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ID PMID Title PublicationDate abstract
22466888 Discovery of putative salivary biomarkers for Sjögren's syndrome using high resolution ma 2012 Mar The purpose of the current study was to determine if saliva contains biomarkers that can be used as diagnostic tools for Sjögren's syndrome (SjS). Twenty seven SjS patients and 27 age-matched healthy controls were recruited for these studies. Unstimulated glandular saliva was collected from the Wharton's duct using a suction device. Two µl of salvia were processed for mass spectrometry analyses on a prOTOF 2000 matrix-assisted laser desorption/ionization orthogonal time of flight (MALDI O-TOF) mass spectrometer. Raw data were analyzed using bioinformatic tools to identify biomarkers. MALDI O-TOF MS analyses of saliva samples were highly reproducible and the mass spectra generated were very rich in peptides and peptide fragments in the 750-7,500 Da range. Data analysis using bioinformatic tools resulted in several classification models being built and several biomarkers identified. One model based on 7 putative biomarkers yielded a sensitivity of 97.5%, specificity of 97.8% and an accuracy of 97.6%. One biomarker was present only in SjS samples and was identified as a proteolytic peptide originating from human basic salivary proline-rich protein 3 precursor. We conclude that salivary biomarkers detected by high-resolution mass spectrometry coupled with powerful bioinformatic tools offer the potential to serve as diagnostic/prognostic tools for SjS.
22126431 Oxidative stress, as measured by protein oxidation, is increased in primary Sjøgren's syn 2012 Feb OBJECTIVE: Oxidative stress is an imbalance between the production of reactive oxygen species (ROS) and physiological antioxidant defences. It occurs frequently in conditions characterized by immune activation and inflammation. Plasma levels of oxidized end products have never been evaluated in primary Sjøgren's syndrome (pSS). The aim of this study was to investigate the level of oxidative stress in primary Sjøgren's syndrome. As a secondary outcome, the association between oxidative stress and fatigue was explored. METHODS: A cross-sectional study of 26 pSS patients was carried out. Oxidative stress was assessed using two markers of protein oxidation, protein carbonyl (PC) and advanced oxidation protein products (AOPP). Reference values for the oxidative stress markers were obtained from 15 healthy subjects. RESULTS: AOPP and PC levels were increased in the pSS patients compared to the healthy subjects. This is a novel finding. There were no associations between oxidative stress measures and fatigue in the patients. CONCLUSIONS: Patients with pSS have increased levels of oxidative stress compared to healthy subjects.
21898068 Evaluation of the clinical efficacy of Biotène Oral Balance in patients with secondary Sj 2012 Sep The objective of the present study was to evaluate the efficacy of Oral Balance saliva substitute in alleviating dry mouth symptoms in a sample of patients with secondary Sjögren's syndrome. Twenty-one consecutive secondary Sjögren's syndrome patients with dry mouth complaints and hyposalivation were included in this study. Patients used a lactoperoxidase-system-containing gel (Biotène Oral Balance) for 4 weeks. The effects on subjective oral symptoms were recorded by means of a 7-items questionnaire which contained questions regarding dry mouth sensation and its effect on chewing, swallowing, taste, speech, burning sensation and denture retention. The severity of symptoms was assessed using a visual analogical scale. Oral symptom scores and unstimulated whole salivary flow were recorded at baseline and after 4 weeks' use of the product. Two patients withdrew from the study, because of nausea and unpleasant taste caused by the product. Nineteen patients (all women, mean age 52.7 years) participated throughout the entire study. Wilcoxon signed-ranked tests indicated significant improvements in visual analogical scale scores posttreatment for 5 of the 7 items on the oral dryness questionnaire, although no increase in salivary flow was found. However, the improvement in certain variables did not take a positive course in all cases. Patients with lower salivary flow at baseline tended to have greater improvement in oral symptoms. The study suggests that the use of Oral Balance gel is effective in alleviating the dry mouth symptoms in secondary Sjögren's syndrome patients, but a randomized controlled trial is needed to assess the placebo effect.
20737186 Benefit and a possible risk of tocilizumab therapy for adult-onset Still's disease accompa 2011 Feb We report a 57-year-old female case of intractable adult-onset Still's disease (AOSD). Initial high-dose prednisolone therapy was ineffective, and macrophage-activation syndrome (MAS) manifested after one session of additional tocilizumab therapy. After successful treatment for MAS with lipo-dexamethasone and cyclosporin, tocilizumab therapy aided in the rapid reduction of the therapeutic steroid dose. Tocilizumab may be useful for maintenance therapy for AOSD, although its efficacy is unclear for the highly active phase of the disease.
23089123 [Disseminated histoplasmosis, lymphopenia and Sjögren's syndrome]. 2012 Sjögren's syndrome is an autoimmune disease characterized by decreased exocrine gland secretions; patients may also present several hematological abnormalities, like lymphopenia. We describe the case of a 28 year old man who complained of headache a month of duration, with fever and vomiting in the last 48 hours. He also presented skin lesions on trunk and face, without neck stiffness. The diagnosis of duration infection was confirmed by culture from the skin biopsy and spinal fluid specimens; in addition, the presence of lymphopenia, positive anti Ro-SSA antibodies, poor concentration of the tracer in scintigraphy and lymphocytic infiltration in salivary glands confirmed the diagnosis of Sjögren's syndrome. the patient was successfully treated with liposomal amphotericin and itraconazole. We report this case to emphasize that opportunistic infections, such as disseminated histoplasmosis, may be an uncommon clinical presentation of Sjögren's syndrome.
22360881 How does BAFF activate B cells in patients with autoimmune diseases? 2012 Feb 24 In a study in a recent issue of Arthritis Research & Therapy, Yoshimoto and colleagues demonstrate that peripheral monocytes from patients with Sjögren's syndrome (SS) produce significantly higher amounts of B cell-activating factor (BAFF) and interleukin-6 (IL-6) in comparison with normal monocytes. This difference exists at baseline and is amplified after stimulation with interferon-gamma. Increased IL-6 secretion is partially suppressed by an anti-BAFF antibody, suggesting that signal transduction pathways mediated by BAFF are implicated in the regulation of IL-6 production by monocytes. The origin and pathways involved in this higher susceptibility to BAFF-driven IL-6 induction by monocytes of patients with SS are still unknown.
21531959 Pregnancy and fetal outcome in women with primary Sjogren's syndrome compared with women i 2011 Sep OBJECTIVE: To study pregnancy and fetal outcome in women with primary SS (pSS) compared with women in the general population. METHODS: In a nested case-control setting, variables related to pregnancy and fetal outcomes were compared. Cases (n = 16) were identified through registry linkage (Malmö pSS registry and a database entailing information of all pregnancies and deliveries in Malmö from 1990 through 2006). For each pregnancy with pSS, the following five deliveries from the same registry were chosen as controls (n = 80). RESULTS: All cases fulfilled the American European Consensus Criteria for pSS and were positive for ANA and anti-SSA antibodies. Date of diagnosis was before pregnancy in 10 women and after delivery in 6. Mean age at delivery was significantly higher in women with pSS (33.6 years) vs controls (29.8 years). While pregnancy duration did not differ, mean birthweight was significantly lower in offspring of pSS mothers (3010 g) vs babies of control mothers (3458 g). Normal partus in contrast to vacuum extraction or Caesarean section was significantly more frequent in healthy women than in pSS women (83 vs 56%). Other pregnancy outcomes such as parity, miscarriages and Apgar score did not differ. There were no significant differences between women with a pSS diagnosis before or after the index pregnancy. Only one of the included pregnancies was complicated by intrauterine AV block. CONCLUSION: Pregnancy occurs later in life in pSS women. Mothers with pSS give birth to offspring with lower birthweight and less commonly have normal partus.
21345287 Effects of rituximab therapy on quality of life in patients with primary Sjögren's syndro 2011 Jan OBJECTIVES: To assess the efficacy of the anti-CD20 antibody rituximab in improving physical function and health-related quality of life (HRQoL) in patients with active primary Sjögren's syndrome (pSS), as well as the duration and sources of HRQoL improvements. METHODS: Sixteen patients with pSS received rituximab infusions (375 mg/m2) at weeks 0 and 1 and were followed up for 36 weeks. All patients fulfilled 2002 American-European Consensus Group criteria for pSS and had active disease defined as scores >50 mm on two of four 100-mm visual analogue scales (VAS) evaluating global disease activity, fatigue, pain, and dryness. Standardised evaluations including the Short Form 36 Health Survey (SF-36) were conducted. SF-36 score changes from baseline to weeks 12, 24, and 36 were assessed. RESULTS: Baseline mean SF-36 scores were considerably decreased, compared to the general same-age population. Role-physical (14.1 ± 27.4), role-emotional (12.5 ± 29.9), vitality (26.2 ± 14.3), and general health (32.6 ± 11.2) were the dimensions with the worst scores. Twelve weeks after rituximab, the mental component summary score was improved in 15 patients (mean improvement, 31.2 ± 36.4, p=0.001) and the physical component summary score in 14 patients (mean improvement, 16.9 ± 26.2, p=0.049). Further improvements occurred from week 12 to week 24, and most of the gains were sustained at week 36. Improvements in the physical and mental component summary scores failed to correlate with improvements in the VAS scores. CONCLUSIONS: Substantial alterations in HRQoL were noted in patients with pSS. Rituximab infusions without corticosteroid therapy produced meaningful improvements in HRQoL. Controlled studies of rituximab are needed.
22807546 An unusual cause of fever in an HIV-positive patient. 2012 Jun Patients with HIV frequently present with fever. However, the spectrum of diseases affecting patients with HIV has changed in the era of antiretroviral therapy (ART). Here we present a patient who has an unusual cause for his fever with an eventual diagnosis of adult-onset Still's disease.
23047635 [A case of protein-losing gastroenteropathy accompanied by Sjögren syndrome and mixed con 2012 Oct Case reports of protein-losing gastroenteropathy (PLGE) associated with not only mixed connective tissue disease (MCTD) but also Sjögren syndrome (SjS) are very rare. We report a first case of PLGE in a patient with both MCTD and SjS. A 58-year-old Japanese woman was referred and admitted to our hospital because of abdominal fullness and lower leg edema. Her past medical history revealed SjS at age 40. Physical examination demonstrated lower leg edema and Raynaud's phenomenon. Blood chemistry data showed severe hypoproteinemia. Anti RNP antibody was positive. MCTD was diagnosed. The alpha-1 antitrypsin clearance level was high. The (99m)Tc-DTPA human serum albumin scintigraphy demonstrated abnormal accumulation in the intestine. PLGE associated with both MCTD and SjS was diagnosed, but she was successfully treated by prednisolone.
22085873 Paraneoplastic syndrome mimicking adult-onset Still's disease caused by advanced lung canc 2011 Nov 16 BACKGROUND: Paraneoplastic syndromes (PNSs) are common complications of lung cancer and often develop preceding the diagnosis of primary malignancy. Rheumatologic PNSs mimicking Adult-Onset Still' s Disease (AOSD) is a rare condition with only a limited number of cases reported in the literature, none of which was associated with lung cancer. It is often difficult to differentiate AOSD-like paraneoplasia from coincidental AOSD based on the clinical manifestations. CASE PRESENTATION: Here we present a 56-year-old man with advanced lung adenocarcinoma who developed a remittent fever together with pharyngodynia and joint pain after first cycle of chemotherapy with paclitaxel plus carboplatin. Although a leukocytosis was detected, no evidence of infection was acquired and empirical antibiotic treatment was ineffective. A temple skin rash, abnormal hepatic function and a remarkable elevated level of serum ferritin occurred later in this patient, which highly supported a potential diagnosis of AOSD. The patient was finally diagnosed as AOSD-like PNS considering the good and prompt response to a short-term administration of non-steroidal anti-inflammatory drug and subsequent cycles of effective chemotherapy with pemetrexed plus cisplatin. DISCUSSION AND CONCLUSIONS: Though rare, AOSD-like PNS can be one of the potential diagnoses in lung cancer patients with fever of undetermined origin, especially those having no response to antibiotic treatment. Management consists of control of the underlying malignancy and symptomatic treatment of the syndromes with non-steroidal anti-inflammatory drugs or corticosteroids.
21598496 [Study on total glucosides of peony preventing non-obese diabetic mice from sialoadenitis] 2011 Apr OBJECTIVE: To investigate the immunosuppressive effect of total glucosides of peony (TGP) on sialoadenitis in non-obese diabetic mice (NOD mice) and explore its possible mechanism. METHODS: 27 female five-week-old NOD mice were randomly divided into three groups: TGP, hydroxychloroquine (HCQ) and normal saline (NS) group. One week later, they were administered intragastrically in TGP, HCQ and NS respectively. Three mice from each group were sacrificed at the age of 10, 15 and 20 weeks. The saliva flow, serum and submandibular glands were collected at these time points. Histological changes of submandibular glands were examined by HE staining. The expression of autoantibodies (SSA, SSB and anti-alpha-fodrin) and associated cytokines in serum were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the NS group, salivary flow was significantly increased, the extent of the histological changes were ameliorated, the autoantibodies in serum were significantly decreased and the imbalance of Th1/Th2 cytokines was remedied in the mice treated with TGP and HCQ. There were no significant differences between the two groups treated with TGP and HCQ (P > 0.05). CONCLUSION: TGP can effectively ameliorate sialoadenitis on NOD mice. The mechanism was thought to be associated with the protection of submandibular gland from intense inflammation and the correction of Th1/Th2 cytokines imbalance.
21489323 Is Sjögren's syndrome a retroviral disease? 2011 Apr 13 Circumstantial evidence suggests that retroviruses play a role in the pathogenesis of Sjögren's syndrome. Such evidence, derived from studies of patients with Sjögren's syndrome, includes the following: the presence of serum antibodies cross-reactive with retroviral Gag proteins; the occurrence of reverse transcriptase activity in salivary glands; the detection of retroviral antigens, retrovirus-like particles, or novel retroviral sequences in salivary glands; the occurrence of Sjögren's syndrome-like illnesses in patients having confirmed systematic infections with retroviruses such as human immunodeficiency virus-1 (HIV-1) and human T lymphotropic virus type 1; and the beneficial effect of anti-retroviral treatment on the occurrence of HIV-1-associated sicca syndrome. Additional evidence is provided by animal models.
22415866 Microrheology of human synovial fluid of arthritis patients studied by diffusing wave spec 2012 Oct The viscoelastic properties of synovial fluid (SF) are critical to its functions of lubrication and shock-absorption of joints in human body; a change in the viscoelastic properties, even of only a few percents, is often concomitant with arthritis. In this work, the elastic modulus G '(f) and the viscous modulus G ''(f) of SF from patients suffering from three kinds of joint diseases, namely, osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), were determined as a function of frequency "f " (in the low frequency range from f ∼ 0.1 to 10 Hz) by Diffusing Wave Spectroscopy (DWS) and correlated with the white blood cell (WBC) count. A strong correlation was observed, showing a higher WBC count corresponding to lower elastic and viscous moduli, G ' and G ''; further details depend on inflammatory vs. non-inflammatory, and on the severity of inflammation. Different types of arthritis lead to different degrees of decreasing viscoelasticity. Identical measurements were carried out with a commercial visco-supplementation (or artificial SF) to serve as reference. In general, the reduction in both G ' and G '' was most severe in the case of GA and least severe in the case of OA. Besides, in all cases, the reduction in G ' was more prominent than the reduction in G '', indicating that in general, the deterioration in the elasticity of SF by inflammation is more severe than that in the viscosity. This simple method for quantitative physical characterization of synovial fluid may serve as a useful complementary metric to the conventional biochemical analysis in clinical diagnosis of arthritis.
21786602 [Biological therapy in pediatric rheumatology]. 2011 This article presents the unique experience of Research Centre of Children's Health in the treatment of 438 children with juvenile rheumatoid arthritis using biological preparations, viz. infliximab (270), adalimumab (55), ethanercept (25), rituximab (74), and tocilizumab (34). It is shown that differential biological therapy, unlike treatment with classical immunodepressants (methotrexate, cyclosporine, leflunomide, etc.), permits to achieve clinico-laboratory remission in 70% and markedly decrease activity of the disease in 20% of the patients within 1 year after the onset. It is concluded that treatment with gene-engineered drugs improves the quality of life of the children and their families, normal growth and development of the patients and affects prognosis of this formerly incurable chronic autoimmune disease.
22374442 [Autoantigen BiP and autoimmune diseases]. 2012 Immunoglobulin Binding Protein (BiP) is a member of heat shock protein 70 famaily, and is also known as an autoantigen in rheumatoid arthritis (RA) patients. Serum anti-BiP antibody is detected up to 60% of RA patients, and recent reports demonstrated that serum anti-BiP antibody is also detected in systemic lupus erythematosus patients. Notably, anti-citrullinated BiP antibody is revealed as another member of anti-citrullinated protein/peptide antibodies (ACPAs). Since ACPAs are supposed to be closely associated with RA pathogenesis, immune responses to citrullinated BiP could play an important role in RA. Indeed, immunization of citrullinated BiP exacerbated inflammatory arthritis in mice. Moreover, T cell responses to BiP were reported in human RA and mice models. In mice models, native BiP administration induced IL-4 and IL-10 producing CD4(+) T cells and regulated inflammatory arthritis. In this way, immune responses to BiP are various, and dysregulation of the balances between pro-inflammatory and regulatory responses to BiP could lead to the autoimmune responses and diseases.
22257915 Cardiovascular involvement in psoriatic arthritis. 2011 Nov 9 Psoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2-3% of the Caucasian population. A considerable proportion of these patients develop a form of inflammatory arthritis known as psoriatic arthritis (PsA), although the prevalence of this has not been well defined. Patients with PsA have a higher mortality rate than the general population and the risk of mortality is related to disease severity at the time of presentation. Endothelial dysfunction and early atherosclerosis have been found in patients with PsA without any cardiovascular disease (CVD) risk factors, and experts believe that CVD is one of the leading causes of death, as it is in patients with rheumatoid arthritis (RA). Various disease-related mechanisms may be involved in the development of premature vascular damage in both cases, including an increased synthesis of proinflammatory mediators (such as cytokines, chemokines and adhesion molecules), autoantibodies against endothelial cell components, perturbations in T-cell subsets, genetic polymorphisms, hyperhomocysteinemia, oxidative stress, abnormal vascular repair, and iatrogenic factors. In a recent study of 22 patients with PsA without any signs of CVD, we found that the plasma concentration of asymmetric dimethylarginine (ADMA) levels were significantly high and coronary flow reserve (CFR) was significantly reduced. Moreover, there was a significant correlation between CFR and plasma ADMA levels in the PsA group. The significant correlation between the reduced CRF and increased ADMA levels suggests that, like patients with early RA, PsA patients suffer from endothelial dysfunction and impaired coronary microcirculation. Active PsA is a risk factor for CVD, and so PsA patients should be screened for subclinical forms of the disease and its risk factors, and an early treatment approach should be adopted.
22560378 Chikungunya fever. 2012 Jun Chikungunya fever (CF) is an acute illness caused by Chikungunya virus (CHIKV) belonging to the alphavirus genus of the Alphaviruses (Togaviridae) family. The virus is transmitted by Aedes mosquitoes. CF is primarily tropical disease occurring in Africa, Asia and Indian Ocean islands but in the last decade an outbreak of CHIKV autochthonous infections were reported in Italy and France. It is associated with viral genome mutations facilitating transmission of the disease by Aedes albopictus, a mosquito occurring in several European countries. The CF is highly symptomatic, characterized by fever, cutaneuos rash and severe athralgia and arthritis. In some patients severe neurological or hemorrhagic manifestations occur. The disease is self-limiting but a part of the patients suffers from a long-lasting arthritis akin to rheumatoid arthritis. Treatment is only symptomatic. Prevention includes reduction of mosquito bite (mosquito net, repellent) or application of measures against mosquito larvae. Vaccination is not currently available but investigations are in progress. CF presents a significant worldwide health problem affecting in the last decade millions of person, and currently dangerous also for European countries.
21947161 Use of radiosynovectomy in recurrent warfarin-related haemarthrosis in degenerative arthri 2011 Sep Radiosynovectomy is a local and minimally invasive radiotherapy for treating various chronic inflammatory arthritis such as rheumatoid arthritis, osteoarthritis and haemophilic arthropathy. In haemophilic arthropathy, it reduces the frequency of haemarthrosis and delays the development of severe joint destruction, which ultimately requires surgical intervention. Its role in warfarin-related haemarthrosis is less clear. Haemarthrosis is an uncommon complication of warfarin use, and anticoagulation may need to be discontinued. We describe yttrium-90 radiosynovectomy use in a 74-year-old man with underlying ischaemic heart disease, atrial fibrillation, previous embolic stroke and recurrent haemarthrosis of an osteoarthritic right knee. Anticoagulation was vital and could not be permanently stopped. Due to continuing anticoagulation, he had multiple hospitalisations with recurrent right knee haemarthrosis. Intraarticular right knee yttrium-90 citrate colloid injection led to a cessation of haemarthrosis for eight months. We examined the available literature for the role of radiosynovectomy in such circumstances.
22407099 [Rheumatic joint disease in childhood and adolescence]. 2012 Mar Rheumatic joint disease in childhood and adolescence is relatively rare. In the general population, 1 child with juvenile arthritis accounts for 100 adult patients with rheumatoid arthritis. At disease onset 50% of affected children are between 2 and 6 years of age. Symptoms are often subtle and pain is usually not the leading symptom. Early treatment of juvenile arthritis is essential in order to prevent long-term sequelae in affected children. Many children are introduced to a pediatric rheumatologist only with considerable delay. Therapy is based on NSAIDs, intra-articular steroid injections, and immunosuppressive drugs. In severe cases patients are treated with biologics. Physical and occupational therapy are important supportive measures in the treatment.