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

ID PMID Title PublicationDate abstract
18360594 Rituximab and its potential for the treatment of rheumatoid arthritis. 2006 Jun Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which causes deforming joint disease and a spectrum of extraarticular manifestations. Poor disease control may lead to functional impairment and loss of independence. In recent times a prominent role for B cells in the pathogenesis of RA has been suggested. Two major theories have been postulated to explain the role of rheumatoid factor (RF) in the RA inflammatory process and the reason for RF overproduction; the loss of tolerance model and the autonomous mutated B cell model. With this in mind, strategies have been adopted to deplete B cells including the use of the anti-CD20 antibody rituximab. Rituximab leads to complement mediated lysis of B cells as well as antibody-dependant cellular cytotoxicity. It has been hypothesized that rituximab may also initiate apoptosis in RA and alter the ability of B cells to respond to antigen and other stimuli. Several recent studies using rituximab have demonstrated significant declines in RA activity providing evidence for the role of B cells in RA. Rituximab would appear to be a major addition to the increasing therapeutic options for sufferers of RA.
16450148 [Imaging methods in rheumatology: imaging in psoriasis arthritis (PsA)]. 2006 Mar Conventional radiography is still the standard method of imaging in PsA since it displays many joints at the same time, thereby allowing different types of joint involvement to be recognized. Moreover, thanks to the high resolution of radiography, bony changes in a single joint are depicted in a brilliant way. Several features of psoriatic arthritis allow the distinction from rheumatoid arthritis, including the frequent involvement of the distal interphalangeal joints, asymmetry of joint involvement, axial involvement of finger joints, oligoarticular involvement; however, symmetric polyarthritis is also possible. At the level of the single joint, there are signs of severe destructive changes potentially leading to mutilation and at the same time signs of periostal bone proliferation and ankylosis may be present. Bony proliferation and/or osteolysis are not restricted to the joint region but can affect also the total phalanx with bone apposition or concentric osteolysis which may lead to a complete disappearance of phalanxes. For purposes of quantification of radiographic changes scoring methods are used that were originally developed for rheumatoid arthritis. So far, there is only one validated scoring method that was specifically designed for PsA and that takes into account both features of PsA, damage as well as proliferation of bone. In contrast to conventional radiography, MRI and sonography are able to visualize inflammatory processes within the soft tissue (joint capsules, tendon sheaths, tendon insertions, etc.), allowing an estimation of disease activity. Scintigraphy is nonspecific and can only be used to detect clinically silent inflammatory spots. The relatively frequent spinal (axial) involvement is similar to that seen in ankylosing spondylitis. However, unilateral sacroiliitis, asymmetry of syndesmophytes and development of parsyndesmophytes may distinguish PsA from ankylosing spondylitis. While conventional radiography demonstrates the bony consequences of inflammation in the spine, MRI also shows the active inflammatory changes in sacroiliacal joints and vertebrae.
17102943 Frequency of rheumatic diseases in patients with autoimmune thyroid disease. 2007 Apr We aimed to investigate the frequency of rheumatic diseases in patients suffering from autoimmune thyroid diseases (ATD). Sixty-five patients (56 F, 9 M), who were followed by diagnosis of ATD, were questioned and examined for the presence of rheumatic disease. Basic laboratory tests and antithyroid antibodies, antinuclear antibody and rheumatoid factor (RF) levels were also measured by appropriate methods. Various rheumatic diseases were detected in 40 (62%) of patients with ATD. The most frequent rheumatic conditions were fibromyalgia, recurrent aphthous stomatitis, osteoarthritis, keratoconjunctivitis sicca and xerostomia and carpal tunnel syndrome which were detected in 20 (31%), 13 (20%), 10 (15%), 9 (14%) and 8 (12%) of patients, respectively. Autoimmune diseases, except Sjogren's syndrome, which were detected in ten patients with ATD, are as follows-vitiligo: two; autoimmune hepatitis: two; oral lichen planus: one, ulcerative colitis: one, inflammatory arthritis in four patients (two of them had rheumatoid arthritis, one had psoriasis and psoriatic arthritis and one had mixed collagen tissue disease). RF was positive in two patients, one of them had rheumatoid arthritis and FANA was positive in six (9%) patients; all of them had hypothyroidism. The frequency of rheumatic diseases seems to be higher in patients suffering from ATD. Initial evaluation and a regular checking for rheumatic diseases in patients suffering from ATD were recommended.
16303821 Serum lipid levels in Sjögren's syndrome. 2006 Apr OBJECTIVES: Altered lipid levels may occur in autoimmune diseases, for example low cholesterol levels have been described in rheumatoid arthritis (RA). Serum lipid profiles in patients with Sjögren's syndrome (SS) have not been investigated. We hypothesized decreased lipid levels in SS patients and an inverse relationship with disease activity. METHODS: Serum lipid levels [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides] and additional data regarding disease measures (clinical immunology parameters, focus score from labial salivary gland biopsy, salivary flow and ophthalmological measures) were available for 46 primary SS patients and 12 xerostomic controls. RESULTS: Significant differences between SS patients and controls means (s.d.) were seen for HDL (P = 0.04) and total cholesterol (P = 0.02). LDL (P = 0.12) and triglyceride (P = 0.08) levels were not different. In SS patients, but not in controls, total cholesterol (P = 0.003) and HDL cholesterol (P = 0.003) predicted immunoglobulin G levels. Anti-SSA antibodies were related to a lower total cholesterol (P = 0.02) and anti-SSB antibodies to a lower HDL cholesterol level (P = 0.0497). CONCLUSIONS: Significant differences were seen in serum lipid levels of primary SS patients and these were associated with serological measures of inflammation. Our results are comparable to earlier findings in RA patients and raise questions related to adverse cardiovascular consequences in SS.
15734239 Increase in sensory neuropeptides surrounding the Achilles tendon in rats with adjuvant ar 2005 Mar The Achilles tendon in rats with adjuvant arthritis was analyzed by radioimmunoassay (RIA) and semi-quantitative immunohistochemistry for the occurrence of two sensory neuropeptides, substance P (SP) and calcitonin gene related peptide (CGRP), and a sensory modulating peptide, galanin (GAL). The tissue concentration of SP and CGRP in the Achilles tendon and its envelope, i.e. the paratenon and bony insertion, as assessed by RIA was increased by 22% and 71%, respectively, compared to normal controls, whereas the level of GAL was unchanged. Semi-quantitative immunohistochemistry applied to different regions of the tendon in arthritic rats disclosed an increased occurrence of SP and CGRP positive nerve fibers in the paratenon and bone tendinous junction, whereas GAL fibers were only increased at the bone tendinous junction. Notably, neither neuropeptides nor inflammatory cells were seen in the tendon proper. The increased occurrence of SP and CGRP in the tendon envelope presumably reflects inflammatory actions, whereas that of GAL implies an endogenous anti-inflammatory response. The observed SP and CGRP upregulation in the paratenon and bony insertion suggests a pathophysiological role in paratenonitis and enthesitis often seen in patients with rheumatoid arthritis. Presumably Achillodynia originates in the tendon envelope rather than the tendon proper. The observations could be used to define new pharmacological targets for mitigating symptoms from tendons in rheumatoid arthritis and possibly also in other disorders. Whether a neuronal pathogenic mechanism underlies tendon overuse disorders in non-arthritic tendinopathies and the development of degeneration, i.e. tendinosis, remains to be studied.
17029074 Clinical characteristics of anti-glucose-6-phosphate isomerase antibody-positive Japanese 2005 Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are known to be arthritogenic in mice. These Abs are elevated in several forms of arthritic condition in humans, although their prevalence in rheumatoid arthritis (RA) patients is still in debate. Some RA patients have increased levels of anti-GPI Abs, but their clinical manifestation and relevance to other Abs are not clearly elucidated. The aims of this study were to explore the clinical and hematological characteristics of RA with anti-GPI Abs, and to compare their prevalence in RA patients, systemic lupus erythematosus (SLE) patients, and healthy subjects (HS) in a Japanese population. Anti-GPI Abs were positive in 16 patients with RA (12%, n = 137), in 10 patients with SLE (8%, n = 131), and in 6 HS (4%, n = 139). C-reactive protein (CRP), immunoglobulin G, and the antinuclear antibody titer were higher in anti-GPI-positive patients than in those who were negative (P = 0.049, P = 0.0003, and P = 0.002, respectively). Moreover, the positivity of anti-GPI Abs was correlated with CRP more than with rheumatoid factor in RA patients. It is unclear whether anti-GPI Abs can predict the progress of disease, but the prevalence of these Abs was higher in active RA patients with severe arthritis, suggesting that anti-GPI Abs may be related to the pathogenesis of severe forms of arthritis.
17029040 The epigenetic alteration of synovial cell gene expression in rheumatoid arthritis and the 2005 Rheumatoid arthritis (RA) is a complex process of chronic and progressive inflammation associated with activation of numerous signaling molecules and transcription factors and hyperproliferation of synoviocytes of the affected joints, although the greater part of its pathophysiological process is explained by activation of nuclear factor kappaB (NF-kappaB). For example, the self-perpetuating nature of the rheumatoid inflammation is ascribable to overexpression of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-1beta, known to elicit the activation cascade for NF-kappaB and activator protein-1 that are responsible for transcriptional induction of these cytokines among other target genes, which conform a positive feedback loop for continuation and expansion of the inflammatory responses. In addition, comparative gene expression profile analyses have revealed activation of a number of genes that explain the "transformed-like" phenotype of synoviocytes. Among the genes expressed in rheumatoid synoviocytes upon inflammatory stimuli, induction of gene expression of Notch proteins and its ligand have been found. Possible roles of Notch signaling in RA synoviocytes are discussed.
16598488 [The TNK ankle: short- and mid-term results]. 2006 May Total ankle replacement has been introduced in the last 30 years. The TNK ankle is build from ceramics, and it was continuously improved. This prosthesis has the longest fellow-up times. Seventy ankle prostheses of the newest generation has been implanted between 1991 and 2001. Of these, 67 prostheses were assessed clinically and radiographically after 62 months (range, 24 to 132 months). Three ankles have been revised. The clinical score improved for the patients with primary or posttraumatic arthritis from 34 to 86, and for the patients with rheumatoid arthritis from 45 to 74. Loosening was found in 4 ankles with non-rheumatoid arthritis, and in 17 ankles with rheumatoid ankles. Total ankle replacement has emerged to a valuable alternative to ankle arthrodesis, and satisfactory results have been achieved with the current implants. The bone-implant interphase might play a most important factor for success. There is evidence that the biologic advantages of ceramics may help to improve long-lasting success in total ankle replacement.
17086384 Ten years of clinical experience with adult onset Still's disease: is the outcome improvin 2007 Jul This study aims to report on the clinical and laboratory picture and the disease course and outcome in patients having adult onset Still's disease (AOSD), to briefly review existing literature on the subject, and to compare our findings with those previously reported. Results are reported for 28 patients with AOSD satisfying the preliminary criteria of Yamaguchi et al. seen in a teaching hospital over the last 10 years. A high percent of the patients with AOSD were women. The mean (+SD) age at disease onset was 27.8 (+8.4) years. We found fever in 100%, rash in 85%, arthritis in 64%, lymphadenopathy in 60%, splenomegaly in 57%, hepatomegaly in 35%, pleural effusion in 17.9%, and pericardial effusion in 3.6% of our patients. Leukocytosis was present in 96% of the patients, a normochromic, normocytic anemia in 54%, and an elevated erythrocyte sedimentation rate (ESR) in all. Serum ferritin levels were raised in 89% of the patients. The mean follow-up of the patients was 3.72 + 2.46 years. The mean delay in diagnosis was 7.32 + 18.0 months. The mean time to enter remission was 9.7 months. Self-limited, intermittent, and chronic disease course was seen in 14.3, 57.1, and 28.6% of patients, respectively. The outcome was good in about 89% of patients, and mortality was nil. No particular clinical or laboratory variable was found to predict the subsequent disease course and outcome in our patients. On comparing our data with important previous series, we found a higher percentage of women and of patients presenting in the age group 16-35 years, a lower frequency of arthritis and pericardial effusion, and some other notable differences. Importantly, the disease course was benign, probably as an outcome of heightened awareness and less diagnostic delay than in the past, allowing for early, aggressive, and appropriate treatment. It is concluded that AOSD is now a relatively benign disease if diagnosed early and treated appropriately.
16142150 [Value of hyperferritinemia and glycosylated ferritin in the diagnosis of adult-onset Stil 2005 Jul 23 INTRODUCTION: The diagnosis of adult-onset Still's disease currently requires application of Yamaguchi's criteria and then exclusion of infectious, hematologic, autoimmune and neoplastic disorders. A recent article suggests that very high levels of serum ferritin together with an unusually low percentage of glycosylated ferritin may serve as diagnostic criteria or even as markers of disease progression. This new score has greater specificity than the other scores, including that of Yamaguchi. CASES: We describe 3 new cases with very high ferritin levels (exceeding 9000 microg/L) and glycosylated ferritin levels lower than 20%. DISCUSSION: The diagnosis of Still's disease was determined in all three cases by both Yamaguchi's score and the new criteria. One patient responded well to treatment with colchicine. CONCLUSION: Ferritin and glycosylated ferritin levels are interesting diagnostic markers. The new score suggested by Fautrel et al. is especially useful in that it does not require the exclusion of a list of differential diagnoses.
16279403 Myopericarditis revealing adult-onset Still's disease. 2005 Sep We report the case of a 33 year-old man presenting with fever, arthralgias, sore throat, dyspnea and chest pain. Myopericarditis was diagnosed on the basis of electrocardiogram, echocardiography and cardiac magnetic resonance imaging (MRI). The dramatic increase in ferritinemia suggested the diagnosis of adult-onset Still's disease (AOSD), which could be established according to criteria of Yamaguchi. Rapid improvement occured under corticosteroids. Myocarditis is very rare in AOSD, pericarditis being more frequent. We report herein the first description of AOSD associated myocarditis evidenced by cardiac MRI.
16956437 Hematologic manifestations of primary Sjögren's syndrome. 2006 Jul Sjögren's syndrome (SS) is a chronic autoimmune disorder, primarily characterized by the mononuclear cell infiltration of exocrine glands exiting in parenchymal damage and secretory impairment. The spectrum of the disease extends from an autoimmune exocrinopathy to a systemic process with extraglandular manifestations. SS is defined as primary (pSS) when isolated, or secondary when associated with another autoimmune disease. Patients with pSS may present hematologic abnormalities, such as anemia, hemocytopenias, monoclonal gammopathies and lymphoprolipherative disorders, predominantly non-Hodgkin's lymphoma of B-cell origin. The increased prevalence of B-cell malignancies suggests that SS may be a boundary disease between autoimmunity and lymphoproliferation. In this paper, the hematologic manifestations of pSS are reviewed.
16118729 [Symmetric polyarthritis in a patient with Churg-Strauss syndrome]. 2005 Aug 19 HISTORY: A 63-year-old man developed a Churg-Strauss syndrome with predominantly motor-sensory polyneuropathy. Initial treatment with cyclophosphamide and steroids achieved complete remission. Subsequent relapse with marked retinal vasculitis at first was refractory to the standard treatment. Renewed remission was obtained with additional infliximab, and was maintained with azathioprine for 12 months before the patient again presented with symmetrical polyarthritis. INVESTIGATIONS: Clinical examination revealed a symmetrical polyarthritis involving the joints of the hand and fingers. The acute-phase parameters were raised, the rheumafactor was highly positive. Radiology showed early erosions in the bones of the hand. There were no indices of renewed activity of the Churg-Strauss syndrome. TREATMENT AND COURSE: These findings indicated sero-positive rheumatoid arthritis and methotrexate was started, later supplemented with sulfsalazine and hydroxychloroquine because of continuing signs of activity. Infliximab was again given because of further progression, but a severe infusion reaction developed during the second infusion. After changing to etanercept remission of the rheumatoid arthritis was achieved. CONCLUSION: The development of rheumatoid arthritis during remission achieved with azathioprine in Churg-Strauss syndrome of four-year duration is very rare. Repeated dosis of infliximab at long intervals greatly increases the risk of an intolerance.
17164948 Abrupt temperature change triggers arthralgia in patients with juvenile rheumatoid arthrit 2006 Dec BACKGROUND AND PURPOSE: Juvenile rheumatoid arthritis (JRA) is the most common form of arthritis in children and affects both quality of life and school attendance. Weather and temperature conditions are believed to affect joint pains; however, very few studies have investigated this issue. This study examined the association between joint pain in JRA patients and weather conditions. METHODS: The daily pain ratings of 52 patients previously diagnosed with JRA were recorded on visual analog scales over 4 months beginning January 1, 2004. These ratings were then compared with weather data to evaluate possible correlation between these two factors. RESULTS: Twenty nine patients kept daily records during the first 2 months. There was no positive correlation between weather parameters (such as temperature, humidity, and barometric pressure) and pain ratings. Interestingly, the pain rating significantly increased the day after the advent of a cold wave (sign test, p<0.01; Wilcoxon signed ranks test, p=0.001). The number of patients who experienced joint swelling was not related to weather conditions. Twenty one participants continued maintaining the diaries during the next 2 months. The patients reported higher pain levels in the first 2 months during the cold wave period than in the next 2 months when the cold wave period had ended (p<0.001). CONCLUSION: A dramatic weather change such as a sudden cold wave might influence the experience of joint pain.
20476973 Use of prognostic markers in early rheumatoid arthritis to identify patients at risk of de 2006 Nov As the benefits of early aggressive treatment of rheumatoid arthritis have become clear, and with the availability of newer (and more expensive) therapies, we need to be able to identify which patients are most at risk of destructive disease and poorer outcomes, and therefore, pinpoint which patients are most likely to benefit from intensive intervention at an early stage. A need for reliable prognostic markers is paramount in identifying these patients. Anticyclic citrullinated peptide antibody and serum inflammatory markers can precede the onset of disease by months and aid in both diagnosis and prognosis. Newer imaging modalities are now available and add to information gained from conventional radiography. This article reviews laboratory markers and imaging currently used in recognizing those patients at risk of nonreversible, destructive disease.
21794327 [Antimalarials: an update in rheumatic diseases]. 2006 Jul Antimalarials are long-standing drugs that have been used since the nineteenth century for the treatment of skin rashes and lesions in lupus and rheumatoid arthritis. In recent decades, their use in these disorders has been consolidated, and new mechanisms of action have been incorporated, broadening the therapeutic perspectives of these drugs. Antimalarials are the treatment of choice in mild and moderate manifestations of systemic lupus erythematosus and are established as part of combined therapy in rheumatoid arthritis. They have been shown to have beneficial effects on atherosclerosis, as well as a possible role in the early treatment of antiphospholipid syndrome. Lastly, they have been shown to have a potential use in other rheumatic diseases such as Sjögren's Syndrome and palindromic rheumatism. This review aims to provide an update on the use of these drugs in rheumatology and to discuss their toxicity profile.
16424181 Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide i 2006 Feb 1 In both collagen-induced arthritis (CIA) and rheumatoid arthritis, T cells recognize a galactosylated peptide from type II collagen (CII). In this study, we demonstrate that the CII259-273 peptide, galactosylated at lysine 264, in complex with Aq molecules prevented development of CIA in mice and ameliorated chronic relapsing disease. In contrast, nonglycosylated CII259-273/Aq complexes had no such effect. CIA dependent on other MHC class II molecules (Ar/Er) was also down-regulated, indicating a bystander vaccination effect. T cells could transfer the amelioration of CIA, showing that the protection is an active process. Thus, a complex between MHC class II molecules and a posttranslationally modified peptide offers a new possibility for treatment of chronically active autoimmune inflammation such as rheumatoid arthritis.
17028819 Doppler sonographic analysis of synovial vascularization in knee joints of patients with r 2005 Synovial vascularization was analyzed by power Doppler and spectral Doppler sonography in 42 knee joints of 28 patients with rheumatoid arthritis. The synovial vessels with greater intensity of color flow signals demonstrated significantly lower indicators of vascular resistance - resistive index (P < 0.01) and pulsatility index (P < 0.01) - than those with lesser intensity. Consequently, an inverse correlation was observed between intensity of color flow signals and both resistive index (P < 0.01) and pulsatility index (P < 0.01).
16601542 Anakinra therapy in a child with systemic-onset juvenile rheumatoid arthritis after human 2006 Apr A 3-year-old patient with biopsy-proven herpesvirus 6 (HHV-6) encephalitis developed a clinical condition consistent with systemic-onset juvenile idiopathic rheumatoid arthritis (SoJIA) and responsive to synthetic interleukin-1 (IL-1) receptor therapy. This suggested both a temporal relationship between HHV-6 infection and the development of SoJIA and the likely involvement of IL-1 in his disease. This case adds to the current experience of IL-1 receptor antagonist therapy in SoJIA. In addition, it suggests that future prospective studies in new-onset SoJIA should include an evaluation for HHV-6 infection.
17029095 Utility of grommets for implant arthroplasty of the great toe in a patient with rheumatoid 2005 We report a case of rheumatoid arthritis treated by bilateral flexible hinge toe implant arthroplasty, using grommets only on one side, which resulted in bilateral fractures requiring removal of the implants 6.5 years after the surgery. Both implants were completely fractured at the bottom of the distal stems. Macroscopically, synovitis was present around both fractured stems, although the severity of synovitis and fragmentation of the fractured implant was relatively mild on the right side in which grommets were used. The shape of the body of the fractured implant was relatively preserved on the right side in which grommets were used. There was no damage or fracture of the grommets. The grommet might have acted to prevent pressures and scratches that would cause synovitis and deformity of the body of the implant, but might not completely prevent fractures of implants.