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ID PMID Title PublicationDate abstract
24252043 Correlation between salivary epidermal growth factor levels and refractory intraoral manif 2014 Jul OBJECTIVE: To assess changes in salivary epidermal growth factor (EGF) levels and the correlation between these levels and the severity of intraoral manifestations in Sjögren's syndrome (SS). METHODS: Forty SS patients and 23 controls were enrolled. Salivary EGF concentration was measured using an enzyme-linked immunosorbent assay, and intraoral manifestations were evaluated using a short version of the Oral Health Impact Profile (OHIP-14). The associations among salivary flow rate, EGF levels and the severity of intraoral manifestations were analyzed. RESULTS: The total salivary EGF output was significantly decreased in the SS patients compared with the controls (9237.6 ± 8447.0 vs. 13296.9 ± 7907.1 pg/10 min, respectively, p = 0.033). In the SS patients, total EGF output and salivary flow rate showed a strong positive correlation (rs = 0.824, p = 0.0005), while total EGF output and disease duration showed a negative correlation (rs = -0.484, p = 0.008). Further, total EGF output was significantly correlated with the OHIP-14 score (rs = -0.721, p = 0.012). CONCLUSIONS: The salivary flow rate and EGF levels are decreased in SS, and this deterioration in saliva quality causes refractory intraoral manifestations. Our findings have provided new therapeutic targets for SS.
24112140 First report of granulomatous mastitis associated with Sjögren's syndrome. 2013 Oct 10 Granulomatous mastitis is a rare and often considered as idiopathic disease. However, clinical examination and thorough diagnostic investigations have to be carried out in order to identify cases that are secondary to infections or systemic diseases since these forms may be cured with appropriate etiologic treatment. To the best of our knowledge, this report is the first to describe the association of granulomatous mastitis with Sjögren's syndrome. We discuss the clinical, pathological and therapeutic implications of this association.
24036814 Different lymphoproliferative disorders in different salivary glands of primary Sjögren s 2013 We report 1 case of primary Sjögren syndrome that showed histologic variation and different lymphoproliferative disorders in different salivary glands.Different salivary glands can show a different transition situation with histologic variation and lymphoproliferative disorders. The larger salivary glands have more potentially progressive transition situation than smaller glands. These findings also supported the theory that the transition of reactive B cells from lymphoepithelial sialadenitis to monoclonal lymphoma is generally a multistep process in different salivary glands within 1 person.
23719365 Autoimmunity and infection in Sjögren's syndrome. 2013 Jul PURPOSE OF REVIEW: To summarize the recent developments concerning the potential viral pathomechanisms and involvement of viruses in Sjögren's syndrome, and to highlight the areas for future research and therapies. RECENT FINDINGS: Activated IFN-1 pathway plays an important part in the autoimmune disease process of Sjögren's syndrome; therefore, several therapies aiming to reduce or inhibit the IFN-1 production and its effects may be a target for future treatment plans. Activated aryl hydrocarbon receptor may interact with latent Epstein-Barr virus (EBV) infection, which in turn may predispose to the development of Sjögren's syndrome. It is estimated that the population is 95% positive for EBV serology. Microbial factors may incite autoimmune disease. Although this hypothesis is proven in a few illnesses such as rheumatic fever, there is no definitive evidence of an infectious environmental trigger in Sjögren's syndrome. However, there are circumstantial data with regard to viruses and several potential mechanisms of disease. These include antigen mimicry, polyclonal lymphocyte activation, and infection-mediated innate end-organ inflammation. In addition, hepatitis C virus infection clearly causes a Sjögren's-syndrome-like illness. SUMMARY: Data continue to implicate viral infection in the cause of Sjögren's syndrome, but there are no definitive studies incriminating a particular virus.
25240612 Do the EULAR Sjögren's syndrome outcome measures correlate with health status in primary 2015 Apr OBJECTIVE: This study sets out to investigate the relationship between health status [EuroQol five-dimensions questionnaire (EQ-5D)] in primary SS and three of the European League Against Rheumatism (EULAR) SS outcome measures-the disease activity index (ESSDAI), the patient reported index (ESSPRI) and the sicca score. In particular, the goal was to establish whether there is a relationship between the EULAR outcome measures and quality of life. METHODS: Health status was evaluated using a standardized measure developed by the EuroQol Group-the EQ5D. This permits calculation of two measures of health status: time trade-off (TTO) values and the EQ-5D visual analogue scale (VAS) scores. We used Spearman's rank correlation analysis to investigate the strength of association between health status and three EULAR measures of physician- and patient-reported disease activity in 639 patients from the UK primary SS registry (UKPSSR) cohort. RESULTS: This study demonstrates that the EULAR SS disease-specific outcome measures are significantly correlated with health outcome values (P < 0.001). Higher scores on the ESSDAI, EULAR sicca score and ESSPRI are associated with poorer health states-i.e. lower TTO values and lower VAS scores. While all three are significantly correlated with TTO values and EQ-5D VAS scores, the effect is strongest for the ESSPRI. CONCLUSION: This study provides further evidence supporting the use of ESSDAI, EULAR sicca score and ESSPRI measures in the clinic. We also discuss the need for disease-specific measures of health status and their comparison with standardized health outcome measures.
23333237 Sjögren syndrome presenting with encephalopathy mimicking Creutzfeldt-Jakob disease. 2013 Mar 15 A 61-year-old man developed subacute progressive dementia, general fatigue, a tonic-clonic seizure, and a decreased level of consciousness. He had a past history of chronic hepatitis type C and was diagnosed as having hepatic encephalopathy due to hyperammonemia. His level of consciousness did not improve even though the serum ammonia level improved. In addition, he had repeated general myoclonic seizures. Head MRI (diffusion-weighted imaging) showed high signal intensities in the right thalamus and the cerebral cortices in the frontal, temporal and parietal lobes (predominantly on the right side). An electroencephalogram (EEG) showed periodic lateralized epileptic discharges (PLEDs). Cerebrospinal fluid analysis revealed high total tau protein and 14-3-3 protein levels. This case was diagnosed as Creutzfeldt-Jakob disease (CJD) based on these clinical data. However, the patient gradually improved without specific treatment. The differential diagnosis was reconsidered, and an increased erythrocyte sedimentation rate and positive serum anti-SS-A and anti-SS-B antibodies were noted. A diagnosis of Sjögren syndrome (SjS) was finally made based on a biopsy of a minor salivary gland showing infiltration of lymphocytes around the gland ducts. Steroid therapy (prednisolone 40mg/day orally) was given, and his clinical condition improved. The lesions on the head MRI decreased, and the EEG findings normalized. This case suggests that SjS has a wide spectrum, including neurological disorders, and that SjS should be considered in the differential diagnosis of CJD.
24773396 Adult-onset Still disease with peculiar persistent plaques and papules. 2014 Jun Adult-onset Still disease (AOSD) is a systemic inflammatory disorder characterized clinically by high spiking fever, polyarthralgia/arthritis, a salmon-pink evanescent rash, predominantly neutrophilic leucocytosis, lymphadenopathy, liver dysfunction, and splenomegaly. Recently, a nonclassic, nonevanescent skin rash has been reported. We report a 27-year-old woman with AOSD showing persistent pruritic papular lesions. Histologically, dyskeratotic keratinocytes were seen in the upper epidermis. We describe this case in detail and review the previous literature. Nonclassic pruritic eruptions with characteristic dyskeratotic keratinocytes might provide an important clue for the diagnosis of AOSD.
24770812 [Adult-Onset Still's Disease, an improbable differential diagnosis: a case report]. 2014 Juvenile idiopathic arthritides (JIA) comprehend a heterogeneous group of inflammatory diseases of the joints, with an unknown aetiology, arising within 16 years of age, and lasting more than six weeks. The systemic form, known as Still's disease, represents from 4 to 17% of all the JIA. AOSD (Adult Onset Still's Disease) is a variant of JIA affecting adults, with identical clinical manifestations. Here we describe the case of a 36 year old woman, with a symptomatology characterized by fever, skin rash, arthralgies and lymphadenopathy. The arise of the fever in this case has uncommonly preceded by several weeks the arise of the other signs; this has determined a considerable delay in the diagnosis: Still's disease diagnosis is made hard as it shares its signs and symptoms with several infectious, immunological as well as tumoral diseases. In this case, the blossoming of the laboratory parameters at the sixth day of hospitalization with leucocytosis and neutrophilia represented the solving clue. Still's disease, though a rare nosographic entity, must be kept into consideration in unclear cases occurring in an internal medicine department.
24128774 Worker productivity outcome measures: OMERACT filter evidence and agenda for future resear 2014 Jan The objective of the Outcome Measures in Rheumatology (OMERACT) Worker Productivity working group is to identify worker productivity outcome measures that meet the requirements of the OMERACT filter. At the OMERACT 11 Workshop, we focused on the at-work limitations/productivity component of worker productivity (i.e., presenteeism) - an area with diverse conceptualization and instrumentation approaches. Various approaches to quantify at-work limitations/productivity (e.g., single-item global and multi-item measures) were examined, and available evidence pertaining to OMERACT truth, discrimination, and feasibility were presented to conference participants. Four candidate global measures of presenteeism were put forth for a plenary vote to determine whether current evidence meets the OMERACT filter requirements. Presenteeism globals from the Work Productivity and Activity Impairment Questionnaire (72% support) and Rheumatoid Arthritis-specific Work Productivity Survey (71% support) were endorsed by conference participants; however, neither the presenteeism global item from the Health and Work Performance Questionnaire nor the Quantity and Quality method achieved the level of support required for endorsement at the present time. The plenary was also asked whether the central item from the Work Ability Index should also be considered as a candidate measure for potential endorsement in the future. Of participants at the plenary, 70% supported this presenteeism global measure. Progress was also made in other areas through discussions at individual breakout sessions. Topics examined include the merits of various multi-item measures of at-work limitations/productivity, methodological issues related to interpretability of outcome scores, and approaches to appraise and classify contextual factors of worker productivity. Feedback gathered from conference participants will inform the future research agenda of the working group.
25437292 Developing evidence-based screening recommendations, with consideration for rheumatology. 2014 Nov Screening for presymptomatic disease provides the potential for early intervention and improved outcomes. However, although this practice has potential benefits, it also has potential harms that must be considered. The U.S. Preventive Services Task Force (USPSTF) is a nonfederal panel of experts convened by the Agency for Health Research and Policy to systematically review the evidence for preventive services, including disease screening, and to create evidence-based recommendations for primary care practice in the United States. As rheumatologists contemplate the potential of screening for preclinical disease, understanding the process used by the USPSTF can help guide research efforts supporting such screening.
25130128 Grade 3 lymphomatoid granulomatosis in a patient receiving methotrexate therapy for rheuma 2014 Lymphomatoid granulomatosis (LyG) is a rare, B-cell derived, lymphoproliferative disorder that often presents as pulmonary nodular lesions with a histopathology of lymphatic invasion of the vascular wall. The development of LyG may be associated with reactivation of the Epstein-Barr virus under an immunosuppressive state. We herein report a case of Grade 3 LyG that developed during methotrexate therapy for rheumatoid arthritis and regressed following the withdrawal of the drug.
24605074 Reproduction of epstein-barr virus infection and pathogenesis in humanized mice. 2014 Feb Epstein-Barr virus (EBV) is etiologically associated with a variety of diseases including lymphoproliferative diseases, lymphomas, carcinomas, and autoimmune diseases. Humans are the only natural host of EBV and limited species of new-world monkeys can be infected with the virus in experimental conditions. Small animal models of EBV infection, required for evaluation of novel therapies and vaccines for EBV-associated diseases, have not been available. Recently the development of severely immunodeficient mouse strains enabled production of humanized mice in which human immune system components are reconstituted and express their normal functions. Humanized mice can serve as infection models for human-specific viruses such as EBV that target cells of the immune system. This review summarizes recent studies by the author's group addressing reproduction of EBV infection and pathogenesis in humanized mice.
23752767 Renal manifestations of rheumatic diseases. A review. 2013 Jun BACKGROUND: Renal manifestations of rheumatic diaseases are sometimes very discrete and mild. At others, they can present the leading symptomatology of a given disease. Systemic lupus erythematosus, systemic scleroderma, renal vasculitis, rheumatoid arthritis, mixed connective tissue disease, Sjögren's syndrome and gout can all manifest in or be accompanied by renal impairment. METHODS AND RESULTS: The authors reviewed the literature on renal manifestation of rheumatic diseases using the key words, lupus erythematosus, systemic autoimmune diseases, rheumatoid arthritis, vasculitis and gout. The review below is accompanied by their own histological findings. CONCLUSION: Diagnosis requires proper interpretation of the clinical situation, laboratory results and image analysis methods plus close interdisciplinary collaboration between nephrologist and clinical pathologist/nephropathologist.
27708900 New platelet indices as inflammatory parameters for patients with rheumatoid arthritis. 2014 Dec OBJECTIVE: To test new platelet indices for patients with rheumatoid arthritis (RA) as new acute phase reactants. MATERIAL AND METHODS: In total, 120 patients with RA and 40 patients in the control group were analyzed. A DAS 28 score over 2.6 was accepted as active disease, and a DAS 28 score lower than 2.6 was accepted as under remission. Platelet distribution width, plateletcrit, and mean platelet volume were analyzed for three groups: patients with active RA, patients under remission, and the control group. RESULTS: There were 72 patients with active disease and 48 patients under remission. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), mean platelet volume (MPV), plateletcrit (PTC), and platelet distribution width (PDW) scores were all statistically different among groups. In our data, PTC was found to be a positive acute phase reactant and others were negative acute phase reactants for patients with RA. CONCLUSION: These new indices are cheap, widely available, and useful parameters for routine clinical rheumatology practice.
24112701 Radial head, radiocapitellar and total elbow arthroplasties: a review of recent literature 2014 Feb The outcome of prosthetic elbow surgery is continually evolving. We thoroughly reviewed the literature on this issue to analyse the indications, outcomes and complications of the numerous types of implants currently in use. Radial head replacement is recommended in comminuted fractures of the radial head and in post-traumatic conditions. Medium- and long-term results prove to be satisfactory in the majority of cases, with no evidence to indicate that some prostheses (monopolar vs. bipolar; cemented vs. press-fit) are more effective than others; nonetheless, the bipolar-cemented implant was found to be associated with a lower revision rate than other prostheses. Unicompartmental arthroplasty has recently been used for the treatment of osteoarthritis and rheumatoid arthritis when the lateral compartment is prevalently involved; the results reported to date have been encouraging, although further studies are warranted to confirm the validity of these implants. Total elbow arthroplasty is performed in a range of conditions, including distal humerus fractures in the elderly and elbow arthritis. In the former condition, linked elbow replacement yields excellent results with few complications and a low revision rate. In elbow arthritis, total elbow arthroplasty is indicated when patients suffer from disabling pain, stiffness and/or instability that prevent them from performing daily activities. Unlinked elbow arthroplasty, which is used above all in rheumatoid arthritis, also yields satisfactory results, although the risk of instability persists. The use of linked elbow arthroplasty, which yields similar results but lower revision rates, has consequently increased. Lastly, the results yielded by linked elbow prosthesis in post-traumatic conditions are good, although not quite as good as those obtained in rheumatoid arthritis. Early mechanical failure may occur in younger and more active patients after elbow arthroplasty. However, the careful selection of patients who are prepared to accept functional limitations imposed by elbow implants will enable indications for elbow arthroplasty to be extended to young subjects, particularly when no other therapeutic options are available.
25431465 Republished: The association between inflammatory markers, serum lipids and the risk of ca 2014 Dec OBJECTIVE: To examine the association of serum inflammatory markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and serum lipid measures (low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol) with risk of myocardial infarction (MI) and ischaemic stroke (IS) among rheumatoid arthritis (RA) patients. METHODS: We conducted a retrospective cohort study using 2005-2010 data from a US commercial health plan. Eligible patients had two or more physician diagnoses of RA during a baseline period of at least 180 days with continuous medical and pharmacy coverage. We computed age-adjusted incidence rates of MI and IS, and used spline regression to assess non-linear associations and Cox-regression to quantify the independent association between the laboratory values and the outcomes. RESULTS: We identified 44 418 eligible RA patients (mean age 49 years; 76% women). CRP>10 mg/L compared with <1 mg/L was associated with increased MI risk (HR 2.12; 95% CI 1.02 to 4.38). ESR>42 mm/h compared with <14 mm/h was associated with increased risk of MI (HR 2.53; 95% CI 1.48 to 4.31) and IS (HR 2.51; 95% CI 1.33 to 4.75) risk. HDL-cholesterol ≥60 mg/dL (1.6 mmol/L) compared with <40 mg/dL (1.0 mmol/L) was associated with reduced MI risk (HR 0.37; 0.21 to 0.66). The association between LDL and MI was not linear; the lowest risk was observed among patients with LDL between 70 mg/L (1.8 mmol/L) and 100 mg/L (2.6 mmol/L). We did not observe a significant association between LDL and IS. CONCLUSIONS: This study provides evidence supporting the hypothesis that RA-related systemic inflammation plays a role in determining cardiovascular risk and a complex relationship between LDL and cardiovascular risk.
24723086 A review of CT-P13: an infliximab biosimilar. 2014 Jun CT-P13 (Remsima™; Inflectra™), a biosimilar of reference infliximab (Remicade(®)), is approved by the European Medicines Agency for use in all indications for which reference infliximab is approved, including rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriatic arthritis and psoriasis. Infliximab is a chimeric human-murine monoclonal antibody against the proinflammatory cytokine tumour necrosis factor-α. The CT-P13 infliximab formulation is identical to that of reference infliximab and it has similar physiochemical characteristics. The approval of CT-P13 was based on the results of a rigorous, comparability exercise. This article reviews the results of that exercise, focusing on the clinical evaluation programme. In two well-designed clinical trials, CT-P13 was equivalent to reference infliximab in terms of pharmacokinetic properties in patients with ankylosing spondylitis and in terms of efficacy in patients with rheumatoid arthritis. In both studies, CT-P13 was generally well tolerated with a similar tolerability profile to that of reference infliximab. Immunogenicity evaluations demonstrated that the proportion of patients developing anti-drug antibodies was similar with each agent. Preliminary data from trial extensions demonstrated that in patients who switched from reference infliximab to CT-P13, efficacy was sustained and similar to those who were treated continuously with CT-P13. As with all biosimilar and generic agents, CT-P13 has the potential to reduce treatment costs compared with those of reference infliximab, and modelled analyses predict significant cost savings compared with reference infliximab. In conclusion, CT-P13 is an infliximab biosimilar that provides a useful alternative to reference infliximab in patients requiring infliximab therapy.
24196651 Putative effects of potentially anti-angiogenic drugs in rheumatic diseases. 2014 Feb A role for angiogenesis has been described in several rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic sclerosis, systemic lupus erythematosus, vasculitides, and osteoarthritis, leading to the possibility that angiogenesis inhibition may be an additional useful therapeutic arm. While the role of anti-angiogenic therapy in rheumatoid arthritis has received attention, it is conceivable that the inhibition of pathological angiogenesis may also be a useful therapeutical approach in other rheumatic diseases. Numerous compounds, such as, for example, various interleukins, antibodies directed against angiogenic factors, peptides, estrogen metabolites, disease-modifying anti-rheumatic drugs, have been found to have anti-angiogenic properties. However, additional research is needed to obtain a clear understanding of the pathogenic mechanism of angiogenesis and the potential applications of anti-angiogenic therapy in rheumatic diseases.
24819586 Autoimmunity in 2013. 2014 Aug The peer-reviewed publications in the field of autoimmunity published in 2013 represented a significant proportion of immunology articles and grew since the previous year to indicate that more immune-mediated phenomena may recognize an autoimmune mechanism and illustrated by osteoarthritis and atherosclerosis. As a result, our understanding of the mechanisms of autoimmunity is becoming the paradigm for translational research in which the progress in disease pathogenesis for both tolerance breakdown and inflammation perpetuation is rapidly followed by new treatment approaches and clinical management changes. The similarities across the autoimmune disease spectrum outnumber differences, particularly when treatments are compared. Indeed, the therapeutics of autoimmune diseases are based on a growing armamentarium that currently includes monoclonal antibodies and small molecules which act by targeting molecular markers or intracellular mediators with high specificity. Among the over 100 conditions considered as autoimmune, the common grounds are well illustrated by the data reported for systemic lupus erythematosus and rheumatoid arthritis or by the plethora of studies on Th17 cells and biomarkers, particularly serum autoantibodies. Further, we are particularly intrigued by studies on the genomics, epigenetics, and microRNA at different stages of disease development or on the safe and effective use of abatacept acting on the costimulation of T and B cells in rheumatoid arthritis. We are convinced that the data published in 2013 represent a promising background for future developments that will exponentially impact the work of laboratory and clinical scientists over the next years.
25428646 Targeting the alternatively spliced soluble isoform of CTLA-4: prospects for immunotherapy 2014 CTLA-4 is an inhibitory protein that contributes to immune homeostasis and tolerance, a role that has led to its exploitation as a therapeutic in several clinical settings including cancer and autoimmune disease. Development of CTLA-4 therapies focused largely on the full-length receptor isoform but other CTLA-4 isoforms are also expressed, including a secretable form of CTLA-4 (soluble CTLA-4 [sCTLA-4]). The contribution of sCTLA-4 to immune regulation has been less well studied, primarily because it was identified some years after the original description of CTLA-4. Here, we examine how sCTLA-4 might contribute to immune regulation and ask whether it might be a biomarker to inform current CTLA-4 therapies or represent a novel CTLA-4 target for future therapeutics.