Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
23868732 [Multimorbidity in elderly rheumatic patients part 2]. 2013 Aug While diseases, such as cardiovascular diseases and osteoporosis in the elderly are categorized as comorbidities of rheumatoid arthritis, elderly rheumatic patients are often additionally affected by thyroid dysfunctions and diabetes mellitus type 2, so that the risk of multimorbidity (coexistence of at least two chronic and/or acute diseases) will increase significantly in elderly patients already suffering from systemic rheumatic diseases. Restricted cognition, adherence or compliance may additionally complicate the treatment of elderly rheumatic patients. Furthermore, the pharmacokinetics of the elderly is another challenging task. Referring to selected aspects of geriatric pharmacotherapy, the use of certain substance classes is described in this context.
23576058 Silicone implant incompatibility syndrome (SIIS): a frequent cause of ASIA (Shoenfeld's sy 2013 Jul Silicon has a molecular mass of 28 daltons. In nature, silicon is found as silicon dioxide (silica) or in a variety of silicates (e.g., in talc or asbestos). Furthermore, silicon is present in silicones, polymerized siloxanes, which are often used as medical silicones in breast implants. Silicon exposure is associated with different systemic autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, and vasculitis. Remarkably, silicon in silicone-filled breast implants is considered to be safe, not increasing the risk of developing autoimmune diseases. We analyzed the impact of silicone-filled breast implants on the immune system in 32 consecutive patients attending a specialized autoimmunity clinic. All 32 patients had silicone implant incompatibility syndrome and complaints fulfilling the diagnostic criteria of ASIA (autoimmune/inflammatory syndrome induced by adjuvants). Furthermore, in 17 of the 32 patients, a systemic autoimmune disease was diagnosed, and 15 of the 32 patients had an impaired humoral immune system. Patients developed symptoms and signs after long-term follow-up, suggesting that these symptoms and signs started after implant aging and/or rupture. We postulate that silicon in silicone-filled breast implants may increase the risk of developing (auto) immune diseases and immune deficiencies.
23544341 [A case of prolonged hypercapnea after interscalene brachial plexus block]. 2013 Mar An 83-year-old woman was scheduled for surgery of the left upper and lower extremity fracture. She had past history of lung partial resection for lung cancer and rheumatoid arthritis, and recent history of pneumonia. She also had fluid retention in the thoracic cavity. Open resection of the femoral neck fracture was first performed uneventfully under spinal anesthesia with bupivacaine 0.5% 2 ml. Then, interscalene blaxioplexus block was performed with 0.75% ropivacaine 15 ml and 1% lidocaine 10 ml for tension band wiring of the fractured olecranon. Midazolam 1 mg and propofol 1.5 mg x kg(-1) x hr(-1) were administered for sedation. Thirty minutes after the block, oxgen saturation decreased to 92% under O2 3 l x min(-1) by a mask. She was intubated and arterial carbon dioxide tension was above 150 mmHg. A few hours later, she became conscious and mask CPAP was used after extubation for one day. Pa(CO2) was 90-100 mmHg for 3 days and decreased to 56.9 mmHg on the 6th day, but her consciousness had been clear. Phrenic nerve palsy and sedation in the patient with decreased lung function might have induced prolonged hypercapnea.
23321502 Simultaneous romiplostin, eltrombopag, and prednisone were successful in severe thrombocyt 2013 May A 58-year-old woman presented with rheumatoid arthritis-associated Evans syndrome (simultaneous autoimmune hemolytic anemia and autoimmune thrombocytopenic purpura); she was treated unsuccessfully with steroids, romiplostin, rituximab, immunoglobulin G, and splenectomy. The platelet count responded to the combined use of prednisone, eltrombopag, and romiplostin. It may be more reasonable to use combined treatments than sequential monotherapies.
23112137 Gold nanoparticles downregulate interleukin-1β-induced pro-inflammatory responses. 2013 Feb 11 Interleukin 1 beta (IL-1β)-dependent inflammatory disorders, such as rheumatoid arthritis and psoriasis, pose a serious medical burden worldwide, where patients face a lifetime of illness and treatment. Organogold compounds have been used since the 1930s to treat rheumatic and other IL-1β-dependent diseases and, though their mechanisms of action are still unclear, there is evidence that gold interferes with the transmission of inflammatory signalling. Here we show for the first time that citrate-stabilized gold nanoparticles, in a size dependent manner, specifically downregulate cellular responses induced by IL-1β both in vitro and in vivo. Our results indicate that the anti-inflammatory activity of gold nanoparticles is associated with an extracellular interaction with IL-1β, thus opening potentially novel options for further therapeutic applications.
22833242 The incidence and associations of malignancy in a large cohort of patients with biopsy-det 2013 Apr The South Australian (SA) myositis database has registered all patients with biopsy-proven inflammatory myositis in SA from 1980 to 2009. We determined the incidence and associations of malignancy in myositis by linking this database with the SA cancer registry. Standardized incidence ratios (SIR) for malignancy were determined using the total SA population over the same time period, stratified by age and gender. The SIR for cancer in the myositis population (n = 373) was 1.39, p = 0.047. There was a trend towards an increased SIR in dermatomyositis but no increased risk of malignancy in polymyositis or inclusion body myositis. Malignancies of the lung and prostate were the commonest and 28 % of malignancies occurred within one year of IIM diagnosis. The odds of developing cancer were significantly raised in the presence of a shawl sign, male gender, and in patients with overlap syndrome or rheumatoid arthritis whilst myalgia was a significant protective factor. HLA-A28 allele was overrepresented in patients with malignancy (11 vs 2 %, p = 0.006). Patients in SA with myositis are at modestly increased risk for malignancy. We report clinical and genetic risk factors allowing the identification of patients at greatest risk for malignancy.
22678997 Non-invasive identification of proteoglycans and chondrocyte differentiation state by Rama 2013 Feb Proteoglycans (PGs) are crucial extracellular matrix (ECM) components that are present in all tissues and organs. Pathological remodeling of these macromolecules can lead to severe diseases such as osteoarthritis or rheumatoid arthritis. To date, PG-associated ECM alterations are routinely diagnosed by invasive analytical methods. Here, we employed Raman microspectroscopy, a laser-based, marker-free and non-destructive technique that allows the generation of spectra with peaks originating from molecular vibrations within a sample, to identify specific Raman bands that can be assigned to PGs within human and porcine cartilage samples and chondrocytes. Based on the non-invasively acquired Raman spectra, we further revealed that a prolonged in vitro culture leads to phenotypic alterations of chondrocytes, resulting in a decreased PG synthesis rate and loss of lipid contents. Our results are the first to demonstrate the applicability of Raman microspectroscopy as an analytical and potential diagnostic tool for non-invasive cell and tissue state monitoring of cartilage in biomedical research.
23229350 Modulation of Th1 cytokines and inflammatory mediators by Euphorbia hirta in animal model 2013 Oct Euphorbia hirta L. (Euphorbiaceae) (E. hirta) is a tree locally used as a traditional medicine in Africa and Australia to treat numerous diseases such as hypertension, respiratory ailments, tumors, antipyretic, anti-inflammatory activities. In the present study, we investigated the anti-arthritic activity of fresh leaves of E. hirta ethanol extract that was found to inhibit the production of inflammatory mediators and cytokines of adjuvant arthritis in rats. Adjuvant arthritis was induced in rats (Wistar) by the subplantar injection of 0.05 ml freshly prepared suspension (5.0 mg/ml) of steam killed Mycobacterium tuberculli in liquid paraffin. Animals were treated with graded doses of 25, 50, 100 and 200 mg/kg of E. hirta ethanol extract, p.o. E. hirta significantly inhibited the swelling of the adjuvant-induced arthritis. Moreover, E. hirta at higher dose (200 mg/kg) showed 40.54 ± 1.09 % of CD3+, 15.1 ± 0.76 % of CD4+, 12.2 ± 1.18 % of CD8+ T cell receptor and 17.6 ± 1.11 % gated of CD19+ B cell receptor revealing a down regulation of adjuvant-induced arthritis as compared to the corresponding valves of the arthritic control rats. According to the results shown in Tables 1, 2, the production of IL-1β, TNF-α, IL-2 and IFN-γ were increased in splenocytes of arthritic rats and this increased level was reduced by E. hirta. Also, E. hirta significantly down regulated lipopolysaccharide (LPS)-induced production of nitric oxide production in peritoneal macrophages. These results suggest that E. hirta exhibits an improvement in adjuvant-induced arthritis through down regulation of activated macrophages and T lymphocytes functions. Such unique effects of E. hirta shown on adjuvant arthritis rat model may be advantageous to the long-term treatment of clinical rheumatoid arthritis. Table 1 Effect of E. hirta and prednisolone (Pred) on LPS-induced IL-1β and TNF-α productions from splenocytes in Mycobacterium tuberculli-induced inflammatory arthritic rats Treatment Dose (mg/kg) IL-1β (pg/ml) TNF-α (pg/ml) Arthritic control (AC) - 323.56 ± 31.65 180.91 ± 24.12 E. hirta 25 311.19 ± 29.08* 171.43 ± 22.54* E. hirta 50 287.12 ± 26.98* 164.54 ± 21.76** E. hirta 100 243.12 ± 19.21*** 157.30 ± 18.54*** E. hirta 200 215.21 ± 16.05*** 138.43 ± 17.98*** Prednisolone (Pred) 5 187.18 ± 15.21*** 123.77 ± 15.12*** Normal control (NC) - 54.12 ± 12.54 71.94 ± 12.12 Each value indicates the mean ± SEM of six animals AC arthritic control, NC normal control; E. hirta (25, 50, 100 and 200 mg/kg) and prednisolone (5 mg/kg) were given p.o. from day 0 to day 21 after Mycobacterium tuberculli injection, respectively * p < 0.05; ** p < 0.01; *** p < 0.001, compared to arthritic control Table 2 Effect of E. hirta and Prednisolone (Pred) on Con A-induced IL-2 and IFN-γ productions from splenocytes in Mycobacterium tuberculli-induced inflammatory arthritic rats Treatment Dose (mg/kg) IL-2 (pg/ml) IFN-γ (pg/ml) Arthritic control (AC) - 235.98 ± 15.23 165.95 ± 13.87 E. hirta 25 225.12 ± 14.76** 154.76 ± 11.07** E. hirta 50 207.76 ± 13.87** 134.76 ± 11.01** E. hirta 100 189.98 ± 12.65 *** 110.64 ± 10.98*** E. hirta 200 157.84 ± 14.32 *** 98.54 ± 10.76*** Prednisolone (Pred) 5 131.08 ± 13.31*** 87.65 ± 10.61*** Normal control (NC) - 78.12 ± 12.04 31.87 ± 10.12 Each value indicates the mean ± SEM of six animals AC arthritic control, NC normal control; E. hirta (25, 50, 100 and 200 mg/kg) and prednisolone (5 mg/kg) were given p.o. from day 0 to day 21 after Mycobacterium tuberculli injection, respectively * p < 0.05; ** p < 0.01; *** p < 0.001, compared to arthritic control.
24173434 Persistence of Staphylococcus aureus colonization among individuals with immune-mediated i 2014 Feb OBJECTIVE: We investigated the relationship between Staphylococcus aureus colonization and the use of immunosuppressive therapies in patients with immune-mediated inflammatory diseases (IMIDs). METHODS: We prospectively enrolled IMID patients from the rheumatology and dermatology departments of Oregon Health & Science University. At enrolment, we surveyed patients for S. aureus infection risk factors and those using immune-modulating therapies, and evaluated their colonization status with bilateral nares and inguinal fold cultures. Patients were asked to follow up 6-12 months later for reassessment of colonization status by repeat culture. S. aureus isolates were tested for the presence of methicillin resistance by PCR. RESULTS: We enrolled a total of 548 IMID patients. At enrolment, 219 (40.0%) patients were colonized with S. aureus, of which 27 (12.3%) were methicillin-resistant S. aureus (MRSA). Baseline colonization rates were similar between TNF-α inhibitor users and non-users (40.5% and 39.4%, P = 0.79), but were significantly higher for psoriasis patients compared with those with RA (43.5% and 31.8%, P = 0.02). A total of 384 patients were available for follow-up. Patients who were colonized at enrolment were more likely to be colonized at follow-up if they were treated with TNF-α inhibitors during the study as compared to patients without TNF-α inhibitor exposure [odds ratio (OR) = 2.2 (95% CI 1.1, 4.2), P = 0.02]. CONCLUSION: Patients with psoriasis are more likely to be colonized with S. aureus than patients with RA. Patients who are colonized with S. aureus are more likely to remain colonized if exposed to TNF-α inhibitors.
24331070 Methods for systematic reviews of administrative database studies capturing health outcome 2013 Dec 30 This report provides an overview of methods used to conduct systematic reviews for the US Food and Drug Administration (FDA) Mini-Sentinel project, which is designed to inform the development of safety monitoring tools for FDA-regulated products including vaccines. The objective of these reviews was to summarize the literature describing algorithms (e.g., diagnosis or procedure codes) to identify health outcomes in administrative and claims data. A particular focus was the validity of the algorithms when compared to reference standards such as diagnoses in medical records. The overarching goal was to identify algorithms that can accurately identify the health outcomes for safety surveillance. We searched the MEDLINE database via PubMed and required dual review of full text articles and of data extracted from studies. We also extracted data on each study's methods for case validation. We reviewed over 5600 abstracts/full text studies across 15 health outcomes of interest. Nearly 260 studies met our initial criteria (conducted in the US or Canada, used an administrative database, reported case-finding algorithm). Few studies (N=45), however, reported validation of case-finding algorithms (sensitivity, specificity, positive or negative predictive value). Among these, the most common approach to validation was to calculate positive predictive values, based on a review of medical records as the reference standard. Of the studies reporting validation, the ease with which a given clinical condition could be identified in administrative records varied substantially, both by the clinical condition and by other factors such as the clinical setting, which relates to the disease prevalence.
25278892 Correlation of posterior occipitocervical angle and surgical outcomes for occipitocervical 2014 Oct Study Type Retrospective cohort study. Introduction Craniocervical instability is a surgical disease, most commonly due to rheumatoid arthritis, trauma, erosive pathologies such as tumors and infection, and advanced degeneration. Treatment involves stabilization of the craniovertebral junction by occipitocervical instrumentation and fusion. However, the impact of the fixed occipitocervical angle on surgical outcomes, in particular the need for revision surgery and the incidence of dysphagia, remains unknown. Occipitocervical fusions (OCFs) at a single institution were reviewed to evaluate the relationships between postoperative neck alignment, the need for revision surgery, and dysphagia. Objective The objective of this study is to determine whether an increased posterior occipital cervical angle results in an increase in the need for revision surgery, and secondary, dysphagia. Methods A retrospective review of spinal surgery patients from January 2007 to June 2013 was conducted searching for patients who underwent an occipitocervical instrumented fusion utilizing diagnostic and procedural codes. Specifically, a current procedural code of 22590 (arthrodesis, posterior technique [craniocervical]) was queried, as well those with a description of "craniocervical" or "occipitocervical" arthrodesis. Ideal neck alignment before rod placement was judged by the attending surgeon. A review of all cases for revision surgery or evidence of dysphagia was then conducted. Results From January 2007 to June 2013, 107 patients were identified (31 male, 76 female, mean age 63). Rheumatoid arthritis causing myelopathy was the most common indication for OCF, followed by trauma. Twenty of the patients were lost to follow-up and seven died within the perioperative period. Average follow-up for the remaining 80 patients was 16.4 months. The mean posterior occipitocervical angle (POCA), defined as the angle formed by the intersection of a line drawn tangential to the posterior aspect of the occipital protuberance and a line determined by the posterior aspect of the facets of the third and fourth cervical vertebrae, calculated after stabilization, was 107.1 degrees (range, 72-140 degrees). Reoperation was required in 11 patients (11/107, 10.3%). The mean POCA for the reoperation group was 109.5 degrees (range, 72-123) and was not significantly different than patients not requiring reoperation (106.5, p > 0.05). However, for all pathologies excluding infection as a cause for reoperation, the mean POCA was significantly higher, 115.14 degrees (p = 0.039) (Table 1). Seven patients (6.5%) complained of dysphagia postoperatively with a significantly higher POCA of 115 degrees (p = 0.039). Of these seven patients, six underwent posterior-only procedures. One patient underwent anterior and posterior procedures for a severe kyphotic deformity. The dysphagia resolved in six patients over a mean of 3 weeks (range, 2-4 weeks). One patient, whose surgery was posterior only, required the insertion of a gastrostomy tube. Conclusions An elevated POCA may result in need for reoperation due to increased biomechanical stress upon adjacent segments or the construct itself due to flexion in an attempt to maintain forward gaze. Further, an elevated POCA seems to also correlate with a higher incidence of dysphagia. Further investigation is necessary to determine the ideal craniocervical angle which is likely individualized to a particular patient based on global and regional spinal alignments.
24379815 Serum adipokines and adipose tissue distribution in rheumatoid arthritis and ankylosing sp 2013 Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are inflammatory rheumatic diseases that may modify body composition. Adipose tissue has the ability to release a wide range of products involved in physiologic functions, but also in various pathological processes, including the inflammatory/immune response. RA and AS are both associated with the development of cardiovascular complications. It is has been established that central/abdominal, and particularly intra-abdominal or visceral adiposity is closely linked to cardiovascular events. Thus, in this study, we aimed to evaluate the body composition of patients with RA or AS compared to healthy controls (HC), with a special emphasis on the visceral region. In parallel, we measured adipose products or adipokines, namely leptin, adiponectin and its high molecular weight (HMW) isoform, resistin, and ghrelin, a gastric peptide that plays a role in energetic balance. The homeostasis model assessment for insulin resistance (HOMA-IR) and atherogenic index were used to evaluate cardiovascular risk. One hundred and twelve subjects were enrolled (30 patients with RA, 31 with AS, and 51 HC). Body composition was measured using dual-energy X-ray absorptiometry to determine total fat mass and lean mass, adiposity, fat in the android and gynoid regions, and visceral fat. Patients and HC did not differ in terms of body mass index. On the contrary, adiposity was increased in RA (p = 0.01) while visceral fat was also increased, but only in women (p = 0.01). Patients with AS tended to have lower total fat mass (p = 0.07) and higher lean mass compared to HC (p = 0.07). Leptin and leptin/fat mass were decreased in male patients with AS (p < 0.01), while total adiponectin and the ratio of HMW to total adiponectin were both increased in RA (p < 0.01). There were no changes in serum resistin and ghrelin in any group of patients. HOMA-IR and the atherogenic index were not modified in RA and AS. These results confirm that body composition was altered in RA and AS, affecting distinct soft tissue compartments. The effect of the increased visceral adipose tissue on cardiovascular risk is presumably attenuated by the favorable cardiometabolic profile in women with RA, as suggested by the normal HOMA-IR and atherogenic index.
23754128 Somatic hypermutations confer rheumatoid factor activity in hepatitis C virus-associated m 2013 Sep OBJECTIVE: Hepatitis C virus (HCV) is the most frequent cause of mixed cryoglobulinemia (MC), which is characterized by endothelial deposition of rheumatoid factor (RF)-containing immune complexes and end-organ vasculitis. MC is a lymphoproliferative disorder in which B cells express RF-like Ig, yet its precise antigenic stimulus is unknown. We have proposed that IgG-HCV immune complexes stimulate B cell expansion and somatic hypermutation (SHM)-induced affinity maturation in part via engagement of an RF-like B cell receptor. This study was undertaken to test the hypothesis that SHM augments RF activity. METHODS: RFs cloned from single B cells from 4 patients with HCV-associated MC (HCV-MC) were expressed as IgM, IgG, or IgG Fab. Selected Ig were reverted to germline. RF activity of somatically mutated Ig and germline-reverted Ig was determined by enzyme-linked immunosorbent assay. RESULTS: Ig with SHM had RF activity, with the preference for binding being highest for IgG1, followed by IgG2 and IgG4, and lowest for IgG3, where there was no detectable binding. In contrast, reverted germline IgG exhibited markedly diminished RF activity. Competition with 1 μg/ml of protein A abrogated RF activity, suggesting specificity for IgG Fc. Swapping of mutated heavy-chain pairs and light-chain pairs also abrogated RF activity, suggesting that context-specific pairing of appropriate IgH and Igκ, in addition to SHM, is necessary for RF activity. CONCLUSION: SHM significantly contributes to RF activity in HCV-MC patients, suggesting that autoreactivity in these patients arises through antigen-dependent SHM, as opposed to nondeletion of autoreactive germline Ig.
24006460 Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment 2013 Oct 1 The JAKs receive continued interest as therapeutic targets for autoimmune, inflammatory, and oncological diseases. JAKs play critical roles in the development and biology of the hematopoietic system, as evidenced by mouse and human genetics. JAK1 is critical for the signal transduction of many type I and type II inflammatory cytokine receptors. In a search for JAK small molecule inhibitors, GLPG0634 was identified as a lead compound belonging to a novel class of JAK inhibitors. It displayed a JAK1/JAK2 inhibitor profile in biochemical assays, but subsequent studies in cellular and whole blood assays revealed a selectivity of ∼30-fold for JAK1- over JAK2-dependent signaling. GLPG0634 dose-dependently inhibited Th1 and Th2 differentiation and to a lesser extent the differentiation of Th17 cells in vitro. GLPG0634 was well exposed in rodents upon oral dosing, and exposure levels correlated with repression of Mx2 expression in leukocytes. Oral dosing of GLPG0634 in a therapeutic set-up in a collagen-induced arthritis model in rodents resulted in a significant dose-dependent reduction of the disease progression. Paw swelling, bone and cartilage degradation, and levels of inflammatory cytokines were reduced by GLPG0634 treatment. Efficacy of GLPG0634 in the collagen-induced arthritis models was comparable to the results obtained with etanercept. In conclusion, the JAK1 selective inhibitor GLPG0634 is a promising novel therapeutic with potential for oral treatment of rheumatoid arthritis and possibly other immune-inflammatory diseases.
25085045 Comparison of grip strength among 6 grip methods. 2014 Nov PURPOSE: To measure grip strengths using several methods by serially excluding 1 or 2 phalanges using a flexion-block orthosis and comparing those with standard grip posture in order to facilitate prediction of clinical or functional outcomes that relate to the contribution of each finger to grip strength. METHODS: Two hundred healthy men aged 25 to 30 years were included in the survey. Demographic variables were collected, and anthropometric measurements of the forearm and hand were obtained. Grip strength was measured using all fingers, all fingers except the thumb, all fingers except the index finger, all fingers except the middle finger, all fingers except the ring and little fingers, and all fingers except the little finger. The contribution of each finger to the total grip strength was estimated using the weight value concept. RESULTS: Grip strength using all 5 fingers was greatest, and the grip strength without the thumb was the second greatest. Grip strengths without the middle finger and without the ring and little fingers were the lowest. Various degrees of positive correlations between each grip method and 8 anthropometric parameters were found. Contributions of the thumb, index, middle, and ring and little fingers to the grip strength were 17%, 22%, 31%, and 29%, respectively. CONCLUSIONS: The middle finger was the most important contributor to grip strength. The next most important was the combination of the ring and little fingers. CLINICAL RELEVANCE: The present estimated contributions of each finger to grip strength may facilitate prediction of the clinical or functional outcomes of various pathological conditions.
24757284 IL-21 receptor expression in human tendinopathy. 2014 The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1β) in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy.
25447121 Erythrocyte sedimentation rate as baseline predictor for the development of uveitis in chi 2015 Feb PURPOSE: To analyze inflammatory parameters as possible predictors for the development of uveitis in juvenile idiopathic arthritis (JIA) patients. Further, to analyze the predictive value of demographic and clinical factors at the onset of arthritis. DESIGN: Retrospective cohort study. METHODS: In 358 children with oligoarthritis and rheumatoid factor-negative polyarthritis, erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, presence of antinuclear antibodies (ANA), presence of human leukocyte antigen (HLA-)B27, age of onset of JIA, and sex were analyzed for their predictive value for the onset of uveitis. RESULTS: One hundred forty-seven patients (41%) were diagnosed with chronic anterior uveitis. Young age of onset, presence of ANA, and elevated ESR appeared to be predictive factors according to univariate analyses (P = .029, P = .007, and P = 5E(-4), respectively). According to multivariate analysis, young age of onset and elevated ESR appeared to be predictive after adjusting for the other relevant factors (P = .004 and P = .001, respectively). A prediction model was developed. CONCLUSIONS: Elevated ESR appears to be a predictor for the occurrence of uveitis in patients with JIA. Since ESR is already routinely tested in patients with recently diagnosed arthritis, its use as a biomarker can easily be implemented in daily practice.
24588828 Neuroimmune aspects of Sjogren's syndrome: role of VIP/VPAC system in immune and salivary 2014 Sjogren's syndrome (SS) is a chronic inflammatory disease characterized by salivary and lacrimal gland dysfunction although extraglandular manifestations are also found. Suitable study models and in vitro cell culture designs are used to approach SS pathogenic mechanisms. Cellular and molecular pathways involved in gland homeostasis loss and the autoimmune response are focused in the search of novel drug targets and biomarkers. Vasoactive intestinal peptide (VIP) has trophic, pro-secretory and immunomodulatory effects in several chronic and autoimmune disease models. Here we review evidence pointing to its role as an endogenous modulator of gland homeostasis at early stages of the disease. Particularly, mechanisms involving VIP/VPAC system in the course of salivary function impairment in the non obese diabetic (NOD) mouse model of Sjögren's syndrome are described.
24287194 Management of xerostomia and other complications of Sjögren's syndrome. 2014 Feb This article provides an overview of the published literature in English in the past 63 years involving the management of xerostomia and other oral complications of Sjögren's syndrome. The evidence supporting studied interventions was evaluated using published criteria.
23833066 Corneal nerve structure and function in patients with non-sjogren dry eye: clinical correl 2013 Aug 1 PURPOSE: To evaluate the relationship between the in vivo confocal microscopic (IVCM) morphology of subbasal corneal nerves, corneal sensitivity, and clinical parameters in patients with non-Sjögren dry eye disease (NSDD). METHODS: Forty-three patients with NSDD and 14 healthy age- and sex-matched control subjects were included. Each patient underwent an evaluation of ocular surface disease symptoms using the Ocular Surface Disease Index (OSDI); tear film break-up time (TBUT); corneal and conjunctival staining (Oxford scale); the Schirmer test; corneal sensation testing using the Cochet-Bonnet esthesiometer; and corneal subbasal nerve analysis with IVCM. One eye of each subject was included in the study. RESULTS: Mean corneal sensitivity was significantly lower in the NSDD group as compared with the control group (P = 0.014). Corneal subbasal nerves showed significant changes in NSDD patients as compared with normal subjects: lower density (P < 0.001); increased tortuosity (P < 0.001); number of beadings (P < 0.001); and width (P = 0.041). In patients with NSDD, corneal subbasal nerve density was correlated to age (r = -0.352, P = 0.021); the Oxford scale (r = -0.486, P = 0.01); and central corneal sensitivity (r = 0.383, P = 0.041). The maximum length of nerve fibers within a frame (MaxL) was correlated to the OSDI (r = -0.265, P = 0.019) and the Oxford scale (r = -0.307, P = 0.039). In multivariate analysis after adjustment for age, corneal subbasal nerve density remained correlated to the Oxford score (P < 0.001). The Oxford score was also correlated to central corneal sensitivity (r = -0.304, P = 0.042). CONCLUSIONS: NSDD patients have both structural and functional alterations of subbasal corneal nerves and these changes are related to the severity of dry eye.