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ID PMID Title PublicationDate abstract
20655576 Neuromyelitis optica spectrum disorder as an initial presentation of primary Sjögren's sy 2011 Feb OBJECTIVES: Longitudinal myelitis in patients with Sjögren's syndrome (SS) is a rarely reported occurrence. Here, we present a patient with longitudinal myelitis who was found to have both primary SS and a positive antibody to aquaporin-4 (NMO-IgG). We review the recent literature concerning the overlap between primary SS-associated myelitis and the presence of NMO-IgG, suggestive of a neuromyelitis optica spectrum disorder (NMOSD). METHODS: A patient with longitudinal myelitis, SS, and a positive NMO-IgG is presented. A review of the relevant English literature based on a PubMed and Embase search is then discussed. The keywords used were Sjögren's syndrome, myelitis (longitudinal and transverse), neuromyelitis optica, and Devic's disease. RESULTS: Our patient fulfills the criteria for both primary SS and NMOSD. Several small studies have shown that most SS patients with longitudinal myelitis are positive for the antibody to aquaporin-4. Additionally, minor salivary gland biopsies of patients with NMO or NMOSD have evidence of lymphocytic inflammation, suggesting that there may be an overlap in the mechanism of NMOSD and longitudinal myelitis secondary to primary SS. This overlap in mechanism may have important ramifications with regard to prognosis and treatment of SS-related myelitis. CONCLUSION: The presentation of longitudinal myelitis in a patient with SS should be considered a possible NMOSD. Checking for the presence antiaquaporin-4 antibodies provides important prognostic information and may help to guide treatment decisions.
19688700 Ocular surface injuries in autoimmune dry eye. The severity of microscopical disturbances 2009 Oct Autoimmune dry eye (Sjögren's syndrome, SS) is a chronic systemic disease characterized by salivary and lacrimal gland inflammation and tissue damage leading to keratoconjunctivitis sicca and xerostomia. In this review attention has been devoted to the cause of the development of oxidative injuries of the ocular surface of patients suffering from SS. It was shown that lacrimal glands and diseased conjunctival epithelium reveal increased expression of pro-inflammatory cytokines which are released into the tear fluid. A high amount of pro-inflammatory cytokines highly induce the elevated expression and activity of enzymatic systems that generate reactive oxygen and nitrogen species. An abundant amount of these toxic products leads to a decrease in antioxidants and to the formation of cytotoxic related oxidants, such as peroxynitrite. All these factors, together with reactive oxygen species from polymorphonuclear leukocytes, contribute to the development of oxidative injuries at the ocular surface. From the clinical point of view it is important that the level of severity of the above described microscopical disturbances found in conjunctival epithelial cells goes parallel with the level of severity of dry eye symptoms.
19833744 Serum amyloid A and C-reactive protein concentrations are differently associated with mark 2009 Nov OBJECTIVE: Primary Sjögren's syndrome (pSS) is an autoimmune disease in which the concentration of the acute-phase protein serum C-reactive protein (CRP) is low. We investigated whether levels of another acute-phase protein, serum amyloid A (SAA), are increased in patients with pSS and whether the immunological markers in patients with pSS are associated with variation in SAA levels. METHODS: Serum SAA concentrations were measured by ELISA in 74 patients with pSS and in 56 control subjects with sicca symptoms. RESULTS: Median SAA levels did not differ significantly between patients with pSS and subjects with sicca symptoms. In patients with pSS SAA concentrations correlated significantly with age, leukocyte count, CRP, interleukin 6, and C4. Unlike CRP, there was a significant inverse correlation between SAA and serum IgG levels and anti-SSA antibody titers, as well as a trend towards an inverse correlation between SAA and antinuclear antibody and rheumatoid factor titers. CONCLUSION: Our data imply that high SAA production could constitute a protective element in pSS: high SAA levels inhibit in particular various signs of B cell hyperreactivity, i.e., IgG and autoantibody production.
19671696 Usefulness of initial histological features for stratifying Sjogren's syndrome responders 2009 Oct OBJECTIVES: To evaluate the response of patients with SS to mizoribine therapy in relation to histological features of minor salivary glands. METHODS: Forty patients definitely diagnosed as having SS were treated with mizoribine (150 mg/day). Thirty-four untreated patients matched for age, baseline salivary secretion, etc., served as controls. Salivary secretion volume (measured by the Saxon test) and serum IgG level were measured before and after 24 weeks of treatment. Each histological finding (lymphocytic infiltration, acinar atrophy and intralobular fibrosis) was graded at baseline and the therapeutic responses were compared with the grade at 24 weeks in both the groups. RESULTS: There was a significant increase of the salivary secretion volume after treatment with mizoribine as compared with the untreated control group. The effect of mizoribine on salivary secretion was more marked in patients having moderate lymphocytic infiltration and moderate or less severe acinar atrophy and intralobular fibrosis at baseline. CONCLUSIONS: Mizoribine was clinically effective in patients with SS whose minor salivary glands had moderate cell infiltration and were free of intralobular fibrosis. The drug was less effective in patients who presented intralobular fibrosis. Histological evaluation of the minor salivary glands may serve to predict the response of SS patients to mizoribine therapy.
20410069 Cytokines in Sjogren's syndrome: potential therapeutic targets. 2010 Jun The dysregulated cytokine network in Sjögren's Syndrome (SS) is reflected by local and systemic overexpression of pro-inflammatory cytokines and absent or low levels of anti-inflammatory cytokines. To date, the use of cytokine based therapies in SS has been disappointing. Oral administration of low dose interferon (IFN) alpha showed inconsistent efficacy in various studies and failed to achieve the primary endpoint in a pivotal randomised controlled trial. Similarly, neither of the two tumour necrosis factor (TNF)-alpha blockers tested (etanercept and infliximab) showed efficacy in placebo controlled trials. Although the rationale for low dose oral IFN treatment has not been firmly established, TNF blockade was based on solid preclinical data. Therefore, the reason for the lack of efficacy is unclear, but recent data suggest that unexpected biological effects of TNF antagonists may have contributed to this. Cytokines, given their central role in the pathogenesis of SS, remain attractive targets for future treatments, despite the disappointing early results. Inflammatory cytokines are obvious candidates, and agents against several of them are available or under development for other autoimmune diseases similar to SS. New candidate cytokines such as IL-17 and IL-12 and/or IL-23 may provide promising targets for SS. Additionally, as an alternative to systemic treatment, which has the risk of potentially severe side effects, the use of local cytokine directed therapy should be explored.
20008923 Pulmonary manifestations in Sjogren's syndrome: correlation analysis between chest compute 2010 Feb OBJECTIVE: Sjögren's syndrome (SS) has a varied clinical spectrum and has been associated with various chest computed tomography (CT) findings. We sought to delineate the characteristic CT features in various subsets of SS, especially poor prognosis subsets. METHODS: Retrospectively identified 80 never-smoker SS patients [56 primary SS (1-SS), 24 secondary SS (2-SS)] who underwent chest CT at our institution during a 3-year period from 2004 through 2007 were included in this study. Chest CT findings were qualitatively and semiquantitatively analyzed with comparison between 1-SS and 2-SS, and correlation with anti-SSB/La seropositivity and the presence of clonally derived lymphoproliferative disorder (cLPD), which are known to be pathognomonic and prognostic clinical features of SS patients. RESULTS: All patients were women with median age of 60 years. Anti-SSB/La antibodies were found in 17 primary SS patients and 4 2-SS patients. Eleven patients with cLPD were identified and all of them had 1-SS. The most frequent CT finding in both types of patients was interlobular septal thickening. Secondary SS was associated with a significantly greater frequency and extent of honeycombing versus 1-SS. Univariate and multivariate analysis showed a significant association between honeycombing and 2-SS. In patients with 1-SS and in the SS group as a whole, we observed independent and significant associations between cysts and anti-SSB/La seropositivity or cLPD. CONCLUSION: Cysts are significantly associated with anti-SSB/La seropositivity and cLPD. The presence of lung cysts revealed by chest CT might be a prognostic clinical feature, a clue, or a predictor of cLPD in patients with SS.
19103199 Differential gene expressions in the lacrimal gland during development and onset of kerato 2009 Mar Recently, we reported development of the C57BL/6.NOD-Aec1Aec2 mouse carrying two genetic intervals derived from the NOD mouse. These two genetic regions confer Sjögren's syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. In an attempt to define the molecular bases underlying onset of dacryoadenitis and subsequently keratoconjunctivitis sicca (or xerophthalmia) in the C57BL/6.NOD-Aec1Aec2 mouse model, we have carried out a study utilizing microarray technology. Using oligonucleotide microarrays, gene expression profiles of lacrimal glands at 4, 8, 12, 16 and 20weeks of age were generated for C57BL/6.NOD-Aec1Aec2 male mice. Analyses using Linear Models for Microarray Analysis package and B-statistics, 552 genes were identified as being differentially expressed (adjusted p-value <0.01 and B <1.5) during the development of SjS-like disease. These 552 genes could be arranged into four clusters, with each cluster defining a unique pattern of temporal expression, while the individual genes within each cluster could be grouped according to related function. Using a pair-wise analysis, temporal changes in gene expressions provided profiles indicating that individual genes were differentially expressed at specific time points during development of SjS. In addition, multiple genes that have been reported to show, either in humans or mouse models, an association with autoimmunity and/or SjS, e.g., ApoE, Baff, Clu, Ctla4, Fas/Fasl, Irf5, Lyzs, Nfkb, Socs3, Stat4, Tap2, Tgfbeta1, Tnfa, and Vcam1 were also found to exhibit differential expressions, both quantitatively and temporally. Selecting a few families of genes, e.g., cystatins, cathepsins, metalloproteinases, lipocalins, complement, kallikreins, carbonic anhydrases and tumor necrosis factors, it was noted that only a limited number of family members showed differential expressions, suggesting a restricted glandular expression. Utilizing these genes, pathways of inter-reactive genes have been constructed for apoptosis and fatty acid homeostasis, leading to modeling of possible underlying events inducing disease. Thus, these different approaches to analyze microarray data permit identification of multiple sets of genes of interest whose expressions and expression profiles may correlate with molecular mechanisms, signaling pathways and/or immunological processes involved in the development and onset of SjS in this mouse model, thereby providing new insight into the underlying cause or regulation of this disease.
20852574 Effect of wrist involvement on median nerve electrophysiology in juvenile idiopathic arthr 2009 Oct OBJECTIVES: Localized compression of the median nerve due to wrist arthritis is a frequently reported complication in adult patients with rheumatoid arthritis. However, in only two cases median nerve compression has been reported in juvenile idiopathic arthritis (JIA) patients. In this study, we aimed to assess the effect of wrist involvement on median nerve electrophysiology in JIA patients. PATIENTS AND METHODS: Thirty-three patients fulfilling the diagnostic criteria for JIA according to the International League of Associations for Rheumatology and twenty-three healthy controls were enrolled. All subjects underwent a thorough neuromuscular examination and median and ulnar nerve conduction studies. The presence of wrist arthritis was noted. Complete blood count, erythrocyte sedimentation rate, C reactive protein, renal/liver function tests were measured. RESULTS: Sensory examination and provocative tests for CTS were normal both in patient and control groups. Age, height and electrophysiological data of the subjects were compared within three groups: JIA patients with wrist arthritis, those without wrist arthritis and healthy controls. None of the electrophysiological data of median nerve revealed significant differences between groups. CONCLUSIONS: In the light of our preliminary results, the median nerve seems not to be affected due to wrist involvement in patients with JIA.
20030169 [Environmental factors and autoimmunity]. 2009 Oct Autoimmune diseases have a multifactorial pathogenesis. If many genetic factors, such as the role of major hystocompatibility complex, are called in cause for the risk of these diseases, many environmental factors are discovered as actors in the pathogenesis. In this paper we evaluated the role of the exposition to UVB rays, the role of activation of vitamin-D and the development of autoimmunity. We also observed the role of toxic esogen agents in the air, with particular attention for exposition workers. Finally, the role of cigarette smoking, and the development of particular autoantibodies such as rheumatoid factors and anti-cyclic citrullinated peptide in the pathogenesis of rheumatoid arthritis, are discussed.
20810246 Aberrant expression of CD6 on B-cell subsets from patients with Sjögren's syndrome. 2010 Dec CD6 is one of a pair of related genes encoding CD5-associated receptors on all T cells and a subset of B cells. The current availability of "T1h", a humanized anti-CD6 monoclonal antibody for B cell-mediated autoimmune disorders revives analysis of the B-cell subset expression of CD6, particularly in primary Sjögren's syndrome (SS). Refined phenotype of B-lymphocytes peripheral blood (PB), bone marrow and tonsils revealed that the overlap between the expression of CD6 is less close to that of CD5 than currently acknowledged. In contrast to CD5, CD6 is absent on transitional B cells, while present on mature and memory B cells. Interestingly, the PB proportion of CD6(+) B cells is decreased in patients with primary SS, as opposed to those with rheumatoid arthritis. The reduction in primary SS does not result from the shedding of CD6 from the membrane of B cells, but from the lowering of memory B lymphocytes. It may result from the ability of CD6 to make transmigration of CD27(+) memory B cells into the salivary glands (SGs) easier. Consistent with this view is our finding that CD166 (one of the ligands for CD6) is highly expressed on epithelial cells of patients' SGs. This study is relevant in that the humanized T1h anti-CD6 becomes an alternative to anti-CD20 for treatment of primary SS.
20409741 Psoriatic arthritis: correlation between imaging and pathology. 2010 May Psoriatic arthritis (PsA) is an archetypal type of spondyloarthritis, but may have some features of rheumatoid arthritis, namely a small joint polyarthritis pattern. Most of these features are well demonstrated on imaging, and as a result, imaging has helped us to better understand the pathophysiology of PsA. Although the unique changes of PsA such as the "pencil-in-cup" deformities and periostitis are commonly shown on conventional radiography, PsA affects all areas of joints, with enthesitis being the predominant pathology. Imaging, especially magnetic resonance imaging (MRI) and ultrasonography, has allowed us to explain the relationships between enthesitis, synovitis (or the synovio-entheseal complex) and osteitis or bone oedema in PsA. Histological studies have complemented the imaging findings, and have corroborated the MRI changes seen in the skin and nails in PsA. The advancement in imaging technology such as high-resolution "microscopy" MRI and whole-body MRI, and improved protocols such as ultrashort echo time, will further enhance our understanding of the disease mechanisms. The ability to demonstrate very early pre-clinical changes as shown by ultrasonography and bone scintigraphy may eventually provide a basis for screening for disease and will further improve the understanding of the link between skin and joint disease.
19675584 Progress and Prospects: genetic treatments for disorders of bones and joints. 2009 Aug Gene therapies directed toward the treatment of arthritis and tissue repair continue to be the most active areas of research for bone and joint diseases. In the past 2 years, two trials in rheumatoid arthritis have been completed. a Phase I study reporting safety and a Phase I/II study that has yet to be published. An additional, small study has reported the first evidence of clinical efficacy. Two Phase I trials of gene therapy for osteoarthritis have also been initiated. There is much preclinical activity in developing AAV vectors for future trials in the gene therapy of arthritis. Research into tissue repair and regeneration remains at the preclinical stage, but a considerable volume of research attests to the promise of gene transfer in this arena, especially in the context of bone healing. For tissue repair, the major research questions are still which genes to use and how best to deliver them.
21218014 Juvenile idiopathic arthritis: Diagnosis and differential diagnosis. 2010 Nov Juvenile idiopathic arthritis (JIA) is comprised of a heterogeneous group of several disease subtypes that are characterized by the onset of arthritis before the age of 16 years and has symptoms lasting at least 6 weeks. The previous classification of JIA included seven different categories, whereas its current classification was compiled by the International League of the Association for Rheumatology, and replaced the previous terms of "juvenile chronic arthritis" and "juvenile rheumatoid arthritis," which were used in Europe or North America, respectively, with the single nomenclature of JIA. As mentioned above, JIA is defined as arthritis of unknown etiology that manifests itself before the age of 16 years and persists for at least 6 weeks, while excluding other known conditions. The clinical symptoms of JIA can be quite variable. Several symptoms that are characteristic of arthritis are not necessarily diagnostic of JIA and may have multiple etiologies that can be differentiated with careful examination of patient history. The disease may develop over days or sometimes weeks, thereby making the diagnosis difficult at the time of presentation. To make a clinical diagnosis of JIA, the first step is to exclude arthritis with known etiologies. Of note, late treatment due to excessive delay of diagnosis can cause severe damage to joints and other organs and impair skeletal maturation. Therefore, early detection of JIA is critical to ensure prompt treatment and to prevent long-term complications including the likelihood of disability in childhood.
21218015 Treatment of juvenile rheumatoid arthritis. 2010 Nov The systematic approach to pharmacologic treatment is typically to begin with the safest, simplest, and most conservative measures. It has been realized that the more rapidly inflammation is under control, the less likely it is that there will be permanent sequelae. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of initial treatment for inflammation. In addition, the slow-acting antirheumatic drugs (SAARDs) and disease-modifying antirheumatic drugs (DMARDs) have efficacy of anti-inflammatory action in children with chronic arthritis. New therapeutic modalities for inflammation, such as etanercept and infliximab, promise even further improvements in the risk/benefit ratio of treatment. It is not typically possible at the onset of the disease to predict which children will recover and which will go on to have unremitting disease with lingering disability or enter adulthood with serious functional impairment. Therefore, the initial therapeutic approach must be vigorous in all children.
20819406 Oral manifestations and treatment of a child with Sjögren's syndrome. 2010 May Sjögren's syndrome (SS) is a chronic inflammatory systemic autoimmune disease affecting the exocrine, salivary and lacrimal glands. The condition occurs more often in adults and is rare in childhood. SS should be considered in the differential diagnosis of recurrent parotitis and keratoconjunctivitis sicca. Oral manifestations include early tooth decay and xerostomia. Treatment consists of operative dentistry and saliva management. This paper reports a case of a 10-year-old Brazilian boy with SS, stressing the oral manifestations, treatment conduct, clinical importance and need for an early diagnosis in order to improve the patient's quality of life.
20190674 Oral status and Candida colonization in patients with Sjögren's Syndrome. 2010 Mar 1 OBJECTIVE: To determine the oral status, salivary flow rate, Candida carriage in saliva, and prevalence of Candida albicans colonization in several areas of the mouth in patients with primary and secondary Sjögren's syndrome as opposed to those of healthy subjects. STUDY DESIGN: Thirty-seven patients with Sjögren's syndrome (SS), [14 patients with primary SS (SS-1) and 23 patients with secondary SS (SS-2)], along with 37 healthy controls were examined in regard to number of teeth, pro-bing pocket depth (PPD), approximal plaque index (API), bleeding on probing (BOP), presence of prosthetic appliances and smoking habits. Salivary flow rate (SFR), Candida carriage in saliva, presence of Candida albicans colonization on buccal, angular, palatal and sulcular areas, on dentures and on the tongue's dorsal surface were determined. Statistical analyses were performed using the 2-tailed Fisher exact and Kruskal-Wallis test. RESULTS: No statistically significant difference was found between SS-1 and SS-2 groups based on the parameters analysed. Statistically significant differences were observed between patients with SS and healthy subjects in terms of SFR, oral signs and symptoms, API, BOP, C. albicans colonization on tongue and buccal area, and Candida carriage in saliva. In the gingival crevicular fluid positive C. albicans colonization was found in only one subject of SS subgroup. CONCLUSIONS: SS patients carry a higher risk of having periodontitis and are more predisposed to develop candidiasis. C. albicans is scarcely detected in gingival crevicular fluid despite high scores on C. albicans colonization in different areas of the oral cavity in SS patients.
20040528 Incidence of malignancy in primary Sjogren's syndrome in a Chinese cohort. 2010 Mar OBJECTIVES: To evaluate the incidence of malignancies in a cohort of Chinese patients with primary Sjögren's syndrome (pSS) and to identify the risk factors of malignancy in pSS patients. METHODS: A retrospective analysis was carried out in 1320 pSS patients who were recruited in Peking Union Medical College Hospital from 1990 to 2005 and were followed up for an average of 4.4 years. Among them, 29 patients developed malignancies. Standardized incidence ratios (SIRs) were calculated along with 95% CIs. Clinical characteristics were compared between patients with and without malignancies, as well as patients with haematological and non-haematological tumours. RESULTS: Of the pSS patients, 2.2% developed malignancies during follow-up. Total SIR and SIR for lymphoma were 3.25 and 48.1, respectively. Different types of malignancy were observed including eight lymphomas, two myeloid myelomas and 19 solid tumours, which consisted of invasive thymoma, breast cancer, lung cancer, gastrointestinal adenocarcinoma, hepatoma, squamous cell carcinoma of tongue, uterine cervix cancer, renal carcinoma, thyroid carcinoma and mucoepidermoid carcinoma of parotid gland. Risk factor analysis showed that lymphadenopathy, enlargement of parotid glands, monoclonal immunoglobulin and absence of hypergammaglobulinaemia were correlated with malignancies. CONCLUSIONS: The current study confirms the increased incidence of lymphoma in Chinese patients with pSS, with the majority of B-cell non-Hodgkin's lymphoma. Associations between pSS and other malignant tumours such as myeloid myeloma, mouth cancer, breast cancer and thymoma need to be further observed.
20981451 Effects of reduced saliva production on swallowing in patients with Sjogren's syndrome. 2011 Sep This study aimed to further characterize the nature of swallowing dysfunction in patients with Sjogren's syndrome (SS). Subjects filled out a perception of swallow function form. Measures of stimulated salivary flow rate were also taken, and videofluoroscopic evaluation of swallowing was completed. The amount of saliva produced by patients with SS was significantly less than that produced by normal age-matched controls, and these patients perceived their swallowing to be impaired. Few statistically significant differences were found between the SS group and normal age-matched controls on temporal measures of swallowing, and 96% of swallows in the SS group were judged to be functional. There was no correlation between perception of swallowing and amount of saliva produced. No strong correlations were found between temporal measures of swallowing and salivary flow rate. Results indicated that patients with SS tend to perceive their swallowing to be worse than physiologic swallowing measures indicate. The decreased saliva production in these patients does not appear to be the cause of their perceived swallowing difficulty but may affect their sensory judgment of swallow function. Future studies will focus on how quality of saliva affects swallowing in these patients.
20444862 Disruption of brain white matter microstructure in primary Sjögren's syndrome: evidence f 2010 Aug OBJECTIVES: The relationship between cognitive symptoms and underlying neuropathology in primary SS (PSS) is poorly understood. We used high-resolution quantitative brain MRI to identify potential structural correlates of cognitive symptoms. METHODS: Subjects completed a comprehensive neuropsychometric evaluation. Imaging was performed on a 3 T MRI scanner with T(1) and proton density-weighted, fluid-attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI) sequences. We compared MRI group metrics (impaired PSS, not-impaired PSS and controls) and tested for correlations between DTI results and neuropsychological measurements (significance threshold P = 0.05). RESULTS: Nineteen PSS patients (who met American-European Consensus Group 2002 criteria) and 17 healthy controls completed the cognitive evaluation. MRI scans were performed in six impaired PSS, seven not-impaired PSS and seven controls. No differences were found in regional volumetrics, nor was there a difference in T(2) lesion load between groups. Fractional anisotropy (FA) in the inferior frontal white matter (WM) was lower (P = 0.021) and mean diffusivity higher (P = 0.003) in the impaired PSS relative to the control group. Inferior frontal FA was correlated with cognitive symptoms (P = 0.0064) and with verbal memory (P = 0.0125). CONCLUSIONS: In this exploratory study, frontal region WM microstructure alterations accompanied cognitive symptoms and were associated with mild cognitive impairment in PSS. While additional study is warranted to assess the specificity and stability of these results, DTI could provide novel insight into the pathological processes accompanying the subtle cognitive dysfunction commonly experienced by PSS patients.
20087268 [Adult-onset Still's disease with pulmonary and cardiac involvement and response to intrav 2009 Oct Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.