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ID PMID Title PublicationDate abstract
20549276 Clinical features and prognosis in adult-onset Still's disease: a study of 104 cases. 2010 Sep The objective of this study is to evaluate the clinical features and prognosis of adult-onset Still's disease (AOSD). One hundred and four AOSD patients who were analyzed retrospectively were enrolled in this study. Medical charts were systematically reviewed for: demographic data, clinical features, laboratory findings, treatments, and outcomes. The major clinical features were: spiking fever 100%, evanescent maculopapular rash 95%, polyarthralgia 90%, sore throat 78%, lymphadenopathy 66%, hepatosplenomegaly 57%, hydrohymenitis 30%, neutrophilia 98%, liver disfunction 62%, increased erythrocyte sedimentation rate (ESR) 96%, and hyperferritinaemia 99%. Reactive hyperplasia was shown in all patients who underwent lymph node biopsy. Ninety-five percent and 63% of the patients were treated with glucocorticoid and immune suppressant, respectively. Those with prednisone or its equivalent dosage of > or =0.8 mg/kg/d achieved quicker remission and less relapse. Persistent fever, evanescent rash, arthritis, and sore throat were the most prevalent symptoms in patients with AOSD, with laboratory findings of leukocytosis, elevated liver enzymes, elevated ESR and serum ferritin. Glucocorticoid and immune suppressive drugs are effective for AOSD; however, the relapsing rate is relatively high. High levels of white blood cells, serum ferritin and ESR, as well as glucocorticoid dosage were related to relapse.
19593288 Cardiac tamponade in Still disease: a review of the literature. 2009 Aug Adult onset Still disease is an unusual multisystem inflammatory disorder of unknown etiology and pathogenesis. Among its protean manifestations is pericarditis which occurs in approximately 30-40% of patients. Cardiac tamponade is a rare complication of pericarditis occurring in the context of Still disease. We conducted a review of the English literature pertaining to the occurrence of pericardial tamponade in Still disease. We searched relevant journals and the PubMed Medline databases. A total of eighteen reported cases were identified; ten among children and eight in adults. Treatment of pericardial tamponade was medical therapy alone in two cases versus combined modality, medical and surgical drainage in the remainder of the cases. Outcomes were death among four of the ten children and there was no recurrence of tamponade in the remaining child and adult series. This review re-emphasizes the importance of considering Still disease in the differential diagnosis of the life-threatening emergency of pericardial tamponade.
19592325 Cutaneous polyarteritis nodosa in adult onset Still's disease. 2009 Nov Adult onset Still's disease (AOSD) is a well recognized clinical disorder characterized by a typical rash. However, there have been several atypical cutaneous findings reported in patients with AOSD. Cutaneous polyarteritis nodosa (PAN) is a necrotizing vasculitis of the small and medium sized arteries, distinguishing itself from systemic PAN by its restriction to the skin and to the neurological and osteo-muscular systems. We report the case of a patient with AOSD who is unique in having developed cutaneous polyarteritis nodosa (PAN) during the active phase of her disease. To the best of our knowledge, no previous cases of AOSD associated with a cutaneous variant of PAN have been reported.
19410128 Sjogren's syndrome masquerading as nasopharyngeal carcinoma. 2009 May OBJECTIVE: The aim of the study was to describe a case of nasopharyngeal involvement by Sjogren's syndrome masquerading as nasopharyngeal carcinoma. METHODS: A description of clinical and radiologic features of facial pain, nasopharyngeal bulge, middle ear effusion, restriction of palatal movement, and infiltrating nasopharyngeal mass on imaging was given. Histologic evaluation, response to treatment with steroids and hydrochloroquine, and long-term follow-up, however, subsequently indicated the mass to be secondary to Sjogren's syndrome. CONCLUSION: A previously undescribed manifestation of Sjogren's syndrome is described.
20374359 Myocarditis in adult onset Stills disease. 2009 Sep Adult onset Still's disease (AOSD) is an inflammatory disorder characterized by daily spiking high fevers, arthritis and an evanescent rash. It is a rare disease of unknown aetiology and can have serious systemic and musculoskeletal sequelae. Literature on the association of myocarditis with AOSD is very sparse. Here, we present a case of AOSD associated with myocarditis, in which the patient responded well to systemic steroids.
19781067 Preclinical characterization of DEKAVIL (F8-IL10), a novel clinical-stage immunocytokine w 2009 INTRODUCTION: In this article, we present a comparative immunohistochemical evaluation of four clinical-stage antibodies (L19, F16, G11 and F8) directed against splice isoforms of fibronectin and of tenascin-C for their ability to stain synovial tissue alterations in rheumatoid arthritis patients. Furthermore we have evaluated the therapeutic potential of the most promising antibody, F8, fused to the anti-inflammatory cytokine interleukin (IL) 10. METHODS: F8-IL10 was produced and purified to homogeneity in CHO cells and shown to comprise biological active antibody and cytokine moieties by binding assays on recombinant antigen and by MC/9 cell proliferation assays. We have also characterized the ability of F8-IL10 to inhibit arthritis progression in the collagen-induced arthritis mouse model. RESULTS: The human antibody F8, specific to the extra-domain A of fibronectin, exhibited the strongest and most homogenous staining pattern in synovial biopsies and was thus selected for the development of a fully human fusion protein with IL10 (F8-IL10, also named DEKAVIL). Following radioiodination, F8-IL10 was able to selectively target arthritic lesions and tumor neo-vascular structures in mice, as evidenced by autoradiographic analysis and quantitative biodistribution studies. The subcutaneous administration route led to equivalent targeting results when compared with intravenous administration and was thus selected for the clinical development of the product. F8-IL10 potently inhibited progression of established arthritis in the collagen-induced mouse model when tested alone and in combination with methotrexate. In preparation for clinical trials in patients with rheumatoid arthritis, F8-IL10 was studied in rodents and in cynomolgus monkeys, revealing an excellent safety profile at doses tenfold higher than the planned starting dose for clinical phase I trials. CONCLUSIONS: Following the encouraging preclinical results presented in this paper, clinical trials with F8-IL10 will now elucidate the therapeutic potential of this product and whether the targeted delivery of IL10 potentiates the anti-arthritic action of the cytokine in rheumatoid arthritis patients.
19519881 Age-related changes in arthritis susceptibility and severity in a murine model of rheumato 2009 Jun 11 BACKGROUND: Rheumatoid arthritis (RA) most often begins in females in the fourth-fifth decade of their life, suggesting that the aging of the immune system (immunosenescence) has a major role in this disease. Therefore, in the present study, we sought to investigate the effect of age on arthritis susceptibility in BALB/c mice using the proteoglycan (PG)-induced arthritis (PGIA) model of RA. RESULTS: We have found that young, 1-month-old female BALB/c mice are resistant to the induction of PGIA, but with aging they become susceptible. PG-induced T cell responses decline with age, whereas there is a shift toward Th1 cytokines. An age-dependent decrease in T cell number is associated with an increased ratio of the memory phenotype, and lower CD28 expression. Antigen-presenting cells shifted from macrophages and myeloid dendritic cells in young mice toward B cells in older mice. The regulatory/activated T cell ratio decreases in older mice after PG injections indicating impaired regulation of the immune response. CONCLUSION: We conclude that immunosenescence could alter arthritis susceptibility in a very complex manner including both adaptive and innate immunities, and it cannot be determined by a single trait. Cumulative alterations in immunoregulatory functions closely resemble human disease, which makes this systemic autoimmune arthritis model of RA even more valuable.
20478038 Looking through the 'window of opportunity': is there a new paradigm of podiatry care on t 2010 May 17 Over the past decade there have been significant advances in the clinical understanding and care of rheumatoid arthritis (RA). Major paradigm changes include earlier disease detection and introduction of therapy, and 'tight control' of follow-up driven by regular measurement of disease activity parameters. The advent of tumour necrosis factor (TNF) inhibitors and other biologic therapies have further revolutionised care. Low disease state and remission with prevention of joint damage and irreversible disability are achievable therapeutic goals. Consequently new opportunities exist for all health professionals to contribute towards these advances. For podiatrists relevant issues range from greater awareness of current concepts including early referral guidelines through to the application of specialist skills to manage localised, residual disease activity and associated functional impairments. Here we describe a new paradigm of podiatry care in early RA. This is driven by current evidence that indicates that even in low disease activity states destruction of foot joints may be progressive and associated with accumulating disability. The paradigm parallels the medical model comprising early detection, targeted therapy, a new concept of tight control of foot arthritis, and disease monitoring.'Podiatrists are experts on foot disorders: both patients and rheumatologists can profit from the involvement of a podiatrist'- Korda and Balint, 2004 1.
21794639 [Biologics as first line therapy in the treatment of rheumatoid arthritis. An opposing poi 2009 Apr The development of biologic therapies has improved the prognosis of rheumatoid arthritis (RA). However, at present there is not enough evidence supporting that TNF antagonists, anti CD20 therapy or abatacept used as first line therapy provide relevant long-term benefits in daily clinical practice. Furthermore, clinical trials that analyze the effect of the combination of methotrexate (MTX) plus TNF antagonists against MTX monotherapy have shown that the later provides significant clinical responses and relevant radiological damage arrest in patients with early RA. Therefore, considering that in 5-6 months we can detect which patients do not respond adequately to MTX, we can select those patients for biologic therapy avoiding the exposure to the putative adverse events of combination therapy to those patients with optimal response to MTX monotherapy.
19479686 A prediction rule for disease outcome in patients with undifferentiated arthritis using ma 2009 Jun 15 OBJECTIVE: To evaluate whether magnetic resonance imaging (MRI) of the wrists and finger joints and an analysis of serologic autoantibodies are clinically meaningful for the subsequent development of rheumatoid arthritis (RA) in patients with undifferentiated arthritis (UA). METHODS: A total of 129 patients with UA, a disease status formally confirmed by a rheumatologist over a period of at least 1 year, were included. Gadolinium-diethylenetriamine-enhanced MRI of both wrists and finger joints and serologic variables were examined upon admission to our Early Arthritis Clinic at Nagasaki University. After a prospective followup of 1 year, a predictive value for the development of RA was determined for each patient. RESULTS: The subjects were evaluated for their positive or negative status with respect to 3 objective measures at study entry: anti-cyclic citrullinated peptide (anti-CCP) antibodies and/or IgM-rheumatoid factor, MRI-proven symmetric synovitis, and MRI-proven bone edema and/or bone erosion. The patients who were positive for at least 2 of these measures progressed to RA at 1 year with a 79.7% positive predictive value (PPV), 63.0% negative predictive value, 75.9% specificity, 68.0% sensitivity, and 71.3% accuracy. Furthermore, in 22 UA patients positive for both anti-CCP antibodies and MRI-proven bone edema who were considered to have progressed to RA at 1 year, the PPV was increased to 100%. A close correlation was found between the present rule and that established in the Leiden Early Arthritis Cohort. CONCLUSION: MRI-proven early joint damage in conjunction with serologic autoantibodies is efficient in predicting progression from UA to RA. This method can be used to identify patients who would benefit from early treatment with disease-modifying antirheumatic drugs.
27789996 New and emerging therapies for the treatment of rheumatoid arthritis. 2010 The introduction of tumor necrosis factor (TNF) inhibitors in the late 1990s significantly changed the therapeutic approach for rheumatoid arthritis (RA). With the approval of subsequent TNF inhibitors as well as other biologic agents effective in the management of RA, the treatment paradigm has become increasingly complex. This review examines the current literature regarding the efficacy and toxicity of these and other new anti-rheumatic therapies and discusses effective therapeutic strategies for their use.
22111748 Treatment options for rheumatoid arthritis beyond TNF-α inhibitors. 2010 Sep The treatment of rheumatoid arthritis has changed over the last 15 years. Early and aggressive treatment, use of methotrexate as the anchor drug and combination treatment, with older disease-modifying drugs or biologics, have become the norm. TNF inhibitors were the first biologic agents available to rheumatologists and are still currently used as first-line biologics, in addition to other newer biologic agents. Abatacept, rituximab and tocilizumab are available biologics that use a different mode of action to TNF inhibitors, and can be used after a TNF inhibitor is tried. Abatacept is also currently used as a first-line biologic and others can also be used once data are available.
21794648 [Rituximab and abatacept in rheumatoid arthritis]. 2009 Apr Abatacept and rituximab are two biologic drugs approved in patients with rheumatoid arthritis who have an inadequate response or intolerance to other disease modifying antirheumatic drugs, including one or more tumor necrosis factor (TNF) inhibitors. The current indication for use is the only thing that both drugs have in common because they are different molecules (abatacept is a fusion molecule and rituximab a monoclonal antibody) with different mechanisms of action and different patterns of administration. Both treatments have shown their clinical efficacy, the stop of structural damage and medium term safety in randomized, double-blind clinical trials. In this paper we will review the structure and mechanisms of action of both drugs, presenting studies in which the efficacy and safety data are based and will finally postulate different controversial questions in the use of these drugs.
20429008 Sexual maturation in boys with juvenile rheumatoid arthritis. 2011 Nov This paper aimed to study sexual maturation of boys with juvenile rheumatoid arthritis (JRA) during adolescence. This study was carried out in the Department of Pediatrics, Advanced Pediatrics Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A total of 70 boys (between 9 and 17 years of age) diagnosed as cases of JRA comprised the sample for this study. Every child was examined for the development of genitalia as per criteria given by Tanner (Growth at adolescence, 2nd edn, Blackwell, Oxford, 1962) at half-yearly age intervals. However, with regard to development of hair (pubic, axillary and facial) mere presence or absence was noted. Mean (±SD) age of attainment of different stages of genitalia development as well as for eruption of hair was ascertained amongst boys who entered puberty using conventional statistics. Initiation of genitalia development (i.e. appearance of G-2 stage) was earliest among boys with systemic onset JRA (10.8 ± 1.3 years). None of the boys with JRA could attain final stage (G-5) of genitalia development by the age of 17 years, as compared with normal Chandigarh boys who had attained this by 15.2 years. Age of appearance of axillary, pubic, and facial hair was also earlier in systemic onset type of disease as compared with those with pauciarticular and polyarticular JRA. The timing of initiation of sexual maturity in boys with different types of JRA remains variably affected, and appears to experience substantial delay in completion of puberty.
20003891 Extra domain B fibronectin as a target for near-infrared fluorescence imaging of rheumatoi 2009 Dec Abstract We investigated a molecular imaging approach for the detection of collagen-induced arthritis in rats by targeting the extra domain B (ED-B) of the extracellular matrix protein fibronectin. ED-B is a highly conserved domain (identical in human and rats) that is produced by alternative splicing during embryonic development and during vascular remodeling such as angiogenesis. The hallmark of rheumatoid arthritis is synovitis leading to both angiogenesis in the synovium and the promotion of cartilage and bone disruption. For in vivo diagnostics, the ED-B-binding single-chain antibody fragment AP39 was used as a targeting probe. It was covalently linked to the near-infrared dye tetrasulfocyanine (TSC) to be visualized by near-infrared fluorescence imaging. The resulting AP39-TSC conjugate was intravenously administered to rats with collagen-induced arthritis and the respective controls. Ovalbumin-TSC was used as control conjugate. Optical imaging over a time period of 24 hours using a planar imaging setup resulted in a clear enhancement of fluorescence intensity in joints with moderate to severe arthritis compared with control joints between 3 and 8 hours postinjection. Given that AP39 is a fully human antibody fragment, this molecular imaging approach for arthritis detection might be translated to humans.
19439055 Colony variability under the spotlight in animal models of arthritis. 2009 A recent article by Farkas and colleagues, published in Arthritis Research & Therapy, is from the laboratory of Dr Tibor Glant and his research team in Chicago, who have investigated in considerable depth the immunopathology of experimental arthritis induced by the major cartilage component proteoglycan aggrecan in an animal model that mimics many features of human rheumatoid arthritis and ankylosing spondylitis. This present report takes our understanding a significant step forward by questioning whether genetic drift in distinct colonies of the same inbred strains of mice has an impact on the parity between data published by different laboratories.
19661534 Early psoriatic arthritis. 2009 Aug Early detection of psoriatic arthritis (PsA) can effectively help in reducing the risk of joint damage and disability. Accordingly, the authors offer diagnostic insights in order to improve the approach to the patient's medical history, clinical examination, and the imaging modalities. Early PsA is a condition with a consistent risk of clinical progression. Marked entheseal involvement is a distinctive clinical aspect that helps discriminate early PsA from other conditions observed at their onset, in particular rheumatoid arthritis.
20391508 Early outcomes and improvement of patients with juvenile idiopathic arthritis enrolled in 2010 Apr OBJECTIVE: To determine early outcomes and early improvements in a prospective inception cohort of children with juvenile idiopathic arthritis (JIA) treated with current standard therapies. METHODS: Patients selected were enrolled in an inception cohort of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study. The juvenile rheumatoid arthritis core criteria set measures were completed at enrollment and 6 months later. Frequencies of normal values for each of the core set measures and the American College of Rheumatology (ACR) Pediatric 30, 50, and 70 (Pedi 70) criteria response rates achieved at 6 months after enrollment were calculated for each JIA-onset subtype group. RESULTS: Among 354 patients in the study, the median interval between diagnosis and enrollment was 0.7 months. At 6 months after enrollment, median values of active joint counts were highest in patients with rheumatoid factor (RF)-positive polyarthritis (4) and RF-negative polyarthritis (2), but were 0 or 1 for other subtypes. Fifty percent or more of patients with oligoarthritis, systemic arthritis, enthesitis-related arthritis, and undifferentiated arthritis had no active joints, and the ACR Pedi 70 criteria response rate was 48% or more in those with oligoarthritis, RF-negative polyarthritis, and systemic arthritis. CONCLUSION: With current management strategies in clinical practice, improvement in disease activity was noted in considerable proportions of patients in all of the JIA subtype groups, but low levels of disease activity persisted in many. We expect that these early outcomes will prove to be significant predictors of long-term outcomes.
20361329 An adult onset Still's disease mimicking pneumonia. 2012 Aug Adult onset Still's disease is a rare systemic inflammatory disease of unknown origin. It is common to involve liver and spleen, and less often lungs. A 24-year-old man presenting with spiking fever, pulmonary infiltrations, and pleural effusion on the right side mimicking pneumonia. All serologic tests of infectious causes, antinuclear antibody, and rheumatoid factor were negative. He was diagnosed as Adult onset Still's disease according to the criteria of Yamaguchi. Adult onset Still's disease is considering in the differential diagnosis pneumonia that is unresponsive to antimicrobial treatment, negative cultures and serologically diagnostic laboratory tests, and high-level serum ferritin.
20974942 Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from 2010 Nov 9 DNase II digests the chromosomal DNA in macrophages after apoptotic cells and nuclei from erythroid precursors are engulfed. The DNase II-null mice develop a polyarthritis that resembles rheumatoid arthritis. Here, we showed that when bone marrow cells from the DNase II-deficient mice were transferred to the wild-type mice, they developed arthritis. A deficiency of Rag2 or a lack of lymphocytes accelerated arthritis of the DNase II-null mice, suggesting that the DNase II(-/-) macrophages were responsible for triggering arthritis, and their lymphocytes worked protectively. A high level of TNFα, IL-1β, and IL-6 was found in the affected joints of the DNase II-null mice, suggesting an inflammatory-skewed cytokine storm was established in the joints. A lack of TNFα, IL-1β, or IL-6 gene blocked the expression of the other cytokine genes as well and inhibited the development of arthritis. Neutralization of TNFα, IL-1β, or IL-6 had a therapeutic effect on the developed arthritis of the DNase II-null mice, indicating that the cytokine storm was essential for the maintenance of arthritis in the DNase II-deficient mice. Methotrexate, an antimetabolite that is often used to treat patients with rheumatoid arthritis, had a therapeutic effect with the DNase II-null mice. These properties of arthritis in the DNase II-null mice were similar to those found in human systemic-onset juvenile idiopathic arthritis or Still's disease, indicating that the DNase II-null mice are a good animal model of this type of arthritis.