Dual-Energy CT of Urate Deposits in Costal Cartilage and Intervertebral Disks of Patients With Tophaceous Gout and Age-Matched Controls.

OBJECTIVE: The purpose of this study was to investigate whether monosodium urate (MSU) deposits could be identified within the abdomen and axial skeleton of patients with tophaceous gout using dual-energy CT (DECT). CONCLUSION: DECT of the abdomen, chest wall, and spine revealed extensive MSU deposits in costal cartilages and, to a lesser extent, intervertebral disks in the male patients with gout in our study. These were quantified volumetrically. However, age-matched control subjects showed similar deposits, indicating this was not a disease-specific finding. Thus, MSU deposition in the axial skeleton may be physiologic in middle-aged men.

Relationship between structural joint damage and urate deposition in gout: a plain radiography and dual-energy CT study.

OBJECTIVES: The aim of this work was to examine the relationship between joint damage and monosodium urate (MSU) crystal deposition in gout. METHODS: Plain radiographs and dual-energy CT (DECT) scans of the feet were prospectively obtained from 92 people with tophaceous gout. Subcutaneous tophus count was recorded. The ten metatarsophalangeal joints were scored on plain radiography for Sharp-van der Heijde erosion and joint space narrowing (JSN) scores, and presence of spur, osteophyte, periosteal new bone and sclerosis (920 total joints). DECT scans were analysed for the presence of MSU crystal deposition at the same joints. RESULTS: DECT MSU crystal deposition was more frequently observed in joints with erosion (OR (95% CI) 8.5 (5.5 to 13.1)), JSN (4.2 (2.7 to 6.7%)), spur (7.9 (4.9 to 12.8)), osteophyte (3.9 (2.5 to 6.0)), periosteal new bone (7.0 (4.0 to 12.2)) and sclerosis (6.9 (4.6 to 10.2)), p<0.0001 for all. A strong linear relationship was observed in the frequency of joints affected by MSU crystals with radiographic erosion score (p<0.0001). The number of joints at each site with MSU crystal deposition correlated with all features of radiographic joint damage (r>0.88, p<0.05 for all). In linear regression models, the relationship between MSU crystal deposition and all radiographic changes except JSN and osteophytes persisted after adjusting for subcutaneous tophus count, serum urate concentration and disease duration. CONCLUSIONS: MSU crystals are frequently present in joints affected by radiographic damage in gout. These findings support the concept that MSU crystals interact with articular tissues to influence the development of structural joint damage in this disease.

Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout: a dual energy CT study.

BACKGROUND: The aim of this study was to compare the frequency and volume of dual energy CT (DECT) urate deposits in people with asymptomatic hyperuricaemia and symptomatic gout. METHODS: We analysed DECT scans of the feet from asymptomatic individuals with serum urate ≥540 µmol/L (n=25) and those with crystal proven gout without clinically apparent tophi (n=33). RESULTS: DECT urate deposits were observed in 6/25 (24%) participants with asymptomatic hyperuricaemia, 11/14 (79%) with early gout (predefined as disease duration ≤3 years) and 16/19 (84%) with late gout (p<0.001). DECT urate deposition was observed in both joints and tendons in the asymptomatic hyperuricaemia group, but significantly less frequently than in those with gout (p≤0.001 for both joint and tendon sites). The volume of urate deposition was also significantly lower in those with asymptomatic hyperuricaemia, compared with the early and the late gout groups (p<0.01 for both comparisons). Similar urate volumes were observed in the early and late gout groups. CONCLUSIONS: Although subclinical urate deposition can occur in people with asymptomatic hyperuricaemia, these deposits occur more frequently and at higher volumes in those with symptomatic gout. These data suggest that a threshold of urate crystal volume may be required before symptomatic disease occurs.

Rituximab in diffuse cutaneous systemic sclerosis: should we be using it today?

There is new evidence that B-cell depletion could be an effective intervention in patients with SSc. Observational case-control study data from the European League Against Rheumatism Scleroderma Trials and Research group has suggested that rituximab therapy may reduce progression of skin thickening and lung fibrosis, especially in a subgroup with early dcSSc. These positive data remain preliminary and need to be viewed with caution, recognizing the spontaneous regression of skin thickening that may occur during early disease. In this review, we summarize the clinical evidence for the therapeutic use of rituximab in SSc as well as the basic science evidence suggesting that B cells and autoantibodies are the primary drivers of fibrosis in skin and lung tissue. We have also reviewed the parallels between SSc and the other CTDs where B-cell depletion therapy is efficacious.

Interactions between tenocytes and monosodium urate monohydrate crystals: implications for tendon involvement in gout.

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.

Zoledronate for prevention of bone erosion in tophaceous gout: a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: The osteoclast has been implicated in development of bone erosion in gout. The aim of this study was to determine whether zoledronate, a potent antiosteoclast drug, influences bone erosion in people with tophaceous gout. METHODS: This was a 2-year, randomised, double-blind, placebo-controlled trial of 100 people with tophaceous gout. Participants were randomised to annual administration of 5 mg intravenous zoledronate or placebo. The primary endpoint was change in the foot CT bone erosion score from baseline. Secondary endpoint was change in plain radiographic damage scores. Other endpoints were change in bone mineral density (BMD), bone turnover markers and the OMERACT-endorsed core domains for chronic gout studies. RESULTS: There was no change in CT erosion scores over 2 years, and no difference between the two treatment groups at Year 1 or 2 (p(treat)=0.10, p(time)=0.47, p(treat*time)=0.23). Similarly, there was no change in plain radiographic scores over 2 years, and no difference between the two groups at Year 1 or 2. By contrast, zoledronate increased spine, neck of femur, total hip and total body BMD. Zoledronate therapy also reduced the bone turnover markers P1NP and ß-CTX compared with placebo. There was no difference between treatment groups in OMERACT-endorsed core domains. CONCLUSIONS: Despite improvements in BMD and suppression of bone turnover markers, antiosteoclast therapy with zoledronate did not influence bone erosion in people with tophaceous gout. These findings suggest a disconnect between responses in the healthy skeleton and at sites of focal bone erosion in tophaceous gout.

Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study.

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.

Insights into rheumatoid arthritis from use of MRI.

Magnetic resonance imaging (MRI) is ideal for imaging the joints of rheumatoid arthritis (RA) patients. It produces anatomically detailed images of bone, cartilage, tendons and synovial membrane. It can reveal structural damage, in the form of bone erosion, cartilage thinning and/or tendon rupture, and regions of inflammation, using sequences that reveal water content and vascularity. MRI synovitis, tenosynovitis and bone oedema/osteitis all have prognostic significance, and MRI studies of RA have helped elucidate the mechanisms whereby bone and synovial inflammation lead to joint damage. Bone oedema/osteitis has become an important imaging biomarker, and can be used to help predict progression from undifferentiated arthritis to definite RA. Recent MRI studies have confirmed that subclinical inflammation is often present in patients in clinical remission, and these data may affect disease management. Finally, recent clinical trials are reviewed, in which MRI outcome measures are being established as sensitive response markers.

MRI in rheumatoid arthritis: a useful tool for the clinician?

Over the last two decades, MRI has emerged as an important clinical tool to assist in the diagnosis and management of rheumatic disease. In rheumatoid arthritis (RA), MRI has improved our understanding of the pathological basis of disease and has provided new information about imaging features that reflect joint inflammation and damage. Using MRI, we can now directly observe inflammation involving the synovial membrane and tenosynovium, plus joint damage including bone erosion and cartilage thinning. Inflammation of bone beneath the joint (osteitis) appears as bone oedema which is a feature unique to MRI and yields important diagnostic and prognostic information in patients with inflammatory arthritis. With the introduction of biologics to rheumatology clinical practice, sensitive tools are required to monitor disease activity and progression, so that the disease suppressing effect of these new agents can be measured. MRI fits the bill for this role as it can inform the clinician about the development of bone erosions well before plain radiography, and its ability to reveal cartilage damage is emerging. The use of MRI as a marker of outcome in clinical trials is being paralleled by its increasing role in the clinic. Both extremity and high field MRI have clinical applications in RA and need to be considered along with other advanced imaging techniques as useful tools to add to the clinician's armamentarium. This review will summarise recent advances in this field and will apply current knowledge to specific clinical scenarios relevant to modern rheumatology practice.

Tendon involvement in the feet of patients with gout: a dual-energy CT study.

OBJECTIVES: To examine the frequency and patterns of monosodium urate (MSU) crystal deposition in tendons and ligaments in patients with gout using dual-energy CT (DECT). METHODS: Ninety-two patients with tophaceous gout had DECT scanning of both feet. Two readers scored the DECT scans for MSU crystal deposition at 20 tendon/ligament sites and 42 bone sites (total 1840 tendon/ligament sites and 3864 bone sites). RESULTS: MSU crystal deposition was observed by both readers in 199/1840 (10.8%) tendon/ligament sites and in 399/3864 (10.3%) bone sites (p=0.60). The Achilles tendon was the most commonly involved tendon/ligament site (39.1% of all Achilles tendons), followed by the peroneal tendons (18.1%). Tibialis anterior and the extensor tendons were involved less commonly (7.6-10.3%), and the other flexor tendons, plantar fascia and deltoid ligaments were rarely involved (<5%) (p<0.0001 between sites). Involvement of the enthesis alone was more common in the Achilles tendon (OR (95% CI) 74.5 (4.4 to 1264), p<0.0001), as was any involvement of the enthesis (OR (95% CI) 6.8 (3.6 to 13.0), p<0.0001). CONCLUSIONS: Tendons are commonly affected by MSU crystal deposition in patients with tophaceous gout. The patterns of MSU crystal deposition suggest that biomechanical strain or other local factors may contribute to deposition of MSU crystals.

Imaging in gout: insights into the pathological features of disease.

PURPOSE OF REVIEW: Imaging has the potential to assess various pathological manifestations of gout, including monosodium urate (MSU) crystal deposition, tophus formation and cartilage, soft tissue, and bone pathology. This review discusses recent research examining the role of imaging to assess the manifestations of disease. RECENT FINDINGS: Various imaging techniques are used in the assessment of gout, including plain radiography, ultrasonography, conventional computed tomography (CT), dual energy computed tomography (DECT), and MRI. Potential roles for ultrasonography are MSU crystal detection, measurement of tophi, and assessment of disease complications. Ultrasonography may allow detection of MSU crystals in patients with hyperuricaemia, prior to development of clinically apparent gout. Conventional CT allows excellent visualization of tophi and bone erosion. DECT is a promising method of noninvasive MSU crystal detection. MRI allows assessment of tophi, synovial and soft tissue disease, and bone pathology. The relative absence of MRI bone marrow oedema in gout suggests that the mechanisms of bone erosion in gout are quite different from those in other erosive arthropathies. SUMMARY: Imaging modalities have provided important insights into the pathology of gout. The role of various imaging techniques in gout diagnosis, monitoring, and prediction of outcome is rapidly developing.

Effects of skim milk powder enriched with glycomacropeptide and G600 milk fat extract on frequency of gout flares: a proof-of-concept randomised controlled trial.

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.

Prescription and dosing of urate-lowering therapy, rather than patient behaviours, are the key modifiable factors associated with targeting serum urate in gout.

BACKGROUND: Long term serum urate (SU) lowering to a target of <0.36 mmol/l (6 mg/dl) is recommended for effective gout management. However, many studies have reported low achievement of SU targets. The aim of this cross-sectional study was to examine the clinical and psychological factors associated with SU targets in patients with gout. METHODS: Patients with gout for <10 years were recruited from primary and secondary care settings. SU target was defined as SU concentration <0.36 mmol/L at the time of the study visit. Both clinical and psychological factors associated with SU target were analysed. The relationship between SU target and measures of gout activity such as flare frequency, tophi, work absences, and Health Assessment Questionnaire-II was also analysed. RESULTS: Of the 273 patients enrolled into the study, 89 (32.6%) had SU concentration <0.36 mmol/L. Urate-lowering therapy (ULT) use was strongly associated with SU target (p < 0.001). In those patients prescribed ULT (n = 181), allopurinol dose, patient confidence to keep SU under control, female sex, and ethnicity were independently associated with SU target. Other patient psychological measures and health-related behaviours, including adherence scores, were not independently associated with SU target in those taking ULT. Creatinine clearance, diuretic use, age, and body mass index were not associated with SU target. Patients at SU target reported lower gout flare frequency, compared with those not at target (p = 0.03). CONCLUSIONS: ULT prescription and dosing are key modifiable factors associated with achieving SU target. These data support interventions focusing on improved use of ULT to optimise outcomes in patients with gout.

The Work Instability Scale predicts absenteeism in people with gout and suggests a higher risk for those in manual occupations.

BACKGROUND: Gout occurs in working-age people and may be associated with significant work disability. There are no longitudinal studies to examine risk factors for work disability in people with gout. OBJECTIVES: The purpose of this study was to determine the validity of the Work Instability Scale (WIS) in patients with gout and to see if baseline WIS scores predicted future work absences. METHODS: We conducted a longitudinal, cohort study with patients who had gout for less than 10 years. Sick leave over the previous 3 months was recorded by patient recall at baseline and at 12 months. Self-report health status measures and disease characteristics including C-reactive protein and serum urate were measured at baseline. Work Instability Scale scores were fitted to a Rasch model, and nonparametric statistics were used to determine associations between disease features or future sick leave and WIS scores. RESULTS: One hundred seventy-six participants were recruited, and follow-up information was available for 133 (76%). The WIS instrument showed satisfactory internal, construct, and predictive validity. Participants in nonmanual occupations had lower (better) WIS scores (median, 0 vs. 5.5; P < 0.001). Only 7% of working participants reported any sick leave in the 3 months before the 12-month follow-up. Work Instability Scale scores were associated with future sick leave: a cutoff of 4.5 was found to have the best combined sensitivity (88%) and specificity (72%) for predicting at least 1 day of sick leave. CONCLUSIONS: The WIS instrument can identify people with gout who have a higher risk of future work disability and might be a useful guide to targeted vocational counseling or job modification, especially in people in manual occupations. However, further research is required to confirm these findings and to refine the instrument for optimal performance in this population.

Assessment of tophus size: a comparison between physical measurement methods and dual-energy computed tomography scanning.

BACKGROUND: Dual-energy computed tomography (DECT) has recently been described as a sensitive method to detect urate deposits in patients with gout. OBJECTIVES: The aim of this study was to compare the reproducibility of DECT with various physical measurement methods of tophus size assessment. METHODS: Sixty-four tophi from 25 patients were analyzed. Each tophus was assessed by 2 independent observers using Vernier calipers and tape measure. All patients proceeded to DECT scanning of both feet. Urate volume within index tophi was assessed by 2 independent observers using automated DECT volume assessment software (n = 55 tophi). Five patients returned within 1 week for repeat physical assessment of tophus size. Dual-energy computed tomography scans from the returning patients were scored twice by both observers. Intraobserver and interobserver reproducibility was assessed by intraclass correlation coefficient (ICC) and limits-of-agreement analysis. RESULTS: Overall, DECT was more reproducible than the physical methods with interobserver ICCs for DECT of 0.95, for calipers 0.78, and for tape measurement 0.88, and intraobserver ICCs for DECT of 1.00, for calipers 0.75, and for tape measurement 0.91. Vernier caliper and tape measurements correlated highly with each other (rs = 0.84, P < 0.0001) but less well with DECT (for index tophi, r(s) = 0.46, P = 0.004 for both). Large variation was observed in the amount of urate deposits documented by DECT in tophi of similar physical size. CONCLUSIONS: Dual-energy computed tomography scanning is a highly reproducible method for measuring urate deposits within tophi. This imaging modality reveals the composition of tophi that contain variable urate deposits embedded within soft tissue.

Monosodium urate monohydrate crystals inhibit osteoblast viability and function: implications for development of bone erosion in gout.

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.

Methods of tophus assessment in clinical trials of chronic gout: a systematic literature review and pictorial reference guide.

OBJECTIVE: To identify methods of tophus measurement for gout studies, summarise the properties of these methods and compile a detailed pictorial reference guide to demonstrate the methods. METHODS: A systematic search strategy for methods of tophus measurement was formulated. For each method, papers were assessed by two reviewers to summarise information according to the specific components of the Outcomes Measures in Rheumatology (OMERACT) filter: feasibility, truth and discrimination. Detailed images were obtained to construct the reference guide. RESULTS: Eight methods of tophus measurement were identified: counting the total number of tophi, physical measurement using tape measure, physical measurement using Vernier callipers, digital photography, ultrasonography (US), MRI, CT and dual energy CT. Feasibility aspects of the methods are well documented. Physical measurement techniques are more feasible than advanced imaging methods, but do not allow for assessment of intra-articular tophi or for data storage and central reading. The truth aspect of the filter has been documented for many methods, particularly Vernier callipers, US, MRI and CT. Reliability of most methods has been reported as very good or excellent. Sensitivity to change has been reported for all methods except MRI and CT. CONCLUSION: A variety of methods of tophus assessment have been described for use in clinical trials of chronic gout. Physical measurement techniques (particularly the Vernier calliper method) and US measurement of tophus size appear to meet most aspects of the OMERACT filter.

Development of a computed tomography method of scoring bone erosion in patients with gout: validation and clinical implications.

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.

Measuring bone erosion and edema in rheumatoid arthritis: a comparison of manual segmentation and RAMRIS methods.

PURPOSE: To investigate the reliability, feasibility, and validity of a computer-assisted manual segmentation (outlining) technique for measuring magnetic resonance imaging (MRI) bone erosion and edema at the wrist in rheumatoid arthritis (RA). MATERIALS AND METHODS: The 3T MRI scans were obtained in 22 RA patients (<2 years). Bone erosion and edema volumes were scored by two readers using outlining and were compared with RAMRIS scores. RESULTS: Using outlining, intraobserver reliability for erosions and edema was high: intraclass correlation coefficients (ICCs) = 0.994 (0.991, 0.997) and 0.996 (0.994, 0.998), respectively (Reader 1). Interobserver reliability was high for bone erosion (ICC [90% confidence interval, CI] = 0.80 [0.64, 0.92]) and comparable to RAMRIS scoring (ICC 0.78 [0.64, 0.92]), but was only moderate for bone edema (0.46 [0.00, 0.96]), compared with RAMRIS (ICC = 0.84 [0.73, 0.94]). The methods were highly correlated for erosion scores, r = 0.90, 0.82 (Readers 1 and 2) and moderately correlated for edema, r = 0.57, 0.87. CONCLUSION: Segmentation (outlining) can be used to measure the volume of MRI bone erosion and edema at the wrist in RA patients. When compared with RAMRIS scoring, outlining had similar reliability for quantifying erosions but reliability was lower for bone edema, possibly reflecting difficulty delineating the borders of affected bone.

Cellular characterization of the gouty tophus: a quantitative analysis.

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.