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ID PMID Title PublicationDate abstract
27789466 2016 American College of Rheumatology/European League Against Rheumatism classification cr 2017 Jan OBJECTIVES: To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS. METHODS: We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgement. We then validated the performance of the classification criteria in a separate cohort of patients. RESULTS: The final classification criteria are based on the weighted sum of five items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm(2), each scoring 3; an abnormal Ocular Staining Score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 min and an unstimulated salivary flow rate of ≤0.1 mL/min, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, that is, 96% (95% CI92% to 98%) and 95% (95% CI 92% to 97%), respectively. CONCLUSION: Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well suited as criteria for enrolment in clinical trials.
25579246 Usefulness of antibodies and minor salivary gland biopsy in the study of sicca syndrome in 2015 May OBJECTIVES: To assess the association between histologic findings in the minor salivary gland biopsy (MSGB) and anti La (La/SS-B)y antiRo antibodies (Ro/SS-A), antinuclear antibodies (ANA) and Rheumatoid Factor (RF),and compare the value of the latter as diagnostic tests with MSGB, considered as the gold standard. MATERIAL AND METHOD: Patients with suspected Primary Sjögren Syndrome (PSS) referred for MSGB were included. Antibody measurements were performed. Grade III and IV biopsy results were considered positive. RESULTS: Two hundred and eighteen (218) patients were included, 95% females, with a median age of 54 years and 12 months median duration of sicca symptoms. 36 of the biopsies were positive. 33% of patients had positive anti Ro/SS-A anti La/SS-B antibodies, 62% had positive ANA, and 31% positive RF. A statistically significant association was found between MSGB and anti Ro/SS-A anti La/SS-B, ANA and RF. ANA were the most sensitive antibodies (84%. 95% CI: 75- 92), and the most specific were: Anti Ro/ SS-A and/or anti La/ SS-B (78%. 95% CI: 71-85) and RF (78%. 95% CI: 69-87). CONCLUSION: On PSS clinical suspicion, anti Ro/ SS-A y anti La/ SS-B antibodies have a great value to achieve the diagnosis, with MSGB useful for diagnosis of seronegative patients. The results also suggest the importance of ANA and RF for PSS classification.
27392501 Microbiota at the crossroads of autoimmunity. 2016 Sep Autoimmune diseases have a multifactorial etiology including genetic and environmental factors. Recently, there has been increased appreciation of the critical involvement of the microbiota in the pathogenesis of autoimmunity, although in many cases, the cause and the consequence are not easy to distinguish. Here, we suggest that many of the known cues affecting the function of the immune system, such as genetics, gender, pregnancy and diet, which are consequently involved in autoimmunity, exert their effects by influencing, at least in part, the microbiota composition and activity. This, in turn, modulates the immune response in a way that increases the risk for autoimmunity in predisposed individuals. We further discuss current microbiota-based therapies.
26557037 Neutrophil extracellular traps (Nets) impact upon autoimmune disorders. 2015 Friend or foe? This is often asked question when it comes to neutrophil extracellular traps studies. There is no simple answer to that. At the time of their discovery they were considered to be protectors of our well-being. Excellent pathogen fighting skills were described as purely beneficial. But it was not long before those guardians of immunity reveal their dark side. What seemed to be profitable could also take its toll. They are perfectly constructed, made from nucleic deoxyribonucleic acid ornamented with cytoplasmic and granular proteins, to fight invaders. But this unique build is prone to become considered by our body as a threat. Since there is a thin line which when crossed turns a savior into enemy, it was postulated that Nets can play a significant role in autoimmune disorders pathogenesis and disease exacerbation. Recent years have brought a new insight into autoimmune disorders trying to connect the old knowledge and suspicions with modern discoveries.
26597492 Nailfold capillaroscopic findings in primary Sjögren's syndrome with and without Raynaud' 2016 Mar The aim of this study was to assess nailfold capillaroscopic (NC) findings in patients with primary Sjögren's syndrome (PSS) with and without Raynaud's phenomenon (RP) as well as in the presence of positive anti-SSA/Ro and anti-SSB/La antibodies. Videocapillaroscopy was performed in 150 patients with PSS. Data collected included demographics, presence of RP, PSS symptoms, antinuclear antibodies, rheumatoid factor, anti-Ro, anti-La, anti-CCP, salivary scintigraphy, labial biopsy, and NC findings. RP was present in 32% of PSS, keratoconjunctivitis sicca in 91%, oral xerosis in 93%, and skin or genital xerosis in 53%. In patients with positive anti-SSA/Ro (75%) and positive anti-SSB/La (40%), NC showed normal findings in 53% of cases and non-specific in 36%. In patients with PSS, NC was normal in 51% of cases and non-specific in 34%. Scleroderma pattern was found in 14 patients. RP associated with PSS had non-specific capillaroscopy in 40% of cases (p = 0.1). Pericapillary haemorrhages (p = 0.06) and capillary thrombosis (p = 0.2) were not increased, but more dilated capillaries were detected in 48% of cases. Patients with positive anti-Ro and/or anti-La have not a distinct NC profile. Patients with RP associated with PSS had more dilated capillaries, but neither pericapillary haemorrhages nor capillary thrombosis was observed.
26706653 An Online Tailored Self-Management Program for Patients With Rheumatoid Arthritis: A Devel 2015 Dec 25 BACKGROUND: Every day rheumatoid arthritis (RA) patients make many decisions about managing their disease. An online, computer-tailored, self-management program can support this decision making, but development of such a program requires the active participation of patients. OBJECTIVE: To develop an online, computer-tailored, self-management program integrated with the nursing care, as nurses have an important role in supporting self-management behavior. METHODS: The intervention mapping framework was used to develop the program. Development was a multistep process: (1) needs assessment; (2) developing program and change objectives in a matrix; (3) selecting theory-based intervention methods and practical application strategies; (4) producing program components; (5) planning and adoption, implementation, and sustainability; and (6) planning for evaluation. RESULTS: After conducting the needs assessment (step 1), nine health-related problems were identified: (1) balancing rest and activity, (2) setting boundaries, (3) asking for help and support, (4) use of medicines, (5) communicating with health professionals, (6) use of assistive devices, (7) performing physical exercises, (8) coping with worries, and (9) coping with RA. After defining performance and change objectives (step 2), we identified a number of methods which could be used to achieve them (step 3), such as provision of general information about health-related behavior, self-monitoring of behavior, persuasive communication, modeling, and self-persuasion and tailoring. We described and operationalized these methods in texts, videos, exercises, and a medication intake schedule. The resulting program (step 4) consisted of an introduction module and nine modules dealing with health-related problems. The content of these modules is tailored to the user's self-efficacy, and patients can use the online program as often as they want, working through a module or modules at their own speed. After implementation (step 5), the program will be evaluated in a two-center pilot trial involving 200 RA patients. Log-in data and qualitative interviews will used for a process evaluation. CONCLUSIONS: The intervention mapping framework was used to guide development of an online computer-tailored self-management program via a process which could serve as a model for the development of other interventions. A pilot randomized controlled trial (RCT) will provide insight into the important outcome measures in preparation for a larger RCT. The process evaluation will provide insight into how RA patients use the program and the attrition rate. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR4871; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4871 [accessed 13-NOV-15] http://www.webcitation.org/6d1ZyIoEy.
29539556 Diagnosing a possible case of juvenile idiopathic arthritis: A palaeopathology study from 2016 Dec In the summer of 1967, a relatively complete skeleton of a juvenile was excavated from the Ishkeenickh River Cave Site (now the Ksi Hlginx River) in British Columbia, Canada, dating from approximately 2000 years ago. This individual, likely aged between 10 and 12 years at time of death, displays osteological features consistent with a chronic arthropathy. The most striking pathological changes are on the spine, with bony ankylosis present on several of the cervical and thoracic vertebrae. Lesions can also be observed on the ribs, the ilia, the femora, and a tibia. The arthritic conditions of juvenile-onset ankylosing spondylitis, juvenile psoriatic arthritis, and juvenile-onset adult-type rheumatoid arthritis, along with Klippel-Feil syndrome, are possible aetiologies discussed as part of a differential diagnosis. The presence of post-mortem damage as well as missing bones makes an absolute diagnosis of a disease impossible, however the lesions present on this skeleton seem to be most consistent with juvenile-onset ankylosing spondylitis. The majority of published research on these diseases appears in clinical contexts, therefore this case study represents a unique opportunity to observe the bony changes that occur with juvenile idiopathic arthritis in the context of palaeopathology.
27708972 Surgery for lumbar spinal stenosis in patients with rheumatoid arthritis: A multicenter ob 2016 Jun OBJECTIVE: To compare clinical outcomes following microdecompression surgery or laminectomy for central lumbar spinal stenosis (LSS) between patients with rheumatoid arthritis (RA) and patients without rheumatic disease. MATERIAL AND METHODS: Data were collected from the Norwegian Registry for Spine Surgery. The primary outcome was change in the Oswestry Disability Index (ODI) score at 1 year. The secondary endpoints were health-related quality of life that was measured using the Euro-Qol-5D (EQ-5D), back pain numerical rating scale (NRS), leg pain NRS, and complications. RESULTS: A total of 1433 patients were included (1396 controls and 37 patients with RA). For all the patients, there was an improvement in ODI score 16.7 points; 95% confidence interval (CI), 15.7, 17.7; p<0.001). There were no differences between controls and patients with RA with respect to the mean changes of ODI scores (-2.5 points; 95% CI, -9.0 to 4.1; p=0.462), EQ-5D (p=0.295), back pain NRS (p=0.194), leg pain NRS (p=0.927), and complications within 3 months of surgery (12.8% vs. 13.5%, p=0.806). At 1 year, 68.6% (n=775) of controls had achieved a minimal clinically important difference (≥8 points ODI score improvement) compared with 65.5% (n=19) of patients with RA (p=0.726). CONCLUSION: Patients with RA experienced similar and large improvements in patient-reported outcomes following surgical decompression for LSS compared with patients without rheumatic disease. There was no increased risk of complications in patients with RA.
27565213 Folate receptor targeted three-layered micelles and hydrogels for gene delivery to activat 2016 Dec 28 New folic acid (FA) coupled three layered micelles (3LM) were designed to encapsulate DNA, and their application as delivery system that specifically targets activated macrophages was investigated for new treatment options in rheumatoid arthritis (RA). FA coupled poly(l-lactide)-b-poly(ethylene glycol) (FA-PEG-PLLA) was synthesized via the NHS-ester activated/amine coupling method. Fluorescein labeled folic acid was used for flow cytometric detection of the expression of functional folic receptor β in LPS-activated and resting macrophages. FA coupled 3LM were formulated in a two-step procedure and characterized regarding hydrodynamic diameters and zeta potentials. The presence of the targeting ligand was shown not to increase the size of the 3LM compared to their non-targeted counterparts. Targeted and non-targeted 3LM were used in vitro to optimize uptake conditions in the RAW 264.7 macrophage cell line. The amount of FA coupled polymer in the final formulation was found to be optimal at 75% FA-PEG-PLLA and 25% PLLA-PEG-PLLA. Subsequently, transgene expression in vitro in RAW 264.7 cells and ex vivo in primary activated and resting mouse macrophages was determined as a function of FR-mediated internalization of 3LM encapsulating GFP expressing plasmid. FR-overexpressing activated cells, as successfully identified by internalization of FA-fluorescein, showed significantly higher GFP expression in vitro and ex vivo than resting macrophages with only a basal level of FR expression. Lastly, injectable hydrogels as depot formulation were formed by stereocomplexation, and their degradation, DNA release profiles, and dissociation into intact 3LM were found to be beneficial for potential in vivo application. Our findings confirm that FA-3LM are taken up by activated macrophages via folate receptor mediated endocytosis and that their hydrogels release intact 3LM for efficient transfection of primary macrophages. Therefore, FA-3LM could become a promising delivery system for receptor-mediated drug or gene delivery and novel therapy for rheumatoid arthritis in an in situ forming gel formulation.
28066502 A Correlated Binary Model for Ignorable Missing Data: Application to Rheumatoid Arthritis 2016 Apr Incomplete data are common phenomenon in research that adopts the longitudinal design approach. If incomplete observations are present in the longitudinal data structure, ignoring it could lead to bias in statistical inference and interpretation. We adopt the disposition model and extend it to the analysis of longitudinal binary outcomes in the presence of monotone incomplete data. The response variable is modeled using a conditional logistic regression model. The nonresponse mechanism is assumed ignorable and developed as a combination of Markov's transition and logistic regression model. MLE method is used for parameter estimation. Application of our approach to rheumatoid arthritis clinical trials is presented.
25596076 Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to 2015 May Autoimmune diseases are chronic, destructive diseases that can cause functional disability and multiple organ failure. Despite significant advances in the range of therapeutic agents, especially biologicals, limitations of the routes of administration, requirement for frequent long-term dosing and inadequate targeting options often lead to suboptimal effects, systemic adverse reactions and patient non-compliance. Nanotechnology offers promising strategies to improve and optimize autoimmune disease treatment with the ability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we focus on nanomedicine-based delivery strategies of biological immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis and type 1 diabetes. This comprehensive review details the concepts and clinical potential of novel nanomedicine approaches for inducing immunosuppression and immunological tolerance in autoimmune diseases in order to modulate aberrant and pathologic immune responses. FROM THE CLINICAL EDITOR: The treatment of autoimmune diseases remains a significant challenge. The authors here provided a comprehensive review, focusing on the current status and potential of nanomedicine-based delivery strategies of immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis, and type 1 diabetes.
27888056 Sclerostin expression and functions beyond the osteocyte. 2017 Mar Sclerostin, the product of the SOST gene, is a secreted inhibitor of Wnt signaling that is produced by osteocytes to regulate bone formation. While it is often considered an osteocyte-specific protein, SOST expression has been reported in numerous other cell types, including hypertrophic chondrocytes and cementocytes. Of interest, SOST/sclerostin expression is altered in certain pathogenic conditions, including osteoarthritis and rheumatic joint disease, and it is unclear whether sclerostin plays a protective role or whether sclerostin may mediate disease pathogenesis. Therefore, as anti-sclerostin antibodies are being developed for the treatment of osteoporosis, it is important to understand the functions of sclerostin beyond the regulation of bone formation.
25813458 Incidence and predisposing factors of periprosthetic proximal femoral fractures: a literat 2015 Sep PURPOSE: The purpose of this review article was to investigate the incidence and predisposing factors for periprosthetic proximal femoral fractures (PFF) following total hip arthroplasty. METHODS: We performed a comprehensive search of the medical literature in MEDLINE and EMBASE databases to review articles related to PFF, their incidence and risk factors. RESULTS AND CONCLUSIONS: The incidence of PPF after primary THA was, in general, lower than after revision THA both for intra- and postoperative PFF. The rate of intraoperative PFF ranged from 0.1% to 27.8% and of postoperative PFF from 0.07% to 18%. Predisposing factors for intraoperative PFF are osteoporosis, rheumatoid arthritis, femoral preparation and surgical technique used to insert the rasp or femoral component, the use of press-fit cementless stems, and revision THA. In case of postoperative PFF, the following seem to be significant risk factors: advanced age, female gender, post-traumatic osteoarthritis, osteoporosis and rheumatoid arthritis, proximal femoral deformities, previous surgery of the affected hip, implant type (especially cementless stems and press-fit implantation), technical errors such as cortical perforation, cortical stress risers, low-energy trauma, osteolysis, loosening and revision THA.
27979873 2016 update of the EULAR recommendations for the management of early arthritis. 2017 Jun OBJECTIVES: Since the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis. METHODS: In accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of 'management' and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process. RESULTS: The updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research. CONCLUSIONS: These recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.
29900954 Obesity Associated With Active, but Preserved Joints in Rheumatoid Arthritis: Results From 2016 Sep OBJECTIVES: This study aims to investigate the prevalence of obesity in patients with rheumatoid arthritis (RA) and associations with disease outcomes. PATIENTS AND METHODS: The study population comprised of 1,038 patients with RA (198 males, 840 females; mean age 56.1±12.6 years; range 19 to 94 years) who had been included in National RA-Registry. RA disease activity measures, physical function, quality of life, joint destruction, laboratory tests, as well as pain, fatigue, general health, and patient and physician global health assessments on a visual analog scale were collected. RESULTS: Our patients had established RA with mean disease duration of 10.2±8.8 years and moderate disease activity (disease activity score in 28 joints: mean 3.7±1.6). According to the body mass index (BMI), 70% of the patients were overweight (n=362, 34.9%) or obese (n=364, 35.1%). These patients had higher disease activity scores in 28 joints, visual analog scale-pain and visual analog scale-patient global scores, and higher levels of fasting blood glucose; however, they had lower radiographic scores than normal-BMI patients (p<0.05). Regression analyses showed that the BMI was independently and inversely associated with disease activity scores in 28 joints and Sharp/van der Heijde scores after the adjustments for biologic and treatment-related factors (p<0.05). CONCLUSION: Our findings indicate that obesity is more common in patients with RA than the general population. High disease activity and low radiographic damage were associated with high BMI in this National RA-Registry.
26917565 Cerebrovascular Disease in Rheumatic Diseases: A Systematic Review and Meta-Analysis. 2016 Apr BACKGROUND AND PURPOSE: Some rheumatic diseases are associated with stroke. Less is known about associations with stroke subtypes or stroke risk by age. We quantified the association between stroke, its subtypes, and rheumatic diseases and identified when stroke risk is greatest. METHODS: Searches of EMBASE (from 1980) and MEDLINE (from inception) to end 2014 and manual search of reference lists for studies of stroke and stroke subtypes in rheumatic diseases as well as studies measuring cerebrovascular disease from magnetic resonance imaging. RESULTS: Prior published meta-analyses and new pooled analyses of any stroke in rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, gout, and psoriasis show an excess risk of stroke over the general population with odds ratio (OR) ranging from 1.51 (95% confidence interval: 1.39-1.62) to 2.13 (1.53-2.98). New meta-analyses of stroke subtypes in rheumatoid arthritis [ischemic: OR, 1.64 (1.32-2.05); hemorrhagic: OR, 1.68 (1.11-2.53)] and systemic lupus erythematosus [ischemic: OR, 2.11 (1.66-2.67); hemorrhagic: OR, 1.82 (1.07-3.09)] show an excess risk of stroke over the general population. Stroke risk across rheumatic diseases is highest in those aged <50 years [OR, 1.79 (1.46-2.20)] and reduces relatively with ageing [>65 years: OR, 1.14 (0.94-1.38); difference P<0.007]. Inflammatory arthropathies conveyed higher stroke risk than noninflammatory diseases (OR, 1.3, 1.2-1.3). It was not possible to adjust ORs for risk factors or treatments. CONCLUSIONS: Risk of any stroke is higher in most rheumatic diseases than in the general population, particularly <50 years. Rheumatoid arthritis and systemic lupus erythematosus increase ischemic and hemorrhagic stroke risk by 60% to 100% relative to the general population.
26392589 Impaired signaling through the Fms-like tyrosine kinase 3 receptor increases osteoclast fo 2016 Mar Osteoclasts are bone-resorbing cells that accumulate in the joints of patients with rheumatoid arthritis causing severe bone damage. Fms-like tyrosine kinase 3 ligand is enriched in the synovial fluid of patients with rheumatoid arthritis, and local exposure to Fms-like tyrosine kinase 3 ligand aggravates arthritis in mice. Because Fms-like tyrosine kinase 3 ligand has been suggested to facilitate osteoclast differentiation, we asked whether Fms-like tyrosine kinase 3 ligand affects bone remodeling in arthritis. The effect of Fms-like tyrosine kinase 3 signaling on osteoclast development was studied by immunohistochemistry in methylated bovine serum albumin-induced arthritis using mice that lack the gene for Flt3l (Flt3L(-/-)) and by an in vitro assay. Bone and joint changes were studied morphologically and by microcomputer tomography. We found that Flt3L(-/-) mice had increased accumulations of osteoclasts in the periarticular area of the arthritic joint. This triggered bone destruction and trabecular bone loss. The increased number of osteoclasts in Flt3L(-/-) mice may be a consequence of insufficient expression of interferon regulatory factor 8. Treatment of Flt3L(-/-) mice with Fms-like tyrosine kinase 3 ligand increased expression of interferon regulatory factor 8, reduced the number of osteoclasts in arthritic mice, and promoted trabecular bone formation. Finally, the reduced number of regulatory T cells in the bone marrow of Flt3L(-/-) mice could further contribute to the increased osteoclastogenesis by reducing the ratio of regulatory T cells to T helper 17 cells. This study shows that Fms-like tyrosine kinase 3 ligand may serve as a negative regulator of osteoclast development by promoting transcription of interferon regulatory factor 8 and sustaining a balance between protective regulatory T cells and pathogenic T helper 17 cells in the pathogenesis of arthritis.
27914593 Systemic and localized infection by Candida species in patients with rheumatic diseases re 2016 Nov OBJECTIVE: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. METHODS: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. RESULTS: 194 patients [67 with rheumatoid arthritis (RA), 47 with ankylosing spondylitis (AS), 36 with juvenile idiopathic arthritis (JIA), 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42±16 years, with 68 (35%) male and mean disease duration of 15±10 years. Sixty-four (33%) patients were receiving adalimumab, 59 (30%) etanercept and 71 (36%) infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5%) patient had localized fungal infection (vaginal candidiasis). None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. CONCLUSIONS: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.
27470087 A phase II investigator-initiated pilot study with low-dose cyclosporine A for the treatme 2016 Sep This study aims to investigate the efficacy and safety of low-dose cyclosporine A (CyA) in patients with primary Sjögren's syndrome (pSS) and articular involvement. This phase II open-label clinical study included 30 patients meeting the American-European Consensus group criteria for pSS with active joint involvement under stable symptomatic therapy. Treatment consisted of approximately 2 mg kg(-1) body weight of CyA day(-1) over a period of 16 weeks. The primary endpoint was defined as a reduction in the number of painful and/or swollen joints at end of treatment (EOT). Secondary endpoints included the changes in general health, sicca symptoms, European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI), arthrosonography, and safety profile. At baseline (BL), the mean number of tender joints (68 count) was 16.2 (±13.2) and at EOT 10.4 (±11.9; p = 0.002). The mean number of swollen joints (66 counts) was reduced from 3.2 (±3.3) at BL to 1.3 (±3.2) at EOT (p < 0.001). Overall, 21 (70 %) and 13 (43.3 %) patients had a reduction of two or more tender and swollen joints, respectively, in the 68/66 joint counts. The disease activity score (DAS28) showed a statistically and clinically meaningful decrease over the 16-week period of treatment. Treatment was well tolerated, and adverse events were consistent with the known safety profile of CyA (e.g., hypertension, headache). In this pilot study, promising effects of low-dose CyA treatment on articular involvement were observed in patients with pSS justifying further controlled studies in this indication. No new or unexpected safety observations were made. TRIAL REGISTRATION: Low-Dose Cyclosporin A in Primary Sjögren Syndrome (CYPRESS), ClinicalTrials.gov Identifier: NCT01693393 .
26892480 Three cases of pigmented cosmetic dermatitis-like eruptions associated with primary Sjögr 2016 Aug Pigmented cosmetic dermatitis-like (Riehl's melanosis-like) pigmentation was reported in three of 27 patients with primary Sjögren's syndrome. But case reports of such eruptions are rare. We describe three cases of such eruptions associated with primary Sjögren's syndrome or anti-SSA antibody and possible associations with specific types of human leukocyte antigen (HLA) and infiltrating lymphocytes. These middle-aged Japanese women had reticular facial pigmentation and histopathological examination revealed interface dermatitis, melanophages, and dense lymphocytic infiltration around hair follicles and sweat ducts. HLA typing revealed common antigenic equivalents or genetic typing of HLA-A2, DR52, DPA1(02:02) and DPB1(05:01). Immunohistochemical staining revealed major subsets of T cells to be CD8 and CD45RO. Some Foxp3- and few IL17-positive cells were found in strong contrast to the major CD4 subset of infiltrated T cells in annular erythema associated with Sjögren's syndrome. Apparently, our patients' pigmentation represented a specific etiology associated with primary Sjögren's syndrome or anti-SSA antibody.