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Objectives: In 2015, the 20-item Tophus Impact Questionnaire (TIQ-20) was developed as a tophus-specific patient-reported outcome measure. The aim of this study was to determine whether TIQ-20 scores change during urate-lowering therapy., Methods: We analysed data from a 2-year clinical trial of allopurinol dose escalation using a treat-to-target serum urate approach. For participants with tophaceous gout, the longest diameter of up to three index tophi was measured, using Vernier calipers, and the TIQ-20 was recorded at study visits. Participants at the one site were invited to participate in a dual-energy CT (DECT) substudy. Participants were included in this analysis if they had tophaceous gout and TIQ-20 scores available at baseline, Year 1 and Year 2 (n = 58, 39 with DECT data). Data were analysed using a mixed-model approach to repeated measures., Results: Improvements were observed in all tophus measures over the 2-year period. The mean (s.d.) TIQ-20 scores reduced over 2 years from 3.59 (1.77) to 2.46 (1.73), P < 0.0001, and the mean (95% CI) TIQ-20 change over the 2 years was -1.13 (-1.54, -0.71). The effect size (Cohen's d) for the change in the sum of the index tophi diameter over 2 years was 0.68, for the DECT urate volume was 0.50, and for the TIQ-20 was 0.71., Conclusion: For people with tophaceous gout treated with allopurinol using a treat-to-target serum urate approach, improvements in TIQ-20 occurred, as did improvements in physical and imaging tophus measures. These findings demonstrate that the TIQ-20 is a responsive patient-reported instrument of tophus impact., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Dual energy computed tomography (DECT) allows direct visualization of monosodium urate crystal deposition in gout. However, DECT urate volume data are often highly skewed (mostly small volumes with the remainder considerably larger), making statistical analyses challenging in longitudinal research. The aim of this study was to explore the ability of various analysis methods to normalise DECT urate volume data and determine change in DECT urate volumes over time., Methods: Simulated datasets containing baseline and year 1 DECT urate volumes for 100 people with gout were created from two randomised controlled trials. Five methods were used to transform the DECT urate volume data prior to analysis: log-transformation, Box-Cox transformation, log(X-(min(X)-1)) transformation; inverse hyperbolic sine transformation, and rank order. Linear regression analyses were undertaken to determine the change in DECT urate volume between baseline and year 1. Cohen's d were calculated as a measure of effect size for each data treatment method. These analyses were then tested in a validation clinical trial dataset containing baseline and year 1 DECT urate volumes from 91 people with gout., Results: No data treatment method successfully normalised the distribution of DECT urate volumes. For both simulated and validation data sets, significant reductions in DECT urate volumes were observed between baseline and Year 1 across all data treatment methods and there were no significant differences in Cohen's d effect sizes., Conclusions: Normalising highly skewed DECT urate volume data is challenging. Adopting commonly used transformation techniques may not significantly improve the ability to determine differences in measures of central tendency when comparing the change in DECT urate volumes over time., Competing Interests: Declaration of Competing Interest Lisa Stamp reports grants or contracts from Health Research Council of New Zealand, personal royalties or licenses from UptoDate, and consulting fees from Pharmac. Nicola Dalbeth reports grants or contracts from Health Research Council of New Zealand and Novotech, personal consulting fees from AstraZeneca, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, PTC Therapeutics, Protalix, Cello Health, JPI, Unlocked Labs, and LG, payment or honoraria from Novartis and Hikma. The other authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout., Methods: We undertook a 2-year, double-blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate-lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate-lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points., Results: Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between-group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) improved in both groups over 2 years, with no between-group differences. Adverse event and serious adverse event rates were similar between the groups., Conclusion: Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate-lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout., (© 2021 American College of Rheumatology.)

Elevated serum urate is the most important causal risk factor for developing gout. However, in longitudinal cohort studies, a small proportion of people with normal urate levels develop gout and the majority of those with high urate levels do not. These observations may be due to subsequent variations in serum urate over time. Our analysis examined whether single or repeat testing of serum urate more accurately predicts incident gout over time. Individual participant data from three publicly-available cohorts were included. Data from paired serum urate measures 3-5 years apart, followed by an assessment of gout incidence 5-6 years from the second urate measure were used to calculate the predictive ability of four measures of serum urate on incident gout: the first measure, the second measure, the average of the two measures, and the highest of the two measures. Participants with prevalent gout prior to the second measure were excluded. Receiver operator characteristic (ROC) curves and area under the curve (AUC) statistics were computed to compare the four measures. A total of 16,017 participants were included across the three cohorts, with a mean follow-up from the first serum urate test of 9.3 years (range 8.9-10.1 years). Overall, there was a small increase in the mean serum urate between the first and second measures (322 μmol/L (5.42 mg/dL) vs. 340 μmol/L (5.71 mg/dL), P<0.001) which were a mean of 3.5 years apart, but the first and second measures were highly correlated (r = 0.81, P<0.001). No differences were observed in the predictive ability of incident gout between the four measures of serum urate measurement with ROC curve AUC statistics ranging between 0.81 (95% confidence intervals: 0.78-0.84) and 0.84 (95% confidence intervals: 0.81-0.87). These data show that repeat serum urate testing is not superior to a single measure of serum urate for prediction of incident gout over approximately one decade., Competing Interests: ND has received grants and personal fees from AstraZeneca, personal fees from Horizon, Abbvie, AstraZeneca, Janssen, PK Med, Hengrui JW Pharmaceutical Corporation, Dyve Biosciences, Selecta, and Arthrosi, and grants from Amgen and AstraZeneca outside the submitted work. These organisations had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: The aim of this study was to determine whether serum urate (SU)-associated genetic variants differ in their influence on gout risk in people taking a diuretic compared to those not taking a diuretic., Methods: This research was conducted using the UK Biobank Resource (n = 359,876). Ten SU-associated single-nucleotide polymorphisms (SNP) were tested for their association with gout according to diuretic use. Gene-diuretic interactions for gout association were tested using a genetic risk score (GRS) and individual SNP by logistic regression adjusting for relevant confounders., Results: After adjustment, use of a loop diuretic was positively associated with prevalent gout (OR 2.34, 95% CI 2.08-2.63), but thiazide diuretics were inversely associated with prevalent gout (OR 0.60, 95% CI 0.55-0.66). Compared with a lower GRS (< mean), a higher GRS (≥ mean) was positively associated with gout in those not taking diuretics (OR 2.63, 2.49-2.79), in those taking loop diuretics (OR 2.04, 95% CI 1.65-2.53), in those taking thiazide diuretics (OR 2.70, 2.26-3.23), and in those taking thiazide-like diuretics (OR 2.11, 95% CI 1.37-3.25). No nonadditive gene-diuretic interactions were observed., Conclusion: In people taking diuretics, SU-associated genetic variants contribute strongly to gout risk, with a similar effect to that observed in those not taking a diuretic. These findings suggest that the contribution of genetic variants is not restricted to people with "primary" gout, and that genetic variants can play an important role in gout susceptibility in the presence of other risk factors.

Objective: The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout., Methods: Participants with gout in the Genetics of Gout in Aotearoa study with available genotyping were included (n = 1648). Early-onset gout was defined as the first presentation of gout <40 years of age. Single nucleotide polymorphisms (SNPs) for the 10 loci most strongly associated with serum urate were genotyped. Allelic association of the SNPs with early-onset gout was tested using logistic regression in an unadjusted model and in a model adjusted for sex, body mass index, tophus presence, flare frequency, serum creatinine and highest serum urate. The analysis was also done in two replication cohorts: Eurogout (n = 704) and Ardea (n = 755), and data were meta-analysed., Results: In the Genetics of Gout in Aotearoa study, there were 638 (42.4%) participants with early-onset gout. The ABCG2 rs2231142 gout risk T-allele was present more frequently in participants with early-onset gout compared with the later-onset group. For the other SNPs tested, no differences in risk allele number were observed. In the allelic association analysis, the ABCG2 rs2231142 T-allele was associated with early-onset gout in unadjusted and adjusted models. Analysis of the replication cohorts confirmed the association of early-onset gout with the ABCG2 rs2231142 T-allele, but not with other serum urate-associated SNPs. In the meta-analysis, the odds ratio (95% CI) for early-onset gout for the ABCG2 rs2231142 T-allele was 1.60 (1.41, 1.83)., Conclusion: In contrast to other serum urate-raising variants, the ABCG2 rs2231142 T-allele is strongly associated with early-onset gout., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To examine whether urate-associated genetic variants differ in their influence on gout risk according to body mass index (BMI)., Methods: This research was conducted using the UK Biobank Resource (n = 358,728). Participants were divided into 3 groups: BMI <25 kg/m 2 (low/normal), BMI ≥25 kg/m 2 -<30 kg/m 2 (overweight), and BMI ≥30 kg/m 2 (obese). Gene-BMI interactions for gout association were tested by logistic regression using a urate genetic risk score (GRS)., Results: Compared to participants with a GRS less than the mean, the prevalence of gout was higher in those with a GRS greater than or equal to the mean in the low/normal BMI group (0.27% versus 0.77%), in the overweight BMI group (1.02% versus 3.02%), and in the obese BMI group (2.49% versus 6.23%). A GRS greater than or equal to the mean was positively associated with gout compared to a GRS less than the mean in the low/normal BMI group (odds ratio [OR] 2.89 [95% confidence interval (95% CI) 2.42-3.47]), in the overweight BMI group (OR 3.09 [95% CI 2.84-3.36]), and in the obese BMI group (OR 2.65 [95% CI 2.46-2.86]). There was a mildly attenuated effect of the GRS on gout risk in the obese BMI group compared to the overweight BMI group, but no difference in the effect of the GRS between the low/normal BMI and overweight BMI groups, nor between the low/normal BMI and obese BMI groups., Conclusion: The association of a urate GRS with gout is mildly attenuated in obese individuals compared to overweight individuals. However, genetic variants have a strong effect on gout risk in those with overweight and obese BMIs, with an effect similar to that observed in low/normal BMI., (© 2020, American College of Rheumatology.)

Background: Sex-specific differences in the effect of genetic variants on serum urate levels have been described. The aim of this study was to systematically examine whether serum urate-associated genetic variants differ in their influence on gout risk in men and women., Methods: This research was conducted using the UK Biobank Resource. Thirty single nucleotide polymorphisms (SNPs) associated with serum urate were tested for their association with gout in men and women of European ancestry, aged 40-69 years. Gene-sex interactions for gout risk were analysed using an interaction analysis in logistic regression models., Results: Gout was present in 6768 (4.1%) men and 574 (0.3%) women, with an odds ratio (95% confidence interval) for men 13.42 (12.32-14.62) compared with women. In men, experiment-wide association with gout was observed for 21 of the 30 serum urate-associated SNPs tested, and in women for three of the 30 SNPs. Evidence for gene-sex interaction was observed for ABCG2 (rs2231142) and PDZK1 (rs1471633), with the interaction in ABCG2 driven by an amplified effect in men and in PDZK1 by an absence of effect in women. Similar findings were observed in a sensitivity analysis which excluded pre-menopausal women. For the other SNPs tested, no significant gene-sex interactions were observed., Conclusions: In a large population of European ancestry, ABCG2 and PDZK1 gene-sex interactions exist for gout risk, with the serum urate-raising alleles exerting a greater influence on gout risk in men than in women. In contrast, other serum urate-associated genetic variants do not demonstrate significant gene-sex interactions for gout risk.

Objective: To examine whether illness perceptions independently predict mortality in early-onset gout., Methods: Between December 2006 and January 2014, a total of 295 participants with early-onset gout (<10 years) were recruited in Auckland and Wellington, New Zealand. The participants were followed up until February 2015, and mortality information was collected. Participants with complete data were included in the current study (n = 242). Cox proportional hazards models were used to examine the association between illness perceptions and mortality risk, after adjustment for covariates associated with disease severity and mortality in gout., Results: In a Cox proportional hazards model adjusted for predictors of disease severity and mortality in gout (number of tophi, serum urate level, and frequency of flares), consequence beliefs, identity beliefs, concern beliefs, and emotional response to gout were associated with all-cause mortality (hazard ratios [HRs] 1.29, 1.15, 1.18, and 1.19, respectively; P < 0.05 for all). In the fully saturated model, the association between consequence beliefs and mortality remained robust after additional adjustment for ethnicity, disease duration, diuretic use, serum creatinine, and pain score (HR 1.18 [95% confidence interval 1.02-1.37]; P = 0.029)., Conclusion: Negative beliefs about the impact of gout and severity of symptoms, as well as concerns about gout and the emotional response to gout, were independently associated with all-cause mortality. Illness perceptions are important and potentially modifiable risk factors to target in future interventions., (© 2016, American College of Rheumatology.)

Objective: To determine mortality rates and predictors of death at baseline in people with a recent onset of gout., Methods: People with gout disease duration < 10 years were recruited from primary and secondary care settings. Comprehensive clinical assessment was completed at baseline. Participants were prospectively followed for at least 1 year. Information about death was systematically collected from primary and secondary health records. Standardized mortality ratios (SMR) were calculated and risk factors for mortality were analyzed using Cox proportional hazard regression models., Results: The mean (SD) followup duration was 5.1 (1.6) years (a total 1511 patient-yrs accrued). Of the 295 participants, 43 (14.6%) had died at the time of censorship (SMR 1.96, 95% CI 1.44-2.62). In the reduced Cox proportional hazards model, these factors were independently associated with an increased risk of death from all causes: older age (70-80 yrs: HR 9.96, 95% CI 3.30-30.03; 80-91 yrs: HR 9.39, 95% CI 2.68-32.89), Māori or Pacific ethnicity (HR 2.48, 95% CI 1.17-5.29), loop diuretic use (HR 3.99, 95% CI 2.15-7.40), serum creatinine (per 10 µ mol/l change; HR 1.04, 95% CI 1.00-1.07), and the presence of subcutaneous tophi (HR 2.85, 95% CI 1.49-5.44). The presence of subcutaneous tophi was the only baseline variable independently associated with both cardiovascular (CV) cause of death (HR 3.13, 95% CI 1.38-7.10) and non-CV cause of death (HR 3.48, 95% CI 1.25-9.63)., Conclusion: People with gout disease duration < 10 years have an increased risk of death. The presence of subcutaneous tophi at baseline is an independent predictor of mortality, from both CV and non-CV causes.

Objectives: Advanced imaging studies have demonstrated that urate deposition in periarticular structures, such as tendons, is common in gout. The aim of this study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on tenocyte viability and function., Methods: The histological appearance of tendons in joints affected by advanced gout was examined using light microscopy. In vitro, colorimetric assays and flow cytometry were used to assess cell viability in primary rat and primary human tenocytes cultured with MSU crystals. Real-time PCR was used to determine changes in the relative mRNA expression levels of tendon-related genes, and Sirius red staining was used to measure changes in collagen deposition in primary rat tenocytes., Results: In joint samples from patients with gout, MSU crystals were identified within the tendon, adjacent to and invading into tendon, and at the enthesis. MSU crystals reduced tenocyte viability in a dose-dependent manner. MSU crystals decreased the mRNA expression of tendon collagens, matrix proteins and degradative enzymes and reduced collagen protein deposition by tenocytes., Conclusions: These data indicate that MSU crystals directly interact with tenocytes to reduce cell viability and function. These interactions may contribute to tendon damage in people with advanced gout., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Previous laboratory studies have identified two dairy fractions, glycomacropeptide (GMP) and G600 milk fat extract (G600), with anti-inflammatory effects in models of acute gout. The aim of this proof-of-concept clinical trial was to test the hypothesis that daily intake of skim milk powder (SMP) enriched with GMP and G600 can prevent gout flares., Methods: This was a 3-month randomised double-blind controlled trial of milk products for prevention of gout flares. One hundred and twenty patients with recurrent gout flares were randomised to one of three arms: lactose powder control, SMP control and SMP enriched with GMP and G600 (SMP/GMP/G600). The primary end point was change in the frequency of gout flares using a daily flare diary measured monthly for 3 months., Results: The frequency of gout flares reduced in all three groups over the 3-month study period compared with baseline. Over the 3-month study period there was a significantly greater reduction in gout flares in the SMP/GMP/G600 group (analysis of covariance p(group)=0.031, Tukey post hoc test compared with lactose control, p=0.044). Following treatment with SMP/GMP/G600 over the 3-month period, greater improvements were also observed in pain and fractional excretion of uric acid, with trends to greater improvement in tender joint count. Similar adverse event rates and discontinuation rates were observed between the three groups., Conclusions: This is the first reported controlled trial of dietary intervention in patients with gout, and suggests that SMP enriched with GMP and G600 may reduce the frequency of gout flares.

Objective: Illness perceptions are key determinants of behavior directed at managing disease. Although suboptimal disease management has been reported in patients with gout, patients' perceptions of illness have not been systematically studied. The aim of this study was to examine illness perceptions in patients with gout., Methods: A total of 142 patients with gout for <10 years were recruited from primary and secondary care settings. Participants completed a gout-specific Brief Illness Perception Questionnaire, questionnaires about medication beliefs and adherence to urate-lowering therapy (ULT), and had a comprehensive assessment of gout disease activity. Serum urate, flare frequency, and Health Assessment Questionnaire (HAQ-II) scores were recorded at baseline and after 1 year., Results: Patients viewed gout as a chronic condition that was responsive to treatment but not strongly influenced by personal actions. Overall, gout was seen as having a moderate impact on their life. Most patients believed that gout was caused by dietary factors. Adherence to ULT was positively associated with a greater perceived understanding of gout and inversely associated with perceived severity and consequences of disease. Of the clinical factors assessed, pain scores were most strongly associated with negative illness perception scores at baseline. Baseline illness perception scores (perceived severity of symptoms and consequences, lower personal and treatment control) predicted worsening musculoskeletal disability at 1 year as determined by the HAQ-II. This relationship was independent of baseline disability scores., Conclusion: Negative or pessimistic views about gout are associated with poorly controlled disease, lower adherence to ULT, and progression of musculoskeletal disability in patients with gout., (Copyright © 2011 by the American College of Rheumatology.)

Background: Bone erosion is a common manifestation of chronic tophaceous gout., Objectives: To investigate the effects of monosodium urate monohydrate (MSU) crystals on osteoblast viability and function., Methods: The MTT assay and flow cytometry were used to assess osteoblast cell viability in the MC3T3-E1 and ST2 osteoblast-like cell lines, and primary rat and primary human osteoblasts cultured with MSU crystals. Quantitative real-time PCR and von Kossa stained mineralised bone formation assays were used to assess the effects of MSU crystals on osteoblast differentiation using MC3T3-E1 cells. The numbers of osteoblasts and bone lining cells were quantified in bone samples from patients with gout., Results: MSU crystals rapidly reduced viability in all cell types in a dose-dependent manner. The inhibitory effect on cell viability was independent of crystal phagocytosis and was not influenced by differing crystal length or addition of serum. Long-term culture of MC3T3-E1 cells with MSU crystals showed a reduction in mineralisation and decreased mRNA expression of genes related to osteoblast differentiation such as Runx2, Sp7 (osterix), Ibsp (bone sialoprotein), and Bglap (osteocalcin). Fewer osteoblast and lining cells were present on bone directly adjacent to gouty tophus than bone unaffected by tophus in patients with gout., Conclusions: MSU crystals have profound inhibitory effects on osteoblast viability and differentiation. These data suggest that bone erosion in gout occurs at the tophus-bone interface through alteration of physiological bone turnover, with both excessive osteoclast formation, and reduced osteoblast differentiation from mesenchymal stem cells.

Objectives: To develop a method of scoring bone erosion in the feet of patients with gout using CT as an outcome measure for chronic gout studies, consistent with the components of the OMERACT filter., Methods: Clinical assessment, plain radiographs and CT scans of both feet were obtained from 25 patients with chronic gout. CT scans were scored for bone erosion using a semi-quantitative method based on the Rheumatoid Arthritis MRI Scoring System (RAMRIS). CT bone erosion was assessed at 22 bones in each foot (total 1100 bones) by two independent radiologists. A number of different models were assessed to determine the optimal CT scoring system for bone erosion, incorporating the frequency of involvement and inter-reader reliability for individual bones., Results: An optimal model was identified with low number of bones required for scoring (seven bones/foot), inclusion of bones over the entire foot, high reliability and ability to capture a high proportion of disease. This model included the following bones in each foot: first metatarsal (MT) head, second to fourth MT base, cuboid, middle cuneiform and distal tibia (range 0-140). Scores from this model correlated with plain radiographic damage scores (r = 0.86, P < 0.0001) and disease duration (r = 0.42, P < 0.05). Scores were higher in those with clinically apparent tophaceous disease than in those without tophi (P < 0.0001)., Conclusions: We have developed a preliminary method of assessing bone erosion in gout using conventional CT. Further testing of this method is now required, ideally in prospective studies to allow analysis of the sensitivity to change of the measure.

Objectives: Recent observational studies have highlighted the beneficial role of dairy ingestion in gout prevention. The aims of this study were to determine the acute effects of milk ingestion on serum urate concentrations and examine the mechanisms of these effects., Methods: This was a short-term randomised controlled crossover trial of milk in 16 healthy male volunteers. The following products were tested (each 80 g protein): soy control, early season skim milk, late season skim milk (containing high concentrations of orotic acid, a naturally occurring uricosuric agent) and ultrafiltrated MPC 85 skim milk. Each participant received a single dose of each product in random order. Serum and urine were obtained immediately before and then hourly over a 3 h period after ingestion of each study product., Results: Ingestion of the soy control led to an increase in serum urate concentrations by approximately 10%. In contrast, ingestion of all milks led to a decrease in serum urate concentrations by approximately 10% (p<0.0001). All products (including soy) rapidly increased the fractional excretion of uric acid (FEUA). Late season milk led to a greater increase in FEUA than MPC 85 (p=0.02) and early season milk (p=0.052). There were no differences over time in serum oxypurines or purine-containing nucleosides. However, all products increased the fractional excretion of xanthine., Conclusions: Intact milk has an acute urate-lowering effect. These data provide further rationale for long-term intervention studies to determine whether such dietary interventions have an adjunctive role in the management of individuals with hyperuricaemia and gout.

Objective: To characterize the cellular architecture of the tophus and to determine the presence of cytokines implicated in the initiation and resolution of gouty inflammation., Methods: Sixteen fixed, paraffin-embedded, uninfected tophus samples were surgically obtained from 12 patients with microscopically proven gout and were analyzed by quantitative immunohistochemistry. The number of cells present in the corona and fibrovascular zones of the tophus was analyzed by Genmod mixed models analysis., Results: Numerous CD68+ mononucleated and multinucleated cells were present within the corona zone. Mast cells were identified in all tophus samples and at similar densities throughout the corona and fibrovascular zones. In contrast, neutrophils were rarely observed. Plasma cells were present in very high numbers within the corona zone. The overall number of CD20+ B cells was much lower. However, in 6 of 12 patients (50%), at least 1 B cell aggregate was present in the fibrovascular zone. Large numbers of cells expressing interleukin-1beta (IL-1beta) were observed in the corona zone. Transforming growth factor beta1 (TGFbeta1)-expressing mononucleated cells were also identified. The number of CD68+ cells correlated with the number of cells expressing IL-1beta (r = 0.691, P = 0.009) and the number expressing TGFbeta1 (r = 0.518, P = 0.04)., Conclusion: The tophus represents a complex and organized chronic inflammatory tissue response to monosodium urate monohydrate crystals involving both innate and adaptive immune cells. The coexpression of IL-1beta and TGFbeta1 suggests that both proinflammatory and antiinflammatory factors present within the tophus contribute to a cycle of chronic inflammation, attempted resolution, and tissue remodeling.

Objective: Although gout has recognized prevention and treatment options, some patients have recurrent unplanned hospital admissions with gout flares. The aim of this study was to identify factors associated with recurrent hospital admissions with gout., Methods: A 1:1 case-control study was designed; cases were patients with 2 or more gout-related hospital admissions during any 12-month period between 2002 and 2007 (n = 48). Each case was matched with an age, sex and ethnicity-matched control patient with gout but without hospital admission, identified from the rheumatology clinic (n = 48)., Results: Patients with recurrent hospital admissions had a higher number of comorbid medical conditions, particularly higher rates of heart disease (odds ratio 2.9, P = 0.013). Cases also had more hospital admissions for other medical problems (mean number of admissions in the preceding year 5.8 vs. 0.6, P < 0.0001). Although cases had higher rates of tophaceous disease and higher serum urate concentrations, there was no difference in gout disease duration. Cases were less likely to be on allopurinol (odds ratio 0.06, P < 0.0001), and those on allopurinol were on lower doses (median dose 200 mg/d vs. 300 mg/d, P = 0.0019)., Conclusion: Medical comorbidity, hyperuricemia, and inadequate allopurinol use are associated with repeated unplanned hospitalization for gout. These data suggest that the use of intensive urate-lowering therapy may prevent such admissions.

Objectives. Bone erosion has been linked with tophus deposition in gout but the roles of osteitis (MRI bone oedema) and synovitis remain uncertain. Our aims in this prospective 3 T MRI study were to investigate the frequency of these features in gout and determine their relation to one another.Methods. 3 T MRI scans of the wrist were obtained in 40 gout patients. Scans were scored independently by two radiologists for bone oedema, erosions, tophi and synovitis. Dual-energy CT (DECT) scans were scored for tophi in a subgroup of 10 patients.Results. Interreader reliability was high for erosions and tophi [intraclass correlation coefficients (ICCs) 0.77 (95% CI 0.71, 0.87) and 0.71 (95% CI 0.52, 0.83)] and moderate for bone oedema [ICC = 0.60 (95% CI 0.36, 0.77)]. Compared with DECT, MRI had a specificity of 0.98 (95% CI 0.93, 0.99) and sensitivity of 0.63 (95% CI 0.48, 0.76) for tophi. Erosions were detected in 63% of patients and were strongly associated with tophi [odds ratio (OR) = 13.0 (95% CI 1.5, 113)]. In contrast, no association was found between erosions and bone oedema. Using concordant data, bone oedema was scored at 6/548 (1%) sites in 5/40 patients (12.5%) and was very mild (median carpal score = 1, maximum = 45). In logistic regression analysis across all joints nested within individuals, tophus, but not synovitis, was independently associated with erosion [OR = 156.5 (21.2, >999.9), P < 0.0001].Conclusion. Erosions were strongly associated with tophi but not bone oedema or synovitis. MRI bone oedema was relatively uncommon and low grade. These findings highlight the unique nature of the osteopathology of gout. [ABSTRACT FROM PUBLISHER]