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Active Arthritis (active + arthritis)
Selected AbstractsThe spectrum of cutaneous lesions in rheumatoid arthritis: a clinical and pathological study of 43 patientsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2003C. M. Magro Introduction:, Rheumatoid arthritis (RA) is an idiopathic arthropathy syndrome that has a propensity to affect the small joints of the hands and feet with extra-articular manifestations comprising skin lesions, neuropathy, pericarditis, pleuritis, interstitial pulmonary fibrosis and a systemic polyarteritis nodosa (PAN)-like vasculitic syndrome. The most widely recognized skin lesion is the rheumatoid nodule. Other skin manifestations are poorly defined. Materials and methods:, Using a natural language search of the authors' outpatient dermatopathology databases, skin biopsies from 43 patients with RA were selected for retrospective analysis in an attempt to define the dermatopathological spectrum of RA and its clinical correlates. Results:, The biopsies were categorized by the dominant histologic pattern, recognizing that in most cases there were additional minor reaction patterns. Palisading and/or diffuse interstitial granulomatous inflammation was the dominant pattern seen in 21 patients; the lesions included nodules, plaques and papules with a predilection to involve skin over joints. Besides interstitial histiocytic infiltrates and variable collagen necrobiosis, these cases also showed interstitial neutrophilia, vasculitis and pauci-inflammatory vascular thrombosis. The dominant morphology in 11 other patients was vasculopathic in nature: pauci-inflammatory vascular thrombosis, glomeruloid neovascularization, a neutrophilic vasculitis of pustular, folliculocentric, leukocytoclastic or benign cutaneous PAN types, granulomatous vasculitis, and lymphocytic vasculitis and finally occlusive intravascular histiocytic foci for which the designation of ,RA-associated intravascular histiocytopathy' is proposed. Rheumatoid factor (RF) positivity and active arthritis were common in this group, with anti-Ro and anticardiolipin antibodies being co-factors contributing to vascular injury in some cases. Immunofluorescent testing in three patients revealed dominant vascular IgA deposition. In nine patients, the main pattern was one of neutrophilic dermal and/or subcuticular infiltrates manifested clinically as urticarial plaques, pyoderma gangrenosum and panniculitis. Conclusions:, The cutaneous manifestations of RA are varied and encompass a number of entities, some of which define the dominant clinical features, such as the rheumatoid papule or subcutaneous cords, while others allude to the histopathology, i.e. rheumatoid neutrophilic dermatosis. We propose a more simplified classification scheme using the adjectival modifiers of ,rheumatoid-associated' and then further categorizing the lesion according to the dominant reaction pattern. Three principal reaction patterns are recognized, namely extravascular palisading granulomatous inflammation, interstitial and/or subcuticular neutrophilia and active vasculopathy encompassing lymphocyte-dominant, neutrophil-rich and granulomatous vasculitis. In most cases, an overlap of the three reaction patterns is seen. Co-factors for the vascular injury that we believe are integral to the skin lesions of RA include RF, anti-endothelial antibodies of IgA class, anti-Ro and anticardiolipin antibodies. [source] Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: Effect of route of administration on variability in intracellular methotrexate polyglutamate concentrationsARTHRITIS & RHEUMATISM, Issue 6 2010Mara L. Becker Objective Intracellular methotrexate (MTX) polyglutamates (MTXGlu) have been shown to be potentially useful biomarkers of clinical response in adult patients with rheumatoid arthritis. The present study was undertaken to measure intracellular MTXGlu concentrations in a cohort of patients with juvenile idiopathic arthritis (JIA) to determine the predictors of MTXGlu variability in these patients. Methods Blood samples were obtained from patients with JIA who were being treated with a stable dose of MTX for ,3 months. Clinical data were collected by chart review. Concentrations of MTXGlu1,7 in red blood cell lysates were quantitated using an innovative ion-pairing chromatography procedure, with detection by mass spectrometry. Results Patients with JIA from a single center (n = 99; mean ± SD age 117.8 ± 56.5 months, 69 female) were included in the analysis. The mean ± SD dose of MTX was 0.51 ± 0.25 mg/kg per week, with a median treatment duration of 18 months (interquartile range 3,156 months). MTX was administered subcutaneously in 66 patients (67%). Fifty-six patients (57%) had active arthritis at the time of the clinic visit. Total intracellular MTXGlu (MTXGluTOT) concentrations varied 40-fold, with a mean ± SD total concentration of 85.8 ± 48.4 nmoles/liter. Concentrations of each MTXGlu subtype (MTXGlu1,7) were measured individually and as a percentage of MTXGluTOT in each patient. MTXGlu3 was the most prominent subtype identified, comprising 42% of MTXGluTOT, and the interindividual variability in the concentration of MTXGlu3 was the most highly correlated with that of MTXGluTOT (r = 0.96). The route of MTX administration was significantly associated with MTXGlu1,5 subtypes; higher concentrations of MTXGlu1 + 2 were observed in patients receiving oral doses of MTX, whereas higher concentrations of MTXGlu3,5 were observed in patients receiving subcutaneous doses of MTX (P < 0.0001). Conclusion In this cohort of patients with JIA, the MTXGluTOT concentration varied 40-fold. Individual MTXGlu metabolites (MTXGlu1,7), which have, until now, not been previously reported in patients with JIA, were detected. The route of MTX administration contributed to the variability in concentrations of MTXGlu1,5. [source] Indoleamine 2,3 dioxygenase,mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 5 2009Gabriel Criado Objective Indoleamine 2,3 dioxygenase (IDO) is a catabolic enzyme that initiates the kynurenine pathway of tryptophan degradation and has immunomodulatory properties. The aim of this study was to investigate the regulation of collagen-induced arthritis by tryptophan catabolism mediated by IDO. Methods Arthritis was induced by immunization with type II collagen. After induction of arthritis, the expression of IDO was analyzed by quantitative reverse transcription,polymerase chain reaction. The effect of IDO deficiency on collagen-induced arthritis was assessed in vivo by administration of 1-methyltryptophan and clinical and histologic evaluation of IDO-deficient mice. The requirement for IDO activation was bypassed by administration of L -kynurenine. Results IDO was induced in lymph node dendritic cells after collagen immunization. Systemic inhibition of tryptophan catabolism during active arthritis increased disease severity. Conversely, bypassing the requirement for tryptophan degradation by the administration of L -kynurenine resulted in amelioration of arthritis. Furthermore, IDO-deficient mice showed a higher incidence of arthritis and exacerbated disease severity compared with IDO-competent mice. Such increased disease activity in IDO-deficient mice correlated early with increased production of the proinflammatory cytokines interferon-, and interleukin-17 by lymph node T cells and later with increased infiltration of Th1 and Th17 cells in the inflamed joints. Conclusion Our data indicate that the induction of IDO controls the accumulation of Th1 and Th17 pathogenic T cells at the site of inflammation during collagen-induced arthritis. Therefore, manipulation of the kynurenine pathway of tryptophan degradation provides the potential for therapeutic intervention in rheumatoid arthritis. [source] Functional and prognostic relevance of the ,173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 5 2003Fabrizio De Benedetti Objective To address the functional and prognostic relevance of the ,173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. Methods A total of 136 patients with systemic-onset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. Results Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. Conclusion Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA. [source] Epidemiology and clinical pattern of psoriatic arthritis in Germany: a prospective interdisciplinary epidemiological study of 1511 patients with plaque-type psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2009K. Reich Summary Background, Because psoriatic arthritis (PsA) usually develops years after the first manifestation of skin symptoms, in many cases the initial diagnosis of PsA depends on the dermatologist. Objectives, To investigate the prevalence and clinical pattern of PsA in a daily practice population of patients with psoriasis. Methods, Patients were enrolled in an observational prospective cross-sectional cohort study at 48 community and academic centres. Demographic and medical parameters were recorded, including severity of skin symptoms (Psoriasis Area and Severity Index, PASI), previous and current treatments, concomitant diseases, and the impact of psoriasis on productivity and health-related quality of life (Dermatology Life Quality Index, DLQI). Patients with joint symptoms were referred to a rheumatologist for diagnosis and to record the activity and pattern of arthritis. Results, Among 1511 patients 20·6% had PsA; in 85% of the cases PsA was newly diagnosed. Of these patients more than 95% had active arthritis and 53·0% had five or more joints affected. Polyarthritis (58·7%) was the most common manifestation pattern, followed by oligoarthritis (31·6%) and arthritis mutilans (4·9%). Distal interphalangeal involvement was present in 41·0% and dactylitis in 23·7% of the patients. Compared with patients without arthritis, patients with PsA had more severe skin symptoms (mean PASI 14·3 vs. 11·5), a lower quality of life (mean DLQI 11·6 vs. 7·7) and greater impairment of productivity parameters. Conclusions, The findings are consistent with a high prevalence of undiagnosed cases of active PsA among patients with psoriasis seen by dermatologists. As many of these patients also have significant skin symptoms, treatment strategies are required that are equally effective in the control of skin and joint symptoms of psoriasis. [source] | ||||||||||