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

ID PMID Title PublicationDate abstract
20018022 Replication of recently identified associated single-nucleotide polymorphisms from six aut 2009 Dec 15 Many autoimmune diseases share similar underlying pathology and have a tendency to cluster within families, giving rise to the concept of shared susceptibility genes among them. In the Genetic Analysis Workshop 16 rheumatoid arthritis (RA) data we sought to replicate the genetic association between single-nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies (GWAS) on RA and five other autoimmune diseases. We identified 164 significantly associated non-HLA SNPs (p < 10-5) from 16 GWAS and 13 candidate gene studies on six different autoimmune diseases, including RA, systemic lupus erythematosus, type 1 diabetes, Crohn disease, multiple sclerosis, and celiac disease. Using both direct and imputation-based association test, we replicated 16 shared susceptibility regions involving RA and at least one of the other autoimmune diseases. We also identified hidden population structure within cases and controls in Genetic Analysis Workshop 16 RA data and assessed the effect of population structure on the shared autoimmunity regions. Because multiple autoimmune diseases share common genetic origin, these could be areas of immense interest for further genetic and clinical association studies.
19458935 [Value of histological work-up for synovial diseases]. 2009 Jun At times clinicians and pathologists underestimate the value and significance of histopathological diagnostics for synovial tissue. However, the most common diseases of the synovium show specific morphological hallmarks that allow an exact diagnosis. Using the synovitis score allows one to distinguish between degenerative (low-grade synovitis) and inflammatory rheumatic (high-grade synovitis) diseases. Synovial biopsies are not only especially indicated when there are atypical patterns of arthritis, clinical options have been exhausted or monarthritis of unknown origin occurs, but also in patients with known rheumatoid arthritis. Joint infections, crystal-induced arthritis or pigmented villonodular synovitis can also be diagnosed as secondary synovial diseases. Providing clinical information when submitting biopsies/tissue specimens is essential to classify even unspecific morphological changes. Immunohistochemical staining, polarization microscopy or molecular biology techniques (PCR) may be used to ensure diagnoses.
21243296 Glucocorticoid-induced osteoporosis in rheumatic diseases. 2010 The aim of this article is to review rheumatological diseases that are associated with glucocorticoid-induced osteoporosis or fractures and to perform a critical analysis of the current guidelines and treatment regimens. The electronic database MEDLINE was searched using the date range of July 1986 to June 2009 and the following search terms: osteoporosis, bone mineral density, fractures, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, vasculitis, juvenile rheumatoid arthritis, juvenile idiopathic arthritis and juvenile dermatomyositis. Osteopenia and osteoporosis respectively account for 1.4 to 68.7% and 5.0 to 61.9% of adult rheumatological diseases. Among juvenile rheumatological disorders, the frequency of low bone mass ranges from 38.7 to 70%. In general, fracture rates vary from 0 to 25%. Although glucocorticoid-induced osteoporosis has a high rate of prevalence among rheumatic diseases, a relatively low number of patients on continuous glucocorticoid treatment receive adequate diagnostic evaluation or preventive therapy. This deficit in patient care may result from a lack of clear understanding of the attributed risks by the patients and physicians, the high complexity of the treatment guidelines and poor patient compliance.
20147480 Imaging in psoriasis and psoriatic arthritis: GRAPPA 2008. 2010 Feb At the 2008 meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), the primary focus of the imaging session was the enthesis. Presentations from Dennis McGonagle (Leeds, UK), Richard Hodgson (Leeds, UK), and Paolo Gisondi (Verona, Italy) elaborated on this theme and prepared the meeting attendees for group discussions of further work in this area. Imaging, notably magnetic resonance imaging (MRI) and ultrasonography, provides evidence of pathological change at the enthesis in psoriatic arthritis (PsA). Further, imaging abnormalities are found at sites that are asymptomatic in both PsA and psoriasis. The role of newer imaging modalities, such as ultra-short echo time (UTE) MRI, is promising but remains to be fully elucidated. The implication of these findings in relation to subclinical and predisease status is intriguing and requires further study in longitudinal studies. Further work is also required to examine the proposed common biomechanical basis between joint and skin, the mechanism of the resulting inflammation, and how these mechanisms differ from those seen in rheumatoid arthritis.
22368690 A case of idiopathic hypertrophic cranial pachymeningitis presenting high values of matrix 2010 This report concerns a 53-year-old male patient with idiopathic hypertrophic cranial pachymeningitis who presented with multiple cranial nerve palsies (I, II, III, IV, V, VI). Brain magnetic resonance imaging showed diffuse thickening and gadolinium enhancement of the cerebral dura mater. A biopsy of the cerebral dura mater showed granulomatous vasculitis with histiocyte infiltration. Although both the serum rheumatoid factor (RF) and matrix metalloproteinase-3 (MMP-3) were high, the patient showed no signs of arthritis. He was anti-cyclic citrullinated peptide antibody negative, which makes the presence of comorbid chronic rheumatoid arthritis (RA) unlikely. The aetiology of the pachymeningitis was unknown, which led to the diagnosis of idiopathic hypertrophic cranial pachymeningitis. Steroid pulse therapy successfully diminished the patient's pachymeningitis and lowered both RF and MMP-3. High values of RF suggest the possible involvement of an autoimmune mechanism, and the MMP value may be an important indicator of the aetiology of pachymeningitis with granulomatous vasculitis.
20655174 Memory B-cell aggregates in skin biopsy are diagnostic for primary Sjögren's syndrome. 2010 Nov There is a crucial need for reliable diagnostic criteria for SS. Our objective was to evaluate the frequency of xerosis in patients with primary Sjögren's syndrome (SS), and compare histopathology of cutaneous sweat glands and labial salivary glands (LSGs), with respect to their contribution to the diagnosis. Twenty-two patients with primary SS and 22 matched normal volunteers were invited to rate their skin dryness on a visual analog scale. The skin was dryer (58.3 ± 10.1 versus 38.9 ± 7.6, P < 0.01), and xerosis more frequent (9 of 22 versus 2 of 22, P < 0.02) in the patients than in the controls. The axilla skin was chosen for a 6-mm punch biopsy. Lymphocytic infiltration was seen in the skin of 8 of the 12 patients tested. Two of them had normal LSGs. Most interestingly, B cell infiltrates were identified in patients' skin infiltrates, so that their presence might be a clue to the diagnosis of primary SS. These cell aggregates associated memory CD10-/CD20+/CD27+/IgD- B lymphocytes and immature CD20+/CD24 + lymphocytes. These latter findings strongly suggest that skin biopsies warrant inclusion into the routine clinical care of patients suspected of suffering from primary SS.
19962436 Screening of analgesic and anti-inflammatory activities of Citrullus colocynthis from sout 2010 Mar 2 ETHNOPHARMACOLOGICAL RELEVANCE: Inflammations and immune-related diseases such as rheumatoid arthritis are growing global concerns. Most of the drugs from plants which have become important in modern medicine had a folklore origin and are traditional in systems of medicine. Citrullus colocynthis Schrad. (cucurbitaceae), endemic in Southern Tunisia, is used in folk medicine to treat many inflammation diseases. AIM OF STUDY: To evaluate the acute toxicity of different parts of Citrullus colocynthis and then to screen the analgesic and anti-inflammatory activities of aqueous extracts from roots and stems of the plant and from fruits and seeds at different maturation stages. MATERIALS AND METHODS: After identification and acute toxicity assay Citrullus colocynthis Schrad. aqueous extracts were screened for analgesic and anti-inflammatory activities using, respectively, the acetic acid writhing test in mice and the carrageenan-induced paw edema assay in rats. RESULTS: All extracts displayed analgesic and anti-inflammatory activities at different doses without inducing acute toxicity. Topic results were obtained with immature fruits followed by seeds. The stem and root extracts were shown to possess the less significant inhibitory activity against analgesic and anti-inflammatory models. CONCLUSIONS: Based on this study, we confirmed that Citrullus colocynthis Schrad. is a potentially useful drug suitable for further evaluation for rheumatoid arthritis, and its folk medicinal use as an analgesic and anti-inflammatory agents is validated.
19771179 Epstein-Barr-Virus-Infected CD15 (Lewis X)-Positive Hodgkin-Lymphoma-Like B Cells in Patie 2009 Sep 7 Patients with rheumatoid arthritis (RA), especially those who are treated with methotrexate (MTX), might have an increased risk of Hodgkin lymphoma (HL), a malignancy that is associated with Epstein-Barr virus (EBV). Here we describe a monoclonal EBV-infected B-lymphoblastoid cell line (LCL) called TKS-1 that was established from cells that spontaneously converted from an MTX-treated RA patient. TKS-1 has properties similar to HL cells and it is distinctly different from control LCLs established from normal individuals. TKS-1 cells express the HL -associated surface markers CD15 and CD30 (Takei et al. 1989). Like Hodgkin Reed-Sternberg (H-RS) cells of EBV-positive HL, TKS-1 cells express EBNA1 mRNA transcribed from the Qp promoter of the virus, whereas control LCLs use the Cp or Wp promoter to transcribe mRNA. TKS-1 cells can proliferate in an anchorage-independent manner and possess a cloning efficiency comparable to that of the Burkitt lymphoma (BL) line Raji. In addition, two EBV-positive LCLs established by cocultivated CD34+ cells isolated from the bone marrow of patients with RA and peripheral blood B lymphocytes from a healthy EBV-seronegative individual also expressed CD15. These results indicate that EBV-infected B-lymphoblastoid cells from patients with RA tend to acquire properties similar to HL cells.
20017975 Graphic analysis of population structure on genome-wide rheumatoid arthritis data. 2009 Dec 15 Principal-component analysis (PCA) has been used for decades to summarize the human genetic variation across geographic regions and to infer population migration history. Reduction of spurious associations due to population structure is crucial for the success of disease association studies. Recently, PCA has also become a popular method for detecting population structure and correction of population stratification in disease association studies. Inspired by manifold learning, we propose a novel method based on spectral graph theory. Regarding each study subject as a node with suitably defined weights for its edges to close neighbors, one can form a weighted graph. We suggest using the spectrum of the associated graph Laplacian operator, namely, Laplacian eigenfunctions, to infer population structures instead of principal components (PCs). For the whole genome-wide association data for the North American Rheumatoid Arthritis Consortium (NARAC) provided by Genetic Workshop Analysis 16, Laplacian eigenfunctions revealed more meaningful structures of the underlying population than PCA. The proposed method has connection to PCA, and it naturally includes PCA as a special case. Our simple method is computationally fast and is suitable for disease studies at the genome-wide scale.
18992831 Luteolin inhibits proliferation and affects the function of stimulated rat synovial fibrob 2009 Feb Hyperproliferation of synovial fibroblasts is considered to be a pivotal event in the pathogenesis of rheumatoid arthritis (RA). Luteolin, a flavonoid, inhibits the proliferation of synovial fibroblasts in collagen-induced arthritic rats. Treatment with luteolin also decreases the secretion of matrix metalloprotease-1 and -3 and the expression of IL-6, IL-8, IL-15, and TGF-beta. Luteolin treatment caused a delay of cells in the G(2)/M phase. Interestingly, combination treatment with luteolin and TNF-alpha exhibited a synergistic inhibitory effect in all experiments. Western blotting demonstrated that treatment with luteolin alone or combined with TNF-alpha inhibited the MAPK/ERKs and PI3K-Akt pathways. These results indicate that luteolin inhibits the proliferation and partially blocks the pathogenic function of synovial fibroblasts in rheumatoid arthritis.
20101675 A case report of successful treatment with plasma exchange for adult-onset Still's disease 2010 Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology and pathogenesis. The disease is characterized by typical spiking fever with evanescent rash, sore throat, polyarthralgias or polyarthritis, and involvement of various organs. Most of the reported cases with liver involvement occurred during the period of treatment with hepatotoxic drugs, whereas AOSD associated autoimmune hepatitis (AIH) is extremely rare. AIH may be an indicator of the poor prognosis of AOSD. Herein we describe a case of successful treatment with plasma exchange for AOSD-associated AIH.
19691930 Update on the treatment of peripheral arthritis in psoriatic arthritis. 2009 Aug Psoriatic arthritis is a chronic, disabling disease for which therapies have been borrowed from rheumatoid arthritis and spondylitis. Traditional disease-modifying antirheumatic drugs (DMARDs) remain the first choice for the treatment of peripheral arthritis despite scarce evidence of their efficacy or ability to halt radiographic progression. Tumor necrosis factor antagonists have the greatest level of evidence for symptom control and radiographic progression. They are currently used after the failure of DMARDs to effectively treat peripheral arthritis, enthesitis, and dactylitis, and are the first choice when axial disease predominates. Despite the use of these treatments, 30% to 40% of patients will still have active disease. Among new drugs, evidence of efficacy has already been published with regard to anti-IL12/23 monoclonal antibody (ustekimumab) and golimumab. Results are forthcoming from trials with certolizumab pegol, abatacept, and rituximab. As knowledge of the pathogenesis of psoriatic arthritis evolves and differences among other arthritis conditions become evident, therapies targeting these distinct features are needed.
20018087 Assessment of sex-specific effects in a genome-wide association study of rheumatoid arthri 2009 Dec 15 Rheumatoid arthritis (RA) is three times more common in females than in males, suggesting that sex may play a role in modifying genetic associations with disease. We have addressed this hypothesis by performing sex-differentiated and sex-interaction analyses of a genome-wide association study of RA in a North American population. Our results identify a number of novel associations that demonstrate strong evidence of association in both sexes combined, with no evidence of heterogeneity in risk between males and females. However, our analyses also highlight a number of associations with RA in males or females only. These signals may represent true sex-specific effects, or may reflect a lack of power to detect association in the smaller sample of males, and thus warrant further investigation.
19595525 Sex-related differences in pain. 2009 Aug 20 This article provides an overview of sex-related differences in musculoskeletal pain and the role sex hormones and response to analgesic drugs may play in these differences. Some common pain conditions that include temporomandibular disorders, rheumatoid arthritis, fibromyalgia syndrome and tension-type and migraine headaches, show fairly marked sex-related differences in their occurrence, however, with the exception of rheumatoid arthritis, these pain conditions are also characterized by a lack of understanding of their basic underlying pathophysiology. The association of pain symptoms of these musculoskeletal pain conditions with the reproductive cycle of women is strongly suggestive of a role of the estrogens and/or progesterones, the main female sex hormones, in sex-related differences in pain. Nevertheless, an alternative suggestion that testosterone, the major male sex hormone, protects men from these chronic musculoskeletal pain conditions, has also been made. Indeed, emerging evidence suggests that both male and female sex hormones may contribute to the marked sex-related differences in the occurrence of certain musculoskeletal pain conditions. Men and women also appear to differ in response to pain treatment with certain analgesic drugs. The mechanistic basis for these sex-related differences is not entirely understood but sex hormones are thought to be one of the influencing factors. An improved understanding of mechanisms which underlie sex-related differences in musculoskeletal pain and response to analgesic drugs should permit improved pain management strategies for male and female musculoskeletal pain patients in the clinical setting.
20505630 [Sjögren's Syndrome or Multiple Sclerosis? A dilemma in clinical practice]. 2010 Jan The authors present a clinical case of a male, 53-years old with a multiple sclerosis like syndrome, progressive, with 3 years of evolution. The patient also referred dry eye and inflammatory arthralgias, the complementary workup was according with Sjögren's Syndrome. The central nervous system involvement of Sjögren's Syndrome and the difficulty of differential diagnosis with neurological diseases such as Multiple sclerosis is discussed.
20558868 [Nailfold videocapillaroscopy - a useful tool for screening patients with juvenile idiopat 2010 Jun 15 Inflammation of the vascular wall with endothelial dysfunction and subsequent activation of inflammatory immune response play pivotal roles in the early development of the atherosclerotic process not only in adults with rheumatoid arthritis (RA), but also in children with juvenile idiopathic arthritis (JIA). This hypothesis was supported by our findings from autopsy examination, revealing atherosclerosis lesions in about 30% children with JIA. The established methods of assessing pre-clinical atherosclerosis include measurement of biochemical markers of endothelium impairment and ultrasonographic examination of vessels (FMD, IMT). The authors suggest that revealing structural and functional impairment of peripheral microvessels by means of static and dynamic videocapillaroscopy can give clinicians a chance to identify even younger patients with JIA/RA at high risk of atherosclerosis.
20374320 Lest we forget Hansen's disease (leprosy): an unusual presentation with an acute onset of 2009 Apr Several forms of arthritis and rheumatism can sometimes complicate leprosy. However, its presentation as an acute onset arthritis is unusual. We report two adult male naïve patients who presented to our rheumatology outpatient clinic with acute onset inflammatory polyarthritis, skin rash and mild sensory neurodeficit. Borderline lepromatous leprosy (in type I lepra reaction) was diagnosed. We also refer to 19 case records of Hansen arthritis in the clinic database (1998-2007) from approximately 35,000 patients and a community study to highlight the missed diagnosis of Hansen's disease and its unusual association with rheumatoid arthritis. In countries like India where leprosy is endemic, this disease also merits attention in rheumatology clinics.
19250229 Bone marrow edema. 2009 Feb A bone marrow edema pattern on MRI has a similar signal quality as an inflamed synovium and may, in fact, reflect true inflammatory infiltrates rather than a pure accumulation of extracellular fluid. Bone lesions near sites of rheumatoid arthritis-related inflammation are heavily vascularized, contributing to the high water content and enhanced visibility on MRI. However, even without erosive change, periarticular bone marrow lesions may be seen. This chapter describes the nature of bone marrow lesions detected by MRI in patients with inflammatory arthritis.
20827117 Peripheral nervous system manifestations of Sjögren syndrome: clinical patterns, diagnost 2010 Sep Sjögren syndrome is among the most common autoimmune diseases affecting adults in the United States, and is frequently regarded as an immune-mediated exocrinopathy exclusively causing dry eyes and dry mouth. However, as a systemic rheumatic disease, there can be various "extraglandular" complications. The eclectic permutation of peripheral nervous system (PNS) syndromes which occur in Sjögren patients are among the most common and severe extraglandular complications. This review article highlights the evaluation, differential diagnosis, immunopathogenic mechanisms, and potential treatment options of these PNS complications encountered by neurologists. The sensory neuropathies constitute the most frequent PNS complication. Sjögren patients can suffer from severe neuropathic pain, with small-fiber neuropathy causing lancinating or burning pain which can disproportionately affect the proximal torso or extremities, and the face (ie, in a "non-length-dependent distribution"). The technique of skin biopsy, assessing for the intraepidermal nerve fiber density of unmyelinated nerves, provides a useful technique for neurologists to diagnose small-fiber neuropathies, especially when there is such a non-length-dependent distribution. Other diagnostic techniques (ie, electromyography/nerve-conduction studies, evoked potentials, nerve and muscle biopsy) may be useful in specific subtypes of neuropathies. A rational approach to treatment requires a careful appraisal of the clinical subtype of the neuropathy, as well as a familiarity with such discriminating immunopathogenic mechanisms. The application of the traditional armamentarium used for neuropathic pain can be especially challenging. Sjögren patients can suffer from debilitating fatigue, sicca symptoms, and autonomic findings; as such manifestations can be complications of various neuropathic agents, neurologists should understand how to minimize such iatrogenic complications. Therefore, this article will empower neurologists to more effectively collaborate with rheumatologists, in the diagnosis and treatment of Sjögren patients with PNS complications.
20585824 Evaluation of quality of life in relation to anxiety and depression in primary Sjögren's 2010 Dec The aim of this study was to evaluate health-related quality of life (HR-QOL) in patients with primary Sjögren's syndrome (pSS) using both Short-Form 36 (SF-36) and World Health Organization Quality of Life Assessment-BREF (WHOQOL-BREF) questionnaires and to determine the effects of anxiety and depression on HR-QOL using the Hospital Anxiety-Depression Scale (HADS). In this cross-sectional study, 107 female patients with pSS (mean age 54.10 ± 10.2 years), fulfilling US-European Consensus Criteria and 109 female controls (mean age 53.4 ± 10.9 years) were included. Student's t test, Mann-Whitney U test, and analysis of variance (ANOVA) were used for statistical analysis. P values > 0.05 were accepted as significant. All domains of the SF-36, with the exception of "Vitality", and all domains of the WHOQOL-BREF with the exception of "Environment", were significantly lower in pSS patients compared with healthy controls. In pSS patients having anxiety according to HADS, the scores of all domains of WHOQOL-BREF were significantly lower, and in patients having depression according to HADS, three of four domains of WHOQOL-BREF were significantly lower compared with the rest of the group. However, the scores of two domains of the SF-36, namely "Role-Physical" and "Role-Emotional" domains, were significantly higher in pSS patients having depression according to HADS. We confirmed the presence of impaired HR-QOL in pSS. Whereas the presence of anxiety and/or depression generally showed a negative affect on HR-QOL, interestingly, depression seemed to improve the scores of "Role-Physical" and "Role-Emotional" domains of the SF-36. This surprising finding might be related to adaptation to changing health. Social support based upon cultural traditions might also have contributed.