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

ID PMID Title PublicationDate abstract
16283419 Acute respiratory failure revealing adult-onset Still's disease: diagnostic value of low g 2006 Sep The authors report three cases of adult-onset Still's disease with severe hypoxemic pulmonary involvement, mimicking severe pulmonary sepsis. Clinicians must be aware of this rare form of such disease. Low (<20%) glycosylated ferritin level in the presence of unexplained prolonged fever with leukocytosis can help in the diagnosis.
16507116 Intra-articular injection of recombinant TRAIL induces synovial apoptosis and reduces infl 2006 We demonstrated previously that local, intra-articular injection of an adenoviral vector expressing human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a rabbit knee model of inflammatory arthritis stimulated synovial apoptosis and reduced inflammation. To examine whether intra-articular injection of recombinant chimeric human TRAIL protein (rTRAIL) also induces apoptosis of proliferating rabbit synovium and reduces inflammation, we used an experimental rabbit arthritis model of rheumatoid arthritis, induced by intra-articular introduction of allogeneic fibroblasts genetically engineered to secrete human IL-1beta. Analysis of synovium isolated from the rabbits treated with intra-articular injection of rTRAIL, relative to saline control, showed areas of extensive acellular debris and large fibrous regions devoid of intact cells, similar to adenoviral mediated TRAIL gene transfer. Extensive apoptosis of the synovial lining was demonstrated using TUNEL analysis of the sections, corresponding to the microscopic findings in hematoxylin and eosin staining. In addition, leukocyte infiltration into the synovial fluid of the inflamed knee joints following rTRAIL treatment was reduced more than 50% compared with the saline control. Analysis of the glycosaminoglycan synthetic rate by cultured cartilage using radiolabeled sulfur and cartilage histology demonstrated that rTRAIL did not adversely affect cartilage metabolism and structure. Analysis of serum alanine aminotransferase showed that intra-articular injection of rTRAIL did not have adverse effects on hepatic function. These results demonstrate that intra-articular injection of rTRAIL could be therapeutic for treating pathologies associated with rheumatoid arthritis.
18662511 MRI in psoriatic arthritis: insights into pathogenesis and treatment response. 2008 Aug Psoriatic arthritis (PsA) is a clinically heterogeneous condition, and not surprisingly, its MRI features are diverse. Synovitis and accompanying synovial effusions are clearly depicted, and enthesitis is characterized by extracapsular inflammation at the insertions of ligaments and tendons plus accompanying bone edema at bony attachments. Other forms of MRI bone edema include subchondral and diaphyseal involvement; the latter seeming relatively specific to PsA. The pathology of dactylitis can also be elucidated by MRI, which frequently reveals tenosynovitis and soft tissue edema in conjunction with various degrees of synovitis, bone edema, and erosion. Bone erosions differ from those seen in rheumatoid arthritis in their distribution and associated features such as bone proliferation and sometimes periostitis. Finally, MRI can be used to score and quantify these pathologic features, providing a sensitive tool with which to evaluate disease progression.
18540187 [Adult-onset Still's disease--case report]. 2007 We report diagnostic difficulties in the patient with fever of unknown origin. The patient was diagnosed with adult-onset Still's disease, which is a rare seronegative arthritis. Thirty seven year old patient was admitted to the hospital because of symptoms lasting for 6 weeks: fever, evanescent skin rash, arthritis and sore throat with the suspicion of fever of unknown origin. After exclusion the infectious aetiology, Still's adult-onset disease was recognised based on clinical picture, biochemical, serological and radiography, sonography results and after reumatological consultation. Treatment with nonsteroidal anti-inflammatory drugs was introduced with good clinical effect. CONCLUSIONS: Diagnosis of fever of unknown origin is great challenge for doctors and requires realising careful anamnesis, performing overstandard examinations and good co-operation with consultants of other specialities.
18552533 [Long-term results of total hip arthroplasty in patients with juvenile rheumatoid arthriti 2008 Mar OBJECTIVES: We evaluated the long-term results of total hip arthroplasty (THA) in patients with juvenile rheumatoid arthritis (JRA). METHODS: The study included 37 hips of 23 patients (22 females, 1 male; mean age 22 years; range 17 to 30 years) who underwent THA for hip degeneration secondary to JRA. All arthroplasties were performed through an anterolateral approach by the same senior surgeon. The mean body surface of the patients was 1.5 m2 (range 1.1 to 1.7 m2) and the mean symptom duration to surgery was 12 years (range 7 to 16 years). Twenty-three hips received cemented, 14 hips received hybrid prostheses. In seven hips with an extremely narrow femoral medulla and shallow acetabulum, a CDH prosthesis was used. The hips were evaluated using the Harris hip score. Prosthetic loosening and displacement and heterotopic bone formation were assessed on follow-up radiographs. The mean follow-up period was 135 months (range 58 to 212 months). RESULTS: The mean Harris hip score increased from 27.2 (range 11 to 69) to 79.5 (range 37 to 87) postoperatively. At final follow-ups, all the patients were satisfied with the outcome and were able to walk without support. Three hips (8.1%; 3 patients) required revision. The overall Kaplan-Meier implant survival rate was 86.5%. There were no significant correlations between the Harris hip score and radiographic loosening and the presence of calcification around the prosthesis. Heterotopic bone formation of grade I was observed in 17 hips (46%). CONCLUSION: Even though it is performed at young ages, THA considerably improves quality of life of patients with JRA having hip joint involvement and has a comparable implant survival.
16981975 A case of progressive pseudorheumatoid arthropathy of 'childhood' with the diagnosis delay 2006 Oct Progressive pseudorheumatoid arthropathy of childhood (PPAC) is a rare single gene disorder which is frequently misdiagnosed as juvenile rheumatoid arthritis. It is characterised with arthralgia, joint contractures, bony swelling of metacarpophalangeal and interphalangeal joints and platyspondyly. Clinical and laboratory signs of joint inflammation such as synovitis, a high erythrocyte sedimentation rate and an elevated C-reactive protein level are usually absent. Although the disease begins early in life (usually between 3 and 8 years of age), the diagnosis may be delayed. In the present case report, we describe a male patient diagnosed with PPAC at the age of 46 years, although he had been exhibiting the typical radiological and clinical features of the disease since the age of 7 years.
18593758 The TRAF1/C5 region is a risk factor for polyarthritis in juvenile idiopathic arthritis. 2008 Nov OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a chronic disorder in which both genetic and environmental factors are involved. Recently, we identified the TRAF1/C5 region (located on chromosome 9q33-34) as a risk factor for rheumatoid arthritis (RA) (p(combined) = 1.4 x 10(-8)). In the present study the association of the TRAF1/C5 region with the susceptibility to JIA was investigated. METHODS: A case-control association study was performed in 338 Caucasian patients with JIA and 511 healthy individuals. We genotyped the single nucleotide polymorphism rs10818488 as a marker for the TRAF1/C5 region. RESULTS: The A allele was associated with the susceptibility to rheumatoid factor-negative polyarthritis with an 11% increase in allele frequency (OR 1.54, 95% CI 1.09 to 2.18; p = 0.012). This association was stronger when combining subtypes with a polyarticular phenotype (OR 1.46, 95% CI 1.12 to 1.90; p = 0.004). In addition, we observed a trend towards an increase in A allele frequency in patients with extended oligoarthritis versus persistent oligoarthritis (49%, 38% respectively); p = 0.055. CONCLUSIONS: Apart from being a well replicated risk factor for RA, TRAF1/C5 also appears to be a risk factor for the rheumatoid factor-negative polyarthritis subtype of JIA and, more generally, seems to be associated with subtypes of JIA characterised by a polyarticular course.
17277081 Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. 2007 Feb 13 Mast cells are immune sentinels that participate in the defense against bacteria and parasites. Resident within the joint, mast cells become activated in human rheumatoid arthritis and are implicated in the pathogenesis of experimental murine synovitis. However, their arthritogenic role remains undefined. Using a model of autoantibody-induced arthritis, we show that mast cells contribute to the initiation of inflammation within the joint by elaboration of IL-1. Mast cells become activated to produce this cytokine via the IgG immune complex receptor FcgammaRIII. Interestingly, mast cells become dispensable for the perpetuation of arthritis after delivery of IL-1, highlighting the contribution of this lineage to arthritis induction. These findings illuminate a mechanism by which mast cells can participate in the pathogenesis of autoimmune inflammatory arthritis and provide insights of potential relevance to human rheumatoid arthritis.
18360581 Etoricoxib for arthritis and pain management. 2006 Mar Nonsteroidal antiinflammatory drugs (NSAIDs), including selective cyclooxygenase (COX)-2 inhibitors, have come to play an important role in the pharmacologic management of arthritis and pain. Clinical trials have established the efficacy of etoricoxib in osteoarthritis, rheumatoid arthritis, acute gouty arthritis, ankylosing spondylitis, low back pain, acute postoperative pain, and primary dysmenorrhea. Comparative studies indicate at least similar efficacy with etoricoxib versus traditional NSAIDs. Etoricoxib was generally well tolerated in these studies with no new safety findings during long-term administration. The gastrointestinal, renovascular, and cardiovascular tolerability profiles of etoricoxib have been evaluated in large patient datasets, and further insight into the cardiovascular tolerability of etoricoxib and diclofenac will be gained from a large ongoing cardiovascular outcomes program (MEDAL). The available data suggest that etoricoxib is an efficacious alternative in the management of arthritis and pain, with the potential advantages of convenient once-daily administration and superior gastrointestinal tolerability compared with traditional NSAIDs.
17923970 Care delivery for the child to grow up despite the pain: the family's experience. 2007 Jul This study aimed to understand the meaning of the experience of families having a child experiencing pain due to Juvenile Rheumatoid Arthritis and to construct a theoretical model representing this experience. Grounded Theory and Symbolic Interactionism were used as methodological framework and theoretical framework, respectively. Data were collected by semistructured interviews with 12 families. Data analysis allowed for the construction of the theoretical model Caring for the child to grow despite the pain, which describes an experience based on motivational elements: wanting to see the child without pain and wanting to see the child live a normal life, reviewing how the family lives the transition in its development cycles, retaking and integrating them in the family dynamic with the appearance of the disease and pain in the child. This theoretical model provides a framework for teaching, research and care, permitting advances in terms of theoretical nursing knowledge.
21794335 [Criterios utilizados por médicos de atención primaria para el diagnóstico y derivació 2006 Sep INTRODUCTION: Rheumatoid arthritis (RA), an important cause of disability, affects 1% of the population. Early diagnosis and referral to a rheumatologist are positive prognostic factor but diagnosis in many cases is in the hands of primary care physicians (PCP). OBJECTIVE: To determine the criteria used by PCP for diagnosis of RA and referral of these patients to a rheumatologist; to evaluate how many cases can be classified as RA according to the ACR. METHODS: Retrospective study of 530 patients referred by PCP and seen as outpatients at a rheumatology clinic in 2002. Patients with referral diagnosis of RA were identified and symptoms, signs, functional capacity and ACR criteria for RA were evaluated by 2 rheumatologists. RESULTS: 302 patients had a referral diagnosis of RA, 33 male (10.9%) and 269 female (89.1%), median age 50.5 years, with a median time since diagnosis of 45.2 months. 57.9% had FC stage II. 100% of cases had "generalized" joint pain, 67.5% arthritis of 3 or more joints and 51.7% arthritis of hand joints. Arthritis was symmetrical in 58.9% and 77.2% of the patients had morning stiffness (> 30 min). 49.7% of the cases had positive rheumatoid factor, 19.2% had a negative RF and 31.1% had none reported. In 2% ESR was measured. X-ray erosions were reported in 6.6% of cases. When using the ACR criteria, 17.8% of patients had 1, 28.7% had 2 and 53.5% had 3 or more criteria. In only 59 cases (20%) did the rheumatologist agree with the referral diagnosis of RA. CONCLUSIONS: 80% of PCP referrals of RA to the rheumatologist were another disease. A poor clinical evaluation and little support from laboratory and x-rays was noticed. The delay in diagnosis and referral was 3 years, worsening prognosis. A vigorous effort in educating PCP is needed to achieve early diagnosis and referral of RA cases.
17924851 Diagnostic usefulness of a third-generation anti-cyclic citrulline antibody test in patien 2007 BACKGROUND: The high specificity of anti-cyclic citrullinated peptide antibodies (anti-CCP) helps substantially in the diagnosis of rheumatoid arthritis (RA), combined with classical markers such as rheumatoid factor (RF). The recent introduction of third-generation methods (anti-CCP3) for anti-CCP detection could further improve diagnostic efficiency. The aim of this study was to determinate the diagnostic efficiency (sensitivity and specificity) of anti-CCP using a new anti-CCP3 method and to compare it with the previous second-generation method (anti-CCP2). METHODS: Anti-CCP were studied in sera of 234 patients with recent-onset polyarthritis (ROP) (age > or =16 years; evolution time > or =4 weeks < or =1 year; 2 or more inflamed joints, without drug therapy). After 1 year, 124 patients were diagnosed with RA (American College of Rheumatology criteria). Two ELISAs, an anti-CCP2 and an anti-CCP3, were performed. RESULTS: The best sensitivity according to receiver operating characteristic curves was 51.5% and 54.8% for anti-CCP3 and anti-CCP2, with a specificity of 96.2% and 98.1%, respectively (optimal cutoffs 14.2 and 18.7 U/mL). Significant correlations were obtained (p<0.001) when the methods were compared to each other and to RF. CONCLUSIONS: Testing with both types of anti-CCP kit is highly specific for the presence of RA. In our ROP group, anti-CCP2 and anti-CCP3 exhibited similar diagnostic efficiency.
18812028 The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuva 2008 Oct Ursolic acid (UA) is pentacyclic triterpenoic acid that naturally occurs in many medicinal herbs and plants. In this study, we examined the possible suppressive effect of UA extracted from Oldenlandia diffusa on zymosan-induced acute inflammation in mice and complete Freund's adjuvant (CFA)-induced arthritis in rats. UA treatment (per oral) dose-dependently (25-200 mg kg(-1)) suppressed zymosan-induced leucocyte migration and prostaglandin E2 (PGE(2)) production in the air pouch exudates. Since the maximal effective dose of UA was 50 mg kg(-1) in the zymosan experiment, we used this dose of UA in a subsequent study using an adjuvant-induced rheumatoid arthritis model. UA treatment (50 mg kg(-1), per oral, once a day for 10 days) was started from day 12 after adjuvant injection. UA dramatically inhibited paw swelling, plasma PGE(2) production and radiological changes in the joint caused by CFA injection. Moreover, UA significantly suppressed the arthritis-induced mechanical and thermal hyperalgesia as well as the spinal Fos expression, as determined by immunohistochemistry, which was increased by CFA injection. In addition, overall anti-arthritic potency of UA was comparable with ibuprofen (100 mg kg(-1), oral) while UA did not induce significant gastric lesions as compared with the ibuprofen treatment group. These findings strongly suggest that UA is a useful suppressive compound for rheumatoid arthritis treatment with low risk of gastric problems.
18226202 Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis 2008 INTRODUCTION: The aim of our study was to investigate the association between arthritic disease activity and antibodies to mutated citrullinated vimentin (anti-MCV), because such a relation has been suggested. METHODS: Anti-MCV levels were measured in 162 patients with early arthritis (123 with rheumatoid arthritis and 39 with undifferentiated arthritis) at baseline and at 1 and 2 years of follow up. Disease activity was measured using the disease activity score (Disease Activity Score based on 28 joints [DAS28]) and serum C-reactive protein. General estimation equation analysis was used to assess the relation between anti-MCV levels and DAS28 over time. RESULTS: Both, anti-MCV levels and DAS28 exhibited a significant decrease during the first and second year. However, the association between anti-MCV levels and DAS28, adjusted for dependency on sequential measurements within one individual, was very low (beta = 0.00075). In a population of patients with rheumatoid arthritis or undifferentiated arthritis, anti-MCV had a specificity of 92.3% and a sensitivity of 59.3% when using the recommended cut-off of 20 U/ml. Specificity and sensitivity of antibodies against second-generation cyclic citrullinated peptide, using the recommended cut-off value of 25 U/ml, were 92.1% and 55.3%, respectively. Anti-MCV-positive early arthritis patients had significantly higher Sharp-van der Heijde score, erythrocyte sedimentation rate and C-reactive protein levels than did anti-MCV-negative patients at all time points (P < 0.005), but DAS28 was higher in anti-MCV-positive patients at 2 years of follow up only (P < 0.05). CONCLUSION: Because the correlation between anti-MCV levels and parameters of disease activity was very low, we conclude that it is not useful to monitor disease activity with anti-MCV levels.
17066036 Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages 2006 Oct 26 A large amount of chromosomal DNA is degraded during programmed cell death and definitive erythropoiesis. DNase II is an enzyme that digests the chromosomal DNA of apoptotic cells and nuclei expelled from erythroid precursor cells after macrophages have engulfed them. Here we show that DNase II-/-IFN-IR-/- mice and mice with an induced deletion of the DNase II gene develop a chronic polyarthritis resembling human rheumatoid arthritis. A set of cytokine genes was strongly activated in the affected joints of these mice, and their serum contained high levels of anti-cyclic citrullinated peptide antibody, rheumatoid factor and matrix metalloproteinase-3. Early in the pathogenesis, expression of the gene encoding tumour necrosis factor (TNF)-alpha was upregulated in the bone marrow, and administration of anti-TNF-alpha antibody prevented the development of arthritis. These results indicate that if macrophages cannot degrade mammalian DNA from erythroid precursors and apoptotic cells, they produce TNF-alpha, which activates synovial cells to produce various cytokines, leading to the development of chronic polyarthritis.
17546023 Collagen-induced arthritis. 2007 The collagen-induced arthritis (CIA) mouse model is the most commonly studied autoimmune model of rheumatoid arthritis. Autoimmune arthritis is induced in this model by immunization with an emulsion of complete Freund's adjuvant and type II collagen (CII). This protocol describes the steps necessary for acquisition, handling and preparation of CII, as well as selection of mouse strains, proper immunization technique and evaluation of the arthritis incidence and severity. Typically, the first signs of arthritis appear in this model 21-28 days after immunization, and identification of the arthritic limbs is not difficult. Using the protocol described, the investigator should be able to reproducibly induce a high incidence of CIA in various strains of genetically susceptible mice as well as learn how to critically evaluate the pathology of the disease. The total time for the preparation of reagents and the immunization of ten mice is about 1.5 h.
16785476 Autoimmune diseases in asthma. 2006 Jun 20 BACKGROUND: Previous research has suggested an inverse relationship between T-helper 2-related atopic disorders, such as asthma, and T-helper 1-related autoimmune diseases. One controversial hypothesis postulates that asthma provides a protective effect for the development of autoimmune-related disorders. OBJECTIVE: To assess the rate of newly diagnosed autoimmune disorders in a large cohort of young adults. DESIGN: Using cross-sectional data from the Israeli Defense Force database, the authors analyzed the prevalence of autoimmune disorders in asthmatic and nonasthmatic military personnel between 1980 and 2003. A follow-up study traced newly diagnosed autoimmune disorders among asthmatic and nonasthmatic individuals from the time of enrollment in military service until discharge (22 and 36 months for women and men, respectively). SETTING: General community. PATIENTS: 307,367 male and 181,474 female soldiers in compulsory military service who were between 18 and 21 years of age. MEASUREMENTS: Cases of type 1 diabetes mellitus, vasculitis, immune thrombocytopenic purpura, inflammatory bowel disease, rheumatoid arthritis, and the antiphospholipid syndrome. RESULTS: Of 488,841 participants at enrollment, significantly more women than men had autoimmune disorders. Compared with asthmatic women, nonasthmatic women had a significantly higher prevalence of all autoimmune disorders except for the antiphospholipid syndrome. Type 1 diabetes mellitus, vasculitis, and rheumatoid arthritis were less prevalent in men with asthma than in those without. During the follow-up period, vasculitis and rheumatoid arthritis were more frequently diagnosed in nonasthmatic persons of both sexes. There was a significantly higher incidence of immune thrombocytopenic purpura, inflammatory bowel disease, and the antiphospholipid syndrome in nonasthmatic women and a statistically significantly higher incidence of type 1 diabetes mellitus in nonasthmatic men. LIMITATIONS: The study was limited to a population of young military recruits; therefore, its findings are not necessarily applicable to the general population. Because of the noninterventional nature of the study, it describes associations but cannot prove causality. CONCLUSIONS: Asthma status may affect the prevalence of major autoimmune disorders. Preexisting asthma seems to protect against the development of autoimmune disorders to varying degrees in men and women.
16644783 Performance of response criteria for assessing peripheral arthritis in patients with psori 2006 Oct BACKGROUND: In recent clinical trials in patients with psoriatic arthritis (PsA), the response criteria and disease activity measures that have been used were those developed for rheumatoid arthritis. However, these have not yet been validated in PsA. OBJECTIVE: To compare the responsiveness and discriminative capacity of the psoriatic arthritis response criteria (PsARC), American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the Disease Activity Score (DAS) and core-set measures in patients with PsA and peripheral arthritis, using the data from two randomised placebo-controlled trials of tumour necrosis factor inhibitors. METHODS: In an infliximab trial, 104 patients with active PsA were randomised to receive placebo or infliximab for 16 weeks. In an etanercept trial, 60 patients with active PsA were randomised to receive placebo or etanercept for 12 weeks. Data from baseline and the end of the intervention phase were used from each study. Responsiveness was assessed using the standardised response mean and effect size. Capacity to discriminate between the active drug and placebo was assessed using t values or a chi2 test. Measures were ranked in order of their t value or chi2 value. RESULTS: The EULAR criteria performed better in discriminating the active drug from placebo than the ACR20 improvement criteria, which in turn performed better than the PsARC. It was also found that the pooled indices (DAS and DAS28) were generally more responsive, and performed better in discriminating active drug from placebo, than the single core-set measures. CONCLUSION: Response criteria and pooled indices developed for rheumatoid arthritis are useful for the assessment of arthritis in PsA clinical trials.
18466569 Two-dimensional linkage analyses of rheumatoid arthritis. 2007 Rheumatoid arthritis (RA) is a multifactorial disease with complex genetic etiology, about which little is known. Here, we apply a two-stage procedure in which a quick first-stage analysis was used to narrow down targets for a more thorough and detailed testing for gene x gene interaction. Potentially interesting regions were first identified by testing for major gene effects using non-parametric linkage methods. To select regions of interest, we first tested for linkage to three different RA-related traits one at a time: RA affection status and the quantitative phenotypes rheumatoid factor IgM and anti-cyclic citrullinated peptide levels. These linkage analyses identified regions on chromosomes 3, 5, 6, 8, 16, 18, 19, and 20. We subsequently analyzed the selected regions in a pairwise manner to detect gene x gene interactions influencing RA using a recently developed two-dimensional linkage method. We found evidence of interacting loci on chromosomes 5, 6, and 18.
18928222 Spinal epidural abscess associated with infliximab treatment for psoriatic arthritis. Case 2008 Sep Tumor necrosis factor-alpha inhibitors are used to treat numerous chronic inflammatory and rheumatological diseases, such as Crohn disease, rheumatoid arthritis, and psoriatic arthritis. Because the mechanism of these inhibitors is to decrease the body's inflammatory response, the primary complication of treatment is infection. The authors present the first case of a spinal epidural abscess in a patient receiving long-term infliximab therapy for severe psoriatic arthritis. Infliximab and its side-effect profile are discussed, along with other associated complications.