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ID PMID Title PublicationDate abstract
17579802 Listeria infections associated with infliximab: case reports. 2007 Dec Infliximab is a human-murine chimeric monoclonal antibody directed against tumor necrosis factor alpha (TNFalpha). Infliximab and other TNF blockers are used to treat inflammatory diseases such as rheumatoid arthritis (RA). TNF blockers are suspected to play a key role in some infections. We report here two cases of Listeria monocytogenes sepsis associated with infliximab treatment for RA. The first patient developed a terminal ileitis and a bacteraemia after three doses of infliximab; the second RA patient presented a bacteraemia associated with a prosthetic joint arthritis of the left hip, both related to Listeria. Those two cases occurred in a population of 518 patients treated with TNF blockers in our hospitals since the year 2000. Those events are of particular interest because of the severity of the infection, because the treatment differs from other infections, and because that, in the rheumatology unit, septic arthritis can mimic RA symptoms. They enhance the likelihood for this drug to increase the risk for infections with germs like Listeria.
17237793 Dickkopf-1 is a master regulator of joint remodeling. 2007 Feb Degenerative and inflammatory joint diseases lead to a destruction of the joint architecture. Whereas degenerative osteoarthritis results in the formation of new bone, rheumatoid arthritis leads to bone resorption. The molecular basis of these different patterns of joint disease is unknown. By inhibiting Dickkopf-1 (DKK-1), a regulatory molecule of the Wnt pathway, we were able to reverse the bone-destructive pattern of a mouse model of rheumatoid arthritis to the bone-forming pattern of osteoarthritis. In this way, no overall bone erosion resulted, although bony nodules, so-called osteophytes, did form. We identified tumor necrosis factor-alpha (TNF) as a key inducer of DKK-1 in the mouse inflammatory arthritis model and in human rheumatoid arthritis. These results suggest that the Wnt pathway is a key regulator of joint remodeling.
17569750 Interleukin (IL)-23 p19 expression induced by IL-1beta in human fibroblast-like synoviocyt 2007 Aug OBJECTIVES: To explore the source of the p19 subunit of interleukin-23 (IL-23) in joints with rheumatoid arthritis (RA), the effects of IL-1beta and tumour necrosis factor (TNF)-alpha on IL-23 gene expression in RA fibroblast-like synoviocytes and the effect of IL-23 on proinflammatory cytokines. METHODS: Expression of IL-23 p19 in joints was examined by immunohistochemical analysis of patients with RA and osteoarthritis (OA). The effects of IL-1beta and TNF-alpha on the expression, of IL-23 p19 and IL-12 p35 subunits in human fibroblast-like synoviocytes from RA patients (HFLS-RA) were determined by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and western blotting assay. Blockade of nuclear factor kappaB (NF-kappaB) or AP-1 activation was used to verify the involvement of intracellular signal pathways of the induction of p19. IL-23-induced IL-8 and IL-6 productions were determined in HFLS-RA by RT-PCR and enzyme-linked immunosorbent assay. RESULTS: IL-23 p19 was expressed in the synovium from RA, but not from OA patients. Similar to the protein expression, IL-23 p19 mRNA could be detected by RT-PCR in four of five RA synovial fluid mononuclear cells (SFMC). IL-1beta and TNF-alpha could induce RA fibroblast-like synoviocytes to produce the IL-23 p19 subunit. The effects of IL-1beta were much stronger than TNF-alpha. These responses were observed in both a dose-responsive and time-dependent manner. IL-1beta produced weakly enhanced gene expression of the p35 subunits of IL-12. IL-1beta also promotes the p35 expression, a subunit of IL-12, but weakly. In addition, the NF-kappaB and the AP-1 inhibitors down-regulated the expression of IL-23 p19 mRNA induced by IL-1beta. IL-23 receptor (IL-23R) was of constitutive expression in HFLS-RA. Moreover, IL-23 up-regulated the IL-8 and IL-6 mRNA and protein levels in a dose-dependent manner in HFLS-RA. CONCLUSIONS: Our results demonstrate that IL-23, produced by mononuclear cells in synovial fluid with RA and HFLS-RA, promotes inflammatory responses in RA by inducing IL-8 and IL-6 production from HFLS. IL-1beta regulates IL-23 p19 expression via NF-kappaB and AP-1 pathways. This report also demonstrates that IL-23 could promote inflammatory responses in HFLS-RA by stimulating IL-8 and IL-6 production.
16096332 Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique Jak3 and STA 2006 Feb BACKGROUND: Modulation of Jak-STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis. OBJECTIVE: To document Jak-STAT expression in a cohort of patients with active rheumatoid arthritis (RA), spondyloarthritis (SpA), and osteoarthritis (OA) and compare these subsets with normal synovial tissue. METHODS: Synovial tissue biopsy specimens from patients with RA, OA, and SpA and histologically normal tissue (n = 10 in each arthritis group) were examined for the presence of Jak3, STAT1, STAT4, and STAT6 expression using immunohistochemistry. Phenotyping was performed using immunohistochemistry and immunofluorescence. Clinical and serological characteristics of patients with RA expressing Jak3-STAT4 were assessed. RESULTS: STAT1, STAT4, and Jak3 protein expression was generally increased in inflammatory arthritis. In contrast, STAT6 expression was relatively heterogeneous. A subpopulation of CD1a positive dendritic cells unique to seropositive patients with RA was detected. These cells showed intense protein expression for Jak3, STAT4, and STAT6. CONCLUSION: CD1a positive dendritic cells intensely express Jak3, STAT4, and STAT6 in seropositive RA tissue and may be an alternative marker for dendritic cells in their early stages of activation as well as providing a tool for identifying RA at the level of the synovium. Jak3 inhibition may be a potential therapeutic target to prevent dendritic cell maturation in RA. STAT1 expression is increased in inflammatory arthritis, suggesting that its pro-apoptotic and anti-inflammatory effects cannot effectively counteract inflammation. STAT6 expression is heterogeneous in synovium, suggesting a possible homoeostatic role in addition to any anti-inflammatory effects.
16636937 Low-dose methotrexate-induced pancytopenia. 2007 Jan Methotrexate (MTX) has gained wide acceptance among both patients and rheumatologists due to its efficacy and safe therapeutic window in a variety of inflammatory rheumatological disorders. However, it has the potential to cause serious, life-threatening complications and even mortality. In the present series, we have reviewed our data of five patients who developed serious pancytopenia after the use of MTX, including one who died. Two of these resulted from prescription errors by primary care physicians. The clinical, laboratory, and outcome profile of all five cases are discussed with a brief review of the literature about MTX-induced pancytopenia. There is an urgent need to increase awareness in primary care physicians, patients, and pharmacists toward informed prescribing, dispensing, and monitoring of MTX to prevent such mishaps in the future.
16546029 Autoimmune disorders: gastrointestinal manifestations and endoscopic findings. 2006 Jan The gastrointestinal tract can be involved in many autoimmune disorders, and women are affected more than men in most of the disease processes discussed. As this article outlines, gastrointestinal manifestations can be either part of the clinical presentation or complications of treatment. Depending on the disease process and the severity of symptoms, gastrointestinal evaluation and treatment can have an important role in the management of these diseases.
18398946 Antibodies against mutated citrullinated vimentin are a better predictor of disease activi 2008 Jun OBJECTIVE: To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA). METHODS: The ACPA, e.g., antibodies against mutated citrullinated vimentin (MCV), cyclic citrullinated peptides (CCP) type 2 and 3 (both of IgG isotype) and 3.1 (of both IgG and IgA isotypes), were analyzed at baseline in patients with early RA (n = 210) and in population controls (n = 102) using an enzyme immunoassay. A receiver-operating characteristic curve was constructed for each antibody. Disease activity [swollen and tender joints, visual analog scale for global health, and erythrocyte sedimentation rate (ESR)] was evaluated at baseline and regularly for 24 months. Radiographs of hands and feet were graded using the Larsen score. RESULTS: Patients with anti-MCV antibodies had significantly less reduction in Disease Activity Score (DAS28) over time (p < 0.01), and significantly increased area under the curve (AUC) for DAS28 (p < 0.05), ESR (p < 0.01), C-reactive protein (p < 0.01), and swollen joint count (p = 0.057) compared to those without. Corresponding differences were not found in patients with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression (p < 0.0001-0.01) and radiological outcome (p < 0.0001-0.01) at 24 months were significantly predicted by all ACPA after baseline adjustments. PTPN22 T variant and HLA-DRB1 alleles were not related to radiological progression or inflammatory activity over time. CONCLUSION: Anti-MCV antibodies are associated with a more severe RA disease, as measured by DAS28, ESR, and swollen joint count over time, compared with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression was predicted equally by all 4 autoantibodies.
17951656 Quantitative image analysis of synovial tissue. 2007 Quantitative image analysis is a form of imaging that includes microscopic histological quantification, video microscopy, image analysis, and image processing. Hallmarks are the generation of reliable, reproducible, and efficient measurements via strict calibration and step-by-step control of the acquisition, storage and evaluation of images with dedicated hardware and software. Major advantages of quantitative image analysis over traditional techniques include sophisticated calibration systems, interaction, speed, and control of inter- and intraobserver variation. This results in a well controlled environment, which is essential for quality control and reproducibility, and helps to optimize sensitivity and specificity. To achieve this, an optimal quantitative image analysis system combines solid software engineering with easy interactivity with the operator. Moreover, the system also needs to be as transparent as possible in generating the data because a "black box design" will deliver uncontrollable results. In addition to these more general aspects, specifically for the analysis of synovial tissue the necessity of interactivity is highlighted by the added value of identification and quantification of information as present in areas such as the intimal lining layer, blood vessels, and lymphocyte aggregates. Speed is another important aspect of digital cytometry. Currently, rapidly increasing numbers of samples, together with accumulation of a variety of markers and detection techniques has made the use of traditional analysis techniques such as manual quantification and semi-quantitative analysis unpractical. It can be anticipated that the development of even more powerful computer systems with sophisticated software will further facilitate reliable analysis at high speed.
17221253 [Revision of the recommendations of the Commission on Pharmacotherapy of the German societ 2007 Feb Inflammatory rheumatic illnesses are associated with various types of pain as well as handicaps. The so called basic therapies are not sufficiently effective in many patients or are terminated due to side effects. This is where tumor necrosis factor blockers (TNF) can be used. In many cases, they lead to a substantial improvement of the symptoms, a reduction in disease related laboratory parameters, improvement in quality of life to stopping disease related damage when their effect is rapid. Common and severe side effects are few, although long-term data are still limited. The following contribution lists recommendations for the indications and symptomatology for the use of TNF blockers.
17626840 Natural killer cells trigger differentiation of monocytes into dendritic cells. 2007 Oct 1 Circulating monocytes can differentiate into dendritic cells (moDCs), which are potent inducers of adaptive immune responses. Previous reports show that granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 induce monocyte differentiation into moDCs in vitro, but little is known about the physiological requirements that initiate moDC differentiation in vivo. Here we show that a unique natural killer (NK) cell subset (CD3(-)CD56(bright)) that accumulates in lymph nodes and chronically inflamed tissues triggers CD14(+) monocytes to differentiate into potent T-helper-1 (T(H)1) promoting DC. This process requires direct contact of monocytes with NK cells and is mediated by GM-CSF and CD154 derived from NK cells. It is noteworthy that synovial fluid (SF) from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), but not osteoarthritis (OA), induces monocytes to differentiate into DC. However, this process occurs only in the presence of NK cells. We propose that NK cells play a role in the maintenance of T(H)1-mediated inflammatory diseases such as RA by providing a local milieu for monocytes to differentiate into DC.
17424694 Reliability of measuring long-standing lower extremity radiographs. 2007 Apr The mechanical axis of the lower extremity was measured using preoperative long-standing radiographs in 56 patients undergoing total knee arthroplasty with the Stryker Navigation System (Stryker, Kalamazoo, Mich). Each radiograph was measured by four physicians, three times, in random order, and at delayed intervals. Measurements from each physician produced intraclass correlation coefficients of 0.9872, 0.9973, 0.9958, and 0.9839. An intraclass correlation coefficient of 0.9844 was noted between each of the raters. Pre- and postoperative axial alignments were determined with Stryker Navigation. Preoperatively, each rater overestimated deformity approximately 1 degrees (P>.05); however, postoperatively each rater underestimated the degree of deformity by approximately 1 degrees (P>.05). Measuring long-standing lower extremity radiographs provides significant inter- and intrarater reliability in determining lower extremity alignment.
16889669 Failure of catecholamines to shift T-cell cytokine responses toward a Th2 profile in patie 2006 To further understand the role of neuro-immunological interactions in the pathogenesis of rheumatoid arthritis (RA), we studied the influence of sympathetic neurotransmitters on cytokine production of T cells in patients with RA. T cells were isolated from peripheral blood of RA patients or healthy donors (HDs), and stimulated via CD3 and CD28. Co-incubation was carried out with epinephrine or norepinephrine in concentrations ranging from 10(-5) M to 10(-11) M. Interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-10 were determined in the culture supernatant with enzyme-linked immunosorbent assay. In addition, IFN-gamma and IL-10 were evaluated with intracellular cytokine staining. Furthermore, basal and agonist-induced cAMP levels and catecholamine-induced apoptosis of T cells were measured. Catecholamines inhibited the synthesis of IFN-gamma, TNF-alpha, and IL-10 at a concentration of 10(-5) M. In addition, IFN-gamma release was suppressed by 10(-7) M epinephrine. Lower catecholamine concentrations exerted no significant effect. A reduced IL-4 production upon co-incubation with 10(-5) M epinephrine was observed in RA patients only. The inhibitory effect of catecholamines on IFN-gamma production was lower in RA patients as compared with HDs. In RA patients, a catecholamine-induced shift toward a Th2 (type 2) polarised cytokine profile was abrogated. Evaluation of intracellular cytokines revealed that CD8-positive T cells were accountable for the impaired catecholaminergic control of IFN-gamma production. The highly significant negative correlation between age and catecholamine effects in HDs was not found in RA patients. Basal and stimulated cAMP levels in T-cell subsets and catecholamine-induced apoptosis did not differ between RA patients and HDs. RA patients demonstrate an impaired inhibitory effect of catecholamines on IFN-gamma production together with a failure to induce a shift of T-cell cytokine responses toward a Th2-like profile. Such an unfavorable situation is a perpetuating factor for inflammation.
17204487 Pulmonary rheumatoid nodules demonstrating features usually associated with rheumatoid syn 2007 May OBJECTIVES: To describe the unusual immunohistological characteristics of two pulmonary rheumatoid nodules showing ectopic lymphoid follicles and the features normally associated with rheumatoid synovial membrane, and to discuss the implications of this novel observation. METHODS: Two formalin-fixed wax-embedded pulmonary rheumatoid nodules were processed for immunohistology. RESULTS: The central structure of the pulmonary nodules was typical of that uniformly expected in a rheumatoid nodule with central necrosis surrounded by a palisade of macrophages. However, a feature not previously observed in nodules was the presence of lymphoid aggregates containing B lymphocytes and, in some cases, showing characteristic features of lymphoid follicles. CONCLUSIONS: The presence of B lymphocytes and the development of ectopic lymphoid follicles in rheumatoid nodules have not been described previously. It is similar to synovial membrane, and contrasts with the expected structure of subcutaneous nodules where B cells and lymphoid follicles are normally absent. These observations establish that the morphology of rheumatoid nodules can vary in different tissues. They further suggest that the inflammatory process in the nodule and synovial membrane are likely to be similar, and that the characteristics of different tissues may be an important determinant of apparent differences between inflammatory lesions in synovial membrane and extra-articular nodules in rheumatoid arthritis.
17526198 [Osteogenon in therapy of distal radial bone fractures in patients with secondary osteopor 2007 AIM: To assess efficacy of osteogenon in consolidation of solitary fractures of distal part of the radial bone (RB) in patients with secondary osteoporosis (SO) due to rheumatoid arthritis (RA) and chronic renal failure (CRF). MATERIAL AND METHODS: The study group consisted of 7 patients with documented RA and 8 patients with CRF caused by chronic glomerulonephritis or chronic pyelonephritis in the predialysis period. The control group comprised 13 patients (6 and 7 patients, respectively). The patients were matched by clinico-demographic and therapy characteristics. Patients of the study group received osteogen from the fracture diagnosis to its consolidation. RESULTS: Osteogenon has an analgetic effect, improves well being, raises physical activity, reduces duration of fracture consolidation in patients with SO.
17717956 Topical review-connective tissue diseases: orofacial manifestations including pain. 2007 Summer This topical review presents an overview of orofacial manifestations associated with the more common connective tissue diseases affecting multiple organs. The orofacial manifestations associated with these autoimmune disorders include oral mucosa alterations, salivary gland pathosis, sensory neuropathies, headaches, and temporomandibular disorders. Since many of these orofacial manifestations may be painful, the practitioner managing pain patients should be familiar with them. An understanding of the orofacial manifestations associated with these systemic diseases will enable the pain practitioner to establish an appropriate diagnosis within the context of the underlying systemic disease. This will allow the practitioner the opportunity to contribute and collaborate as a member of a multidisciplinary health-care team in the management of these systemic autoimmune diseases.
17603257 [Imatinib mesylate as a novel therapeutic drug for systemic rheumatic diseases]. 2007 Jun Platelet-derived growth factor (PDGF) is a topic in the pathophysiology of various systemic rheumatic diseases. For example, autoantibody against PDGF receptor was identified in patients with systemic sclerosis. Imatinib mesylate has been well tolerable and widely used for chronic myeloid leukemia and gastrointestinal stromal tomor. Imatinib also inhibits the activation of c-Abl, which is a key downstream molecule of transforming growth factor-beta signaling, and PDGF receptors. Thus, imatinib effectively suppresses the activation and proliferation of fibroblasts, mesangial cells and smooth muscle cells. Therefore, imatinib may overcome the limitation of current therapeutic strategy with corticosteroids and immunosuppressive agents for refractory diseases.
16622728 Pneumocystis jiroveci pneumonia in a patient with rheumatoid arthritis as a complication o 2006 We report that a-63-year-old woman developed Pneumocystis jiroveci pneumonia (PCP) as a complication from treatment with infliximab for rheumatoid arthritis. Although there was neither symptoms of dyspnea nor typical observations on a chest X-ray examination, low levels of oxygen saturation and findings of high-resolution chest computed tomographic scanning suggested a possibility of interstitial pneumonia. A polymerase chain reaction-based detection of Pneumocystis jiroveci in induced sputum allowed an early diagnosis of PCP and subsequent effective treatment.
18695080 Geographic variation in rheumatoid arthritis incidence among women in the United States. 2008 Aug 11 BACKGROUND: The geographic variation in rheumatoid arthritis (RA) incidence in the United States is unknown. METHODS: We studied residential region from January 1, 1921, to May 31, 1976, and RA risk in a prospective cohort of women, the Nurses' Health Study. Information on state of residence was collected at baseline in 1976 (when participants were aged 30-55 years) and on state of residence at birth, at age 15 years, and at age 30 years in 1992. Among 83,546 participants reporting residence for all 4 time points, 706 incident RA cases from June 1, 1976, to May 31, 2004, were confirmed by screening questionnaire and record review for American College of Rheumatology criteria. Residential region was classified as West, Midwest, mid-Atlantic, New England, and Southeast. Multivariate Cox proportional hazards regression models were used to assess relationships between region and RA risk, adjusting for age, smoking, body mass index, parity, breastfeeding, postmenopausal status, postmenopausal hormone use, father's occupation, race, and physical activity. Analyses were performed in participants who lived in the same regions, or moved, over time. RESULTS: Compared with those in the West, women in New England had a 37% to 45% elevated risk of RA in multivariate models at each time point (eg, state of residence in 1976: rate ratio [RR], 1.42; 95% confidence interval [CI], 1.10-1.82). In analyses of women who lived in the same region at birth, age 15 years, and age 30 years, living in the Midwest was associated with greater risk (RR, 1.47; 95% CI, 1.05-2.05), as was living in New England (RR, 1.40; 95% CI, 0.98-2.00). Compared with living in the West at birth, age 15 years, and age 30 years, RA risk was higher in the East. CONCLUSIONS: In this large cohort of US women, significant geographic variation in incident RA existed after controlling for confounders. Potential explanations include regional variation in behavioral factors, climate, environmental exposures, RA diagnosis, and genetic factors.
17329305 Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the tre 2007 Jun OBJECTIVE: To evaluate the safety and effectiveness of adalimumab alone or in combination with standard disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA). METHODS: Patients with active RA despite treatment with DMARDs or prior treatment with a tumour necrosis factor antagonist participated in a multicentre, open-label clinical study of adalimumab 40 mg every other week for 12 weeks with an optional extension phase. Patients were allowed to continue with pre-existing traditional DMARDs. Long-term safety results are reported for all patients (4210 patient-years (PYs) of adalimumab exposure). The observed effectiveness results at week 12 are reported using American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria. RESULTS: Among the 6610 treated patients, adalimumab was generally well tolerated. Serious infections occurred in 3.1% of patients (5.5/100 PYs, including active tuberculosis, 0.5/100 PYs). Demyelinating disease (0.06%) and systemic lupus erythematosus (0.03%) were rare serious adverse events. The standardised incidence ratio of malignancy was 0.71 (95% CI 0.49 to 1.01). The standardised mortality ratio was 1.07 (95% CI 0.75 to 1.49). At week 12, 69% of patients achieved an ACR20 response, 83% a moderate, and 33% a good EULAR response. Adalimumab was effective in combination with a variety of DMARDs. The addition of adalimumab to antimalarials was comparably effective to the combination of adalimumab and methotrexate. CONCLUSIONS: Considering the limitations of an open-label study, adalimumab alone or in combination with standard DMARDs appeared to be well tolerated and effective in 6610 difficult-to-treat patients with active RA treated in clinical practice.
17419061 Assessment of foot impairment in rheumatoid arthritis patients by dynamic pedobarography. 2008 Jan OBJECTIVES: Impaired foot function may jeopardize the mobility of patients with rheumatoid arthritis (RA). However, there are still no guidelines concerning the adequate early treatment of painful rheumatoid feet which do not yet require surgery. An assessment method for RA feet appears necessary in order to detect foot problems before functional limitations develop. Therefore, the aim of the present study was to evaluate the use of pedobarographic measurements for detecting changes in plantar loading characteristics and their relationship to foot pain in patients with RA. METHODS: One hundred and twelve patients with RA (55.0+/-11.0 years of age) were divided into three groups according to their Health Assessment Questionnaire (HAQ) Score and compared to a control group of 20 healthy adults (CG). Thirty-six patients with good physical capacity belonged to group 1 (RA1; HAQ-score: 0-1.0), 38 patients with moderate capacity to group 2 (RA2; score: 1.1-2.0) and 38 patients with low capacity to group 3 (RA3; score: 2.1-3.0). Each patient's foot pain was clinically assessed. Pedobarography was used to analyze foot loading parameters while walking barefoot. RESULTS: In the forefoot, average pressures under the lateral forefoot were higher in RA1 patients than in RA2 patients and controls (p<0.05) despite an inconspicuous clinical examination of the foot in RA1 patients. RA1 patients also demonstrated higher plantar pressures than RA2 under the second metatarsal head (p<0.05). In contrast, no significant differences in maximum force could be demonstrated between patient groups. Furthermore, in RA3 patients with lower physical capacity, foot pain was increased as compared to RA1 and RA2 patients. CONCLUSION: In RA patients, pedobarographic patterns show specific changes which characterize the level of functional capacity. In patients with foot involvement, pedobarographic measurements can be useful during the earlier stages of the disease, when clinical examination does not yet indicate the need for more aggressive treatment or orthopedic interventions.