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ID PMID Title PublicationDate abstract
15971417 Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective stu 2005 May OBJECTIVE: To determine the diagnostic value of serum and synovial procalcitonin (PCT) for bacterial arthritis and to determine the cellular origin of synovial PCT. METHODS: A prospective study enrolled 42 patients with acute arthritis including 11 bacterial arthritis, 18 rheumatoid arthritis and 13 crystal induced arthritis. Diagnostic values of serum and synovial PCT levels were determined by a immunoluminometric assay (Lumitest PCT) and compared to those of classical inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, synovial fluid cellularity and both serum and synovial IL-6 and TNF alpha). Using fibroblast-like synoviocyte (FLS) cultures derived from rheumatoid arthritis (n = 4) and osteo-arthritis (n = 3) synovium, with or without stimulation by lipopolysaccharid or recombinant streptococcal protein 1/II, we attempted to determine whether synovial cells could be a source of PCT. RESULTS: Serum PCT was the best parameter to distinguish patients with acute bacterial arthritis from patients with crystal induced arthritis or rheumatoid arthritis. In setting of an acute arthritis serum PCT (> 0.5 ng/mL) achieved 55% sensitivity and 94% specificity for the diagnosis of bacterial arthritis, while CRP (> 50 mg/L) had 100% sensitivity but poor specificity (40%). Serum PCT appeared to be higher in patients with septic arthritis resulting from "systemic infection" than in cases resulting from direct inoculation. Synovial PCT was not useful to discriminate between infectious and non infectious arthritis in clinical practice. PCT could not be detected at significant levels in the conditioned medium from fibroblast-like synoviocyte cultures. CONCLUSION: Serum PCT is a poorly sensitive but specific marker of bacterial arthritis. Use of serum PCT in association with CRP could nevertheless be useful in an emergency situation for the diagnosis of bacterial arthritis.
16378497 Antibody treatments of inflammatory arthritis. 2005 Inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis are extremely common in the community, with a prevalence of up to 5%, and they cause substantial morbidity. The development of anti-TNF agents for use initially in rheumatoid arthritis, and subsequently more broadly in inflammatory arthritis, represents the biggest advance in management of these conditions since the introduction of corticosteroid agents, and is a major vindication of public funded arthritis research. However, there are limitations of even these highly effective agents. A significant minority of patients with inflammatory arthritis do not respond to these anti-TNF agents, they are associated with substantial risk of toxicity, require parenteral administration, and are extremely expensive. New antibody treatments in development can be divided into anti-cytokine agents, cell-targeted therapies, co-stimulation inhibitors, and treatments aimed at preventing joint erosion consequent on inflammation. This review discusses the state of the art in the development of these agents for management of this common group of diseases.
16142737 Rituximab treatment in patients with primary Sjögren's syndrome: an open-label phase II s 2005 Sep OBJECTIVE: To investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sjögren's syndrome of short duration (early primary SS) and patients with primary SS and mucosa-associated lymphoid tissue (MALT)-type lymphoma (MALT/primary SS). METHODS: Fifteen patients with primary SS were included in this phase II trial. Inclusion criteria for the early primary SS group were B cell hyperactivity (IgG >15 gm/liter), presence of autoantibodies (IgM rheumatoid factor, anti-SSA/SSB), and short disease duration (<4 years). Inclusion criteria for the MALT/primary SS group were primary SS and an associated MALT-type lymphoma (Ann Arbor stage IE) localized in the parotid gland. Patients were treated with 4 infusions of rituximab (375 mg/m2) given weekly after pretreatment with prednisone (25 mg) and clemastine. Patients were evaluated, using immunologic, salivary/lacrimal function, and subjective parameters, at baseline and at 5 and 12 weeks after the first infusion. RESULTS: Significant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human anti-chimeric antibodies (HACAs) developed in 4 of 15 patients (27%), all with early primary SS. Three of these patients developed a serum sickness-like disorder. Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1. CONCLUSION: Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS. The high incidence of HACAs and associated side effects observed in this study needs further evaluation.
20569595 Minimally invasive atlanto-odontoid joint injection for involvement in rheumatoid arthriti 2006 Dec 15 This report shows that CT fluoroscopy guided anterior approach injections can be effectively utilized for inflammatory conditions affecting the atlanto-odontoid joint, and that steroid injections thus injected can provide pain relief lasting six months in properly selected patients. Patients with underlying rheumatoid arthritis demonstrating significant aggravation of neck pain with side to side (rotational) neck movements and refractory to medical therapy may be good candidates for the procedure.
17121486 Psoriatic arthritis update. 2006 Psoriatic arthritis is an inflammatory arthritis occurring in up to 30% of patients with psoriasis. Its clear distinction from rheumatoid arthritis has been described clinically, genetically, and immunohistologically. Updated classification criteria have been recently derived from a large international study. Key pathophysiologic cellular processes are being elucidated, increasing our understanding of potential targets of therapy. Therapies that target cells, such as activated T cells, and proinflammatory cytokines, such as tumor necrosis factor alpha (TNFalpha), are rational to pursue. Outcome measures have been "borrowed" from rheumatoid arthritis and psoriasis studies. A variety of domains are assessed including joints, skin, enthesium, dactylitis, spine, function, quality of life, and imaging assessment of disease activity and damage. The performance qualities of outcome measures in these various domains is being evaluated by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), and improved measures are being developed and validated specifically for psoriatic arthritis. Traditional therapies for psoriatic arthritis have included nonsteroidal anti-inflammatory agents, oral immunomodulatory drugs, topical creams, and light therapy. These therapies have been helpful in controlling both musculoskeletal and dermatologic aspects of the disease, but they may not be fully effective in all disease domains, may eventually show diminished benefit, and may produce treatment-limiting toxicities. In the past several years, use of biologic agents has generally yielded greater benefit across more domains, yielding significant and enduring benefits for clinical manifestations, function, and quality of life, and especially with the anti-TNF agents, inhibition of structural damage. Adverse effects with these agents can be significant but are usually manageable. Cost is also significant, but cost-effectiveness analysis is demonstrating reasonable trade-off between cost and benefit.
16787214 A review of current knowledge of the complement system and the therapeutic opportunities i 2006 The complement activation system, a key component of the innate immune system, protects the host from microorganisms such as bacteria, and other foreign threats including abnormal cells. However, it is also double-edged in that it can have negative effects in the host; excessive complement activation damages the host and can even kill in anaphylactic shock and septic shock. Regulation of the complement system is a useful strategy to control inflammatory diseases, including inflammatory arthritis. Rheumatoid arthritis is a common inflammatory disease worldwide. Many medicines are developed to control inflammation, including recently developed biological response modifiers such as anti-TNF and IL-6 agents. Nevertheless, in some patients disease remains difficult to control because of complications, side effects and tolerance of medicines. In inflammatory arthritis, including rheumatoid arthritis, there is abundant evidence implicating complement activation in humans and animal models. Therefore, anti-complement agents might be beneficial as part of clinical treatment. However, at present, there are still no applicable agents for therapeutic regulation of excessive complement activation in chronic disease. Novel agents in development might be useful as a strategy to control complement activation. Here I describe recent knowledge of the complement system in inflammatory arthritis, the recent developments in anti-complement agents and their considerable potential for the future.
16100470 Macrophage activation syndrome in a child with systemic juvenile rheumatoid arthritis. 2005 Aug Macrophage activation syndrome (MAS) is a rare and potentially fatal complication of rheumatic disorders in children. We describe a 13-month-old boy in whom MAS developed as a complication of systemic juvenile rheumatoid arthritis (S-JRA). He suffered from fever and generalized rash followed by multiple joints swelling for four months before admission. Physical examination revealed cervical lymphadenopathy and hepatosplenomegaly. Laboratory findings were: abnormal liver enzymes, increased triglyceride and ferritin levels, coagulopathies resembling disseminated intravascular coagulation, anemia and thrombocytopenia. Hyperplasia of hemophagocytic macrophages was remarkable in his bone marrow. Methylprednisolone and cyclosporin therapy resulted in clinical and laboratory improvements. This is the third case of MAS associated with S-JRA in Koreans, and the first one, in which hemophagocytic macrophages were proven in bone marrow.
16780097 [A case of severe adult-onset Still' s disease presenting with pleuropericarditis]. 2006 May Adult-onset Still' s disease (AOSD) is an uncommon rheumatic disease characterized by high spiking fever, arthritis, an evanescent skin rash and variety of systemic symptoms, though initial onset of pleuropulmonary manifestation is relatively rare and could be responsible for a delay in diagnosis. We report a case of AOSD presenting with pleuritis with concomitant pericardial effusion. A 42-year-old Japanese man was admitted with a spiking fever of 40 degrees C, hyperleucocytosis (21.6 x 10(9)/l), and a high titer of C-reactive protein (16.84mg/dl). Chest X-ray film and computed tomography showed bilateral pleural effusion and massive pericardial effusion which both required tube drainage. Analyses of fluids revealed that both were exudative and sterile, and pleural biopsy showed nonspecific inflammation with mild fibrosis. Neither antibiotics nor antituberculosis drugs were effective. Rash, hepatosplenomegaly, polyarthritis, pharyngitis and right hypochondralgia were accompanied by serum hyperferritinemia. After exclusion of the possibility of infection, other connective tissue disease and malignancy, a diagnosis of AOSD was made. Improvement was not observed with nonsteroidal anti-inflammatory drug and corticosteroid therapy. Double filtration plasmapheresis (DFPP) following steroid pulse therapy alleviated the symptoms and the laboratory data immediately and corticosteroids could be tapered. DFPP is a safe therapeutic procedure and can be an alternative for refractory AOSD.
16761498 The role of epithelial cells in the initiation and perpetuation of autoimmune lesions: les 2006 Sjögren's syndrome (SS) is a chronic autoimmune disease affecting epithelial tissues. Exocrine glands are the primary target and their functional impairment comes as a result of immune attack of epithelial cells of the affected organs (autoimmune epithelitis). In this interplay, the role of the epithelial cell is pivotal. Extensive data point to an intrinsically activated status. Moreover, the epithelial cells possess all the features needed in order to act as non-professional antigen presenting cells. Through apoptosis and exosomes release endocellular antigens contributing to tolerance breakdown. In addition, produce cytokines and chemokines that recruit lymphocytes in the immunopathogenic lesion. Herein, we review all the aforementioned aspects of the epithelial activity that lead to the perpetuation of the lesion as well as the probable viral factors for the intrinsic activation. Finally, we propose a model for SS pathogenesis that integrates the knowledge accumulated during the last decade.
16427379 Pathogenesis of hemophilic arthropathy. 2006 Jan Intra-articular bleeding is the most common clinical manifestation of hemophilia, and can adversely affect joints and lead to arthropathy. Affected joints are associated with changes to the synovium, bone, cartilage and blood vessels. Iron plays a critical role in the pathogenesis of this condition, and may exert its effects through a variety of different mechanisms. Hemophilic arthropathy shares some injury characteristics with rheumatoid arthritis, although the degree of analogy is a matter of some debate. The influences of the mechanisms underlying joint inflammation are better understood for rheumatoid arthritis than for hemophilia, and it is hoped that this knowledge can be used to provide a more comprehensive knowledge of the pathological process of hemophilic arthropathy. This, in turn, may enable novel targets for therapeutic intervention to be identified.
16102490 Clinical course and outcome of uveitis in children. 2005 Aug PURPOSE: We sought to evaluate the clinical course, complications, and visual outcome of pediatric uveitis. METHODS: Our sample included 38 consecutive children with uveitis treated between 1986 and 2002: 15 with idiopathic uveitis, 10 with Behcet disease, 9 with juvenile rheumatoid arthritis, 4 with other diagnoses. The last group was excluded from the analysis because of its small size. Appropriate ophthalmologic and laboratory examinations were obtained. Treatment consisted of topical, periocular, or systemic steroids with or without immunosuppression. RESULTS: Complications occurred in all 3 groups, although they tended to be more severe in the patients with juvenile rheumatoid arthritis. Visual acuity improved from presentation to final examination; the difference was statistically significant for the patients with idiopathic uveitis (P < 0.0005) and Behcet disease (P = 0.004). CONCLUSIONS: These findings support an intensive treatment approach to childhood uveitis. The visual prognosis is good even in patients with a severe clinical course.
16949136 Pathogenesis and management of adult-onset Still's disease. 2006 Dec OBJECTIVE: To review recent literature regarding the pathogenesis and treatment of adult-onset Still's disease (AOSD). METHODS: We searched MEDLINE and PUBMED from 1971 to present using the following terms: adult-onset Still's disease, AOSD, or adult Still's disease. In addition we manually retrieved relevant abstracts from recent American College of Rheumatology and European League Against Rheumatism meetings. RESULTS: The etiology of AOSD, a rare, immune-mediated, multisystem inflammatory disorder characterized by quotidian spiking fevers, evanescent rash, and arthritis, remains unknown. An infectious etiology has been postulated, although a definitive agent has yet to be identified. Cytokines, such as interleukin (IL)-1, IL-6, interferon (IFN)-gamma, and tumor necrosis factor-alpha, are elevated in patients with AOSD. IL-18 and macrophage-colony stimulating factor also seem to play a role. Treatment historically consisted of nonsteroidal antiinflammatory drugs, often in combination with low-dose corticosteroids. Immunosuppressants (mainly methotrexate, but also intramuscular gold, azathioprine, cyclosporine A, leflunomide, and cyclophosphamide) and intravenous gamma-globulin are efficacious and have been used as steroid-sparing drugs. The recently reported use of anticytokine (anti-TNF-alpha, anti-IL-1, and anti-IL-6) agents in refractory cases has opened new horizons in the treatment of AOSD and provided important clues for its pathophysiology. CONCLUSIONS: Advances in immunology have enhanced our understanding of the role of cytokines in AOSD pathogenesis. Early, promising studies of anticytokine agents in AOSD may provide further insight into the pathogenetic mechanisms of this complex disease.
15847040 Sjogren's syndrome presenting with interstitial lung disease. 2005 Feb We report a patient of primary Sjogren's syndrome presenting with interstitial lung disease. The clinical picture was dominated by respiratory symptoms leading to a delay in diagnosis.
17029063 Anaphylactic reaction to infliximab in two rheumatoid arthritis patients who had previousl 2005 Here we report on two cases of anaphylactic reaction following infliximab infusion in patients with active rheumatoid arthritis (RA). Both individuals had received infliximab treatment during a clinical trial approximately 2 years prior to further therapy; subsequent infusion of this agent led to anaphylactic reactions in both cases. In light of these findings, we recommend that future treatments with infliximab in RA patients who have previously received this agent should be carefully monitored.
17041996 How people with rheumatoid arthritis perceive leisure activities: a qualitative study. 2005 OBJECTIVE: To explore how people with rheumatoid arthritis (RA) perceive leisure activities. METHOD: A phenomenographic approach using semi-structured interviews to explore the impact of RA on leisure pursuits was used. RESULTS: Three descriptive categories containing 11 conceptions emerged: (1) Experiencing constraints included four conceptions: seeing limitations, needing time, finding balance, being dependent. (2) Experiencing coherence included four conceptions: accepting feelings participating in a social context, being active, having insight. (3) Finding solutions included three conceptions: choosing, planning, and adapting. CONCLUSIONS: This study emphasizes the limited choices and problems people with RA had participating in leisure activities, as well as its impact on self-esteem.
17029082 Total knee arthroplasty with a long-stemmed component for fractures adjacent to the knee i 2005 Four rheumatoid arthritis patients with fractures adjacent to the knee were treated by total knee arthroplasty with a long-stemmed component. All four fractures healed; joint reconstruction and limb realignment were achieved simultaneously. Total knee arthroplasty with a long-stemmed component was useful in stabilizing the fracture and rapidly restoring function in the joint and the limb.
19804006 The use of antirheumatic disease drugs during pregnancy. 2006 Nov Many connective tissue diseases occur more frequently in women, the female:male ratio for systemic lupus erythematosus is 9:1 and for rheumatoid arthritis is 3:1. These diseases frequently afflict young women, many of whom wish to become mothers. While some diseases (for example, rheumatoid arthritis) generally improve during pregnancy, other immune-mediated diseases may be exacerbated by pregnancy, putting both the mother and fetus at risk and making control of maternal disease a top priority. This review examines the current literature pertaining to the use of antirheumatic drugs during pregnancy, including aspirin and nonsteroidal anti-inflammatory drugs, corticosteroids, anticoagulants, the 4-aminoquinoline antimalarial drugs, immunomodulating drugs, antimetabolite drugs and other agents including sulfasazine and anticytokine therapy.
17029111 Beneficial effect of complementary alternative medicine on lymphedema with rheumatoid arth 2005 Lymphedema of the limbs can be an added complication in a small number of rheumatoid arthritis cases, becoming a long-standing problem even when there is good control of inflammatory joint disease. In the present article, we describe a patient with RA who developed lymph-edema of the forearms successfully treated with TJ-48 (Juzentaihoto) as a complementary alternative medicine (CAM). This kind of edema does not seem to show any consistent relationship with the severity of arthritis in the literature surveyed. In contrast, lymphedema in this case improved in parallel with RA disease activity. We discuss the utility of CAM treatments and review the literature.
16380240 Chemokines and leukocyte trafficking in rheumatoid arthritis. 2006 Feb 21 Leukocyte infiltration into the joint space and tissues is an essential component of the pathogenesis of rheumatoid arthritis (RA). In this review, we will summarize the current understanding of the mechanisms of leukocyte trafficking into the synovium, focusing on the role of adhesion molecules, chemokines, and chemokine receptors in synovial autoimmune inflammation. The process by which a circulating leukocyte decides to migrate into the synovium is highly regulated and involves the capture, firm adhesion, and transmigration of cells across the endothelial monolayer. Adhesion molecules and chemokine signals function in concert to mediate this process and to organize leukocytes into distinct structures within the synovium. Chemokines play a key regulatory role in organ-specific leukocyte trafficking and activation by affecting integrin activation, chemotaxis, effector cell function, and cell survival. Consequently, chemokines, their receptors, and downstream signal transduction molecules are attractive therapeutic targets for RA.
16278145 A longitudinal study of the relationship between galactosylation degree of IgG and rheumat 2005 Sep Although IgG with reduced content of galactose has been implicated as important in the autoimmune rheumatoid factor (RF) response in rheumatoid arthritis (RA), relatively little is known about the temporal relationship between RF and the degree of galactosylation of IgG in vivo. We established an experimental model for studying the dynamic association between changes in the relative extent of galactosylation of IgG antigen(s) and the main parameters of RF activity, such as the titer, specificity and functional affinity/avidity. Rabbits hyperimmunized with BSA were used for examining the influence of long-term antigenic stimulation on the galactosylation status of IgG and rheumatoid factor production. The results showed that the galactosylation profile of IgG varied during the humoral anti-BSA response in rabbits and that the accompanying RF response fluctuated in titer and binding avidity for differently galactosylated IgG. The immune complexes (IC) were found to be composed of differently galactosylated IgG differing in capacity to inhibit the agglutination activity of RF. Moreover, the ability of circulating RF to react avidly with rather small IC was associated with a lower content of galactose in complexed IgG. The results suggest that a certain dynamic relationship exists between the oligosaccharide moiety of IgG and the titer and avidity of RF during the normal anti-BSA response of rabbits.