Search

Introduction: The aim of this study was to assess the distribution of bone erosions in the feet of patients with gout using CT and thereby to test the hypothesis that gout is an asymmetric arthropathy. Methods: 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 1,100 bones) by two independent radiologists. Symmetry was assessed by two methods: (i) comparing right and left foot scores for each patient; and (ii) calculating the proportion of paired joints with or without erosions. Results: Observer agreement was excellent (intra-class correlation coefficient 0.92). In the group overall, the difference in scores between the feet was not significant (Student's t-test P = 0.8). In 17 of 25 patients, the difference in erosion scores between the two feet was less than the inter-observer difference. In 24 of 25 patients, the proportion of paired joints was greater than 0.5, indicating symmetric disease. Conclusions: Erosive disease from gout is, in fact, a symmetric process in our patient group. This finding is contrary to the established view of gout as an asymmetric arthritis and lends new insight into the behaviour of this common disease. [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]

Objective Tophi are strongly associated with structural damage in gout, and urate-lowering therapy reduces tophus size. Pegloticase leads to dramatic reductions in serum urate and subcutaneous tophi in treatment responders. The aim of this analysis was to examine whether profound urate lowering can alter radiographic findings in gout. Methods Serial plain radiographs of the hands and feet were obtained from 8 patients with tophaceous gout treated with pegloticase. Radiographs were scored for erosion and joint space narrowing (JSN) according to the gout-modified Sharp/van der Heijde method. Scorers were blinded to each other's scores and to the clinical characteristics of the patients (including the clinical response to pegloticase). A detailed qualitative site-by-site analysis was undertaken to define additional changes observed from baseline. Results All patients experienced a profound urate-lowering response (serum urate level <1 mg/dl) during pegloticase treatment. For the entire group, the median total radiographic scores reduced from 69.25 (range 1.5-138) at baseline to 57.25 (range 1.5-110) at 12 months ( P = 0.02). Median erosion scores reduced over 1 year ( P = 0.008), but JSN scores did not change ( P = 0.50). Further reductions were observed in total scores and erosion scores in 5 patients with 24-month followup films (one-way analysis of variance P = 0.009 for total score, 0.02 for erosion, and 0.95 for JSN). Qualitative site-by-site analysis identified regression of soft tissue masses, increased sclerosis, and filling in of erosions in the followup films. Conclusion This exploratory study suggests that profound urate lowering can lead to improvement in structural damage, particularly bone erosion, in patients with tophaceous gout. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective Patients may be defined as nonadherent if they do not take their medications as prescribed by their physicians. Determinants of nonadherence may vary between and within patient groups. This study investigated the extent to which patients with systemic lupus erythematosus (SLE) show intentional and unintentional nonadherence, and the associations of nonadherence with psychological and medical parameters. Methods The study included 106 patients who were receiving at least one immunosuppressive agent to control their SLE. Level of self-reported adherence and a measure of both intentional and unintentional nonadherence were obtained. Questionnaires were completed to assess associations between adherence and problems with cognitive functioning, beliefs about medicines, illness perceptions, emotional health, and disease characteristics. Results The mean self-reported adherence rate for the total patient group was 86.7%. At least occasional intentional nonadherence was reported by 46.2% of patients and 58.5% of patients were at least occasionally unintentionally nonadherent. Problems with cognitive functioning, concerns about adverse effects of medication, and younger age were the strongest predictors of (non)adherence. Patients who were emotionally affected by their SLE were more likely to report low adherence, but this was not a significant predictor after accounting for other variables. Disease characteristics showed no relationship to measures of adherence. Conclusion Although SLE patients reported high levels of adherence on average, they commonly reported intentional and unintentional nonadherence. Adherence was associated with both cognitions and emotions. Nonadherence may be reduced by targeting emotional and cognitive functioning and by fine tuning doctor-patient communication to address patients' individual concerns about their medications. [ABSTRACT FROM AUTHOR]

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.

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]

Background: The anti-cyclic citrullinated peptide (anti-CCP) antibody test is a new serological marker with high specificity for rheumatoid arthritis (RA). Aims: This study evaluated the frequency of anti-CCP antibodies in comparison to rheumatoid factor (RF) in a group of patients with inflammatory polyarthritis. Methods: Samples were obtained from 106 patients with established RA and non-RA inflammatory polyarthritis. Anti-CCP (second generation assay – INOVA) and RF antibodies were measured by enzyme-linked immunosorbent assay. Patient demographics, disease duration and clinical diagnosis were obtained. Results: Fifty-five patients had established RA and the remaining 51 had non-RA inflammatory polyarthritis. The sensitivity of the anti-CCP2 assay for a diagnosis of RA was 73% compared with 56% for RF. In the RA group, half the RF negative patients (12/24) tested positive for anti-CCP. The specificity of anti-CCP was extremely high at 98% compared with RF at 94%. In the non-RA group, only one patient with lupus tested positive for anti-CCP compared with three who were RF positive (all of whom also had lupus). Conclusion: The second generation anti-CCP assay was more sensitive and specific than RF for a diagnosis of RA in this population. This test may improve accuracy of diagnosis in patients with long-standing polyarthritis. [ABSTRACT FROM AUTHOR]

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]

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.

A response by F. McQueen and E. Duvall to a letter to the editor about their article "Using a quality control approach to define an "adequately cellular" liquid-based cervical cytology specimen" in the August 2006 issue is presented.

Objective: To analyze cellular mechanisms of bone erosion in gout., Methods: Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with gout were analyzed for the presence of osteoclast precursors. Fixed tophus and bone samples were analyzed by immunohistochemistry. Mechanisms of osteoclastogenesis were studied by culturing murine preosteoclast RAW 264.7 cells, bone marrow stromal ST2 cells, and human synovial fibroblasts with monosodium urate monohydrate (MSU) crystals., Results: PBMCs from patients with severe erosive gout had the preferential ability to form osteoclast-like cells in culture with RANKL and monocyte colony-stimulating factor (M-CSF). The number of PBMC-derived tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells strongly correlated with the number of tophi (r = 0.6296, P = 0.630). Patients with severe erosive and tophaceous gout also had higher circulating concentrations of RANKL and M-CSF. Furthermore, greater numbers of TRAP-positive multinucleated cells were cultured from SFMCs derived from gouty knee effusions than from paired PBMCs (P = 0.004). Immunohistochemical analysis demonstrated numerous multinucleated cells expressing osteoclast markers within tophi and at the interface between soft tissue and bone. MSU crystals did not directly promote osteoclast formation from RAW 264.7 cells in vitro. However, MSU crystals inhibited osteoprotegerin gene and protein expression in ST2 cells and human synovial fibroblasts, without significantly altering RANKL gene expression. Conditioned medium from ST2 cells cultured with MSU crystals promoted osteoclast formation from RAW 264.7 cells in the presence of RANKL., Conclusion: Chronic tophaceous and erosive gout is characterized by enhanced osteoclast development. These data provide a rationale for the study of osteoclast-targeted therapies for the prevention of bone damage in chronic gout.

Objective: To determine whether magnetic resonance imaging (MRI) evidence of tendinopathy in early rheumatoid arthritis (RA) could be used to predict the course of tendon involvement in later disease and specifically the risk of tendon rupture., Methods: The occurrence, pattern, and progression of tendinopathy were studied prospectively over 6 years in a cohort of patients who had presented with RA. Of 42 patients enrolled, full MRI and clinical data were available for 31 at 6 years. MRI scans of the dominant wrist were scored for tendinopathy by 2 radiologists using a validated system. These data were compared with MRI synovitis, erosion scores, and disease activity measures. Prognostic factors for tendon inflammation and rupture were sought., Results: Thirty-four patients (81%) had MRI evidence of tendinopathy at baseline, falling to 59% at 1 year and 68% at 6 years. The most commonly affected site was the extensor carpi ulnaris. MRI tendinopathy and synovitis scores were correlated at baseline (r = 0.37, P = 0.01) and 1 year (r = 0.45, P = 0.003) but not at 6 years (r = 0.11, P = 0.5). The strongest predictor of the 6-year tendinopathy score was the 1-year tendinopathy score (R(2) = 0.36, P = 0.0003 [beta = 1.28, SE = 0.31]). In 4 patients, extensor tendon rupture had occurred by 6 years. Their baseline and 1-year tendinopathy scores were higher than in the nonrupture group (medians 2.8 versus 1.0 [P = 0.04] and 4.3 versus 0.8 [P = 0.03], respectively), as were their Health Assessment Questionnaire scores (1.33 versus 0.54 [P = 0.02], 1.18 versus 0.25 [P = 0.03], and 0.98 versus 0.37 [P = 0.01] at 0, 1, and 6 years, respectively). For the group as a whole, the baseline tendinopathy score was predictive of rupture at 6 years (odds ratio [OR] 1.52, 95% confidence interval [95% CI] 1.02-2.32, P = 0.03), as was the 1-year score (OR 1.57, 95% CI 1.03-2.04, P = 0.02)., Conclusion: MRI can be used to quantify tendinopathy at the wrist in RA patients. High scores in early disease were predictive of tendon rupture in a small group of patients, but further studies are required to determine whether this has clinical relevance.

Objective: Magnetic resonance imaging (MRI) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis (RA), as well as bone edema and erosion. These features are visible before radiographic joint damage occurs. We sought to examine whether MRI of one body region (the wrist) can be used to predict whole-body radiography scores reflecting joint damage at 6 years., Methods: We conducted a 6-year prospective study of a cohort of patients who fulfilled the criteria for RA at presentation, using clinical parameters, radiographs, and MRI scans of the dominant wrist. Of the 42 patients enrolled at baseline, full MRI, radiographic, and clinical data were available for 31 at 6-year followup. MRI scans were scored by 2 radiologists, using a validated scoring system. Radiographs of the hands and feet were graded using the modified Sharp scoring method. MRI and radiography scores obtained at baseline and 6 years were compared, and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years., Results: At 6 years, the total Sharp score correlated significantly with the total MRI score and the MRI erosion score (r = 0.81, P < 0.0001 and r = 0.79, P < 0.0001, respectively). The 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores (r = 0.56, P < 0.0001 and r = 0.33, P = 0.03, respectively). MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years, but bone erosion scores progressed (P = 0.0001), consistent with radiographic deterioration. Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline (odds ratio 6.5, 95% confidence interval 2.78-18.1). Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002). Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort. A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R(2) = 0.59, adjusted R(2) = 0.44)., Conclusion: MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage, allowing disease-modifying therapy to be targeted to patients with aggressive disease.