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ID PMID Title PublicationDate abstract
18360651 Infliximab (Remicade) in the treatment of psoriatic arthritis. 2006 Dec Elucidation of the cellular immunopathology and cytokine profile of psoriatic arthritis (PsA), a chronic inflammatory disease associated with psoriasis, has resulted in the development of a number of novel biologic therapies. Among these biologics, tumor necrosis factor-alpha (TNF-alpha) inhibitors have been used successfully to treat patients suffering from rheumatoid arthritis or psoriasis. The pivotal role of TNF-alpha in the pathogenesis and progression of PsA suggested that anti-TNF-alpha agents could be effective in controlling PsA. The results from two large, randomized, double-blind, placebo-controlled trials in patients with moderate to severe PsA indicated that the anti-TNF-inhibitor, infliximab, can control both the joint and skin manifestations of the disease. This review focuses on the clinical development of infliximab as a treatment for PsA. The development of other anti-TNF-alpha biologics is also discussed.
27157079 PET Imaging of Arthritis. 2006 Apr Fluorodeoxyglucose (FDG) PET imaging of arthritis is still in its infancy. Neither the optimal methodology nor the real clinical value is known at this time. Nevertheless, initial results are highly encouraging and the feasibility of the technique is demonstrated. PET findings are correlated with results obtained with state-of-the-art MRI and ultrasonography as well as with established clinical assessment of rheumatoid arthritis. There are indications that FDG-PET may provide unique information regarding the prognosis and early response to treatment. The mechanism of FDG uptake in the diseased joints has to be clarified further, but the available data indicate that it is well suited for imaging inflammatory joint disorders and, possibly, osteoarthritis. What lies ahead is the important work of clinical validation to verify the diagnostic and prognostic accuracy before envisioning a clinical role in routine practice.
18396348 Pustulosis acuta generalisata with joint involvement in an HLA-A2- and HLA-B35-positive pa 2008 Jun Pustulosis acuta generalisata (PAG) is a rare poststreptococcal disease of the skin, which has been reported in children and adults after streptococcal throat infection. Herein, we report on the case of a 47-year-old woman with typical clinical and histologic findings of PAG emerging after a pharyngeal infection in whom inflammatory joint-involvement developed. The patient was found to be HLA-A2 and HLA-B35 positive. Whereas HLA-B35 might be associated with pustular skin diseases, HLA-A2 is a risk factor for the development of rheumatoid arthritis.
17947698 Exacerbation of antigen-induced arthritis in IFN-gamma-deficient mice as a result of unres 2007 Nov 1 Proinflammatory Th1 responses are believed to be involved in the induction and perpetuation of rheumatoid arthritis. However, the role of IFN-gamma, the major cytokine produced by Th1 cells, is still incompletely defined. In the present study, we investigated the effects of IFN-gamma deficiency (IFN-gamma(-/-)) on the course of experimental murine Ag-induced arthritis (AIA). In the acute stage of disease, IFN-gamma(-/-) AIA mice showed significantly increased inflammatory responses compared with wild-type C57BL/6 AIA mice, i.e., exacerbated joint swelling, increased delayed-type hypersensitivity reaction, and increased histopathological scores of arthritis. Intraarticular administration of exogenous IFN-gamma at induction of AIA significantly suppressed these acute aggravation effects. Stimulated cells isolated from lymph nodes and spleen of IFN-gamma(-/-) AIA mice showed increased production of IL-2, IL-4, IL-5, IL-6, but most prominently of IL-17. These elevations were paralleled by decreased humoral immune responses, with low serum levels of total and Ag-specific IgG (IgG1, IgG2a(b), IgG2b, IgG3). At immunohistology, the knee joints of IFN-gamma(-/-) AIA mice showed massive neutrophil granulocyte infiltration. Treatment with mAbs neutralizing IL-17 diminished the acute inflammation. In vitro, Th cell expansion and production of IL-17 upon restimulation were effectively and dose dependently inhibited by IFN-gamma. These results clearly demonstrate that IFN-gamma has anti-inflammatory properties during the initial phase of AIA, and indicate that IFN-gamma deficiency exerts disease-promoting effects, preferentially via IL-17-modulated pathways.
17131799 [Polymyalgia rheumatica]. 2006 Sep 17 Polymyalgia rheumatica is a disorder that affects people over 50 years of age. The etiology of the disease has not been hitherto clarified exactly. Its incidence among people over 50 is in the range of 0.1-0.5%. The incidence rate peaks in the age group of 60-70 years. It is also found in younger people, but far less frequently. The diagnosis is based primarily on locomotor complains--namely on pronounced pain, morning stiffness of the shoulder girdle, pelvic girdle and neck. Complaints relating to the arms and legs (such as muscular weakness, oedema, tendonitis etc.) are also observed, however, in one third of the cases. The diagnostic criteria are defined empirically. Polymyalgia rheumatica was formerly considered to be a form of elderly onset rheumatoid arthritis. The progressive erosion process is absent in the case of polymyalgia rheumatica unlike in the case of rheumatoid arthritis. Numerous factors are known, which point to a link between polymyalgia rheumatica and giant cell vasculitis, arthritis, but the precise nature of this relationship remains unknown. Both conditions affect the same age group in the general population and they are even found--not infrequently--in the same patient. Polymyalgia rheumatica can be found in 40% of the patients suffering from arthritis while the histological examination detected mild vasculitis in approximately 10% of the patients suffering for "isolated" polymyalgia rheumatica. The response to be given to the acute phase is similar in both disorders. Scandinavian authors consider polymyalgia rheumatica as the appearance of generalised arthritis. Arthroscopic, nuclear magnetic resonance imaging as well as isotopic studies show unequivocally, that in the background of the osteo-muscular symptoms, complaints, inflammation is to be found partly of the joints but primarily that of the periarticular synovial structures. The above mentioned--dominant--proximal symptoms can often mask the distal locomotor disorders (pitting oedema of the hands and feet, tendonitis, tendosynovitis, carpal tunnel syndrome). The disorder may be accompanied by atypical generalised symptoms (loss of appetite, weight loss, fever, fatigue). An excellent indicators of the acute phase reactions are erythrocyte sedimentation rate, C-reactive protein and interleukin-6. These are suitable for monitoring the effectiveness of the therapy, for indicating a relapse/recurrence. It should be noted, that polymyalgia rheumatica may also be present if the erythrocyte sedimentation rate and C-reactive protein values are low. This disorder is also characterised by fast and effective response to corticosteroid, which should be administered for 1-2 years. In some individual cases a different dosage regime may be necessary: steroid administered in low dosage over a longer period of time. Administration of methotrexate and anti-tumor necrotic factor-alpha may also be considered as alternative or adjuvant therapy for lowering the quantity of corticosteroid. Further multicenter, double blind studies should, however, be performed on large number of patients in this regard.
18315965 Short-term results of our first 49 Scandanavian total ankle replacements (STAR). 2008 Feb BACKGROUND: Forty-seven consecutive patients treated for ankle arthritis with a Scandinavian total ankle replacement (STAR) by one surgeon were investigated retrospectively. MATERIALS AND METHODS: A modification of the Foot Function Index (FFI), which scores pain and task difficulties, was followed prospectively. Patients were assessed clinically and radiologically. Failure was defined as revision of the prosthesis or arthrodesis for any reason. RESULTS: In 47 patients (16 male, 31 female) 49 total ankle replacements were carried out between May 1999 and June 2004. Indication for surgery was end stage arthritis for rheumatoid arthritis in 29 cases, post-traumatic arthritis in 12, osteoarthritis in five and arthritis secondary to degenerative flatfoot in three. Mean followup time was 28 (12 to 67) months. The modified FFI (range, 0 to 100, a high score meaning more pain and disability) improved significantly from 59 before to 35 after surgery. The mean postoperative Kofoed ankle score was 68. Sixteen procedures were complicated by fractures or temporary neurological damage. At the time of followup, 45 prostheses survived, while four replacements had failed. Radiological examination at followup showed radiolucent lines, osteolysis, and malposition of the components in 31 cases. CONCLUSION: Our results are comparable with those reported in the literature. The clinical outcome improved significantly. Due to aseptic and septic loosening, 8.2% of the prosthesis failed.
16228217 Incidence and outcomes of uveitis in juvenile rheumatoid arthritis, a synthesis of the lit 2006 Mar BACKGROUND: Juvenile rheumatoid arthritis (JRA) is the most common systemic cause of pediatric uveitis in Europe and North America. Uveitis is commonly perceived as a frequent sequela of JRA and JRA-associated uveitis is commonly considered to have a complicated course with frequent adverse visual outcomes. METHODS: We performed a systematic literature search for series of consecutive patients with JRA (as defined by the American College of Rheumatology criteria) reporting on the frequency of uveitis and/or complications of uveitis, published between January 1980 and December 2004. The main outcome measures were: the cumulative incidence of uveitis in JRA, the cumulative incidence of adverse visual outcome and that of complications in JRA-associated uveitis. Additionally, the influence of gender, presence of antinuclear antibody (ANA) and disease onset subtype to the likelihood of developing uveitis were examined. RESULTS: Analysis of pooled data from the 26 eligible series suggested a cumulative incidence of uveitis in JRA of 8.3% [95% confidence intervals (CI), 7.5-9.1%]. The cumulative incidence of uveitis varied according to geographic location, being highest in Scandinavia, then the US, then Asia and lowest in India. JRA-associated uveitis was more common in pauciarticular than polyarticular onset patients [odds ratio (OR) = 3.2, 95% CI, 2.33-4.36] and in ANA-positive than ANA-negative patients (OR = 3.18, 95% CI, 2.22-4.54). Female gender was only a weak risk factor for the development of uveitis in JRA patients (OR = 1.69, 95% CI 1.09-2.62) and was not statistically significant after considering disease onset subtypes. In JRA-associated uveitis the cumulative incidence of cumulative incidence of adverse outcome (visual acuity < 20/40 OU) was 9.2% (95% CI: 4.7-15.8) of cataracts 20.5% (95% CI: 15.5-26.3), of glaucoma 18.9% (95% CI: 14.4-24.2) and of band keratopathy 15.7% (95% CI: 10.9-21.7). CONCLUSION: The cumulative incidence of uveitis in JRA varies according to geographic location, presence of ANA, type of JRA onset and gender. Uveitis, adverse visual outcome, and complications in JRA are less frequent than commonly accepted.
18332018 Two to five year follow-up of the LPM ceramic coated proximal interphalangeal joint arthro 2008 Feb This paper presents a retrospective series of 20 LPM semi-constrained ceramic coated cobalt chrome proximal interphalangeal joint arthroplasties performed consecutively in 12 patients for arthritis of the proximal interphalangeal joint by a single surgeon between 2000 and 2004. Eleven were performed for osteoarthritis, four for post-traumatic arthritis and five for rheumatoid arthritis. Although 12 joints had an improvement in pain and an increased functional arc of movement, six joints required revision surgery for implant failure at an average of 19 months, with clinical signs of increasing pain, deteriorating motion and radiological signs of implant loosening and subsidence. This rate of revision is higher than in published series for other PIP joint implants and, therefore, close surveillance of all patients with this prosthesis currently in situ is recommended. Use of the prosthesis has ceased in this unit.
19132146 [Magnetic resonance imaging of the joints: a revolution for the practicing rheumatologist] 2008 Oct In the last 15 years, new imaging techniques have changed the life of practicing rheumatologists in terms of both diagnostic approach and knowledge of disease mechanisms. Clinical symptoms, disease signs and the results of physical examination have been more closely related to their anatomical basis. In particular, magnetic resonance imaging allow diagnosis of disease in its early phase and its follow-up with a previously unknown sensitivity. Novel imaging studies have contributed to elucidate several pathogenetic mechanisms in musculoskeletal diseases, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polymyalgia rheumatica and osteoarthritis; allow evaluation of the real degree of joint inflammation, which is often uncoupled from clinical signs; and possibly reduce the need for large clinical trials. In conclusion, new imaging techniques and refinements of the established techniques have opened exciting perspectives in our understanding and treatment of many rheumatic diseases. Much attention should be paid to the training of new generations of rheumatologists in this field.
19062578 [Paraoxonase: biological activity and clinical implications]. 2008 The involvement of paraoxonase family in antiathrogenesis has recently attracted attention of many researchers to these enzymes. Type 1 paraoxonase (PON 1) is a Ca-dependent hydrolase with a broad spectrum of substrate specificity. It is tightly bound to plasma high density lipoproteins (HDLP) and exhibits antioxidative and antiatherogenic activities. This review analyses publications concerning the structure, biological activity, and clinical significance ofparaoxonases, in the first place PON 1. Consideration of genetic and regulatory aspects of PON 1 is important for better understanding clinical and prognostic implications of this enzyme. These data are supplemented by the results of original observations of 60 patients with systemic lupus erythematosus and 20 with rheumatoid arthritis admitted to the Institute of Rheumatology. They confirm the published reports indicating reduced activity of this enzyme in patients compared with healthy donors.
16652429 Clinical significance of decreased serum concentration of cartilage oligomeric matrix prot 2006 May OBJECTIVE: Serum cartilage oligomeric matrix protein (COMP) concentration is elevated in patients with early osteoarthritis and early rheumatoid arthritis, and may be a biomarker of cartilage turnover. We investigated whether serum COMP concentration could be a clinically significant marker of arthritis and/or growth impairment in juvenile idiopathic arthritis (JIA). METHODS: Specimens were collected from 82 healthy blood donors under 22 years of age with no growth impairment who served as healthy controls, and from 24 patients with JIA (6 with oligoarthritis, 10 with polyarthritis, 8 with systemic JIA) presenting with active arthritis. Serum COMP concentration was determined using a human COMP assay kit. RESULTS: Serum COMP concentrations were significantly higher in all controls less than 16 years of age than in all controls aged 16 years or older. There was a significant negative correlation between serum COMP concentration and serum C-reactive protein in patients with JIA. Serum COMP concentrations in patients with systemic JIA were significantly lower than those in controls. CONCLUSION: Serum COMP concentrations in healthy children reflected increased cartilage turnover in the growth phase. Because the serum COMP concentration was decreased in cases of systemic JIA in which growth impairment was pronounced, the systemic inflammation occurring in systemic JIA may have an effect on cartilage turnover, which plays an important role in growth. Serum COMP concentration may prove to be a marker that indicates growth impairment in systemic JIA.
18822923 [Progress on study of clinical application of xinhuang tablet on orthopedic diseases]. 2008 Jul By retrieval of medical periodicals published in the recent 23 years, 155 papers concerning Xinhuang Tablet were searched, among them 28 were dealing with its clinical application in orthopedics disease, involving gouty arthritis, soft tissue injury, osteoarthritis, ankylosing spondylosis, rheumatoid arthritis, etc. Besides the traditional oral administration mode, Xinhuang Tablet may be used externally for local absorption through transcutaneous manner by mixing with some adjuvant as honey, vinegar, wine, and egg white.
18495794 Complement deficiency and disease. 2008 Sep There are approximately 30 serum complement proteins (15% of the globulin fraction), excluding cell surface receptors, and regulatory proteins. Many are manufactured in the liver, and reduced complement is a feature of severe liver failure. Complement proteins contribute to the acute phase response, and high levels are seen in chronic untreated inflammation (eg, rheumatoid arthritis). Once activated, complement is strongly pro-inflammatory. Indeed, almost half of the complement system proteins/receptors play regulatory roles, reflecting the importance of controlling inappropriate activation. This review focuses on disease states arising as a direct consequence of complement deficiency or dysfunction.
16485060 Etanercept for the treatment of psoriasis. 2006 Feb Etanercept has recently been approved for the treatment of moderate-to-severe plaque psoriasis at a dose of 50mg twice per week for 12 weeks followed by a maintenance dose of 50mg once weekly thereafter. Clinical studies have shown excellent efficacy and a good safety profile in patients with psoriasis. Extensive information on etanercept safety is available as this biological agent has been used for many years for other indications such as rheumatoid arthritis, and psoriatic arthritis.
17016504 Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks 2006 Nov BACKGROUND AND PURPOSE: The chemokine receptor CCR1 is a potential target for the treatment of rheumatoid arthritis. To explore the impact of CCR1 blockade in experimental arthritis and the underlying mechanisms, we used J-113863, a non-peptide antagonist of the mouse receptor. EXPERIMENTAL APPROACH: Compound J-113863 was tested in collagen-induced arthritis (CIA) and three models of acute inflammation; Staphylococcus enterotoxin B (SEB)-induced interleukin-2 (IL-2), delayed-type hypersensitivity (DTH) response, and lipopolysaccharide (LPS)-induced tumour necrosis factoralpha (TNFalpha) production. In the LPS model, CCR1 knockout, adrenalectomised, or IL-10-depleted mice were also used. Production of TNFalpha by mouse macrophages and human synovial membrane samples in vitro were also studied. KEY RESULTS: Treatment of arthritic mice with J-113863 improved paw inflammation and joint damage, and dramatically decreased cell infiltration into joints. The compound did not inhibit IL-2 or DTH, but reduced plasma TNFalpha levels in LPS-treated mice. Surprisingly, CCR1 knockout mice produced more TNFalpha than controls in response to LPS, and J-113863 decreased TNFalpha also in CCR1 null mice, indicating that its effect was unrelated to CCR1. Adrenalectomy or neutralisation of IL-10 did not prevent inhibition of TNFalpha production by J-113863. The compound did not inhibit mouse TNFalpha in vitro, but did induce a trend towards increased TNFalpha release in cells from synovial membranes of rheumatoid arthritis patients. CONCLUSIONS AND IMPLICATIONS: CCR1 blockade improves the development of CIA, probably via inhibition of inflammatory cell recruitment. However, results from both CCR1-deficient mice and human synovial membranes suggest that, in some experimental settings, blocking CCR1 could enhance TNF production.
17393408 Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in anim 2007 Apr OBJECTIVE: Interleukin-21 (IL-21) is a T cell-derived cytokine that modulates T cell, B cell, and natural killer cell responses. In this study, the effects of blocking IL-21 were examined in 2 rodent models of rheumatoid arthritis (RA) to determine whether IL-21 contributes to their pathologic processes. METHODS: DBA/1 mice were immunized with bovine type II collagen and then treated with murine IL-21 receptor Fc fusion protein (IL-21R.Fc), which was initiated after the onset of arthritis symptoms in 10% of the cohort. The mice were assessed 3 times per week for signs of disease, including histologic features as well as serum cytokine, Ig, and cytokine messenger RNA (mRNA) levels in the paws. In a separate experiment, Lewis rats were immunized with Freund's complete adjuvant followed by administration of IL-21R.Fc at the peak of inflammation in the joints. Rats were assessed daily for histologic features and for scoring of arthritis severity. In addition, the effects of IL-21R.Fc on the production of interferon-gamma (IFNgamma) by T cells were examined. RESULTS: Treatment of DBA/1 mice with IL-21R.Fc reduced the clinical and histologic signs of collagen-induced arthritis. Nonspecific IgG1 levels were decreased in response to treatment. The levels of IL-6 mRNA in the paws and the serum IL-6 levels were decreased after treatment with IL-21R.Fc. IFNgamma mRNA levels were increased in the paws, and the addition of IL-21R.Fc to collagen-activated lymph node cultures enhanced the levels of IFNgamma. Collagen-specific spleen cell responses in IL-21R.Fc-treated mice were observed as reduced levels of IFNgamma and increased levels of IL-6. Treatment of Lewis rats with IL-21R.Fc after induction of adjuvant-induced arthritis resulted in reversal of disease signs and improvements in histologic parameters. CONCLUSION: These findings demonstrate a pathogenic role for IL-21 in animal models of RA, and support consideration of IL-21 as a therapeutic target in human RA.
17007638 CD97 neutralisation increases resistance to collagen-induced arthritis in mice. 2006 Synovial tissue of rheumatoid arthritis (RA) patients is characterised by an influx and retention of CD97-positive inflammatory cells. The ligands of CD97, CD55, chondroitin sulfate B, and alpha5beta1 (very late antigen [VLA]-5) are expressed abundantly in the synovial tissue predominantly on fibroblast-like synoviocytes, endothelium, and extracellular matrix. Based upon this expression pattern, we hypothesise CD97 expression to result in accumulation of inflammatory cells in the synovial tissue of RA patients. To determine the therapeutic effect of blocking CD97 in an animal model of RA, collagen-induced arthritis was induced in a total of 124 DBA/J1 mice. Treatment was started on day 21 (early disease) or on day 35 (longstanding disease) with the blocking hamster anti-mouse CD97 monoclonal antibody (mAb) 1B2, control hamster immunoglobulin, or NaCl, applied intraperitoneally three times a week. The paws were evaluated for clinical signs of arthritis and, in addition, examined by radiological and histological analysis. Mice receiving 0.5 mg CD97 mAb starting from day 21 had significantly less arthritis activity and hind paw swelling. Furthermore, joint damage and inflammation were reduced and granulocyte infiltration was decreased. When treatment was started on day 35, CD97 mAb treatment had similar effects, albeit less pronounced. The results support the notion that CD97 contributes to synovial inflammation and joint destruction in arthritis.
18946481 A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 di 2009 Mar Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider spectrum of autoimmune diseases. Investigating large patient cohorts from six different autoimmune diseases, that is autoimmune Addison's disease (n=333), type 1 diabetes (n=1086), multiple sclerosis (n=502), rheumatoid arthritis (n=945), systemic lupus erythematosus (n=156) and juvenile idiopathic arthritis (n=505), against 3273 healthy controls, we analyzed four single nucleotide polymorphisms (SNPs) in NALP1. The major allele of the coding SNP rs12150220 revealed significant association with autoimmune Addison's disease compared with controls (OR=1.25, 95% CI: 1.06-1.49, P=0.007), and with type 1 diabetes (OR=1.15, 95% CI: 1.04-1.27, P=0.005). Trends toward the same associations were seen in rheumatoid arthritis, systemic lupus erythematosus and, although less obvious, multiple sclerosis. Patients with juvenile idiopathic arthritis did not show association with NALP1 gene variants. The results indicate that NALP1 and the innate immune system may be implicated in the pathogenesis of many autoimmune disorders, particularly organ-specific autoimmune diseases.
18214362 [Biological therapy of inflammatory diseases]. 2007 The pathophysiology and the treatment of diseases with clinical presentation so different as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and psoriasis vulgaris have been revolutionized by the discovery of common pro-inflammatory effector mechanisms involving TNF-alpha and by the use of targeted therapies, the anti-TNF-alpha antibodies. In the past 10 years, our experience has helped several hundreds of patients who were treated with novel drugs, years before they became routinely available. In parallel tools of metrology were developped that can now be applied to the routine patient. Lastly, clinical research on these new drugs has also generated derived research works allowing the university hospital to satisfactorilly fullfil its specific missions.
18341701 Comparing the prevalence of rheumatic diseases in China with the rest of the world. 2008 Geographic or ethnic differences in the occurrence of disease often provide insights into causes of disease and possible opportunities for disease prevention. Persons in China appear to have a consistently lower prevalence of rheumatoid arthritis and fibromyalgia than persons in the United States and Europe; reasons for these prevalence differences might include genetic differences, differences in environmental exposures or a combination of both. With increasing obesity, gout is becoming endemic in China. Finally, symptomatic knee osteoarthritis is extremely common in China and constitutes a major public health problem there.