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ID PMID Title PublicationDate abstract
12220549 IL-6 in autoimmune disease and chronic inflammatory proliferative disease. 2002 Aug Interleukin 6 (IL-6), which was originally identified as a B-cell differentiation factor, is now known to be a multifunctional cytokine that regulates the immune response, hematopoiesis, the acute phase response, and inflammation. Deregulation of IL-6 production is implicated in the pathology of several disease processes. The expression of constitutively high levels of IL-6 in transgenic mice results in fatal plasmacytosis, which has been implicated in human multiple myeloma. Increased IL-6 levels are also observed in several diseases, including rheumatoid arthritis (RA), systemic-onset juvenile chronic arthritis (JCA), osteoporosis, and psoriasis. IL-6 is critically involved in experimentally induced autoimmune disease, such as antigen-induced arthritis (AIA), and experimental allergic encephalomyelitis. All these clinical data and animal models suggest that IL-6 plays critical roles in the pathogenesis of autoimmune diseases. Here we review the evidence for the involvement of IL-6 in the pathophysiology of autoimmune diseases and chronic inflammatory proliferative diseases (CIPD) and discuss the possible molecular mechanisms of its involvement.
12086292 Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors. 2002 Short-term endoscopic studies of the highly selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) rofecoxib and celecoxib have shown that these agents are well tolerated and have efficacy equivalent to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) with fewer adverse effects on the upper gastrointestinal (GI) tract. These studies are limited, however, as the detection of endoscopic lesions is not well correlated with symptomatic ulcers and ulcer complications. Outcomes studies of the GI safety are, therefore, essential to understanding how coxibs are likely to perform in a clinical practice setting. Four large outcomes studies (Vioxx Gastrointestinal Outcomes Research, VIGOR; Assessment of Difference Between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness trial, ADVANTAGE; Celecoxib Long-term Arthritis Safety Study, CLASS; and the Successive Celecoxib Efficacy and Safety Studies, SUCCESS) examined the GI safety of rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID (naproxen, ibuprofen, or diclofenac). Reduced risk of upper GI events was seen in patients with multiple risk factors and in patients using low-dose aspirin and corticosteroids concomitantly with a coxib. Results of large outcomes studies provide support for the COX-2 hypothesis and demonstrate the long-term safety and tolerability of coxibs.
12398560 Impact of NSAIDs prior authorization policy on patients' QoL. 2002 Nov BACKGROUND: In 1996, the West Virginia Medicaid program targeted nonsteroidal antiinflammatory drugs (NSAIDs) for prior authorization (PA) to ensure cost-effective and appropriate utilization. PA guidelines required that patients must have tried and failed treatment with 2 different classes of generic NSAIDs before a brand-name NSAID could be approved. OBJECTIVE: To evaluate the impact of the requirement of PA for branded NSAIDs on the health-related quality of life (HRQoL) of patients who are chronic users of NSAIDs. DESIGN: Pre- and postintervention quasiexperimental design was used for this study. The sample consisted of continuously eligible Medicaid recipients who were <65 years old and who were diagnosed with rheumatoid arthritis, osteoarthritis, spondylitis, or chronic pain syndromes. Data were collected through a mail survey using the abbreviated version of the Arthritis Impact Measurement Scales. RESULTS: A total of 181 (37.1%) completed surveys were received, 110 (39.2%) from the branded-NSAID user group and 71 (32.7%) from the generic-NSAID user group. Patients who were restricted to generic NSAIDs did not report deterioration in any of the HRQoL domains measured, including mobility, walking and bending, hand and finger function, self care, household activities, social activities, and tension. CONCLUSIONS: The requirement of PA for the use of branded NSAIDs did not compromise patients' HRQoL at 8 weeks follow-up.
15316093 Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molec 2005 Jan Demonstration that IkappaB kinase 2 (IKK-2) plays a pivotal role in the nuclear factor-kappaB-regulated production of proinflammatory molecules by stimuli such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 suggests that inhibition of IKK-2 may be beneficial in the treatment of rheumatoid arthritis. In the present study, we demonstrate that a novel, potent (IC(50) = 17.9 nM), and selective inhibitor of human IKK-2, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), inhibits lipopolysaccharide-induced human monocyte production of TNF-alpha, IL-6, and IL-8 with an IC(50) = 170 to 320 nM. Prophylactic administration of TPCA-1 at 3, 10, or 20 mg/kg, i.p., b.i.d., resulted in a dose-dependent reduction in the severity of murine collagen-induced arthritis (CIA). The significantly reduced disease severity and delay of disease onset resulting from administration of TPCA-1 at 10 mg/kg, i.p., b.i.d. were comparable to the effects of the antirheumatic drug, etanercept, when administered prophylactically at 4 mg/kg, i.p., every other day. Nuclear localization of p65, as well as levels of IL-1beta, IL-6, TNF-alpha, and interferon-gamma, were significantly reduced in the paw tissue of TPCA-1- and etanercept-treated mice. In addition, administration of TPCA-1 in vivo resulted in significantly decreased collagen-induced T cell proliferation ex vivo. Therapeutic administration of TPCA-1 at 20 mg/kg, but not at 3 or 10 mg/kg, i.p., b.i.d., significantly reduced the severity of CIA, as did etanercept administration at 12.5 mg/kg, i.p., every other day. These results suggest that reduction of proinflammatory mediators and inhibition of antigen-induced T cell proliferation are mechanisms underlying the attenuation of CIA by the IKK-2 inhibitor, TPCA-1.
12816989 A role for the lymphotoxin/LIGHT axis in the pathogenesis of murine collagen-induced arthr 2003 Jul 1 A lymphotoxin-beta (LTbeta) receptor-Ig fusion protein (LTbetaR-Ig) was used to evaluate the importance of the lymphotoxin/LIGHT axis in the development and perpetuation of arthritis. Prophylactic treatment with the inhibitor protein LTbetaR-Ig blocked the induction of collagen-induced arthritis in mice and adjuvant arthritis in Lewis rats. Treatment of mice with established collagen-induced arthritis reduced the severity of arthritic symptoms and joint tissue damage. However, in a passive model of anti-collagen Ab-triggered arthritis, joint inflammation was not affected by LTbetaR-Ig treatment precluding LT/LIGHT involvement in the very terminal immune complex/complement/FcR-mediated effector phase. Collagen-II and Mycobacterium-specific T cell responses were not impaired, yet there was evidence that the overall response to the mycobacterium was blunted. Serum titers of anti-collagen-II Abs were reduced especially during the late phase of disease. Treatment with LTbetaR-Ig ablated follicular dendritic cell networks in the draining lymph nodes, suggesting that impaired class switching and affinity maturation may have led to a decreased level of pathological autoantibodies. These data are consistent with a model in which the LT/LIGHT axis controls microenvironments in the draining lymph nodes. These environments are critical in shaping the adjuvant-driven initiating events that impact the subsequent quality of the anti-collagen response in the later phases. Consequently, blockade of the LT/LIGHT axis may represent a novel approach to the treatment of autoimmune diseases such as rheumatoid arthritis that involve both T cell and Ab components.
15156903 Helicobacter pylori associated antigastric autoantibodies: role in Sjögren's syndrome gas 2004 Feb BACKGROUND: Previous studies have shown that Helicobacter pylori seroprevalence in Sjögren's syndrome is comparable with that of the general population. However, the origin of the chronic gastropathy associated with this syndrome and the role of local autoimmunity--possibly triggered by bacterial infection--in its pathogenesis remain unclear. MATERIALS AND METHODS: We initially determined the prevalence of IgG anti H. pylori in dyspeptic subjects with and without Sjögren's syndrome. In subsets of both groups we then determined anti CagA and human tissue-tested anticanalicular/antifoveolar autoantibodies. We also compared activity, atrophy and Mucosa Associated Lymphoid Tissue (MALT) scores, as well as symptoms, before and after bacterial eradication. RESULTS: Prevalence of H. pylori in Sjögren's syndrome patients was similar to controls: 31/54 (57%) vs. 93/150 (62%). Anti CagA prevalence was also similar in the two groups. Twenty weeks after H. pylori eradication, histological activity decreased in both groups, however, atrophy and MALT decreased significantly only in controls. Sixteen months after H. pylori eradication, 75% of Sjögren's syndrome patients still complained of dyspepsia compared with 13% of controls. Finally, antigastric autoantibodies were present in 29% of tested Sjögren's syndrome patients vs. 28% of controls. CONCLUSIONS: H. pylori infection was equally prevalent among dyspeptic Sjögren's syndrome patients and dyspeptic controls. Likewise, there were no differences regarding anti CagA prevalence or antigastric autoantibodies among the two groups. The persistence of symptoms as well as of the lymphocytic infiltration and atrophy after H. pylori eradication in Sjögren's syndrome may underlie the 'endogenous' and still unknown nature of the gastropathy in this condition.
12630566 The role of caspase cascade on the development of primary Sjögren's syndrome. 2003 Feb Primary Sjögren syndrome (SS) is an autoimmune disease characterized by diffuse lymphoid cell infiltrates in the salivary and lacrimal glands, resulting in symptoms of dry eye and dry mouth due to insufficient secretion. Previously, we have identified the 120 kDa alpha-fodrin as an important autoantigen on the development of SS in both animal model and SS patients, but the mechanism of a -fodrin cleavage leading to tissue destruction in SS remains unclear. In murine primary SS model, tissue-infiltrating CD4+ T cells purified from the salivary glands bear a large proportion of Fas ligand (FasL), and the salivary gland duct cells constitutively possess Fas. Infiltrating CD4+ T cells identified significant 51Cr release against mouse salivary gland (MSG) cells. In vitro studies demonstrated that apoptotic MSG cells result in a specific alpha-fodrin cleavage into 120 kDa, and preincubation with caspase-inhibitor peptides blocked alpha-fodrin cleavage. The treatment with caspase-inhibitors in vivo prevented the development of autoimmune lesions in the salivary and lacrimal glands. Thus, an increased activity in caspase cascade may be involved in the progression of alpha-fodrin proteolysis and tissue destruction on the development of SS.
12810429 Antibiotic treatment and long term prognosis of reactive arthritis. 2003 Jul OBJECTIVE: To evaluate whether a three month course of lymecycline has an effect on the long term prognosis of reactive arthritis (ReA). METHODS: In 1987-88 a double-blind controlled study with three month course of lymecycline/placebo was conducted. 17 of 23 patients treated at the outpatient department of Helsinki University Central Hospital volunteered to take part in a follow up study, where a physical examination were performed, and erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and radiographs of the lumbosacral spine and sacroiliac joints and of symptomatic peripheral joints were examined. RESULTS: 16/17 (94%) patients reported some kind of back pain and 10/17 (59%) peripheral joint symptoms during the follow up. Two patients had unilateral grade 1 sacroiliitis, one patient grade 4 sacroiliitis, and one patient bilateral grade 2 sacroiliitis. In one patient the disease had progressed to ankylosing spondylitis (AS), and in another to chronic spondyloarthropathy. In addition, two patients had small erosions in radiocarpal joints. No statistically significant differences were found between placebo and lymecycline groups in the development of chronic arthritis, sacroiliitis, or AS. CONCLUSION: The results of the initial study showed that long term treatment with lymecycline in patients with acute ReA decreased the duration of arthritis in those with Chlamydia trachomatis triggered ReA, but not in other patients with ReA. Ten years after the acute arthritis one patient had developed AS, and three had radiological sacroiliitis, three patients had radiological changes at peripheral joints. Long term lymecycline treatment did not change the natural history of the disease.
15485021 Unilateral destructive wrist synovitis in juvenile idiopathic arthritis. 2004 Sep OBJECTIVE: To describe the clinical and radiographic features of a group of juvenile idiopathic arthritis (JIA) patients who developed unilateral destructive wrist synovitis. METHODS: All wrist radiographs performed yearly between 1986 and 2002 in JIA patients who had wrist involvement were retrospectively reviewed to identify patients who had unilateral erosive wrist synovitis, defined as a difference of at least -3 units in the Poznanski score between the affected wrist and the unaffected wrist, with the Poznanski score in the unaffected wrist being > -2 units throughout the follow-up period. Clinical and radiographic data obtained during follow-up were recorded for all patients. RESULTS: Of a total of 250 patients for whom we had approximately 900 wrist radiographs, 6 patients were found to have unilateral erosive wrist synovitis. The JIA onset subtype was oligoarticular in 5 patients and polyarticular in 1 patient and the disease duration from presentation to the last follow-up visit ranged from 2 to 16 years. The arthritis course was polyarticular in all patients. Five patients had positive antinuclear antibodies (ANA) and 1 had positive rheumatoid factor (RF). At the last follow-up visit, all patients had some impairment of wrist function and 2 patients had wrist subluxation. There was a marked radiographic damage in all affected wrist, with the Poznanski ranging from -8.0 to -8.50 units in 3 patients and being -5.5, -3.1 and -2.4 units, respectively, in 3 patients. The severity of radiographic damage in the ANA-positive patients with the longest disease duration was comparable to that observed in the RF-positive patient. CONCLUSION: Unilateral erosive wrist synovitis seems to be uncommon in JIA. Patients with unilateral wrist synovitis may be at risk of a destructive course irrespective of the JIA onset subtype.
12591902 Selective activation of the c-Jun NH2-terminal protein kinase signaling pathway by stimula 2003 Feb 17 Activation of CD4(+) T cells is governed by interplay between stimulatory and inhibitory receptors; predominance of stimulatory signals favors autoimmune reactions. In patients with rheumatoid arthritis, expression of the critical costimulatory molecule, CD28, is frequently lost. Instead, CD4(+)CD28(null) T cells express killer immunoglobulin-like receptors (KIRs) with a preferential expression of the stimulatory receptor, CD158j. The frequency of CD4(+)CD28(null) T cells in rheumatoid arthritis (RA) correlates with the risk for more severe disease. Moreover, the KIR2DS2 gene, which encodes for CD158j, is a genetic risk factor for rheumatoid vasculitis. CD158j signals through the adaptor molecule, KARAP/DAP12, to positively regulate cytotoxic activity in NK cells. However, the majority of CD4(+)CD28(null) T cell clones lacked the expression of KARAP/DAP12. Despite the absence of KARAP/DAP12, CD158j was functional and augmented interferon-gamma production after T cell receptor stimulation. Cross-linking of CD158j resulted in selective phosphorylation of c-Jun NH(2)-terminal protein kinase (JNK) and its upstream kinase, MKK4 that led to the expression of ATF-2 and c-Jun, all in the absence of extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Mutation of the lysine residue within the transmembrane domain of CD158j abolished JNK activation, suggesting that an alternate adaptor molecule was being used. CD4(+)CD28(null) T cells expressed DAP10 and inhibition of phosphatidylinositol 3-kinase, which acts downstream of DAP10, inhibited JNK activation; however, no interaction of DAP10 with CD158j could be detected. Our data suggest that CD158j in T cells functions as a costimulatory molecule through the JNK pathway independent of KARAP/DAP12 and DAP10. Costimulation by CD158j may contribute to the autoreactivity of CD4(+)CD28(null) T cells in RA.
15538150 Amyloidosis and lymphoproliferative disease in Sjögren syndrome: thin-section computed to 2004 Nov OBJECTIVE: To describe the thin-section computed tomography (CT) findings of Sjogren syndrome accompanying pulmonary amyloidosis and lymphoproliferative disease and to compare these with histopathologic findings. SUBJECTS AND METHODS: The thin-section CT findings of 5 women (age range: 42-59 years, mean age=50 years) with primary Sjogren syndrome accompanying pulmonary amyloidosis and lymphoproliferative disease were reviewed retrospectively by 2 chest radiologists, and decisions on findings were reached by consensus. The pathologic specimens of parenchymal lesions (nodules, dense consolidation, and cystic lesion at CT) obtained using video-assisted thoracoscopic surgery were studied to compare with the thin-section CT findings. RESULTS: Nodules, observed in all 5 patients, were variable in size and ranged from 3 to 24 mm (mean=9.9 mm) in diameter, with lobulated or irregular margins. Nodular calcifications were present in 3 patients. Cysts, which also were observed in all patients, ranged from 4 to 45 mm (mean=18.6 mm) in diameter, with a thin (1-2 mm) or no visible wall. Multiple cysts were observed, especially in the distal portion of narrowed bronchioles. Nodules and cysts showed a random distribution. Mild bronchial wall thickening with bronchial dilatation was seen in all patients, ground-glass opacities were seen in 3, and consolidation was seen in 1. Nodules, consolidation, and bronchial wall thickening at CT were caused histopathologically by the interstitial and peribronchiolar deposition of mixed amyloid and lymphoproliferative cells. Cysts lined with respiratory epithelium contained amyloid deposition and lymphoproliferative cells in their walls. CONCLUSION: Sjogren syndrome accompanying pulmonary amyloidosis and lymphoproliferative disease manifests as multiple, large, thin-walled cysts; multiple nodules; parenchymal opacity; and bronchiectasis. These findings are caused by the interstitial or peribronchial infiltration of mixed amyloid and lymphoproliferative cells.
15113992 Ultrasonography of salivary glands in primary Sjogren's syndrome. A comparison with magnet 2004 Jul OBJECTIVES: To evaluate ultrasonography (US) of salivary glands in primary Sjögren's syndrome (SS) and to compare US with parotid magnetic resonance (MR) imaging and MR sialography. METHODS: US examination of parotid, submandibular and sublingual glands was performed on 27 patients with primary SS, 27 healthy controls and 27 symptomatic controls without SS. The results were compared with parotid MR imaging and MR sialography and the clinical features of the patients. RESULTS: Salivary gland abnormalities, parenchymal inhomogeneity or adipose degeneration, were visualized in 21 (78%) SS patients, in one healthy control and in two symptomatic controls by US. Eighteen (67%) patients had changes in the parotid and submandibular glands and 8 (30%) changes in the sublingual glands. In the comparison, MR sialography was found to be the most sensitive method (96%), followed by MR imaging (81%) and US (78%), in detecting glandular changes. The specificity of US was 94%. The US and MR results were related to anti-Ro/SSA positivity but not to saliva secretion. The focus scores were related only to parotid MR imaging findings. CONCLUSIONS: US, MR imaging and MR sialography with modern technology have reached such a good accuracy in visualizing glandular structural changes that they are promising alternatives to the conventional invasive examinations in the diagnostics of SS.
12581385 The development and initial validation of the Liverpool sicca index to assess symptoms and 2003 Mar BACKGROUND: A validated measure to assess sicca-related symptoms in patients with primary Sjögren's syndrome (1 degrees SS) is required for clinical studies. METHODS: A self-administered questionnaire was developed to assess sicca-related symptoms and dysfunction in 1 degrees SS. This was administered to three groups of 40 respondents to measure construct validity: 1 degrees SS patients, non-SS patients reporting xerostomia and a non-patient group. The frequency of scores and the mean score for each question were calculated for each group. Reliability was assessed by test/retest. RESULTS: The measure consisted of 28 items divided into five domains. Scores for questions in domains were generally worse (higher) for 1 degrees SS patients than for patients with xerostomia. The non-patient group reported the best (lowest) scores for all questions. The Kappa statistic for all but four questions was greater than 0.6, suggesting good reliability. CONCLUSION: Questionnaire showed good construct validity and reliability. The Liverpool sicca index needs to be further validated in larger, multicentre studies.
12453312 Abnormalities of B cell phenotype, immunoglobulin gene expression and the emergence of aut 2002 Primary Sjögren's syndrome (pSS) is an autoimmune disorder characterized by specific pathologic features and the production of typical autoantibodies. In addition, characteristic changes in the distribution of peripheral B cell subsets and differences in use of immunoglobulin variable-region genes are also features of pSS. Comparison of B cells from the blood and parotid gland of patients with pSS with those of normal donors suggests that there is a depletion of memory B cells from the peripheral blood and an accumulation or retention of these antigen-experienced B cells in the parotids. Because disordered selection leads to considerable differences in the B cell repertoire in these patients, the delineation of its nature should provide important further clues to the pathogenesis of this autoimmune inflammatory disorder.
12140862 [Changes of the nerve fibers innervating the minor salivary glands in Sjögren syndrome]. 2002 Jun 30 INTRODUCTION: A large number of nerve fibres containing different neuropeptides/transmitters are also found in the salivary glands. The number and the distribution of nerve fibres is altered in many diseases, including in Sjögren's syndrome. AIM: Therefore in the present study the distribution and precise localisation of the nerve fibres containing the frequently observed neuropeptides were studied in the minor salivary glands. METHODS: Vasoactive intestinal polypeptide, neuropeptide Y, substance P, calcitonin gene-related peptide, somatostatin, nitric oxide synthase and tyrosine beta-hydroxylase antibodies were used as primary antisera, and then by the aid of avidin-biotin-peroxidase complex method the immunoreactive fibers in human labial glands (control and with Sjögren's syndrome) and in minor glands of the root of the rat's tongue were detected. RESULTS: Large number of vasoactive intestinal polypeptide and nitric oxide synthase immunoreactive nerve fibres were seen around the acini. The neuropeptide Y and tyrosine beta-hydroxylase positive nerve fibres were mainly found around the blood vessels. Some of the IR fibers were also found around the excretory ducts. In the biopsy of patients with Sjögren's syndrome, the acini were destroyed and only few excretory ducts were seen. The number of the nerve fibres was significantly decreased and many degenerated fibres were also observed among the acini. The electron-microscopic examinations showed that the immunoreactive nerve fibres were in close association to the secretory cells, to the smooth muscle cells of blood vessels and to the immunocells. The synaptic gap between the nerve fibres and the target cells were 40-200 nm. CONCLUSIONS: On the bases of the distribution of the different transmitters containing nerve fibres and their relationship to effector cells, the authors suppose that these transmitters control the function of the gland and regulate the blood flow. The close association to immunocells and decreasing the nerve fibres in Sjögren's syndrome imply that they may have also a role in the neuroimmunologic processes.
12106503 Analysis of immunoglobulin light chain rearrangements in the salivary gland and blood of a 2002 Patients with Sjögren's syndrome (SS) have characteristic lymphocytic infiltrates of the salivary glands. To determine whether the B cells accumulating in the salivary glands of SS patients represent a distinct population and to delineate their potential immunopathologic impact, individual B cells obtained from the parotid gland and from the peripheral blood were analyzed for immunoglobulin light chain gene rearrangements by PCR amplification of genomic DNA. The productive immunoglobulin light chain repertoire in the parotid gland of the SS patient was found to be restricted, showing a preferential usage of particular variable lambda chain genes (V lambda 2E) and variable kappa chain genes (V kappa A27). Moreover, clonally related V(L) chain rearrangements were identified; namely, V kappa A27-J kappa 5 and V kappa A19-J kappa 2 in the parotid gland, and V lambda 1C-J lambda 3 in the parotid gland and the peripheral blood. V kappa and V lambda rearrangements from the parotid gland exhibited a significantly elevated mutational frequency compared with those from the peripheral blood (P < 0.001). Mutational analysis revealed a pattern of somatic hypermutation similar to that found in normal donors, and a comparable impact of selection of mutated rearrangements in both the peripheral blood and the parotid gland. These data indicate that there is biased usage of V(L) chain genes caused by selection and clonal expansion of B cells expressing particular V(L) genes. In addition, the data document an accumulation of B cells bearing mutated V(L) gene rearrangements within the parotid gland of the SS patient. These results suggest a role of antigen-activated and selected B cells in the local autoimmune process in SS.
11875835 [Undifferentiated connective tissue disease: clinical and serological profile of 578 patie 2002 Feb 3 INTRODUCTION: Evolution of immunopathological diseases is usually slow and progressive. The term the undifferentiated connective tissue disease (UCTD) is used to describe the phase preceding a defined connective tissue diseases (CTD). AIMS: The objective of this work was evaluate the clinical and serological profile of patients with UCTD, who had been followed between 1994-1999. They have investigated the frequency and the type the developed autoimmune diseases from UCTD. PATIENTS: A total of 578 UCTD patients were evaluated. RESULTS: In 143/578 patients (24.7%) with the UCTD differentiated to systemic connective tissue diseases (28 systemic lupus erythematosus, 26 mixed connective tissue disease, 19 progressive systemic sclerosis, 3 polymyositis/dermatomyositis, 45 Sjögren syndrome, and 22 systemic vasculitis). 86.7 percent (124/143) of the systemic connective disease developed in first two years of UCTD. The condition of 435/578 (75.2%) remained UCTD after 5 years, among them in 82 patients with UCTD was regression of the symptoms. The presence of the fever and anti-DNS antibodies correlated with SLE (P = 0.0104, Fisher exact test), arthritis/arthralgia and anti-RNP antibodies with MCTD (P = 0.0302), Raynaud phenomenon and ANA positivity with PSS (P = 0.0144), xerostomia/xerophtalmia and anti-SSA/SSB antibodies with Sjögren syndromes (P = 0.0144). CONCLUSIONS: The UCTD in our patients seem to represents an dynamic phase, one part of the patients show progression to definite connective tissue diseases, one part show regression, and on part of the patients stay in UCTD phase.
14598662 [A case of Poncet's disease (tuberculous rheumatism) in a patient with chronic renal failu 2003 Oct A 78-year-old man who was undergoing hemodialysis therapy was admitted to our hospital because of sore throat, remittent cervical lymphadenopathy, and polyarthritis over the preceding 4 weeks. On admission, he had bilateral cervical lymphadenopathy. He complained of arthralgia associated with tenderness, warmth and swelling of both elbows, left side wrist and left shoulder joint. The C-reactive protein level on admission was 15.3 mg/dl. Rheumatoid factor, antinuclear antibodies, tuberculin skin test and blood culture were negative. Joint fluid was not aspirated. Radiographs of the joints did not reveal any abnormalities. Acid-fast bacilli were demonstrated in the smear of the cervical lymph node with a fluorochrome rhodamine-auramine stain. Mycobacterium tuberculosis DNA was identified by polymerase chain reaction. We found the presence of caseating granuloma on the biopsy specimens and M.tuberculosis was detected from culture. At that point, we diagnosed this patient as having tuberculous lymphadenitis. His general symptoms resolved rapidly after starting with a three-drug regimen consisting of isoniazid, rifampin and pyrazinamide. His polyarthritis also improved dramatically. Finally we considered that his polyarthritis was tuberculous rheumatism, also called Poncet's disease. Poncet's disease is characterized by sterile polyarthritis during active tuberculosis infection. It is considered a reactive arthritis, which is a different entity from tuberculous arthritis. Although this is a rare disease, we should be aware of it in hemodialysis patient clinics, because the incidence of tuberculosis infection has been reported to be increasing in patients with end-stage renal failure.
15457458 Evidence for coxsackievirus infection in primary Sjögren's syndrome. 2004 Sep OBJECTIVE: Primary Sjögren's syndrome (SS) is an autoimmune disease characterized by activation of minor salivary gland (MSG) epithelial cells and B and T lymphocytic infiltrates. These findings have long encouraged the hypothesis that a persistent viral infection of the MSG epithelial cells may drive the autoimmune response; however, the identity of that virus has remained elusive. The aim of this study was to test this hypothesis. METHODS: We applied the differential display protocol to MSG RNA samples from patients with primary SS and healthy controls. We then used seminested reverse transcriptase-polymerase chain reaction to amplify the 5'-noncoding region (5'-NCR) of the enteroviral genome in 8 patients with primary SS, 9 patients with secondary SS, and 8 control subjects. Immunohistochemistry was performed to study the expression of the VP1 enteroviral capsid protein in MSG biopsy samples from 12 patients with primary SS, 8 patients with secondary SS, and 16 controls. RESULTS: Differential display analysis yielded a 94-bp fragment of coxsackievirus B4 (CVB4) P2A gene in the primary SS samples. The 5'-NCR was amplified in 7 samples from patients with primary SS and in no samples from patients with secondary SS or controls. The 7 amplified products were sequenced; 4 of the sequences were found to be 98-99% identical to the 5'- NCR of CVB4, and 3 were found to be 97-98% identical to the 5'-NCR of CVA13. Immunohistochemistry for the enteroviral capsid protein VP1 revealed positive staining in epithelial cells and lymphocytic infiltrates in 11 primary SS samples, 1 secondary SS sample, and no control samples. CONCLUSION: We provide evidence that primary SS may be associated with coxsackievirus infection of the MSG epithelial cells and focal lymphocytic infiltrates. Our findings are formulated in a hypothesis concerning the possible role of coxsackieviruses in the induction and maintenance of autoimmunity in primary SS.
15077311 Inefficacy of infliximab in primary Sjögren's syndrome: results of the randomized, contro 2004 Apr OBJECTIVE: There is no effective treatment for patients with primary Sjögren's syndrome (SS). Since tumor necrosis factor alpha (TNF alpha) could be a key element in the pathogenesis of primary SS, we conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of infliximab in primary SS. METHODS: A total of 103 patients with primary SS were randomly assigned to receive infliximab infusions (5 mg/kg) or placebo at weeks 0, 2, and 6 and were followed up for 22 weeks. All patients fulfilled the new American-European Consensus Group criteria for SS and had active disease as assessed by values >50 mm on 2 of 3 visual analog scales (VAS) (0-100 mm) that evaluated joint pain, fatigue, and buccal, ocular, skin, vaginal, or bronchial dryness. A favorable overall response was defined as the patient having > or =30% improvement between weeks 0 and 10 in the values on 2 of the 3 VAS. Secondary end points were values on each VAS separately, the number of tender and swollen joints, the basal salivary flow rate, results of the Schirmer test for lacrimal gland function, the focus score on labial salivary gland biopsy, the level of C-reactive protein, and the erythrocyte sedimentation rate evaluated at weeks 0, 10, and 22, as well as quality of life evaluated by use of the generic Short Form 36 questionnaire administered at weeks 0, 10, and 22. RESULTS: At week 10, 26.5% of patients receiving placebo and 27.8% of patients treated with infliximab had a favorable overall response (P = 0.89), and at week 22, 20.4% of the placebo group and 16.7% of the infliximab group had a favorable response (P = 0.62). In addition, the 2 groups did not differ in any of the secondary end points over the 22 weeks of the trial. Severe adverse events reported in the infliximab group did not differ from those observed in previous studies. CONCLUSION: This randomized, double-blind, placebo-controlled study of an anti-TNF agent did not show any evidence of efficacy of infliximab in primary SS.