvement and reduction of pain in gout patients. Low Intensity Laser therapy doesn’t affect hyperuricemia or guarantee long-term systemic anti-inflammatory effect, but help to additionally relieve pain in joints and thus enhance treatment effect and quality of patients’ life.

Association between serum urate, gout and comorbidities: a case–control study using data from the UK Biobank

Objectives To examine the association between comorbidities and serum urate (SU), gout and comorbidities, and to determine whether the association between gout and comorbidities is independent of SU. Methods We performed a case–control study using UK Biobank data. Two separate analyses were conducted: one excluding participants with gout to investigate the association between comorbidities and SU and the other with participants with gout as the index condition to examine the association between gout and comorbidities. SU was measured at the baseline visit. Self-reported physician-diagnosed illnesses were used to define gout and comorbidities, except for chronic kidney disease (CKD), which was defined using an estimated glomerular filtration rate cut-off. Participants prescribed urate-lowering treatment were also classified as gout. Logistic regression was used to examine associations. Odds ratios (ORs) and 95% CIs were calculated and adjusted for covariates including comorbidities and SU. Results Data for 458 781 UK Biobank participants were used to examine the association between comorbidities and SU. There was an association between hypertension, ischaemic heart disease (IHD), congestive cardiac failure (CCF), hyperlipidaemia, CKD and SU with and adjusted OR (aOR) of 1.10–3.14 for each 1 mg/dl SU increase. A total of 10 265 gout cases and 458 781 controls were included in the analysis of association between gout and comorbidities. Gout associated independently with hypertension, IHD, CCF, hyperlipidaemia and diabetes, with aORs of 1.21–4.15 after adjusting for covariates including SU. Conclusion Comorbidities associate with increasing SU. The association between gout and cardiometabolic comorbidities was independent of SU, suggesting separate SU-independent mechanisms such as inflammation driven by crystal deposition, pro-inflammatory genotype or non-purine dietary factors.

Ultrasound shows rapid reduction of crystal depositions during a treat-to-target approach in gout patients: 12-month results from the NOR-Gout study

ObjectivesAs ultrasound is sensitive for detecting crystal depositions in patients with gout, our objectives were to explore the main locations for depositions and the extent of dissolution of depositions during a treat-to-target approach with urate lowering treatment (ULT) in patients with gout.MethodsPatients with a recent flare of gout were consecutively included in this single-centre study and managed by a treat-to-target approach with ULT. All patients were assessed at baseline, 3, 6 and 12 months including bilateral ultrasound examinations of joints/tendons/entheses of hands, elbows, knees, ankles and feet. A new semiquantitative scoring system of 0–3 of elementary lesions (double contour (DC), tophi and aggregates) was applied to quantify the amount of depositions during the follow-up.Results209 of the patients were evaluated with ultrasound at baseline (mean (SD) age 56.4 (13.8) years and disease duration 7.9 (7.7) years, 95.2% men). The serum urate levels decreased from baseline to 12 months (mean (SD) 500 (77) to 312 (49) µmol/L) (p<0.001)). The first metatarsophalangeal joint was the most frequent location for all the elementary lesions and erosions were associated with higher levels of crystal depositions. From baseline to 12 months, mean sum scores decreased for DC (4.3 to 1.3), tophi (6.5 to 3.8) and aggregates (9.3 to 6.7) (p<0.001 for all), with DC being most sensitive to change.ConclusionsThe ultrasound scoring system for crystal depositions was sensitive to change and showed that a treat-to-target approach with ULT resulted in significant reductions of all the depositions, most extensively for DC.