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ID PMID Title PublicationDate abstract
17350676 Varied presentations of enthesopathy. 2007 Oct BACKGROUND: The concept of "enthesis organ" allows a new look at the nature of enthesis involvement in some rheumatic and nonrheumatic systemic disorders. OBJECTIVES: To describe the various presentations of enthesopathy in the course of systemic medical disorders using the available literature data. METHODS: Review of relevant articles from 1996 to 2006 retrieved by a Medline search utilizing the index terms "enthesis," "enthesitis," and "tendonitis." The list of articles reviewed herein is not exhaustive, with preference given, where possible, to studies and surveys over case reports as well as the most recent literature reflecting new developments on the subject. RESULTS: Enthesis is defined as the site of insertion of a tendon, ligament, fascia, or articular capsule into bone. Pain originating in the free nerve endings enriched entheses (enthesalgia) may represent a potential cause of chronic musculoskeletal pain in some individuals. Enthesis involvement in the disease process is well appreciated in spondyloarthropathies and in rheumatoid arthritis, though overshadowed by synovitis in the latter. Calcium deposition diseases may constitute the most significant articular cause of enthesopathies in the general population. New data may shed light on the possible pathophysiologic role of enthesopathy in the development of osteoarthritis. Various metabolic and endocrine conditions may manifest with enthesopathy features. The pathogenic mechanisms of enthesis involvement are not uniform and differ in the diverse disorders. CONCLUSIONS: The concept of enthesopathy as a variety of syndromes in the course of many rheumatic, metabolic, and endocrine disorders should be appreciated. Exercise of a high level of suspicion toward enthesopathic involvement, and greater knowledge of enthesopathy's characteristic patterns and diagnostic possibilities, may allow better management of many patients in rheumatology practice.
17158801 TNFalpha kinoid vaccination-induced neutralizing antibodies to TNFalpha protect mice from 2006 Dec 19 The proinflammatory cytokine TNFalpha is a potent mediator of septic shock and a therapeutic target for chronic inflammatory pathologies including rheumatoid arthritis and Crohn's disease. As an alternative to anti-human TNFalpha (hTNFalpha) mAbs and other hTNFalpha blocker approved drugs, we developed an active anti-hTNFalpha immunotherapy, based on a vaccine comprised of a keyhole limpet hemocyanin-hTNFalpha heterocomplex immunogen (hTNFalpha kinoid) adjuvanted in incomplete Freund's adjuvant. In mice transgenic for hTNFalpha (TTg mice), hTNFalpha kinoid vaccination elicited high titers of Abs that neutralized hTNFalpha bioactivities but did not result in a cellular response to hTNFalpha. The vaccine was safe and effective in two experimental models. Kinoid-immunized but not control TTg mice resisted hTNFalpha-driven shock in one model and were prevented from spontaneous arthritis, inflammatory synovitis, and articular destruction in a second model. These data demonstrate an anti-cytokine induction of autoimmune protection against both acute and chronic hTNFalpha exposure. They show that active vaccination against a human cytokine can be achieved, and that the immune response can be effective and safe.
17067439 MAGIC or not MAGIC--does the MAGIC (mouth and genital ulcers with inflamed cartilage) synd 2006 Sep INTRODUCTION: In 1985, Firestein et al. described 5 patients with relapsing polychondritis and Behçet's disease (BD) and proposed the term "MAGIC" syndrome as an acronym for "Mouth and Genital ulcers with Inflamed Cartilage". We report on an additional case of this syndrome and critically review the literature. RESULTS: From 1985 to 2004 eleven cases of MAGIC syndrome were described. All patients had chondritis and oral aphthous ulcers, as well as ocular inflammation (mainly anterior uveitis or scleritis/episcleritis). Most patients also presented with genital ulcers and arthritis. In one case, aortic aneurysm, in another aortic insufficiency was described, one had meningoencephalitis, one had antiphospholipid syndrome and one was HIV positive. Before 1985, we could find 4 additional probable cases. Our own patient presented with oral and genital ulcers, auricular chondritis and episcleritis. HLA-typing was performed and revealed HLA-B*51, B*15, DRB1*04x and DRB1*11x. Only in one Japanese patient from the literature, HLA-typing was available and revealed HLA-B*56, B*62, DRB1*0406 and DRB1*0901. CONCLUSIONS: Relapsing polychondritis is associated with HLA-DRB1*04 suballeles, but not necessarily only with those being associated with RA (DRB1*0401 and 0404). In 2 MAGIC patients these suballeles were found. All patients described in the literature had typical polychondritis, but not all did fulfil the classification criteria for BD. Many features of both diseases overlap and are not specific. As polychondritis is associated with other inflammatory rheumatic conditions such as SLE, spondyloarthropathy, rheumatoid arthritis and systemic vasculitides in 30% of all cases, we suggest that MAGIC syndrome is not a disease entity, but merely the association of BD with polychondritis.
16888164 Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo: therapeutic 2006 Jul CD4+ CD25+ regulatory T cells (Treg) control the immune response to a variety of antigens, including self-antigens, and several models support the idea of the peripheral generation of CD4+ CD25+ Treg from CD4+ CD25- T cells. However, little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+ CD25+ Treg. We have found that the immunosuppressive neuropeptide vasoactive intestinal peptide (VIP) induces functional Treg in vivo. The administration of VIP together with specific antigen to TCR-transgenic mice results in the expansion of the CD4+ CD25+, Foxp-3/neuropilin 1-expressing T cells, which inhibit responder T cell proliferation through direct cellular contact. The VIP-generated CD4+ CD25+ Treg transfer suppression, inhibiting delayed-type hypersensitivity in the hosts, prevent graft-versus-host disease in irradiated host reconstituted with allogeneic bone marrow, and significantly ameliorate the clinical score in the collagen-induced arthritis model for rheumatoid arthritis and in the experimental autoimmune encephalomyelitis model for multiple sclerosis.
18362895 Treatment with DF 2162, a non-competitive allosteric inhibitor of CXCR1/2, diminishes neut 2008 May BACKGROUND AND PURPOSE: Neutrophil migration into tissues is involved in the genesis of inflammatory pain. Here, we addressed the hypothesis that the effect of CXC chemokines on CXCR1/2 is important to induce neutrophil migration and inflammatory hypernociception. EXPERIMENTAL APPROACH: Mice were treated with a non-competitive allosteric inhibitor of CXCR1/2, DF 2162, and neutrophil influx and inflammatory hypernociception were assessed by myeloperoxidase assay and electronic pressure meter test, respectively, in various models of inflammation. KEY RESULTS: DF 2162 inhibited neutrophil chemotaxis induced by CXCR1/2 ligands but had no effect on CXCL8 binding to neutrophils. A single mutation of the allosteric site at CXCR1 abrogated the inhibitory effect of DF 2162 on CXCL-8-induced chemotaxis. Treatment with DF 2162 prevented influx of neutrophils and inflammatory hypernociception induced by CXCL1 in a dose-dependent manner. The compound inhibited neutrophil influx and inflammatory hypernociception induced by carrageenan, lipopolysaccharide and zymosan, but not hypernociception induced by dopamine and PGE(2). DF 2162 had a synergistic effect with indomethacin or the absence of TNFR1 to abrogate carrageenan-induced hypernociception. Treatment with DF 2162 diminished neutrophil influx, oedema formation, disease score and hypernociception in collagen-induced arthritis. CONCLUSIONS AND IMPLICATIONS: CXCR1/2 mediates neutrophil migration and is involved in the cascade of events leading to inflammatory hypernociception. In addition to modifying fundamental pathological processes, non-competitive allosteric inhibitors of CXCR1/2 may have the additional benefit of providing partial relief for pain and, hence, may be a valid therapeutic target for further studies aimed at the development of new drugs for the treatment of rheumatoid arthritis.
17336664 The association of depression and anxiety with medical symptom burden in patients with chr 2007 Mar BACKGROUND: Primary care patients with anxiety and depression often describe multiple physical symptoms, but no systematic review has studied the effect of anxiety and depressive comorbidity in patients with chronic medical illnesses. METHODS: MEDLINE databases were searched from 1966 through 2006 using the combined search terms diabetes, coronary artery disease (CAD), congestive heart failure (CHF), asthma, COPD, osteoarthritis (OA), rheumatoid arthritis (RA), with depression, anxiety and symptoms. Cross-sectional and longitudinal studies with >100 patients were included as were all randomized controlled trials that measure the impact of improving anxiety and depressive symptoms on medical symptom outcomes. RESULTS: Thirty-one studies involving 16,922 patients met our inclusion criteria. Patients with chronic medical illness and comorbid depression or anxiety compared to those with chronic medical illness alone reported significantly higher numbers of medical symptoms when controlling for severity of medical disorder. Across the four categories of common medical disorders examined (diabetes, pulmonary disease, heart disease, arthritis), somatic symptoms were at least as strongly associated with depression and anxiety as were objective physiologic measures. Two treatment studies also showed that improvement in depression outcome was associated with decreased somatic symptoms without improvement in physiologic measures. CONCLUSIONS: Accurate diagnosis of comorbid depressive and anxiety disorders in patients with chronic medical illness is essential in understanding the cause and in optimizing the management of somatic symptom burden.
16891918 Peripheral musculoskeletal manifestations in polymyalgia rheumatica. 2006 Aug OBJECTIVES: The objectives of this study were to evaluate the frequency and characteristics of the peripheral musculoskeletal manifestations in polymyalgia rheumatica (PMR), evaluate if PMR with peripheral synovitis represents a subset with a more severe disease, and examine for clinical and laboratory characteristics at onset of PMR that might later predict rheumatoid arthritis (RA). PATIENTS AND METHODS: Patients were diagnosed with PMR according to the 1982 Chuang criteria. Patients were followed up between 1990 and 2002. The following musculoskeletal manifestations at onset and during the follow up were considered: peripheral synovitis, distal extremity swelling with pitting edema, carpal tunnel syndrome, and distal tenosynovitis. RESULTS: Thirty-eight of the 74 patients (51%) showed distal musculoskeletal symptoms: 29 (39%) had peripheral synovitis, 4 (5%) presented pitting edema, 4 (5%) experienced carpal tunnel syndrome, and one (1.3%) had distal tenosynovitis. These manifestations resolved completely after corticosteroid therapy was initiated. Peripheral synovitis was oligoarticular and often transient. The joints most frequently involved were the wrist, metacarpophalangeal, and knee. Erythrocyte sedimentation rate (ESR) was normal in 7 patients. When comparing patients with PMR with and without peripheral synovitis, no statistically significant differences were found in the studied variables. Through the first year of follow up, 7 patients fulfilled the American College of Rheumatology 1987 criteria for RA, 2 patients developed giant cell arteritis, and 3 had associated malignancy. Patients who developed RA had statistically significantly increased presence of persistent synovitis and a smaller decrease in mean ESR after treatment with corticosteroids. CONCLUSION: Fifty-one percent of the patients with PMR presented distal musculoskeletal manifestations, with peripheral synovitis being the most frequent one. Patients with PMR with peripheral synovitis did not represent a high-risk subgroup with more severe disease. Seven patients who developed criteria for seronegative RA within the first year of follow up had presented statistically significant persistent synovitis compared with those who continued as PMR and also showed a smaller initial decrease in mean ESR after steroid treatment was initiated. The absence of persistent arthritis and the benign course of the arthritis permit the distinction of PMR from other inflammatory arthropathies.
19137862 Suppression of T and B cell responses by Pterodon pubescens seeds ethanolic extract. 2008 Oct 1 The anti-arthritic property of hydro alcoholic extract of Pterodon pubescens seeds was previously demonstrated using the Collagen Induced Arthritis (CIA) in mice, the most similar arthritis experimental model to human rheumatoid arthritis. This disease is characterized by chronic inflamed joints resulting from exacerbated functions of macrophages and T and B lymphocytes. Anti-inflammatory and antinociceptive activities by ethanolic extract of Pterodon pubescens seeds (EEPp) have been also reported. This study describes the effects of EEPp on T and B lymphocytes functions from healthy mice. Delayed Type Hypersensitivity (DTH), in vivo antibody production, T and B lymphocyte proliferation and NO production were determined. Mice treated orally for 7 days with EEPp had inhibited 58% of B cell antibody production (10(-3) mg kg(-1) b.wt.) and 33% of the DTH response (10(-4) mg kg(-1) b.wt.), also reducing tissue leukocyte infiltration. EEPp (10(-2) mg mL(-1)) also inhibited in vitro T (89%) and B (68%) lymphocytes proliferation and NO production (53%) by macrophage cell line J774. The immunosuppression here described for EEPp supports its potential therapeutic use to control exacerbated humoral and/or cellular immune response as in autoimmune and chronic inflammatory diseases.
16707558 Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in infl 2006 Aug Cytokine receptors, which exist in membrane-bound and soluble forms, bind their ligands with comparable affinity. Although most soluble receptors are antagonists and compete with their membrane-associated counterparts for the ligands, certain soluble receptors are agonists. In these cases, complexes of ligand and soluble receptor bind on target cells to second receptor subunits and initiate intracellular signaling. The soluble receptors of the interleukin (IL)-6 family of cytokines (sIL-6R, sIL-11R, soluble ciliary neurotrophic factor receptor) are agonists capable of transmitting signals through interaction with the universal signal-transducing receptor for all IL-6 family cytokines, gp130. In vivo, the IL-6/sIL-6R complex stimulates several types of cells, which are unresponsive to IL-6 alone, as they do not express the membrane IL-6R. We have named this process trans-signaling. The generation of soluble cytokine receptors occurs via two distinct mechanisms-limited proteolysis and translation-from differentially spliced mRNA. We have demonstrated that a soluble form of the IL-6 family signaling receptor subunit gp130, which is generated by differential splicing, is the natural inhibitor of IL-6 trans-signaling responses. We have shown that in many chronic inflammatory diseases, including chronic inflammatory bowel disease, peritonitis, rheumatoid arthritis, asthma, as well as colon cancer, IL-6 trans-signaling is critically involved in the maintenance of a disease state, by promoting transition from acute to chronic inflammation. Moreover, in all these models, the course of the disease can be disrupted by specifically interfering with IL-6 trans-signaling using the soluble gp130 protein. The pathophysiological mechanisms by which the IL-6/sIL-6R complex regulates the inflammatory state are discussed.
18349794 99mTc-depreotide in the evaluation of bone infection and inflammation. 2008 Mar BACKGROUND AND AIM: (99m)Tc-depreotide is a (99m)Tc-labelled somatostatin analogue, with high affinity for the 2, 3 and 5 subtypes of somatostatin receptors. These particular receptors are over-expressed on the surface of activated leucocytes, which mediate inflammatory response. Based on this property this study tried to investigate whether (99m)Tc-depreotide scintigraphy could be a useful complementary method in the investigation of bone infection and inflammation. METHODS: Twenty-three patients, who were investigated for probable osteomyelitis, underwent three-phase bone scintigraphy followed by (99m)Tc-depreotide scintigraphy. Clinical and laboratory findings, complementary imaging procedures, clinical follow-up and bone biopsy established the final diagnosis. (99m)Tc-depreotide scintigraphy was performed 3 h after the intravenous administration of 555-740 MBq of the radiopharmaceutical. Scintigraphic images were, at first, blindly interpreted alone and then in comparative assessment with bone scans. RESULTS: (99m)Tc-depreotide was positive in 12/12 cases of active osteomyelitis, one case of recent femoral head osteonecrosis and 6/9 rheumatoid arthritis sites. Negative (99m)Tc-depreotide scans were acquired in five cases of 'no-inflammation' (an uncomplicated fracture, an aseptic loosening of prosthesis, an old osteonecrosis, a healed and a successfully treated osteomyelitis), as well as in 14/14 total sites of degenerative arthritis-osteoarthropathy. In five cases (septic arthritis, periodontal and soft tissue infections) (99m)Tc-depreotide was positive, though spatially discordant with bone scintigraphy, delineating precisely the focus of infection. CONCLUSION: (99m)Tc-depreotide can be a useful complementary imaging method in the evaluation of bone infection and inflammation. Its combination with three-phase bone scintigraphy seems to be accurate in localizing the infection foci and determining the activity of the inflammatory processes.
17680564 Autoimmunity as a prognostic factor in melanoma patients treated with adjuvant low-dose in 2007 Dec 1 Interferon alpha is used for the adjuvant treatment of malignant melanoma at different dosages (high-, intermediate-, low-dose therapy). Only a minority of patients might benefit from this therapy, and markers to identify such patients are missing. A recent study suggested that melanoma patients developing autoantibodies or clinical manifestations of autoimmunity during adjuvant high-dose interferon alpha treatment had a significant survival benefit. We retrospectively reviewed 134 melanoma patients from our institution treated with adjuvant low-dose interferon alpha therapy and correlated the development of autoimmune diseases with prognosis. Interferon (IFN) therapy was routinely monitored by history, physical examination and laboratory tests before, after the first month and then after every 3 months of therapy. During a median follow up of 46.0 months (8.5-79.0 months) 28 patients (20.9%) suffered from recurrences and melanoma related deaths occurred in 16 patients (11.9%). In 20 patients (14.9%) autoimmune thyroiditis (AIT) was diagnosed during IFN therapy, one of these 20 patients developed rheumatoid arthritis later while continuing IFN therapy. Other autoimmune diseases were not observed. In 2 patients (one with AIT and one with arthritis) the autoimmune disease led to discontinuation of IFN therapy, in the other patients AIT remained subclinical or responded well to treatment while IFN therapy was continued. Kaplan-Meier analyses revealed a significant better recurrence free survival and a trend for a better overall survival for patients with AIT. Thus, autoimmunity triggered by low-dose IFN therapy appears to indicate an improved prognosis and should encourage continuation of IFN therapy.
17310002 Psoriasis and pustular dermatitis triggered by TNF-{alpha} inhibitors in patients with rhe 2007 Feb BACKGROUND: New onset or worsening of psoriasis has been reported in patients treated with tumor necrosis factor alpha (TNF-alpha) inhibitors for a variety of rheumatologic conditions. There is mounting evidence that a key innate immune pathway for triggering common human autoimmune disease, including psoriasis, involves plasmacytoid dendritic cell precursors (PDCs) and type 1 interferon (IFN) production. We present herein a case series with clinical and histopathologic evidence of psoriasis in patients with rheumatologic disease treated with TNF-alpha inhibitors. We propose that the cross regulation between TNF-alpha and IFN may have a role in the pathogenesis of this reaction. OBSERVATIONS: We observed new-onset psoriasis (n = 13) or severe exacerbation of psoriasis (n = 2) in 15 patients with a variety of rheumatologic conditions-rheumatoid arthritis (n = 13), psoriatic arthritis (n = 1), and seronegative arthritis (n = 1)-during treatment with etanercept (n = 6), infliximab (n = 5), and adalimumab (n = 4). Immunohistochemical staining of skin biopsy specimens for myxovirus-resistance protein A (MxA, a surrogate marker for lesional type 1 IFN activity) showed increased staining in TNF-alpha inhibitor-induced psoriasis compared with psoriasis vulgaris. CONCLUSIONS: New onset or severe exacerbation of psoriasis is a rare complication of TNF-alpha inhibitor therapy. The finding of increased production of IFN-alpha in TNF-alpha inhibitor-induced psoriasis is a possible pathophysiologic explanation for this reaction.
17265155 Synovial angiostatic non-ELR CXC chemokines in inflammatory arthritides: does CXCL4 design 2007 Aug In our previous studies, we found higher synovial fluid (SF) levels of angiogenic ELR(+) CXC chemokines such as CXCL1, CXCL5, CXCL6 and CXCL8, which play an important role in neutrophil migration and angiogenesis, and more abundant synovial CXCR2 chemokine receptor expression in patients with rheumatoid arthritis (RA) than those with Behçet's disease (BD), familial Mediterranean fever and osteoarthritis (OA). As a continuation of our previous studies, we investigated synovial levels of angiostatic non-ELR CXC chemokines (CXCL4, CXCL9 and CXCL10) in patients with RA, BD, spondyloarthritis (SpA), and OA. Seventy (17 RA, 15 BD, 19 SpA, and 19 OA) patients were enrolled in the study. The levels of CXCL4, CXCL9, and CXCL10 were measured by ELISA. The SF levels of CXCL4 in patients with RA were higher than those of the patients with BD, SpA, and OA (P = 0.007, P = 0.022, and P = 0.017, respectively). No difference was found with respect to CXCL4 levels among the BD, SpA, and OA patients. The synovial CXCL9 levels of patients with RA and SpA were found to be higher than those of the patients with OA (P = 0.002 and P = 0.005, respectively), while no statistically significant difference was detected among the other groups. With regard to SF CXCL10 levels, patients with RA had higher levels as compared to patients with OA (P = 0.002), but no significant difference was found among the other groups. CXCL9 correlated with CXCL4 and CXCL10 (P < 0.05 for both) in patients with RA. No correlation was found in other parameters. The angiostatic non-ELR CXC chemokines were expressed in synovial inflammation. We proposed that angiostatic non-ELR CXC chemokines may increase to balance angiogenic ELR (+) CXC chemokines in which increased levels were shown in patients with inflammatory arthritides and CXCL4 may contribute to designate the chronicity of synovitis in patients with RA. In addition, as CXCL-9 and CXCL-10 play crucial role in inflammation characterized by Th1 polarization, we suggested that they may contribute to the commencement and the perpetuation of synovitis seen in these groups of arthritides.
16260582 Therapeutic promise of proteinase-activated receptor-2 antagonism in joint inflammation. 2006 Mar Biological therapies such as tumor necrosis factor-alpha inhibitors have advanced the treatment of rheumatoid arthritis, but one-third of patients do not respond to such therapy. Furthermore, these inhibitors are now usually administered in combination with conventional disease-modifying antirheumatic drugs, suggesting they have not achieved their early promise. This study investigates a novel therapeutic target, proteinase-activated receptor (PAR)-2, in joint inflammation. Intra-articular carrageenan/kaolin (C/K) injection in mice resulted in joint swelling that was associated with synovial PAR2 up-regulation. Inhibiting receptor up-regulation using small interfering RNA technology, as confirmed by immunoblotting, substantially reduced the inflammatory response in the joint. Serine proteinase-induced joint swelling was mediated primarily via PAR2 activation, since the response to exogenous application of trypsin and tryptase was absent in PAR2 knockout mice. Furthermore, serine proteinase inhibitors were effective anti-inflammatory agents in this model. Disrupting proteolytic activation of PAR2 using antiserum (B5) directed to the receptor cleavage/activation site also attenuated C/K-induced inflammation, as did the similarly targeted PAR2 monoclonal antibody SAM-11. Finally, we report the activity of a novel small molecule PAR2 antagonist, N1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine (ENMD-1068), that dose dependently attenuated joint inflammation. Our findings represent a major advance in collectively identifying PAR2 as a novel target for the future treatment of arthritis.
18438853 Radiographic progression of ankylosing spondylitis after up to two years of treatment with 2008 May OBJECTIVE: To investigate the effect of etanercept therapy on radiographic progression in patients with ankylosing spondylitis (AS). METHODS: Patients with AS who had previously participated in a 24-week randomized, double-blind, placebo-controlled trial of etanercept therapy were enrolled in a 72-week open-label extension. Radiographs of the cervical and lumbar spine from patients who received etanercept (25 mg twice weekly) for up to 96 weeks were compared with radiographs from patients in a large prevalence cohort (Outcome Assessments in Ankylosing Spondylitis International Study [OASIS]) who had not been treated with anti-tumor necrosis factor alpha (anti-TNFalpha) agents. Radiographs obtained at 2 time points up to 96 weeks apart from patients in both study populations were digitized and read by 2 independent readers who were blinded with regard to patient group and sequence. The primary end point was the 96-week change in the modified Stoke AS Spine Score (mSASSS). RESULTS: A total of 257 patients treated with etanercept were compared with 175 unselected patients from the OASIS study. There was no significant difference in the change in the mSASSS from baseline among patients who received etanercept (mean +/- SD 0.91 +/- 2.45) versus those from the OASIS group (0.95 +/- 3.18). CONCLUSION: Unlike other inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis, structural progression in AS seems to be independent of TNF, despite the fact that TNF is responsible for the signs and symptoms due to inflammation in this disease.
18413443 Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthr 2009 May OBJECTIVE: We undertook an observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different juvenile idiopathic arthritis (JIA) subtypes. METHODS: At baseline we collected patient and disease characteristics of all Dutch patients with JIA who started treatment with etanercept. Disease activity was evaluated (at start of the study, after 3 months and then yearly) according to the JIA core set of the American College of Rheumatology paediatric definition for 30, 50 and 70% improvement (ACR Pedi 30, 50 and 70). Use of etanercept and concomitant drugs was monitored. Adverse events were recorded. RESULTS: We included 146 patients with JIA with a median follow-up of 2.5 years per patient (range 0.3-7.3). JIA subtypes represented: 27% systemic, 8% polyarticular rheumatoid factor positive, 38% polyarticular rheumatoid factor negative, 19% oligoarticular extended, 3% enthesitis-related and 5% psoriatica. Most patients (77%) met the criteria of the ACR Pedi 30 in the first 3 months of treatment. For the majority of patients this improvement was sustained; 53 (36%) of all patients met the remission criteria. No other second-line agents were needed in 43 patients. Although patients with systemic JIA responded initially less to etanercept therapy than patients from other subtypes, those who did respond showed equal effectiveness in the long term. Serious adverse events rate was low (0.029 per patient year). CONCLUSIONS: Etanercept is effective and safe in JIA, even for a large proportion of the patients with systemic JIA. The greatest improvement occurred in the first 3 months of treatment, and was sustained for a long time in most patients (up to 75 months).
17299831 Oxidative status of DBA/1J mice with type II collagen-induced arthritis. 2007 Sep The present study was undertaken to compare the oxidant statuses of mice with collagen-induced arthritis (CIA) and those of healthy mice. For this purpose, serum oxidant products and arthritic profiles were measured in DBA/1J mice with CIA. In addition, the levels of oxidation products and the activities of antioxidant enzymes were determined in liver, heart, spleen, kidney, lung and brain. The induction of arthritis significantly increased anti-collagen antibody, rheumatoid factor, interleukin (IL)-1beta, IL-6, protein carbonyl (PCO), advanced glycation end-products (AGE), malondialdehyde (MDA) and low density lipoprotein (LDL)-cholesterol levels in serum (P < 0.05). CIA in DBA/1J mice was associated with significantly lower activities of superoxide dismutase, glutathione peroxidase and glutathione reductase in spleen but higher levels of oxidation products in spleen, kidney and liver than healthy normal mice (P < 0.05). However, lower concentrations of oxidized protein and higher activities of antioxidant enzymes were observed in CIA mouse lung and brain than in healthy normal mice. Dexamethasone treated CIA mice had decreased arthritis-related indices and showed: reduced PCO and AGE in spleen and brain, and increased PCO and AGE in heart, kidney and lung; increased MDA in heart, spleen, lung and brain; reduced SOD and GR activities in lung and brain; increased GPx activity in spleen and brain; and increased GR activity heart and spleen. These data suggest that mice with CIA were more susceptible to oxidative damage in the spleen and liver under the chronic inflammatory conditions.
18190884 Systemic lupus erythematosus in the elderly. 2008 Jan Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, characterized by multisystemic involvement. Late onset SLE represents a specific sub-group of the disorder, beginning above 50-65 years of age. The incidence of late onset SLE ranges in the interval of 12-18% and the course of the disease is considered to be more benign. According to several authors, skin manifestations, photosensitivity, arthritis and nephritis, occur rarely in the elderly patients with late SLE onset; prevalence of serositis, lung involvement and Sjögren's syndrome were observed more often. Late onset SLE patients manifested higher rate of positive findings of rheumatoid factors, as well as of anti-Ro and anti-La antibodies; and the lower occurrence of anti-RNP antibodies and hypocomplementaemia. A slow onset of the disorder, non-specific manifestations at the beginning of the illness and less frequent prevalence of SLE in the elderly often result in late diagnosis. Treatment of the disease depends on its clinical manifestations. NSAID's, antimalarials or low doses of glucocorticoids are used for the less severe forms. Immunosuppressives and higher doses of glucocorticoids are the treatments of choice for more severe organ involvements and complications. A multidisciplinary approach is recommended for the treatment of late onset SLE patients.
18286282 Detailed analysis of contrast-enhanced MRI of hands and wrists in patients with psoriatic 2008 May OBJECTIVE: The objective was to perform detailed analysis of the involved soft tissues, tendons, joints, and bones in the hands and wrists of patients with psoriatic arthritis (PsA). MATERIALS AND METHODS: We reviewed 23 contrast-enhanced MR imaging studies (13 hands and 10 wrists) in 10 patients with the clinical diagnosis of PsA. We obtained clinical information from medical records and evaluated images for the presence of erosions, bone marrow edema, joint synovitis, tenosynovitis, carpal tunnel, and soft tissue involvement. Two board-certified musculoskeletal radiologists reviewed all images independently. Differences were resolved during a subsequent joint session. RESULTS: The average duration of disease was 71.3 months, ranging from 1 month to 25 years. Eight of the 10 wrists (80%) and 6 of the 13 hands demonstrated bone erosions. Bone marrow abnormalities were shown in 5 of the 10 wrists (50%) and 4 of the 14 hands (31%). Triangular fibrocartilage tears were seen in 6 of the 10 wrists (60%). Wrist and hand joint synovitis were present in all studies (67 wrist joints and 101 hand joints). Wrist soft tissue involvement was detected in 9 of the 10 wrists (90%) and hand soft tissue involvement was present in 12 of the 13 wrists (92%). Findings adjacent to the region of soft tissue involvement included synovitis (4 wrists) and tenosynovitis (3 wrists). Bone marrow edema adjacent to the region of soft tissue involvement was seen in one wrist. Bulge of the flexor retinaculum was seen in 4 of the 10 wrists (40%) and median nerve enhancement was seen in 8 of the 10 wrists (80%). Tenosynovitis was seen in all studies (all 10 of the hands and all 13 of the wrists). The "rheumatoid" type of distribution of bony lesions was common in our study. Interobserver agreement for various findings ranged from 83% to 100%. CONCLUSION: Contrast-enhanced MRI unequivocally demonstrated bone marrow edema, erosions, tendon and soft-tissue disease, and median nerve involvement, with good interobserver reliability in patients with PsA of the hands and wrists. Disease was more extensive in the wrists than in the hands.
17878393 Activation-induced cytidine deaminase expression in follicular dendritic cell networks and 2007 Oct 1 Demonstration of ectopic germinal center-like structures (GC-LSs) in chronically inflamed tissues in patients with autoimmune disorders is a relatively common finding. However, to what extent ectopic lymphoid structures behave as true GC and are able to support class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig genes is still debated. In addition, no information is available on whether CSR and SHM can take place in the absence of GCs at extrafollicular sites in an ectopic lymphoid tissue. In this study, we show that in salivary glands (SGs) of Sjögren's syndrome (SS) activation-induced cytidine deaminase (AID), the enzyme responsible for CSR and SHM is invariably expressed within follicular dendritic cell (FDC) networks but is not detectable in SGs in the absence of ectopic GC-LSs, suggesting that FDC networks play an essential role in sustaining the Ag-driven B cell proliferation within SS-SGs. We also show that the recently described population of interfollicular large B cells selectively expresses AID outside ectopic GC in the T cell-rich areas of periductal aggregates. Finally, we report that AID retains its exclusive association with numerous, residual GCs in parotid SS-MALT lymphomas, whereas neoplastic marginal zone-like B cells are consistently AID negative. These results strongly support the notion that ectopic lymphoid structures in SS-SGs express the molecular machinery to support local autoantibody production and B cell expansion and may play a crucial role toward lymphomagenesis.