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ID PMID Title PublicationDate abstract
19531252 Reducing work disability in Ankylosing Spondylitis: development of a work instability scal 2009 Jun 16 BACKGROUND: The Work Instability Scale for Rheumatoid Arthritis (RA-WIS) is established and is used by physicians to identify patients at risk of job loss for rapid intervention. The study objective was to explore the concept of Work Instability (a mismatch between an individual's abilities and job demands) in Ankylosing Spondylitis (AS) and develop a Work Instability Scale specific to this population. METHODS: New items generated from qualitative interviews were combined with items from the RA-WIS to form a draft AS-WIS. Rasch analysis was used to examine the scaling properties of the AS-WIS using data generated through a postal survey. The scale was validated against a gold standard of expert assessment, a test-retest survey examined reliability. RESULTS: Fifty-seven participants who were in work returned the postal survey. Of the original 55 items 38 were shown to fit the Rasch model (chi(2) 37.5; df 38; p 0.494) and free of bias for gender and disease duration. Following analysis for discrimination against the gold standard assessments 20 items remained with good fit to the model (chi(2) 24.8; df 20; p 0.21). Test-retest reliability was 0.94. CONCLUSION: The AS-WIS is a self-administered scale which meets the stringent requirements of modern measurement. Used as a screening tool it can identify those experiencing a mismatch at work who are at risk of job retention problems and work disability. Work instability is emerging as an important indication for the use of biologics, thus the AS-WIS has the potential to become an important outcome measure.
20010296 The role of exercise therapy in the management of juvenile idiopathic arthritis. 2010 Mar PURPOSE OF REVIEW: The current review summarizes the existing knowledge about exercise therapy in the management of juvenile idiopathic arthritis (JIA) along with activity level, functional abilities and exercise capacity of this population. RECENT FINDINGS: Current studies show that children with JIA are considerably less active than their peers. They have significantly impaired aerobic and anaerobic exercise capacity. The inactivity, decreased exercise capacity and disease course lead to deconditioning and disability. Adolescent girls with polyarticular rheumatoid factor-positive subtype appear to be most vulnerable to disability. Recent trials suggest that structured aerobic training or low-intensity programs do not exacerbate arthritis and can lead to improved physical fitness, quality of life and functional abilities in children and adolescents with JIA. SUMMARY: Inactivity in pediatric patients with JIA leads to deconditioning and disability and decreased bone mass, reduced quality of life and possibly increased mortality in adulthood. Although advances in pharmacology have improved the lives of children with JIA, management should also include a moderate, consistent exercise program or more active lifestyle. Physical activity may improve exercise capacity, decrease disability in adulthood, improve quality of life and, in some patients, decrease disease parameters. Further studies are needed to assess practicality of various programs and long-term effects of exercise in children and adolescents with JIA.
21159837 Temporomandibular joint involvement in children with juvenile idiopathic arthritis. 2011 Mar OBJECTIVE: To determine the rate of temporomandibular joint (TMJ) involvement and find factors associated with TMJ arthritis in a single-center cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Retrospective analysis of all patients with JIA visiting the rheumatology clinic between January 1, 2005, and December 31, 2006. Followup information was included until August 2008. A diagnosis of TMJ arthritis was based on clinical rheumatological and/or radiological findings. RESULTS: After a mean followup time for JIA of 4.6 years (range 0.08-14.17), 86/223 patients (38.6%) had developed TMJ arthritis. The rate of TMJ involvement differed significantly among JIA subtypes (p = 0.0016), with 61% in extended oligoarticular, 52% in polyarticular rheumatoid factor (RF)-negative, 50% in psoriatic, 36% in systemic, 33% in polyarticular RF-positive, 33% in persistent oligoarticular, 30% in unclassified JIA, and 11% in enthesitis-related arthritis. The rate of TMJ involvement in our cohort was statistically significantly lower for patients who were HLA-B27-positive (p = 0.0002). In a multivariate analysis, the association of the following factors was confirmed: JIA subtype (p = 0.0001), a higher erythrocyte sedimentation rate (ESR) at diagnosis (p = 0.0038), involvement of joints of the upper extremity (p = 0.011), the absence of HLA-B27 (p = 0.023), and younger age at onset of JIA (p = 0.050). CONCLUSION: In our cohort of children with JIA, the overall rate of TMJ involvement was 38.6%. Patients with certain JIA subtypes, a higher ESR at disease onset, involvement of upper extremity joints, and younger age at diagnosis were more likely to develop TMJ arthritis. The presence of HLA-B27 seemed to be protective.
19728939 Patterns of psoriatic arthritis. 2009 Sep OBJECTIVE: To describe the clinical patterns of arthritis in psoriasis. STUDY DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY: Combined Military Hospital, Kharian Cantonment, Pakistan, from January to December 2007. METHODOLOGY: One hundred consecutive patients with psoriasis reporting to dermatology outpatient department were included. Pregnant ladies (due to X-ray hazard) and rheumatoid factor positive patients were excluded. The demographic profile of patients was recorded. Psoriatic arthritis was diagnosed on the basis of Moll and Wright criteria. Standardized examination of axial and peripheral joints was made. The severity of psoriasis was assessed by PASI score. The presence of a clinical type of psoriatic arthritis, enthesitis, dactylitis, and nail changes were noted. X-ray films of involved joints were taken. A statistical analysis using chi-square test and student's t-test were done where applicable. RESULTS: The mean age of patients was 39.8+15.8 years. Seventy one percent were males and 29% were females. Forty six percent of the patients gave a history of joint involvement and fulfilled the Moll and Wright criteria. The mean PASI score in non-arthritic patients was 26.8+34.8 and in psoriatic arthritis patients it was 28.4+41.2, p=0.08. Thirteen patients (28.2%) had predominantly axial disease, while the rest had predominantly peripheral disease. Single joint involvement (monoarthritis) was the commonest clinical presentation. Nail involvement was seen in 29% of the patients without arthritis while in patients having arthritis, nail involvement was 74% (p=0.001). CONCLUSION: Joint involvement is common in psoriatic patients. However, the criteria of diagnosis lack consensus.
22131673 Prosthodontic Rehabilitation in Sjogren's Syndrome with a Simplified Palatal Reservoir: Tw 2010 Dec Sjogren's syndrome is a distinct clinical condition which includes xerostomia, ocular dryness, rheumatoid arthritis and other connective tissue disorders. Major oral problems reported by such patients include high caries rate, burning of oral mucosa, early tooth loss, increased tooth wear, poor tolerance for dentures and repeated failure of dental restorations. Prosthodontic therapy for this unique patient group is challenging and neglected due to the limited number of abutments, loss of vertical dimension and poor occlusion. Two year follow up of a patient of Sjogren's syndrome, rehabilitated by a combination of fixed and removable prostheses with a simplified palatal salivary reservoir is presented. Though the patient felt an improvement in quality of life due to the prosthesis, slurred speech and frequent reservoir refilling remained problems.
20981163 P2X(7) receptor at the heart of disease. 2010 Jul Purinergic signaling is a crucial component of disease whose pathophysiological basis is now well established. This review focuses on P2X(7), a unique bifunctional purinoreceptor that either opens a non selective cation channel or forms a large, cytolytic pore depending on agonist application and leading to membrane blebbing and to cell death either by necrosis or apoptosis.Activation of P2X(7) receptor has been shown to stimulate the release of multiple proinflammatory cytokines by activated macrophages, with the IL-1b to be the most extensively studied among them. These findings were verified by the use of knockout P2X(7) ((-/-)) mice.Update information coming from all fields of research implicate this receptor at the very heart of diseases such as rheumatoid arthritis, multiple sclerosis, depression, Alzheimer disease, and to kidney damage, in renal fibrosis and experimental nephritis.Clinical studies are currently underway with the newly developed selective antagonists for P2X(7) receptor, the results of which are eagerly anticipated. These studies together with data from in-vivo experiments with the P2X(7) knockout mice and in-vitro experiments will shed light in this exciting area.
20803107 Orbital inflammatory pseudotumors: etiology, differential diagnosis, and management. 2010 Dec Orbital inflammation is typically an idiopathic process that occasionally may be identified with a specific local or systemic disease as the causative agent. Orbital inflammatory pseudotumor (also known as idiopathic orbital inflammation syndrome, orbital pseudotumor, nonspecific orbital inflammation, and orbital inflammatory syndrome) is defined as an idiopathic tumor-like inflammation consisting of a pleomorphic cellular response and a fibrovascular tissue reaction. Various rheumatologic disorders are associated with orbital inflammation and must be ruled out in cases of orbital inflammatory pseudotumor, including Wegener's granulomatosis, giant cell arteritis, systemic lupus erythematosus, dermatomyositis, and rheumatoid arthritis. The mainstay of therapy is corticosteroid therapy, although there is an increasing trend toward use of antimetabolites, alkylating agents, cytotoxic agents, and other immunosuppressive agents.
20125178 The contribution of Asian researchers to the field of rheumatology. 2010 Feb Asia is home to more than half of the world's population and is a region of diverse ethnicity, culture, microbial endemicity, and economic backgrounds. This diversity is also reflected in the heterogeneity among Asian patients with rheumatic diseases in terms of clinical manifestations, disease courses, treatment responses and outcomes, which provides opportunities for researchers to conduct some unique studies. Several disease entities, such as Behçet syndrome, Takayasu arteritis, Kawasaki disease, and immunological disorders associated with human T-lymphotropic virus type 1 (HTLV-1), were first observed and defined in Asia. In addition, the region's researchers have been at the forefront of research in some interesting scientific topics, which has opened up new research avenues in rheumatology, such as the direct targeting of synovial cells in patients with rheumatoid arthritis via activation of the agonistic Fas pathway, establishment of the field of osteoimmunology, the discovery of regulatory T cells and synoviolin, and the development of tocilizumab, a humanized monoclonal antibody against interleukin-6 receptor.
20071185 Design, synthesis, and biological evaluation of novel estradiol-bisphosphonate conjugates 2010 Feb Bone deficiency causes osteoporosis and often decreases quality of life in patients with rheumatoid arthritis. Estrogens are known to protect elderly women from bone loss. Synthesis of new estradiol-bisphosphonate conjugates (E(2)-BPs) was accomplished and their in vivo activity as bone-specific estrogens were examined. Among them, MCC-565 showed selective estrogenic activity in bones; but it showed little estrogenic activity in the uterus. We also found that the linker moiety in E(2)-BPs was essential for the absorption and specificity of the conjugates.
19616584 Unraveling metalloproteinase function in skeletal biology and disease using genetically al 2010 Jan The metalloproteinase family includes MMP, ADAM and ADAMTS proteases. Mice deficient in individual or pairs of metalloproteinases have been generated, and a number of these genetic models spontaneously develop skeletal abnormalities. Here we review metalloproteinase function in endochondral and intramembranous ossification, as well as in postnatal bone remodeling. We highlight how metalloproteinases enable interactions between distinct bone cell types and how this communication contributes to the skeletal phenotypes observed in knockout mice. In addition to the physiological actions of metalloproteinases in the skeletal system, the experimental manipulation of metalloproteinase-deficient mice has revealed substantial roles for these enzymes in osteoarthritis and rheumatoid arthritis. MMP, ADAM and ADAMTS proteases thus emerge as key players in the development and homeostasis of the skeletal system.
21475837 IL-1β stimulates IL-8 production, including prostaglandin E2 receptor EP4-triggered pathw 2009 May Prostaglandin E2 (PGE2) is an important modulator of cytokine-driven inflammation. Using GeneChip analysis, we found that interleukin (IL)-1β induces the gene expression of PTGER4, which encodes the PGE2 receptor subtype EP4 (PGE2EP4). This subtype is one of four PGE2 receptors occurring in synoviocyte MH7A cells. Immunofluorescence microscopy revealed a corresponding upregulation in the production of PGE2EP4 protein in IL-1β-pretreated MH7A cells. PGE2 alone has no effect on IL-8 production, but in cells pretreated with IL-1β it markedly enhances IL-8 production. Moreover, a stimulatory effect of PGE2 on IL-8 production in the synoviocyte MH7A cells was observed. These results indicate that, in the synovial tissues of patients with rheumatoid arthritis, PGE2 stimulates the release of IL-8 from the fibroblastic cells classified as present, thereby exacerbating inflammation.
21686765 Lymphoedema: a paradoxical effect of tumour necrosis factor inhibitors - case report and r 2009 This report describes the development of lymphoedema in a patient with rheumatoid arthritis (RA) who was treated with tumour necrosis factor α (TNFα) inhibitors.The patient was a 62-year-old woman with a long-standing history of RA that had been uncontrolled with steroids and methotrexate. Eight months after initiation of treatment with TNFα inhibitors she developed progressive symmetrical ascending non-pitting oedema of both legs with extensive keratinisation. A diagnosis of lymphoedema was made based on the clinical presentation and exclusion of alternative diagnoses. Skin biopsy showed dermatosclerosis consistent with lymphoedema. The temporal relationship suggested a link between the initiation of TNFα inhibitors and the development of lymphoedema. TNFα inhibitors are widely used to treat inflammatory diseases including lymphoedema. Paradoxically, there are reports suggesting the appearance of psoriasis, vasculitis and other inflammatory cutaneous conditions after the use of TNFα inhibitors. A review of literature is also presented.
21218179 Cutaneous Connective Tissue Diseases: Epidemiology, Diagnosis, and Treatment. 2009 Jan 1 Connective tissue diseases (CTDs) are a group of clinical disorders that have an underlying autoimmune pathogenesis. These include a diverse set of diseases such as relapsing polychondritis, rheumatoid arthritis, and eosinophilic fasciitis, along with more common entities like Sjogren's syndrome, dermatomyositis, scleroderma, and lupus erythematosus. The latter three will be the focus of this review, as they constitute the most significant and common CTD with cutaneous manifestations. The cutaneous signs often represent the preliminary stages of disease and the presenting clinical symptoms. Therefore, comprehensive knowledge of CTD manifestations is essential for accurate diagnosis, better assessment of prognosis, and effective management. Although the precise etiologies of CTDs remain obscure, recent advances have allowed for further understanding of their pathogenesis and improved disease classifications. In addition, there have been developments in therapeutic options for CTDs. This review provides an overview of the epidemiology, clinical presentations, and current treatment options of cutaneous lupus erythematous, dermatomyositis and scleroderma.
20948646 B cell-targeted therapies in autoimmunity: rationale and progress. 2009 May 28 B cells are recognized as main actors in the autoimmune process. Autoreactive B cells can arise in the bone marrow or in the periphery and, if not properly inhibited or eliminated, can lead to autoimmune diseases through several mechanisms: autoantibody production and immune complex formation, cytokine and chemokine synthesis, antigen presentation, T cell activation, and ectopic lymphogenesis. The availability of agents capable of depleting B cells (that is, anti-CD20 and anti-CD22 monoclonal antibodies) or targeting B cell survival factors (atacicept and belimumab) opens new perspectives in the treatment of diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis.
19093736 Emerging role of interleukin-1 in cardiovascular diseases. 2009 There is an increasing evidence linking dysbalance between various proinflammatory mediators and higher risk of cardiovascular events and pathologies. Likewise, some of the cardiovascular diseases lately appeared to have an autoimmune component. Interleukin-1 (IL-1), a master regulator of diverse inflammatory processes in higher eukaryotes and the key player in numerous autoimmune disorders including rheumatoid arthritis, diabetes mellitus or systemic sclerosis, has recently been proved to be involved in development of several cardiovascular diseases as well. This report aims to give a summary on current knowledge about the IL-1 signaling pathways and about the implication of IL-1 and the IL-1 receptor antagonist (IL-1Ra) in some of the diseases of the cardiovascular system.
18936127 Idiopathic carpal tunnel syndrome and trigger finger: is there an association? 2009 Feb Carpal tunnel syndrome (CTS) and trigger finger are known to occur together in association with conditions such as diabetes mellitus, rheumatoid arthritis and hypothyroidism. Although most cases that present to a hand clinic have no obvious predisposing cause, the two conditions often appear together in the same patient. We performed a prospective study of the prevalence of CTS in hospital outpatients presenting with trigger finger. Six hundred and eighty-one patients with CTS, trigger finger or both conditions were recruited prospectively. Diagnosis of both disorders was made on clinical grounds. The study group comprised 551 patients with no obvious predisposing cause. Of 211 patients with trigger finger, 91 (43%) also had CTS. This prevalence is substantially higher than the population prevalence of CTS of approximately 4%. Our data support an association between idiopathic CTS and idiopathic trigger finger and lend support to common pathophysiological factors.
20112378 Mortality outcomes in pediatric rheumatology in the US. 2010 Feb OBJECTIVE: To describe mortality rates, causes of death, and potential mortality risk factors in pediatric rheumatic diseases in the US. METHODS: We used the Indianapolis Pediatric Rheumatology Disease Registry, which includes 49,023 patients from 62 centers who were newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Deaths were confirmed by death certificates, referring physicians, and medical records. Causes of death were derived by chart review or from the death certificate. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were determined. RESULTS: After excluding patients with malignancy, 110 deaths among 48,885 patients (0.23%) were confirmed. Patients had been followed up for a mean +/- SD of 7.9 +/- 2.7 years. The SMR of the entire cohort was significantly decreased (0.65 [95% CI 0.53-0.78]), with differences in patients followed up for > or =9 years. The SMR was significantly greater for systemic lupus erythematosus (3.06 [95% CI 1.78-4.90]) and dermatomyositis (2.64 [95% CI 0.86-6.17]) but not for systemic juvenile rheumatoid arthritis (1.8 [95% CI 0.66-3.92]). The SMR was significantly decreased in pain syndromes (0.41 [95% CI 0.21-0.72]). Causes of death were related to the rheumatic diagnosis (including complications) in 39 patients (35%), treatment complications in 11 (10%), non-natural causes in 25 (23%), background disease in 23 (21%), and were unknown in 12 patients (11%). Rheumatic diagnoses, age at diagnosis, sex, and early use of systemic steroids and methotrexate were significantly associated with the risk of death. CONCLUSION: Our findings indicate that the overall mortality rate for pediatric rheumatic diseases was not increased. Even for the diseases and conditions associated with increased mortality, mortality rates were significantly lower than those reported in previous studies.
20218619 Discovery and evaluation of 7-alkyl-1,5-bis-aryl-pyrazolopyridinones as highly potent, sel 2010 Apr 8 The p38alpha mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn's disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38alpha inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED(50) < or = 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.
21146219 B cells in spontaneous autoimmune diseases of the central nervous system. 2011 Jun B cells and their secreted products participate in the intricate network of pathogenic and regulatory immune responses. In human autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes, a role for B cells and antibodies is well established. However, in multiple sclerosis (MS), despite the presence of autoantibodies, B cells were less considered as a major participant of autoimmune processes, until recently. Several lines of evidence now indicate a more active role for B cells in disease pathogenesis. In this review, we discuss the diverse roles of B cells in autoimmune diseases with particular focus on multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE) as well as the recently generated spontaneous EAE mouse models.
20143981 Endometriosis-associated Lyme disease. 2010 Feb The aim of this study is to report three cases of patients with endometriosis and infertility, and associated with Lyme disease. The medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease. All cases presented with typical erythema migraines, fever and fatigue. The serological findings were positive for Borrelia burgdorferi, for 3 cases. Two out of 3 women underwent IVF-ET procedures and one of them conceived in the first cycle without complication during pregnancy or after childbirth recorded. We concluded that women with endometriosis are more likely to have chronic fatigue syndrome, systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. A review of the literature confirms the uniqueness of the co-existence of Lyme disease in women with endometriosis in these cases.