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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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]

The clinical course of gout is initially characterized by acute self-limited joint inflammation, but long- standing disease is often associated with chronic inflammation followed by the development of erosive joint damage, which can result in long-term functional impairment. Preventing joint damage is now a major focus of therapeutic intervention in gout. New light has been shed on the mechanisms leading to cartilage and bone damage in patients with this disease. Here, we discuss basic science studies focusing on the cellular immunology of bone and cartilage in gout and the effects of monosodium urate crystals on signaling pathways, cytokine release and the function of osteoclasts, osteoblasts and chondrocytes. We then explore the use of advanced imaging modalities (including MRI, ultrasonography, CT and dual-energy CT) to investigate pathology in gout, as they provide new ways to visualize joint tissues. These modalities vary in their ability to detect the various pathological features of gout and have different clinical applications. Imaging provides information about the inflammatory nature of the joint lesion, position and size of tophaceous deposits, and extent of bone and cartilage damage. Imaging is also increasingly being used to monitor the progression of joint damage and regression of tophi with effective urate-lowering therapy. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are vital effector cells of innate immunity because of their rapid cytotoxic and cytokine-producing responses to cell stress or infection. A distinguishing feature of NK cells is the ability to balance these signals with those of normal homeostasis through the expression of an array of inhibitory and activating receptors. Two functional subsets of NK cells exist: the more mature CD56dim population is potently cytotoxic, whereas CD56bright NK cells have low cytotoxicity but produce much greater amounts of cytokines, and express homing molecules for secondary lymphoid organs and sites of inflammation. NK cells have been identified as important modulatory cells in shaping adaptive immune responses by interacting with dendritic cells (DCs) and T cells. NK cells also interact with cells of the innate immune system such as monocytes and macrophages. This review outlines the biology of NK cells and the potential role of NK cells in modulating gouty inflammation. [ABSTRACT FROM AUTHOR]

MRI scanning is the current gold standard modality for imaging synovitis and tenosynovitis in patients with inflammatory arthritis. Inflamed synovial membrane within the joints and investing tendon sheaths appears thickened on T1-weighted sequences and enhances postcontrast. On T2-weighted sequences, synovitis and synovial effusions typically show a high signal. Studies have shown correlations between the degree of inflammation and vascularity of synovium obtained at biopsy and postcontrast enhancement on matching dynamic MRI scans. Scoring systems have been devised that are based on quantifying synovial membrane thickening and signal intensity on static postcontrast scans and have been validated in multireader settings. Moderate to high reliability has been demonstrated with trained readers and quantification of synovitis in this way is being used increasingly as an outcome measure in clinical trials to assess response to therapy. MRI-observed synovitis is almost invariable in those with active rheumatoid arthritis, but recent studies have also demonstrated its presence in patients in clinical remission, emphasizing the sensitivity of this technique and the importance of subclinical joint inflammation. MRI-observed synovitis has been validated against other imaging modalities, including power Doppler ultrasound, and has also been investigated in normal subjects (where mild enhancement can rarely occur). Studies over 1–2 years have suggested that MRI synovial membrane volume and postcontrast enhancement on dynamic imaging can predict the development of erosions. In the long term, an overall score of inflammation incorporating synovitis, tenosynovitis, and bone edema may be a more useful MRI predictor of aggressive erosive disease. [ABSTRACT FROM AUTHOR]

In 2013, much progress has occurred in gout research. Imaging continues to help elucidate aspects of pathophysiology and now suggests that healing of erosions could occur when urate levels are reduced dramatically. New genetic loci associated with hyperuricaemia have been identified and management strategies for prophylaxis of gout flares continue to evolve. [ABSTRACT FROM AUTHOR]

The article discusses advances in gout research in the fields of radiography, genetics and therapeutics that are conducted in 2013. A study by N. Dalbeth explored radiographic changes in patients with tophaceous gout treated with urate-lowering therapy (ULT), while Kottgen et al. used European ancestry data to identify genetic loci associated with serum uric acid (SUA) concentrations. The efficacy of rilonacept for the prevention of gout flare during ULT usage is examined by E. Mitha et al.

SUMMARY This pictorial essay describes the changes seen in the wrist in early rheumatoid arthritis (RA) on MRI. Magnetic resonance imaging can demonstrate bone erosions, bone marrow signal changes, synovitis and tenosynovitis in early rheumatoid arthritis. Magnetic resonance imaging of the wrist can identify erosions in RA earlier than plain radiographs and can detect more erosions. Common sites include the capitate, lunate and scaphoid. Bone marrow signal changes occur frequently and are most common in the capitate, lunate and triquetrum. Synovial thickening and enhancement are clearly demonstrated with MRI and are most commonly seen in the radiocarpal joint (RCJ). Tenosynovitis can be seen in the wrist in more than half of patients presenting with RA. This most commonly involves the extensor carpi ulnaris tendon and is seen as sheath fluid, thickening and enhancement. [ABSTRACT FROM AUTHOR]

Introduction Magnetic resonance imaging ( MRI) is useful for detecting joint inflammation and damage in the inflammatory arthropathies. This study aimed to investigate MRI cartilage damage and its associations with joint inflammation in patients with gout compared with a group with rheumatoid arthritis ( RA). Methods Forty patients with gout and 38 with seropositive RA underwent 3T- MRI of the wrist with assessment of cartilage damage at six carpal sites, using established scoring systems. Synovitis and bone oedema ( BME) were graded according to Rheumatoid Arthritis MRI Scoring System criteria. Cartilage damage was compared between the groups adjusting for synovitis and disease duration using logistic regression analysis. Results Compared with RA, there were fewer sites of cartilage damage and lower total damage scores in the gout group ( P = 0.02 and 0.003), adjusting for their longer disease duration and lesser degree of synovitis. Cartilage damage was strongly associated with synovitis in both conditions (R = 0.59, P < 0.0001 and R = 0.52, P = 0.0045 respectively) and highly correlated with BME in RA (R = 0.69, P < 0.0001) but not in gout (R = 0.095, P = 0.56). Conclusions Cartilage damage is less severe in gout than in RA, with fewer sites affected and lower overall scores. It is associated with synovitis in both diseases, likely indicating an effect of pro-inflammatory cytokine production on cartilage integrity. However, the strong association between cartilage damage and BME observed in RA was not identified in gout. This emphasizes differences in the underlying pathophysiology of joint damage in these two conditions. [ABSTRACT FROM AUTHOR]

The article presents the pre- and post-treatment radiographic images revealing divergent patterns of joint remodeling following effective urate-lowering therapy in a 35-year-old man with severe tophaceous gout and hyperuricemia.

The clinical course of gout is initially characterized by acute self-limited joint inflammation, but long-standing disease is often associated with chronic inflammation followed by the development of erosive joint damage, which can result in long-term functional impairment. Preventing joint damage is now a major focus of therapeutic intervention in gout. New light has been shed on the mechanisms leading to cartilage and bone damage in patients with this disease. Here, we discuss basic science studies focusing on the cellular immunology of bone and cartilage in gout and the effects of monosodium urate crystals on signaling pathways, cytokine release and the function of osteoclasts, osteoblasts and chondrocytes. We then explore the use of advanced imaging modalities (including MRI, ultrasonography, CT and dual-energy CT) to investigate pathology in gout, as they provide new ways to visualize joint tissues. These modalities vary in their ability to detect the various pathological features of gout and have different clinical applications. Imaging provides information about the inflammatory nature of the joint lesion, position and size of tophaceous deposits, and extent of bone and cartilage damage. Imaging is also increasingly being used to monitor the progression of joint damage and regression of tophi with effective urate-lowering therapy. [ABSTRACT FROM AUTHOR]

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. Uratelowering 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Despite the predilection of gout to the feet, the impact of gout on foot function and biomechanics is currently unknown. The aim of this study was to describe the effects of chronic gout upon function and selected biomechanical parameters associated with gait. Methods: Twenty-five patients with a history of gout were compared with 25 age and gender matched control participants with no history of gout or other forms of arthritis. General function, foot specific disease activity and lower limb activities were determined using the Health Assessment Questionnaire, Foot Function Index (pain domain), and Leeds Foot Impact Scale respectively. Each patient also underwent a gait assessment that included plantar pressure measurements and an evaluation of temporal–spatial gait parameters. Findings: Patients with chronic gout had higher levels of general and foot-specific disability, pain and impairment (P ≤0.001). Significantly lower peak plantar pressures were observed in the hallux of patients with chronic gout (P ≤0.05). Significantly higher pressure–time integrals were observed in the cases at the midfoot (P ≤0.05), but lower values were observed at the hallux (P ≤0.05). Patients with chronic gout walked slower, with longer step and stride lengths compared to the controls. Interpretation: Patients with chronic gout experience pain and disability associated with their feet. Different toe-off strategies may account for functional changes and pain associated with foot problems in chronic gout. [Copyright &y& Elsevier]

The article presents a study which evaluates the cellular framework of gouty tophus and determines the incidence of cytokines in the disease. It includes the collection of paraffin-embedded tophus from 12 patients after surgical removal of tophi followed by its analysis through quantitative immunochemistry. Results of the study reveal the presence of multinucleated cells in the corona area and mast cells in tophus samples with the same desnsities.

A letter to the editor is presented in response to the article "Digital tomosynthesis for bone erosion scoring in gout: comparison with plain radiography and computed tomography" on the June 27, 2014 issue.