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ID PMID Title PublicationDate abstract
16566659 [Tumor necrosis factor blocking agents: a review. Part II: safety and recommendations]. 2006 Feb Blockade of tumor necrosis factor with monoclonal antibodies, has emerged as one of the most promising therapies in some autoimmune conditions as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and Crohn's disease. They have shown effectiveness on reducing symptoms and modifying the progression of the disease. However, they disrupt the balance of inflammatory and immune responses and some risks associated with TNF-blockers have become apparent. The purpose of this article is to review the evidence about benefits and risk associated with the use of TNF-blockers in approved indications and to provide practical recommendations for its use in the management of this conditions.
16450741 [Erythrocyte sedimentation rate--more than an old fashion?]. 2006 Jan The erythrocyte sedimentation rate (ESR) is a time-honored blood test, which assesses the degree of erythrocyte aggregation by acute phase proteins such as fibrinogen and immunoglobulins. Various intrinsic factors may influence the ESR, among them polycytemia, microcytosis or fibrinogen consumption lead to a decreased ESR, while anemia, macrocytosis or hypoalbuminemia lead to an increased ESR. The ESR still is a very valid test for the diagnosis of certain chronic diseases (polymyalgia, rheumatoid arthritis, multiple myeloma, septic arthritis and ostemyelitis) and the follow-up of certain chronic diseases (polymyalgia rheumatica, systemic lupus erythematodes, chronic infections, prostatic cancer, and Hodgkin's disease). In acute disease states and their monitoring C-reactive protein and eventually procalcitonin are the tests of choice. The ESR should not be used for screening and check-up examinations in asymptomatic patients.
17472721 B-lymphocyte depletion ameliorates Sjögren's syndrome in Id3 knockout mice. 2007 Sep Sjögren's syndrome is an autoimmune disease in which immune cells chronically attack the lachrymal and salivary glands. The Id3 knockout mouse is a newly established animal model for primary Sjögren's syndrome. To address the role of B cells in Sjögren's syndrome and autoimmune disease, we studied the effect of CD20 monoclonal antibody treatment on the disease in Id3 knockout mice. Antibody treatment at 2-month intervals led to efficient and sustained B-cell depletion in Id3 knockout mice. A significant improvement of histopathology was observed accompanied by the recovery of saliva secretory function after CD20 antibody treatment. We further show that serum immunoglobulin G3, which is abnormally high in untreated Id3 knockout mice, was reduced after CD20 antibody treatment. This study establishes a new animal model for immunotherapy of Sjögren's symptoms and suggests a possible link between immunoglobulin G3 and disease pathology in Id3 knockout mice.
16541477 Validity of screening tests for Sjögren's syndrome in ambulatory patients with chronic di 2006 May OBJECTIVE: To determine the validity of screening tests for Sjogren's syndrome (SS) in ambulatory patients with chronic diseases. METHODS: Three hundred randomly selected patients from the rheumatology and internal medicine clinics of a tertiary care center were assessed for SS according to the American-European Consensus Group criteria. During the screening phase, an interview, the European questionnaire for sicca symptoms, Schirmer-I test, and the wafer test were carried out in all patients. Patients with positive screening had confirmatory tests including fluorescein staining test, nonstimulated whole salivary flow, and autoantibody testing. Confirmatory tests were also done in 13 patients with negative screening. During the last phase, lip biopsy was proposed to patients who met preestablished criteria. RESULTS: Women made up 79% of the study population. Mean age of subjects was 42.8+/-15.7 years. Two hundred twenty patients (73%) had positive screening. The distribution of positive test results was: xerophthalmia 118 (39%), xerostomia 103 (34%), Schirmer-I test 101 (34%), and wafer test 187 (62%) patients. Forty (13%) patients met criteria for SS. All screening tests were useful for identifying patients with SS; however, the model composed of at least one positive response to the European questionnaire (EQ1), Schirmer-I test, and wafer test showed the best performance. CONCLUSION: Use of the European questionnaire, Schirmer-I test, and wafer test in parallel was useful for identifying patients with SS among ambulatory patients with chronic diseases.
17579059 IL-4-STAT6 signal transduction-dependent induction of the clinical phase of Sjögren's syn 2007 Jul 1 NOD.B10-H2(b) and NOD/LtJ mice manifest, respectively, many features of primary and secondary Sjögren's syndrome (SjS), an autoimmune disease affecting primarily the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes). B lymphocytes play a central role in the onset of SjS with clinical manifestations dependent on the appearance of autoantibodies reactive to multiple components of acinar cells. Previous studies with NOD.IL4(-/-) and NOD.B10-H2(b).IL4(-/-) mice suggest that the Th2 cytokine, IL-4, plays a vital role in the development and onset of SjS-like disease in the NOD mouse model. To investigate the molecular mechanisms by which IL-4 controls SjS development, a Stat6 gene knockout mouse, NOD.B10-H2(b).C-Stat6(-/-), was constructed and its disease profile was defined and compared with that of NOD.B10-H2(b).C-Stat6(+/+) mice. As the NOD.B10-H2(b).C-Stat6(-/-) mice aged from 4 to 24 wk, they exhibited leukocyte infiltration of the exocrine glands, produced anti-nuclear autoantibodies, and showed loss and gain of saliva-associated proteolytic enzymes, similar to NOD.B10-H2(b).C-Stat6(+/+) mice. In contrast, NOD.B10-H2(b).C-Stat6(-/-) mice failed to develop glandular dysfunction, maintaining normal saliva flow rates. NOD.B10-H2(b).C-Stat6(-/-) mice were found to lack IgG1 isotype-specific anti-muscarinic acetylcholine type-3 receptor autoantibodies. Furthermore, the IgG fractions from NOD.B10-H2(b).C-Stat6(-/-) sera were unable to induce glandular dysfunction when injected into naive recipient C57BL/6 mice. NOD.B10-H2(b).C-Stat6(-/-) mice, like NOD.B10-H2(b).IL4(-/-) mice, are unable to synthesize IgG1 Abs, an observation that correlates with an inability to develop end-stage clinical SjS-like disease. These data imply a requirement for the IL-4/STAT6-pathway for onset of the clinical phase of SjS-like disease in the NOD mouse model.
17763210 In vivo interactions of platelets and leucocytes with the endothelium in murine antigen-in 2007 Jul OBJECTIVE: Platelets are thought to participate in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis (RA). We showed recently an in vivo increase in platelet-endothelial cell interactions in mice with antigen-induced arthritis (AiA). The underlying mechanisms are not yet clear. The aim of this study was to investigate the impact of P-selectin in AiA by means of intravital fluorescence microscopy (IVM). METHODS: C57/Bl6 mice and P-selectin-deficient mice were divided into four groups (n = 7; control/AiA per strain). The extent of AiA was assessed by measuring knee joint swelling and by histological scoring. Rolling and adherent fluorescence-labelled platelets and leucocytes were investigated by IVM. RESULTS: In arthritic P-selectin-deficient mice (rolling: 0.05+/-0.01; adherent: 130+/-20 mm(-2)), compared to arthritic C57/Bl6 mice (rolling: 0.20+/-0.04; adherent: 1910+/-200 mm(-2)), platelet interaction was significantly reduced (p<0.05) and reached the level of both control groups without AiA. In addition, interaction of leucocytes in P-selectin-deficient arthritic animals (rolling: 0.12+/-0.06; adherent: 387+/-37 mm(-2)) was significantly decreased in comparison to arthritic C57/Bl6 animals (rolling: 0.21+/-0.06; adherent: 1492+/-284 mm(-2); p<0.05). Swelling of the knee joint and histological scoring were reduced in arthritic P-selectin-deficient mice compared to arthritic C57/Bl6 mice. CONCLUSION: We have demonstrated for the first time in vivo a significant decrease in the interaction of platelets and leucocytes with the endothelium in P-selectin-deficient mice with AiA and a reduction in clinical and histological symptoms of arthritis. These findings suggest that leucocyte-endothelial cell interactions depend at least partially on platelet P-selectin and therefore platelets may be responsible for the leucocyte tissue damage in AiA.
16446378 Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflam 2006 Feb 20 Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the synovial fluid of rheumatoid arthritis (RA) patients. Although the role of PGE2 in RA has been well studied, how much PGI2 contributes to RA is little known. To examine this issue, we backcrossed mice lacking the PGI receptor (IP) to the DBA/1J strain and subjected them to collagen-induced arthritis (CIA). IP-deficient (IP-/-) mice exhibited significant reduction in arthritic scores compared with wild-type (WT) mice, despite anti-collagen antibody production and complement activation similar to WT mice. IP-/- mice also showed significant reduction in contents of proinflammatory cytokines, such as interleukin (IL)-6 in arthritic paws. Consistently, the addition of an IP agonist to cultured synovial fibroblasts significantly enhanced IL-6 production and induced expression of other arthritis-related genes. On the other hand, loss or inhibition of each PGE receptor subtype alone did not affect elicitation of inflammation in CIA. However, a partial but significant suppression of CIA was achieved by the combined inhibition of EP2 and EP4. Our results show significant roles of both PGI2-IP and PGE2-EP2/EP4 signaling in the development of CIA, and suggest that inhibition of PGE2 synthesis alone may not be sufficient for suppression of RA symptoms.
18480308 Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced art 2009 May OBJECTIVES: Patients with rheumatoid arthritis (RA) have defective CD4(+)CD25(+) regulatory T (T(reg)) cells and increased osteoclastogenesis. A similar situation has been described in collagen-induced arthritis (CIA). In this study, it was investigated whether a single transfer of polyclonally activated T(reg) cells inhibits CIA and osteoclastogenesis. METHODS: Purified T(reg) cells were expanded in vitro with anti-CD3 and anti-CD28 antibody-coated beads and injected into DBA/1 mice. Mice were immunised with collagen type II (CII) in complete Freund adjuvant (CFA) and scores of arthritis were recorded. In vitro osteoclastogenesis assays were performed on splenocytes by stimulation with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)kappaB ligand (RANKL). Levels of anti-CII antibody and cytokines were determined in the supernatant using ELISA and Bio-Plex protein array system. RESULTS: It was found that 10(6) activated T(reg) cells significantly counteracted the development of CIA, which was accompanied by decreased serum levels of TNFalpha and IL6, but not by inhibition of autoimmune antibody responses. The differentiation of osteoclasts in splenocyte cultures was significantly reduced in the presence of prestimulated T(reg) cells. Expression of cytokines that are described to inhibit osteoclastogenesis, including granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (IFN)gamma, interleukin (IL)5 and IL10, were dramatically increased upon addition of T(reg) cells. Furthermore, splenocytes from mice that had been treated with T(reg) cells displayed an impaired capacity to develop into mature osteoclasts, suggesting that T(reg) cells abrogated osteoclastogenesis in vivo. CONCLUSIONS: Activated CD4(+)CD25(+) T(reg) cells improve clinical symptoms of CIA, regulate cytokine production and inhibit osteoclastogenesis in vitro and in vivo.
16772045 Induction of PNAd and N-acetylglucosamine 6-O-sulfotransferases 1 and 2 in mouse collagen- 2006 Jun 13 BACKGROUND: Leukocyte recruitment across blood vessels is fundamental to immune surveillance and inflammation. Lymphocyte homing to peripheral lymph nodes is mediated by the adhesion molecule, L-selectin, which binds to sulfated carbohydrate ligands on high endothelial venules (HEV). These glycoprotein ligands are collectively known as peripheral node addressin (PNAd), as defined by the function-blocking monoclonal antibody known as MECA-79. The sulfation of these ligands depends on the action of two HEV-expressed N-acetylglucosamine 6-O-sulfotransferases: GlcNAc6ST-2 and to a lesser degree GlcNAc6ST-1. Induction of PNAd has also been shown to occur in a number of human inflammatory diseases including rheumatoid arthritis (RA). RESULTS: In order to identify an animal model suitable for investigating the role of PNAd in chronic inflammation, we examined the expression of PNAd as well as GlcNAc6ST-1 and -2 in collagen-induced arthritis in mice. Here we show that PNAd is expressed in the vasculature of arthritic synovium in mice immunized with collagen but not in the normal synovium of control animals. This de novo expression of PNAd correlates strongly with induction of transcripts for both GlcNAc6ST-1 and GlcNAc6ST-2, as well as the expression of GlcNAc6ST-2 protein. CONCLUSION: Our results demonstrate that PNAd and the sulfotransferases GlcNAc6ST-1 and 2 are induced in mouse collagen-induced arthritis and suggest that PNAd antagonists or inhibitors of the enzymes may have therapeutic benefit in this widely-used mouse model of RA.
17574466 Reproducibility of metacarpophalangeal bone mass measurements obtained by dual-energy X-ra 2007 Jul The prognostic value of measuring hand bone mineral density (BMD) in patients with early arthritis (EA) has been recently assessed. In this work, we evaluate the reproducibility of measuring juxta-articular BMD by dual-energy X-ray absorptiometry (DXA) at the second to fifth metacarpophalangeal (MCP) joints. We obtained whole hand (WH) and MCP joint BMD measurements from 16 healthy subjects and from 22 patients with EA. The coefficient of variation, intraclass correlation coefficient (ICC), and smallest detectable difference (SDD) were calculated. The coefficient of variation ranged from 1.3% to 0.7% at MCP joints and from 1.4% to 0.9% in the WH measurements, respectively. The intra- and interobserver ICC for both WH and MCP joints ranged from 0.97 to 0.99. The SDD at the different anatomical locations analyzed ranged from 0.006 to 0.022 g/cm2 in healthy controls and from 0.005 to 0.010 g/cm2 in EA. Interestingly, patients who fulfilled rheumatoid arthritis criteria showed a lower bone mass than those with undifferentiated arthritis. Therefore, BMD measurements obtained by DXA at MCP joints were reproducible and it might be useful in the study of patients with EA.
18193705 Accessibility and quality of secondary care rheumatology services for people with inflamma 2007 Dec Secondary care rheumatology services for patients with inflammatory arthritis (IA) in the West Midlands were audited using Arthritis and Musculoskeletal Alliance (ARMA) standards of care. Questionnaires were analysed from 1,715 patients in 11 rheumatology departments. ARMA standards recommend full multidisciplinary team assessment; referral rates to nurse specialists (52.3%), physiotherapists (48.7%) and occupational therapists (36.5%) were, however, lower than expected. Attendance at existing hospital-led education groups was rare (8.9%), awareness of existing helplines was moderate (59.2%) but the proportion of patients reporting satisfaction with advice about their disease was high (80.5%). Significant variations were found between departments. For patients with IA < 2 years (n = 236), 84.5% were seen by a rheumatologist within the ARMA standard of 12 weeks of referral; diagnosis of a type of IA was made at the first rheumatology appointment in 66.4%; 82.8% of rheumatoid arthritis patients had commenced disease-modifying drugs, although time to commencement varied across departments. This study raises issues regarding provision of rheumatology services, prioritisation of patient referral and patient education.
16547285 The potential of adiponectin in driving arthritis. 2006 Apr 1 Articular adipose tissue is a ubiquitous component of human joints, but its local functions are largely unknown. Because recent studies revealed several links between adipose tissue, adipocytokines, and arthritis, we investigated the expression of the adipocytokine adiponectin and its functional role in articular adipose tissue and synovium of patients with different arthritides. In contrast to its protective role in endocrinological and vascular diseases, adiponectin was found to be involved in key pathways of inflammation and matrix degradation in the human joint. The effects of adiponectin in human synovial fibroblasts appear to be highly selective by inducing only two of the main mediators of rheumatoid arthritis pathophysiology, IL-6 and matrix metalloproteinase-1, via the p38 MAPK pathway. Owing to the observation that these effects could be inhibited by different TNF-alpha inhibitors, adipocytokines such as adiponectin may also be key targets for therapeutic strategies in inflammatory joint diseases. In summary, articular adipose tissue and adipocytokines cannot be regarded as innocent bystanders any more in chronic inflammatory diseases such as arthritis.
18481159 The dynamics of articular leukocyte trafficking and the immune response to self heat-shock 2008 Sep INTRODUCTION: Adjuvant arthritis (AA) shares several features with human rheumatoid arthritis, and it can be induced in the Lewis (LEW) rat but not the Wistar Kyoto (WKY) rat (both RT.1(l)) by immunization with heat-killed Mycobacterium tuberculosis (Mtb). We set out to unravel the mechanisms underlying the differential susceptibility to AA of these MHC-compatible rat strains. MATERIALS AND METHODS: We compared the levels of T-cell proliferative and cytokine response to the immunoregulatory self (rat) hsp65 (Rhsp65) after an arthritogenic (Mtb) challenge and the kinetics of migration of adoptively transferred, (111)Indium-labeled, Mtb-primed leukocytes into the hind paw joints of recipient rats. RESULTS AND DISCUSSION: The WKY rats raised a significantly higher level of T-cell proliferative response coupled with a temporally opposite cytokine profile against the disease-regulating Rhsp65 compared to that of LEW rats. Moreover, the arthritogenic leukocytes accumulated into the joints of WKY rats at significantly lower numbers than that in LEW rats. CONCLUSIONS: These results offer novel insights into the immune events influencing the pathogenesis of autoimmune arthritis.
18827803 Chitosan/siRNA nanoparticle-mediated TNF-alpha knockdown in peritoneal macrophages for ant 2009 Jan Secretion of tumor necrosis factor-alpha (TNF-alpha) by macrophages plays a predominant role in the development and progression of rheumatoid arthritis. We demonstrate that knockdown of TNF-alpha expression in systemic macrophages by intraperitoneal (i.p.) administration of chitosan/small interfering RNA (siRNA) nanoparticles in mice downregulates systemic and local inflammation. Chitosan nanoparticles containing an unmodified anti-TNF-alpha Dicer-substrate siRNA (DsiRNA) mediated TNF-alpha knockdown (approximately 66%) in primary peritoneal macrophages in vitro. The presence of Cy3-labeled nanoparticles within peritoneal macrophages and specific TNF-alpha knockdown (approximately 44%) with TNF-alpha siRNA after i.p. injection supports our therapeutic approach. Downregulation of TNF-alpha-induced inflammatory responses arrested joint swelling in collagen-induced arthritic (CIA) mice dosed i.p. with anti-TNF-alpha DsiRNA nanoparticles. The use of 2'-O-Me-modified DsiRNA resulted in the lowest arthritic scores and correlated with reduced type I interferon (IFN) activation in macrophages in vivo compared with unmodified DsiRNA. Histological analysis of joints revealed minimal cartilage destruction and inflammatory cell infiltration in anti-TNF-alpha-treated mice. The onset of arthritis could be delayed using a prophylactic dosing regime. This work demonstrates nanoparticle-mediated TNF-alpha knockdown in peritoneal macrophages as a method to reduce both local and systemic inflammation, thereby presenting a novel strategy for arthritis treatment.
17097618 Triptolide, a diterpenoid triepoxide, suppresses inflammation and cartilage destruction in 2007 Jan 1 Chinese herbal remedy Tripterygium wilfordii Hook. f. (TWHF) has been reported to be therapeutically efficacious in the treatment of rheumatoid arthritis (RA), but its in vivo actions have not been clarified. The purpose of this study was to investigate the effects of triptolide, a diterpenoid triepoxide extracted from TWHF, on inflammation and cartilage destruction in collagen-induced arthritis (CIA) model mice. Histological examination demonstrated that triptolide significantly reduced the inflammatory responses and cartilage damage in the joint tissues. Interestingly, triptolide interfered with CIA-augmented expression of matrix metalloproteinases-13 and -3, which are considered to be key enzymes in the pathological destruction of cartilage, and simultaneously augmented CIA-reduced tissue inhibitors of metalloproteinases-1 and -2 expression in the joints. Moreover, triptolide inhibited prostaglandin E(2) production via selective suppression of the production and gene expression of cyclooxygenase (COX)-2, but not COX-1. The levels of interleukin (IL)-1beta, tumor necrosis factor alpha and IL-6 were also decreased by triptolide in the joint tissues and sera as well as the suppression of CIA-mediated expression of their mRNAs in the joints. In addition, triptolide treatment in vivo was able to reduce an abundance of nuclear factor-kappaB, the transcriptional factor closely related to the inflammatory process, in articular cartilage and synovium in CIA mice. These results suggest that triptolide exerts novel chondroprotective and anti-inflammatory effects on RA, and the therapeutic action of TWHF on RA is, in part, due to the triptolide activities.
18369366 Synoviolin promotes IRE1 ubiquitination and degradation in synovial fibroblasts from mice 2008 May The E3 ubiquitin ligase synoviolin (SYVN1) functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of rheumatoid arthritis. The molecular mechanisms underlying SYVN1 regulation of cell death are largely unknown. Here, we report that elevated SYVN1 expression correlates with decreased levels of the protein inositol-requiring enzyme 1 (IRE1)-a pro-apoptotic factor in the endoplasmic reticulum (ER)-stress-induced apoptosis pathway-in synovial fibroblasts from mice with collagen-induced arthritis (CIA). SYVN1 interacts with and catalyses IRE1 ubiquitination and consequently promotes IRE1 degradation. Suppression of SYVN1 expression in synovial fibroblasts from CIA mice restores IRE1 protein expression and reverses the resistance of ER-stress-induced apoptosis of CIA synovial fibroblasts. These results show that SYVN1 causes the overgrowth of synovial cells by degrading IRE1, and therefore antagonizes ER-stress-induced cell death.
17440622 Epicutaneous immunization with type II collagen inhibits both onset and progression of chr 2007 Apr 18 Epicutaneous immunization is a potential non-invasive technique for antigen-specific immune-modulation. Topical application of protein antigens to barrier-disrupted skin induces potent antigen-specific immunity with a strong Th2-bias. In this study, we investigate whether the autoimmune inflammatory response of chronic collagen-induced arthritis (CCIA) in DBA/1-TCR-beta Tg mice can be modified by epicutaneous immunization. We show that epicutaneous immunization with type II collagen (CII) inhibited development and progression of CCIA and, importantly, also ameliorated ongoing disease as indicated by clinical scores of disease severity, paw swelling and joints histology. Treated mice show reduced CII-driven T cell proliferation and IFN-gamma production, as well as significantly lower levels of CII-specific IgG2a serum antibodies. In contrast, CII-driven IL-4 production and IgE antibody levels were increased consistent with skewing of the CII response from Th1 to Th2 in treated mice. IL-4 production in treated mice was inversely correlated with disease severity. Moreover, T cells from treated mice inhibited proliferation and IFN-gamma production by T cells from CCIA mice, suggesting induction of regulatory T cells that actively inhibit effector responses in arthritic mice. The levels of CD4(+)CD25(+) T cells were however not increased following epicutaneous CII treatment. Together, these results suggest that epicutaneous immunization may be used as an immune-modulating procedure to actively re-programme pathogenic Th1 responses, and could have potential as a novel specific and simple treatment for chronic autoimmune inflammatory diseases such as rheumatoid arthritis.
17894005 Antibodies against alpha-fodrin are associated with sicca syndrome in the general populati 2007 Jun The significance of antibodies against alpha-fodrin compared to antibodies against Ro (SSA) as markers of Sjögren's syndrome has been controversially discussed. We therefore compared the association of alpha-fodrin and Ro antibodies with dry eyes and dry mouth in the general population. In 168 "normal" participants, the prevalence of IgA antibodies against alpha-fodrin was 5% and of IgG antibodies against alpha-fodrin was 3%. IgA antibodies against alpha-fodrin were present in 3 of 4 and IgG antibodies against alpha-fodrin in 2 of 4 participants with the combination of dry eyes and dry mouth (P = 0.0002 and 0.005). Only one participant had antibodies against Ro and had dry eyes but normal saliva production. Antibodies against alpha-fodrin are associated with sicca syndrome and may be valuable diagnostic markers in patients with Sjögren's syndrome lacking Ro antibodies.
17873760 Pulmonary arterial hypertension: a rare complication of primary Sjögren syndrome: report 2007 Sep Primary Sjögren syndrome (pSS) is a fairly common autoimmune disease with glandular and extraglandular manifestations. Pulmonary involvement mainly corresponds to small airways and interstitial lung disease. Pulmonary arterial hypertension (PAH) is rare: to our knowledge, only 32 cases have been reported in pSS patients to date. PAH is a disease of the small pulmonary arteries characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary vascular resistance, and, ultimately, right ventricular failure and death. We report 9 new cases of pSS-associated PAH with a complete assessment including clinical characteristics (of both PAH and pSS), hemodynamic parameters, medical management, and outcome. We also review the 19 fully documented PAH patients with pSS reported in the English-language literature, therefore analyzing a total of 28 cases (27 women; mean age at PAH diagnosis, 50 +/- 11 yr; range, 23-68 yr). Functional impairment at diagnosis was severe, with a New York Heart Association (NYHA) functional class of III or IV in most cases. Seven of 15 (47%) patients for whom data were available had history or evidence of right heart failure at PAH diagnosis. Hemodynamic parameters were moderate to severe with a mean pulmonary artery pressure of 44 +/- 11 mm Hg (range, 24-60 mm Hg) and a cardiac index of 2.91 +/- 0.72 Lmin(-1)m(-2) (range, 1.36-3.88 Lmin(-1)m(-2)). Standard PAH therapy (endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, or prostanoids) was initially effective in some patients but had short-term and long-term failures. Some patients were treated with first-line immunosuppressants alone leading to improvement in some, but second-line standard PAH therapy was added in all cases thereafter. The best treatment strategy remains to be defined. Estimated survival rates were low (73% and 66% at 1 and 3 years, respectively). Compared with pSS patients without PAH, patients with pSS-associated PAH had Raynaud phenomenon, cutaneous vasculitis, and interstitial lung disease significantly more frequently. They also more frequently had antinuclear, anti-Ro/SSA, and anti-RNP autoantibodies, as well as positive rheumatoid factor and hypergammaglobulinemia. These data suggest that systemic vasculopathy, B-cell activation, and autoimmunity could play a role in the pathophysiology of pSS-associated PAH. In conclusion, this report underlines the rarity and severity of PAH in pSS patients. The best therapeutic regimen remains to be defined but should include standard PAH therapy and/or immunosuppressants.
19132150 [Septic arthritis: a 12 years retrospective study in a rheumatological university clinic]. 2008 Oct BACKGROUND: Septic arthritis is a disabling and potentially life-threatening condition that requires prompt diagnosis and treatment. The most important risk factors are joint prosthesis, pre-existing joint disease and immunosuppressive drugs. The aim of our study therefore was to revaluate all septic arthritis cases discharged from our Rheumatologic Unit in the last 12 years, to assess the risk factors, the clinical and laboratory characteristics, the causative microorganisms and its possible increase in frequency. METHODS: The medical records of 42 consecutive patients with septic arthritis discharged from our Rheumatology Unit between January 1995 and December 2006 were reviewed. The patients ranged in age from 23 to 90 and there isn't gender predominance. Septic arthritis was diagnosed based on the finding of purulent material in the joint space and/or the isolation of a bacterial pathogen from joint fluid. Demographic data, risk factors, co-morbidity, clinical manifestations, time interval between symptoms onset and diagnosis, treatment and laboratory data including serum white blood cell count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), synovial white blood cells and culture results were analysed. We considered these parameters in the whole population and in two different age groups (< or =60, >60) and tried to determine if there was a change of microorganisms involved in septic arthritis during the years. RESULTS: Of 42 patients, 47% were aged 60 and younger. Only 10 patients were admitted to our unit before 2001. A predisposing factor was recorded in 90,5% of cases: 15 patients had rheumatoid arthritis, 8 were diabetic, 6 had seronegative arthritis, 4 had a connective tissue disease, 8 patients had a prosthetic infection and 3 were subjected recently to arthrocentesis. We found that patients aged 60 and younger were more frequently affected by joint disease and had a synovial white blood cell count lower than patients older than 60. Staphylococcus aureus caused septic arthritis in 70% of cases before 2001, and only in 35,8 % after 2001. Also, after 2001, some infections were caused by more unusual pathogens, prevalently in patients treated with TNFa inhibitors. Instead Streptococcus infections were found only in patients aged 70 and older. CONCLUSION: The incidence of bacterial arthritis has increased in the last six years and there was a modification of microorganisms involved, possibly related to a greater therapeutic aggressiveness. The increased frequency of joint disease and the use of immunosuppressive drugs in patients under the age of 60 could be responsible for a lower synovial white blood cell count in these patients.