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ID PMID Title PublicationDate abstract
20191568 Measuring joint involvement in polyarticular psoriatic arthritis: an introduction of alter 2010 Jul OBJECTIVE: To compare the reliability of 3 different simplified joint counts with the gold standard 66 swollen/68 tender joint count (JC66/68) for assessing clinical response in patients with polyarticular psoriatic arthritis (PsA). METHODS: The 28-joint count (JC28), in the same way that it is used in rheumatoid arthritis, and 2 measures including distal interphalangeal (DIP) joints (the 32-joint count [JC32], including all finger joints as well as wrists and knees, and 36-joint count [JC36], which additionally included elbows and ankles), were compared with the JC66/68 in 182 patients using data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial 2 trial database. Pearson's correlation coefficients were calculated to compare the swollen and tender JC28, JC32, and JC36 with the corresponding results of the total JC66/68. American College of Rheumatology (ACR) responses based on the individual measures were compared, and their ability in predicting a clinical response of ACR 20% improvement (ACR20) based on the JC66/68 was assessed by calculating the area under the receiver operating characteristic curve via logistic regression and the maximum Youden indices at weeks 14 and 24. RESULTS: All simplified joint counts were highly correlated to the standard JC66/68 both for tenderness and swelling at each individual visit (Pearson's correlation coefficients consistently >0.8, n = 182-200; P < 0.0001). Logistic regression for ACR20 response showed that area under the curve was constantly >0.91, with comparable results for Youden indices of the simplified joint counts. CONCLUSION: All simplified joint counts considered seemed sufficiently sensitive and specific to measure clinical response in trial patients with polyarticular PsA when compared with the JC66/68, no matter whether DIP joints were included (the JC36 and JC32) or excluded (the JC28). Further research will be needed to clarify this issue.
19059799 Exposition to anti-TNF drugs during pregnancy: outcome of 15 cases and review of the liter 2009 Jan OBJECTIVE: To report on the outcome of 15 cases of pregnancies in women treated with anti-TNF drugs during conception or pregnancy METHODS: French rheumatologists connecting to the web-site of CRI site: http://www.cri-net.com were asked to fill in a structured questionnaire reporting the outcome of pregnancy in women still treated by a TNF blocker at the time of conception. RESULTS: Spondylarthropathies (n=8), rheumatoid arthritis (n=4), juvenile idiopathic arthritis (n=2), and psoriatic arthritis (n=1) were treated by infliximab (n=3), adalimumab (n=2), or etanercept (n=10). Miscarriages occurred twice, and elective termination was preferred once. Anti-TNF had been administered during the first, second and third trimester of pregnancy in 12, three and two cases. The 12 babies were in good condition, without apparent malformation or symptoms of neonatal illnesses. CONCLUSION: The number of reported cases exceeds 300, but only 29 women were treated during their whole pregnancy. The rate of congenital malformations observed so far might appear reassuring compared to the general population for women exposed only during conception. Conversely, there are too few reports of exposure during pregnancy to allow any conclusion about the safety of TNF blockers, and additional long term follow-up of children would be welcome in order to rule out minor forms of VACTERL association that might have been overlooked at birth.
19012356 A prospective study comparing celecoxib with naproxen in children with juvenile rheumatoid 2009 Jan OBJECTIVE: To compare the efficacy and safety of celecoxib and naproxen in children with juvenile rheumatoid arthritis (JRA). METHODS: In this multicenter, randomized, double-blind, noninferiority study, subjects with JRA were randomized to receive a target dose of celecoxib 3 mg/kg bid or 6 mg/kg bid, or a target dose of naproxen 7.5 mg/kg bid for 12 weeks (maximum allowed dose=600 mg total daily dose). The primary efficacy measure was the percentage of responders at Week 12 attaining the American College of Rheumatology pediatric 30% improvement criterion (ACR Pediatric-30). RESULTS: Both celecoxib doses were at least as effective as naproxen at Week 12 [ACR Pediatric-30 treatment differences: celecoxib 3 mg/kg bid-naproxen=1.36% (95% CI -13.08 to 15.80); celecoxib 6 mg/kg bid-naproxen=13.02% (95% CI -0.22 to 26.25)]. Celecoxib 6 mg/kg bid had a numerically higher response rate than celecoxib 3 mg/kg bid at all postrandomization visits and a numerically higher response rate than naproxen 7.5 mg/kg bid at Weeks 4, 8, and 12. Improvement in each ACR Pediatric-30 core set measure was comparable to or numerically higher for celecoxib 6 mg/kg bid than naproxen or celecoxib 3 mg/kg bid. Adverse event rates were similar for all treatment groups, except that gastrointestinal adverse events were more common in the naproxen group, although the difference was not statistically significant. CONCLUSION: Celecoxib 3 mg/kg bid and 6 mg/kg bid were at least as effective as naproxen 7.5 mg/kg bid in treating the signs and symptoms of JRA over 12 weeks. All treatments were generally well tolerated.
20157435 Etanercept and venous thromboembolism: a case series. 2010 Jan 15 INTRODUCTION: The treatment with antitumor necrosis factor agents has often been associated with the induction of autoantibodies (antinuclear antibodies, anti-double stranded DNA antibodies and antiphospholipid antibodies). The clinical significance of these antibodies remains unclear, but they may predispose to antiphospholipid syndrome with thromboembolic complications. The association of etanercept with thromboembolic events has not been reported previously in the literature. CASE PRESENTATION: We describe the cases of three patients with rheumatoid arthritis, psoriatic arthritis and seronegative inflammatory arthritis who were treated with etanercept. They developed deep vein thrombosis and/or pulmonary embolism one to three years after the initiation of etanercept therapy. All three patients had a prolonged activated partial thromboplastin time with a positive lupus anticoagulant that persisted even after 12 weeks. CONCLUSION: Although the clinical significance of antiphospholipid antibodies during treatment with antitumor necrosis factor agents remains unclear, they may predispose patients to develop antiphospholipid syndrome when associated with prolonged activated partial thromboplastin time, lupus anticoagulant positivity, or the presence of anti-beta2 glycoprotein I. Clinicians must keep this in mind during therapy with antitumor necrosis factor agents in order to prevent, detect and treat potential consequences such as deep vein thrombosis and pulmonary embolism.
19642462 [Biological therapies in rheumatology]. 2009 May Biological therapies consisting of monoclonal antibodies and soluble receptors have revolutionized the care of rheumatologic patients. These therapies ensued from a better understanding of the physiopathology of rheumatologic disorders. Most of the latter have been concerned: rheumatoid arthritis (for about 10 years), psoriatic arthritis and ankylosing spondilitys (for more or less five years). Rheumatology was among the first disciplines to make use of these advances; it continues to benefit from the results of intense research efforts. These developments request from clinicians an increased expertise in immunology.
19900833 Bone morphogenetic protein signaling and arthritis. 2009 Oct Chronic joint diseases have a major impact on society as patients suffer from pain and disability. The spectrum of arthritic disorders is wide including autoimmune and autoinflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis and related spondyloarthritides but also the more prevalent osteoarthritic diseases. The latter appear to be mainly the consequence of injury, strain and aging in a predisposing genetic background. The therapeutic options for chronic inflammatory and immune joint diseases have greatly increased over the last decade by the use of targeted anti-cytokine or anti-immune cell drugs. However, such a shift towards successful treatment has not been achieved for osteoarthritis. In addition, control of inflammation does not equal cure of the disease as relapse occurs as soon as the treatment is interrupted, and only limited tissue repair has been observed. Bone morphogenetic proteins are potent regulators of cell proliferation, differentiation and apoptosis and they have come into the spotlight in arthritis research. Here, we summarize the recent data on the role of bone morphogenetic proteins in joint protection and repair and but also their potential disease promoting or controlling roles. These data are presented in the context of a systems biology view of joint diseases based on their histomorphological phenotype rather than on existing clinical classifications.
20237125 Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyart 2010 Apr OBJECTIVE: To assess the long-term efficacy and safety of infliximab plus methotrexate in juvenile rheumatoid arthritis (JRA). METHODS: Patients eligible for the open-label extension (OLE, weeks 52-204) received infliximab 3-6 mg/kg every 8 weeks plus methotrexate. RESULTS: Of the 78/122 (64%) children entering the OLE, 42 discontinued infliximab, most commonly due to consent withdrawal (11 patients), lack of efficacy (eight patients) or patient/physician/sponsor requirement (eight patients). Infliximab (mean dose 4.4 mg/kg per infusion) was generally well tolerated. Infusion reactions occurred in 32% (25/78) of patients, with a higher incidence in patients positive for antibodies to infliximab (58%, 15/26). At week 204, the proportions of patients achieving ACR-Pedi-30/50/70/90 response criteria and inactive disease status were 44%, 40%, 33%, 24% and 13%, respectively. CONCLUSIONS: In the limited population of JRA patients remaining in the study at 4 years, infliximab was safe and effective but associated with a high patient discontinuation rate.
20128291 [Observation on the analgesic effect of heat-reinforcing needling manipulation for acute a 2009 Oct OBJECTIVE: To observe the analgesic effect of heat-reinforcing needling manipulation for acute inflammatory arthritis and its underlying mechanism in experimental rheumatoid arthritis rabbits. METHODS: A total of 60 rabbits were randomized into control (n=6), model (n=6), needle-twirling (n=24) and heat-reinforcing (n=24) groups, and the later 2 groups were further divided into 0 h, 0.5 h, 1 h and 2 h subgroups,with 6 cases in each. Rheumatoid arthritis model was established by injecting mixed solution of egg-albumin (4 mg/ml) and equal volume of complete Freund's adjuvant (CFA) into the subcutaneous tissue (6 points around the shoulder, 0.2 ml/point). Fourteen days later,the injection was repeated once again,and another 6 days later, egg-albumin (0.4 ml, 20 mg/ml) solution was injected into the bilateral knee-joints. "Zusanli" (ST 36) and "Hegu" (LI 4) were punctured and stimulated by needle-twirling or by heat-reinforcing needling technique for 1 min, with the needle retained for 30 min. The pain threshold of the paw was detected with K+ import stimulation method. beta-EP and PGE2 contents of the joint tissue were assayed with radioimmunoassay. RESULTS: Compared with model group, the pain threshold of needle-twirling group and heat-reinforcing group at each time-point increased significantly (P<0.01, P<0.05). Compared with needle-twirling group, the pain threshold of heat-reinforcing group at 0.5 h, 1 h and 2 h subgroups increased significantly (P<0.05, P<0.01). Both beta-EP and PGE2 contents of model group were significantly higher than those of control group (P<0.01, P<0.05). In comparison with model group, beta-EP contents of needle-twirling group and heat-reinforcing group at each time-point increased significantly (P<0.01, P<0.05), and PGE2 contents of needle-twirling group and heat-reinforcing group at each time-point decreased significantly (P<0.01, P<0.05). The beta-EP content of heat-reinforcing group was significantly higher than that of needle-twirling group at 2 h (P<0.05), while PGE2 content of the former group was significantly lower than that of needle-twirling group at 0 h (P<0.01). CONCLUSION: Both needle-twirling and heat-reinforcing needling can effectively raise the pain threshold in acute arthritis rabbits, which my be closely associated with their effects in upregulating beta-EP content and lowering PGE2 level in the local joint tissue. The analgesic effect of heat-reinforcing needling manipulation is superior to that of needle-twirling.
20049449 Evaluation of inflammatory change and bone erosion using a murine type II collagen-induced 2011 May The exact mechanism of rheumatoid arthritis (RA) is unclear, but a combination of genetic, environmental and hormonal factors is thought to be involved. This study examined the progressive arthritic reaction of murine type II collagen-induced arthritis (CIA), a representative animal model of RA. Arthritic reactions, including inflammation and bone erosion were examined using an objective non-invasive method. Two scoring systems were used to evaluate changes in cutaneous inflammation and bone erosion during RA progression. The severity of inflammation was evaluated by visual scoring of erythema and edema, while the degree of bone erosion was quantified by macroradiographical erosion analysis of specific bones. A significant difference was observed in both visual (P = 0.0001, n = 7) and radiographic (P < 0.0001, n = 7) examinations for the RA group as compared to the control. The relationship between inflammatory change and erosive change in bone showed a significant positive correlation, r = 0.9550 (P < 0.0001, n = 7). The overall rate of asymmetry was 25.23% in both fore- and hindpaws. The results generated from these experiments show that murine CIA is a promising model for elucidating the mechanism of RA. In addition, the results of this study may be used for monitoring RA progression as well as screening therapy efficacy in the joint pathology.
19819350 Factors influencing polyautoimmunity in systemic lupus erythematosus. 2010 Feb OBJECTIVE: Since characterization of the extent to which particular combinations of autoimmune diseases (ADs) occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms, polyautoimmunity (i.e., ADs co-occurring within patients) in systemic lupus erythematosus (SLE) and its associated factors were investigated. METHODS: This was a cross-sectional study in which 335 consecutive patients with SLE and the history of 22 ADs were investigated. A multivariate analysis was performed. A systematic literature review was done and results were grouped by hierarchical cluster procedure analysis. RESULTS: There were 136 (41%) SLE patients presenting with at least one other AD. A total of 191 ADs were observed, of which the most frequent were autoimmune thyroid disease (AITD), antiphospholipid syndrome (APS) and Sjögren's syndrome (SS), registered in 60 (18%), 48 (14%) and 47 (14%) cases, respectively. Out of a total number of 1515 SLE patients with polyautoimmunity (1379 reported previously and 136 informed here) there were 77 (5.1%) cases with multiple autoimmune syndrome (i.e., two or more ADs in addition to SLE). Female gender, articular involvement, familial autoimmunity, anti-Ro positivity and patient's origin were risk factors for polyautoimmunity while the presence of anti-RNP antibodies was protective. Four clusters of ADs were found. The most hierarchical one was composed of AITD, APS, SS, and systemic sclerosis. CONCLUSION: Polyautoimmunity is frequent in SLE, and it is influenced by clinical and immunological features. These findings support that clinically different autoimmune phenotypes might share common susceptibility variants.
19758218 Rituximab therapy in primary Sjögren's syndrome. 2009 Sep Primary Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of glandular tissues leading to sicca symptoms, namely, dry eyes and dry mouth. In the majority of cases, the disease course is benign, albeit with considerable patient discomfort. Some patients, however, have systemic symptoms with arthritis, cutaneous vasculitis, low complement levels, and cryoglobulinemia. A small but not insignificant percentage of those patients evolve to B cell lymphoma. The increased expression of B cell survival factors, such as B cell activating factor, may promote the perpetuation of a B cell clone and precede the lymphoproliferative disease. Rituximab, a chimeric monoclonal antibody to CD20, leads to B cell depletion and may have a role in Sjögren systemic manifestations as well as in preventing and treating Sjögren-associated lymphoma.
21188195 Rituximab administration and reactivation of HBV. 2010 Rituximab is a drug used for the treatment of B-cell non-Hodgkin's lymphoma, and its range of use has expanded to the treatment of collagen diseases such as idiopathic thrombocytopenic purpura and rheumatoid arthritis. One serious complication of rituximab use is the reactivation of dormant hepatitis B virus, and prevention of this phenomenon has become an urgent issue. This paper provides a general outline of the problem through an analysis of patient cases that we and other groups have experienced to date.
21103262 Anti-TNF-Alpha-Induced Psoriasis - An Unusual Paradox. 2009 Nov 21 Anti-TNF-α agents are currently utilised for the treatment of a vast array of autoimmune conditions including inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis and psoriasis. It is however noted that such therapeutic strategies have been linked to the specific induction of cutaneous-based reactions such as dermatitis, erythema multiforme and psoriasis. Here we present the case of a young female patient with Crohn's disease who developed psoriasis following treatment with the anti-TNF-α drug adalimumab and highlight the possible pathogenetic mechanisms involved in such an occurrence.
20182422 Interleukin-6 as a therapeutic target in candidate inflammatory diseases. 2010 Apr Interleukin (IL)-6 is a multifunctional cytokine that regulates immune response, inflammation, and hematopoiesis. Although IL-6 plays several important physiological roles, deregulated overproduction of IL-6 causes various clinical symptoms and abnormalities in laboratory test results. Overproduction of IL-6 has been shown to underlie a number of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA), systemic-onset juvenile idiopathic arthritis (soJIA), and Castleman's disease, as well as malignancies such as multiple myeloma and mesothelioma. Blocking of IL-6 signaling may be therapeutic in diseases characterized by pathological IL-6 overproduction. This review provides an overview of IL-6 as a therapeutic target in candidate inflammatory diseases.
19434075 Endothelial progenitor cell dysfunction in rheumatic disease. 2009 Jun Rheumatic disease is characterized by inflammation and endothelial dysfunction, which contribute to accelerated atherosclerosis. Circulating endothelial progenitor cells (EPCs) can restore dysfunctional endothelium and thereby protect against atherosclerotic vascular disease. The number and function of EPCs are, however, affected in rheumatic diseases such as psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and antineutrophil cytoplasmic autoantibody-associated vasculitis. rheumatic disease is often characterized by decreased numbers, and impaired function, of EPCs, although numbers of these cells might increase during the initial years of systemic sclerosis. Pioneering studies show that EPC dysfunction might be improved with pharmacological treatment. How best to restore EPC function, and whether achieving this aim can prevent long-term cardiovascular complications in rheumatic disease, remain to be established.
20457280 The birthday of a new syndrome: IgG4-related diseases constitute a clinical entity. 2010 Jul IgG4-related disease is a distinct clinical entity, whose characteristic features are the following; Serum IgG4 is prominently elevated, IgG4-positive plasma cells infiltrate in involved tissues, various mass-forming lesions with fibrosis develop in a timely and spatial manner and the response to corticosteroids is prompt and good. IgG4-related diseases mainly target two organs. One is the pancreas (autoimmune pancreatitis; AIP), and the other comprises the lacrimal and salivary glands, the clinical phenotype is Mikulicz's disease (MD). MD has long been considered a manifestation of Sjögren's syndrome (SS). However, we noticed several clinical differences in case of MD from SS; no deflection of female sex differences, mild sicca syndrome, good response to corticosteroids, no positivity of anti-SS-A/SS-B antibodies. In addition, elevated level of serum IgG4 and abundant infiltration of plasma cells expressing IgG4 were reported in MD patients. Those are common features of IgG4-related diseases. MD often coexisted with IgG4-related diseases such as AIP, retroperitoneal fibrosis, and IgG4-associated nephropathy. Based on those findings, it has been considered to recognize IgG4-related diseases including MD as a new clinical entity. The etiology of IgG4-related systemic diseases remains to be elucidated. It is necessary to accumulate and analyze larger data from patients worldwide.
20436071 IgG4-related diseases including Mikulicz's disease and sclerosing pancreatitis: diagnostic 2010 Jul Since the first report of serum IgG4 elevation in sclerosing pancreatitis in 2001, various systemic disorders have been reported to elevate IgG4, and many names have been proposed from the perspective of the systemic condition. Despite similarities in the organs damaged in IgG4-related Mikulicz's disease and Sjögren's syndrome, there are marked clinical and pathological differences between the 2 entities. The majority of cases diagnosed with autoimmune pancreatitis in Japan are IgG4-related sclerosing pancreatitis, and it should be recognized that this is distinct from the Western type. Diagnosis of IgG4-related disease is defined by both elevated serum IgG4 (> 1.35 g/l) and histopathological features, including lymphocyte and IgG4+ plasma cell infiltration (IgG4+ plasma cells/IgG+ plasma cells > 50% on a highly magnified slide checked at 5 points). Differential diagnosis from other distinct disorders is necessary: these include sarcoidosis, Castleman's disease, Wegener's granulomatosis, lymphoma, cancer, and other existing conditions. The Japanese IgG4 research group has begun multicenter prospective studies to improve diagnostic criteria and treatment strategies.
19155635 Development of a novel transgenic rat overexpressing the P2Y(2) nucleotide receptor using 2009 The G protein-coupled P2Y(2) nucleotide receptor (P2Y(2)R) is upregulated in response to stress and tissue injury and has been postulated to play a role in chronic inflammation seen in atherosclerosis, Alzheimer's disease and Sjogren's syndrome. The role of P2Y(2)R upregulation in vivo is poorly understood, in part due to the lack of a P2Y(2)R overexpressing animal model. The P2Y(2)R overexpressing transgenic rat was generated using a lentiviral vector. Rats overexpressing P2Y(2)R showed a significant increase in P2Y(2)R mRNA levels in all tissues screened as compared to nontransgenic rats. Fura 2 imaging of smooth muscle cells (SMCs) isolated from aorta indicated that the percentage of cells exhibiting increases in the intracellular free calcium concentration in response to P2Y(2)R agonists was significantly greater in freshly isolated SMCs from transgenic rats than wild-type controls. Histopathological examination of tissues revealed that P2Y(2)R overexpressing rats develop lymphocytic infiltration in lacrimal glands and kidneys as early as at 3 months of age. These rats show similarities to patients with Sjogren's syndrome who display lymphocyte-mediated tissue damage. This transgenic rat model of P2Y(2)R overexpression may prove useful for linking P2Y(2)R upregulation with chronic inflammatory diseases, neurodegenerative diseases and Sjogren's syndrome.
19458906 Extreme efficacy of intravenous immunoglobulin therapy for severe burning pain in a patien 2009 Neurological involvement occurs in approximately 20% of patients with primary Sjögren's syndrome. Although neurological symptoms can affect the peripheral nervous system and the central nervous system, the most frequent symptom is polyneuropathy. Small fiber neuropathy (SFN) is a form of painful peripheral polyneuropathy that is common in patients with diabetic neuropathy, but may also occur in toxic, infectious, or immune-mediated neuropathy. We show here a patient with Sjögren's syndrome who developed SFN and was treated with intravenous immunoglobulin (IVIG) therapy, which was immediately and extremely effective. Because of the efficacy of IVIG therapy, we propose that direct immune-mediated mechanisms may be involved in the pathogenesis of SFN complicated by Sjögren's syndrome.
19156421 Methotrexate treatment ameliorated testicular suppression and anorexia related leptin redu 2009 Aug Methotrexate (MTX) has been frequently used in the treatment of rheumatoid arthritis (RA). However, its action on arthritis associated male hypogonadism, or anorexia related low leptin production has not yet been studied. The well-established model of human RA is rat adjuvant-induced arthritis (AA). In the present series we aimed at the evaluation of the effects of MTX on AA induced inflammatory parameters, testosterone suppression, and anorexia associated lowered leptin release. AA was induced in male Lewis rats by intradermal injection of heat killed Mycobacterium butyricum in incomplete Freund's adjuvant in the base of the tail. Arthritic rats were treated with two doses of MTX: 0.3 and 0.5 mg/kg twice a week orally for the period of 28 days. The evaluated parameters were body mass, hind-paw swelling, arthrogram scores, serum albumin, total testosterone and leptin on days 14, 21 and 28 of AA. MTX treatment ameliorated all parameters studied dose dependently. Higher dose of MTX induced a significant reduction in the hind-paw swelling, arthritic score, and an increase in serum albumin in all examined time intervals of AA. This dose also significantly improved the suppressed testosterone and leptin levels found in arthritic rats. Prophylactic MTX treatment of rats with AA improved all inflammatory and arthritic parameters studied indicating its clear anti-inflammatory effects. The significant improvement of testosterone and leptin shows beneficial effects of MTX on reproduction and anorexia related leptin reduction during chronic AA.