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ID PMID Title PublicationDate abstract
16171151 [Quality of life in rheumatoid arthritis. Methods of measurement]. 2005 Interest in quality of life in the medical sciences arises out of a holistic conception of the medical model. Taking into account the whole patient, concentrating efforts not only on extending his/her life in a biological sense, but also on increasing activities whose aim it is to create an active life, similar to the lives of healthy people. A chronic condition, which reduces the quality of life in illness is rheumatoid arthritis (RA). The illness leads to impairment in motor function, changes in excess of those caused by joint damage, and systemic complications, leading in consequence to a lowering in levels of health and living standards for the patient. The quality of life for a patient with RA depends on the individual patient's own skills in overcoming difficulties, on his/her ability to adapt and on psychological and social health resources. The aim of this paper is to present instruments for the measurement of quality of life and health problems of a psychological and social nature in those suffering from chronic and damaging RA. A multidimensional therapeutic approach should aim not only to reduce the difficulties associated with the illness, but also to improve the patient's functioning, and consequently his/her quality of life.
16137610 Hemopoietic stem cell transplantation in rheumatic diseases--an update. 2005 Sep Hematopoietic stem cell transplant (HSCT) for autoimmune diseases has been recognized as a potential treatment for patients who have failed conventional therapy. Autologous (self) donor cells have been preferred over allogeneic (HLA-matched) cells for rescue after high dose immunotherapy, given the previous higher rates of mortality, graft versus host disease (GVHD), and the need for more intense myeloablation associated with the latter. The European Group for bone Marrow Transplantation in Basel Switzerland (EBMT) and various groups within the US funded by the NIH (including the Autologous Blood and Marrow Transplant Registry (ABMTR)) have been pivotal in maintaining registries on patients transplanted as well as promoting homogeneity for future studies including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc). Although, patients transplanted for RA show initial success, relapse of the disease is common. In many, however, a second positive result can be obtained with the addition of DMARD therapy to which they were previously unresponsive, suggesting a "debulking" of disease by HSCT. SLE patients also have a high rate of success after HSCT, although current mortality rates appear high. Transplant in SSc patients has offered durable responses with improving transplant-related mortality related to careful patient selection.
16635271 Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid arthritis in a G 2006 The functional single-nucleotide polymorphism (SNP) of the gene PTPN22 is a susceptibility locus for rheumatoid arthritis (RA). The study presented here describes the association of the PTPN22 1858T allele with RA in a German patient cohort; 390 patients with RA and 349 controls were enrolled in the study. For 123 patients, clinical and radiographic documentation over 6 years was available from the onset of disease. Genotyping of the PTPN22 1858 SNP was performed using an restriction fragment length polymorphism PCR-based genotyping assay. The odds ratio to develop RA was 2.57 for carriers of the PTPN22 1858T allele (95% confidence interval (CI) 1.85-3.58, p < 0.001), and 5.58 for homozygotes (95% CI 1.85-16.79). The PTPN22 1858T allele was significantly associated not only with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) positive RA, but also with RF and anti-CCP negative disease. The frequency of the PTPN22 1858T allele was increased disproportionately in male patients (53.8% compared to 33.0% in female patients, p < 0.001), and the resulting odds ratio for male carriers was increased to 4.47 (95% CI 2.5-8.0, p < 0.001). Moreover, within the male patient population, the rare allele was significantly associated with the HLA-DRB1 shared epitope (p = 0.01). No significant differences in disease activity or Larsen scores were detected. The results provide further evidence that the PTPN22 1858T allele is associated with RA irrespective of autoantibody production. The increased frequency of the risk allele in male patients and its association with the shared epitope indicate that the genetic contribution to disease pathogenesis might be more prominent in men.
16095116 Autoantibodies against oxidized low-density lipoprotein (LDL) and carotid atherosclerosis 2005 Jul OBJECTIVES: To examine the relationship between autoantibodies against oxidized low-density lipoprotein (oxLDL-Abs) and the progression of carotid atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients without evidence of risk factors for atherosclerosis (RA group) and 30 healthy volunteers (normal group) were investigated. The mean intima-media thickness of the common carotid artery (mean CCA-IMT) was measured by high-resolution B-mode ultrasonography. The titer of IgG oxLDL-Abs was measured by enzyme-linked immunosorbent assay. The relationships among mean CCA-IMT, IgG oxLDL-Ab titer and patient factors such as body mass index, systolic blood pressure, diastolic blood pressure, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum lipid levels were examined. RESULTS: Mean CCA-IMT, CRP, ESR and titer of IgG oxLDL-Abs were significantly higher in the RA group than in the normal group. Although mean CCA-IMT showed a positive correlation only with age in multivariate analysis, IgG oxLDL-Ab titers in the RA group were positively associated with mean CCA-IMT and independently with age and sex by multiple regression analysis. CONCLUSIONS: IgG oxLDL-Abs appear to be associated with the degree of carotid atherosclerosis in patients with RA, and are independent of traditional risk factors for atherosclerotic diseases. These results suggest a possible link between autoimmune mechanisms and accelerated atherosclerosis in RA.
15975971 Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced 2006 Feb BACKGROUND: Rheumatoid arthritis (RA) is associated with increased morbidity and mortality attributable to accelerated atherosclerosis and cardiovascular events. OBJECTIVE: To determine the role played by endothelial progenitor cells (EPC) in the defence system against arteriosclerosis. METHODS: The number and function of EPC in 13 young patients with RA with low disease activity (DAS28 3.5 (0.3)) and 13 healthy control subjects was studied. Endothelial function was investigated by agonist-induced, endothelium dependent vasodilatation measured by the forearm blood flow technique. Migratory activity and adhesion of EPC to tumour necrosis factor alpha (TNFalpha) activated mature endothelial cells and components of the extracellular matrix were tested in vitro. Putative precursor populations (CD34(+), CD34(+)/CD133(+), and CD34(+)/KDR(+) haematopoietic stem cells) were measured by flow cytometric analysis. RESULTS: Acetylcholine-induced, endothelium dependent vasodilatation was reduced by about 50% in patients with RA, indicating endothelial dysfunction, whereas endothelium-independent vasodilatation in response to glyceryl trinitrate was at control level. Significantly reduced numbers of EPC were found in the patients compared with controls. Migratory activity of EPC was decreased in patients with RA. Adhesion to mature endothelial cells after activation with TNFalpha was enhanced only in controls. The adhesion to matrix proteins and the number of putative precursor cell lineages was comparable in both groups. CONCLUSION: Endothelial dysfunction in patients with RA with low grade inflammation is associated with a reduced number and partial dysfunction of EPC. Further studies are needed to explore whether interventions that potentially ameliorate the number and function of EPC also improve endothelial function in these patients.
16935912 Selective costimulation modulation using abatacept in patients with active rheumatoid arth 2007 Feb OBJECTIVE: To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE). METHODS: Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE. RESULTS: A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections. CONCLUSION: The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.
16855168 Effects of anti-TNF-alpha treatment on lipid profile in patients with active rheumatoid ar 2006 Jun Cardiovascular morbidity and mortality appear to be increased in rheumatoid arthritis (RA), which might be due to increased prevalence of risk factors for cardiovascular disease, such as an accelerated progression of atherosclerosis. Patients with active RA frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Tumor necrosis factor-alpha (TNF-alpha), a pivotal proinflammatory cytokine implicated in the pathogenesis of atherosclerosis in RA, may be involved in the development of the altered lipid profile observed in active RA. Our aim was to investigate the effects of anti-TNF-alpha treatment in combination with methotrexate (MTX) and corticosteroid therapy on lipid profile in patients with active RA. In this prospective study 34 consecutive RA patients were included (all women, mean age 51.6 +/- 7.9 years, range 46-72 years) with active (defined as Disease Activity Index 28 joint score [DAS-28], of at least 3.2) and refractory RA, in stable treatment with MTX (7.5-10 mg/week) and prednisone (7.5-10 mg/day) for 3 months. All patients received TNF-alpha blockers (n = 16, etanercept 25 mg twice weekly; n = 14, infliximab 3 mg/kg on 0, 2, 6, and every 8 weeks thereafter; and finally, n = 4, adalimumab 40 mg every other week). Total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), triglycerides (TG) and lipoprotein (a) [Lp(a)] levels and the atherogenic index (ratio cholesterol/HDL cholesterol) were measured at base line, and at 16 and 24 weeks. Results were as follows: The DAS-28 was 6.9 +/- 2.1 at base line and decreased to 4.6 +/- 1.8 after 16 weeks, and further to 4.1 +/- 1.3 after 24 weeks (both, P < 0.01). Following anti-TNF-alpha treatment, the mean levels of total cholesterol were 168 +/- 24 mg/dL at base line and increased to 188 +/- 28 mg/dL at 16 weeks (P < 0.01), and 197 +/- 26 mg/dL at 24 weeks (P < 0.001). However, also the mean levels of HDL cholesterol were significantly higher than basal values after 16 and 24 weeks of treatment (34 +/- 12 mg/dL versus 36 +/- 18 mg/dL [P < 0.05] and 38 +/- 14 mg/dL [P < 0.01], respectively). TG and Lp(a) levels, as well as the atherogenic index were not significantly changed. Interestingly, variations in disease activity were significantly and inversely correlated with HDL cholesterol levels. IN CONCLUSION: Short anti-TNF-alpha treatment was associated with a significant increase of both total cholesterol and HDL cholesterol levels, and correlated with decreased disease activity. The atherogenic index showed no changes during the study. Therefore, anti-TNF-alpha treatment might affect lipid profile in RA patients.
16142856 Association of chondromodulin-II Val58Ile polymorphism with radiographic joint destruction 2005 Sep OBJECTIVE: Chondromodulin-II (ChM-II) is a cartilage-derived protein involved in cartilage and bone repair. A study of Japanese patients with rheumatoid arthritis (RA) implicated an association between a 172G --> A (Val58Ile) polymorphism and radiographic damage. We analyzed ChM-II for polymorphisms and investigated the association with radiographically assessed joint destruction in German patients with RA. Possible interactions with the shared epitope (SE) were examined. METHODS: DNA samples from 204 patients with RA, 81 patients with osteoarthritis, and 116 patients with gout, serving as controls, were sequenced. Radiographic damage was assessed by modified Larsen score. Allele and genotype frequencies between groups were compared by Cochrane-Armitage trend tests. RESULTS: Five missense mutations, one silent mutation, and 5 intronic polymorphisms were found. Allele and genotype frequencies were similar in both disease groups. Larsen scores were significantly higher in RA patients carrying the 172AA (Ile/Ile) genotype (Larsen 96.8), than in RA patients with the 172GA (Val/Ile; Larsen 69.5) or 172GG (Val/Val; Larsen 54.8; p = 0.001) genotypes. Odds ratios to develop more severe radiographic joint damage (Larsen score > 90; above 75th percentile) were 4 and 15.5 for the 172GA and 172AA genotypes, respectively. Presence of a 172A allele increased the risk for enhanced radiographic damage 3-fold. SE and ChM-II 172A alleles emerged as 2 independent risk factors. A potentiated interaction of these risk alleles could not be verified. CONCLUSION: Our data indicate that ChM-II Val58Ile polymorphism is associated with radiographic progression of joint destruction, particularly in German patients with RA negative for SE.
15345497 Expression of resistance markers to methotrexate predicts clinical improvement in patients 2005 Apr BACKGROUND: Methotrexate is transported into the cell by the reduced folate carrier (RFC) and out of the cell by members of the multidrug resistance protein family (MRP). Transport proteins may affect the therapeutic efficacy of this drug in patients with rheumatoid arthritis. OBJECTIVE: To investigate the potential benefit of the presence of RFC and the absence of functional MRP for the efficacy of methotrexate treatment. METHODS: The study involved 163 patients (116 female, 47 male; mean age 59.5 years) on methotrexate (mean weekly dose 12.2 mg). RFC was determined using reverse transcriptase polymerase chain reaction, and MRP function by flow cytometry, using a calcein acetoxymethylesther/probenecid assay. Clinical response to methotrexate was evaluated by the EULAR response criteria and the ACR 20% improvement criteria. The clinical data were obtained at the beginning of methotrexate treatment and at the time of blood sampling during ongoing therapy. Patients were divided into four groups according to the presence (+) or absence (-) of RFC and functional (f) MRP. RESULTS: fMRP+/RFC+ and fMRP-/RFC- patients more often had good EULAR response rates (60%, p = 0.014, and 53%, p = 0.035, respectively) in comparison with the fMRP-/RFC+ group (29%); fMRP+/RFC- patients had a low frequency of good disease activity responses. CONCLUSIONS: Absence of fMRP plus presence of RFC did not prove to be related to beneficial effects of methotrexate, but the lack or the presence of both fMRP and RFC led to a significantly better therapeutic outcome. Determination of these markers may predict responsiveness to methotrexate.
17313014 [Professor ZHANG Ji's clinical experience]. 2006 Dec Professor ZHANG Ji has unique experience on therapeutic methods for rheumatoid arthritis, ankylosing spondylitis and obstinate facial palsy. (1) In acupuncture and moxibustion, he adopts the Governor Vessel and etiological analysis and differentiation, local acupuncture three step acupoint selection for treatment of rheumatoid arthritis; and supplementing the liver and kidney and strengthening the Governor Vessel and tonifying yang for ankylosing spondylitis; and dispelling wind and removing dampness, and dredging channels and activating the collaterals for obstinate facial palsy. (2) In Chinese drugs, on the basis of 50 year's clinical practice, he summarizes recipes Guanjie No. I and No. II. Modified Guanjie No. I is mainly used for treatment of rheumatoid arthritis, and modified Guanjie No. II mainly for ankylosing spondylitis, and Qianzheng Powder combined with drugs for clearing away heat and toxic substances are used for treatment of obstinate facial palsy.
16204969 Histamine H4 receptor expression in human synovial cells obtained from patients suffering 2005 Oct While histamine H4 receptor (H4R) has been implicated in immune system disturbances in different organ tissues, the presence and possible roles of H4R in synovial cells (SC) of rheumatoid arthritis (RA) patients has not previously been documented. This study conclusively evidences H4R expression in SC of RA patients by use of RT-PCR method. As RA consists mainly of immunological disturbances in SC of RA patients, this study's findings document a novel histamine action site, and opens potential new avenues to investigate mechanisms and to develop pharmacotherapeutic agents for the disease.
17426837 Blood serum DNA in patients with rheumatoid arthritis is considerably enriched with fragme 2006 Sep We previously hypothesized that the sequence of transcribed region of human ribosomal repeats is selectively accumulated in circulating extracellular DNA due to its increased resistance to double-strand breaks caused by accumulation of single-chain breaks produced by nucleases. The contents of rDNA in blood serum DNA and in DNA from leukocytic nuclei both in healthy donors and in patients with rheumatoid arthritis were compared using dot hybridization method. By the content of non-methylated CpG-repeats, transcribed region of rDNA is identical to bacterial DNA, which is characterized by potent immunostimulatory effect. The transcribed region of rDNA (13.3 kb) contains more than 200 CpG-motifs capable of interacting with TLR9 receptors, which are the mediators of the cell immune response to the action of CpG-rich DNA fragments. The data suggest that DNA from dead cells circulating in the peripheral blood is enriched with sequences possessing potent immunostimulatory properties.
16393764 Investigation of platelet glycoprotein IIIa polymorphism using flow cytometry in patients 2005 Nov OBJECTIVES: Previous work has shown that the human platelet antigen (HPA) 1b polymorphism of platelet glycoprotein IIIa (GPIIIa) is implicated in the development of ischaemic vascular disease. HPA1b positive platelets have a lower threshold for activation and may exert a greater thrombotic tendency than those without the 1b allele. However, platelets heterozygous for the polymorphism are also more sensitive to aspirin than those homozygous for the 1b allele, which have a similar sensitivity to those without the 1b allele. A flow cytometric method has become available to identify this polymorphism. The aim of our study was to evaluate the use of this assay in patients with rheumatoid arthritis (RA) and to determine the incidence of the 1b allele in these patients. We also compared platelet aggregation and platelet/white blood cell interaction in patients with or without this polymorphism. METHODS: We enrolled 99 patients and measured platelet aggregation in whole blood and platelet-rich plasma (prp), platelet/white blood cell interaction and C-reactive protein (CRP). RESULTS: Thirty-four of the 99 patients were unsuitable for analysis because their baseline expression of GPIIIa was outwith the normal range, making the results outwith the limits of the flow cytometric method. The incidence of the 1b allele in the patients was 29%, with incidence being higher in females, although this failed to reach statistical significance. The number of circulating platelet aggregates and adenosine diphosphate (ADP)-induced aggregation in prp was significantly higher in those patients with the 1b allele. CONCLUSIONS: This method may be of use as an initial screening test.
16606649 Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumat 2006 Jul OBJECTIVE: To evaluate the two generations of anti-cyclic citrullinated protein (CCP) antibodies as a diagnostic marker of rheumatoid arthritis (RA) and as a predictor of future development of RA in healthy subjects and in patients with early undifferentiated arthritis. METHODS: A systematic analysis of the literature published between 1999 and February 2006 was conducted. Data were collected on the sensitivity and specificity of the two generations of anti-CCP antibodies for diagnosing RA and predicting future development of the disease. RESULTS: Among 107 studies initially identified, 68 had interpretable data and were analysed. Diagnostic properties were assessed in 58 studies: mean (SD) sensitivity was 53 (10)% (range 41-68) and 68 (15)% (range 39-94) for anti-CCP1 and anti-CCP2, respectively; mean (SD) specificity was 96 (3)% (range 90-99) and 95 (5)% (range 81-100) for anti-CCP1 and anti-CCP2, respectively. Predictive properties were assessed in 14 studies; odds ratio (95% confidence interval) of anti-CCP1 and anti-CCP2 for the future development of RA were 20 (14 to 31) and 25 (18 to 35), respectively, among patients with early undifferentiated arthritis and 64.5 (8.5 to 489) and 28 (8 to 95), respectively, among healthy subjects. CONCLUSION: Sensitivity of the second generation of anti-CCP is close to that of rheumatoid factor, with a higher specificity, for distinguishing RA from other rheumatic diseases. Moreover, anti-CCP antibodies appear to be highly predictive of the future development of RA in both healthy subjects and patients with undifferentiated arthritis.
15911740 Arterial stiffness in chronic inflammatory diseases. 2005 Jul Chronic inflammatory diseases are associated with premature atherosclerosis; however, it is unknown whether arterial stiffness is increased in this setting, possibly as a manifestation of vascular disease preceding and/or independent of atherosclerosis. Carotid ultrasonography and radial applanation tonometry were performed in 101 patients with systemic lupus erythematosus, 80 patients with rheumatoid arthritis, and 105 healthy control subjects. The 3 groups were comparable in age, gender, and carotid artery absolute and relative wall thickness. Atherosclerotic plaque was more common in lupus (46%) and rheumatoid arthritis (38%) patients than in controls (23%) (P<0.003). Although control subjects had higher central and peripheral blood pressures, arterial stiffness was increased in patient groups compared with controls (lupus, rheumatoid arthritis, controls, respectively: beta: 3.36 versus 3.22 versus 2.60, P<0.001; Young's modulus: 441 versus 452 versus 366 mm Hg/cm, P=0.004; Peterson's elastic modulus: 278 versus 273 versus 216 mm Hg, P<0.001) after adjustment for differences in mean brachial pressure. In multivariate analysis involving the entire population, arterial stiffness was independently related to age, serum glucose, and the presence of chronic inflammatory disease. In multivariate analysis restricted to the patients, arterial stiffness was independently related to age at diagnosis, disease duration, serum cholesterol, and C-reactive protein (and IL-6, when substituted for C-reactive protein). When analyses were repeated in the 186 study subjects without carotid plaque, arterial stiffness remained significantly elevated in patient groups after adjustment for differences in age and mean brachial pressure. In conclusion, arterial stiffness is increased in chronic inflammatory disorders independent of the presence of atherosclerosis and is related to disease duration, cholesterol, and the inflammatory mediator C-reactive protein and the cytokine that stimulates its production, IL-6.
16374573 Bone eburnation in rheumatic diseases: a guiding trace in today's radiological diagnosis a 2006 Mar Bone eburnation is a common anatomical trace of chronic arthropathy. However, its topographical analysis in rheumatic diseases can contribute to knowledge about the latter, by explaining today's diagnosis through radiology as well as by giving an historical perspective through paleopathology. After recalling that eburnated areas can also originate in infectious arthritis, the present analysis consists in a comparison between macroscopic and radiological observations of both osteoarthritis (OA) and rheumatoid arthritis (RA) at an advanced stage. It focuses on the human femoral head because of its demonstrative interest. Two main observations emerge from our study. The eburnated surface is less extensive in OA (where it appears to be essentially linked to the original structure of the hip) and more extensive in RA at an advanced stage (where an additional systemic factor is predominant). The size of the associated osteophytes appears to be inversely proportional to the extent of the corresponding eburnated area. In connection with the OA-RA comparison above, the contribution of the original joint structure to bone eburnation was also illustrated by acromiohumeral eburnation in shoulder OA and by the comparison with dog hip OA. It must also be noted that a femoral head bone remodeling similar on the whole to that of OA can occur in ochronotic arthropathies whose causal chondropathy is due to a genetic defect. Originating in an identified chondropathy, eburnation in ochronotic arthropathy gives us the opportunity to study an OA-type bone remodeling per se as in an experiment supplied by nature and involving a human hip. However, since RA and ochronotic arthropathy are due to a diffuse chondropathy, both may create a similar macroscopic (and thus radiological) eburnation topography.
15965818 [Synovialitis score: histopathological grading system for chronic rheumatic and non-rheuma 2005 Jun Standardization of the histopathological assessment of synovial membrane specimens might facilitate the diagnosis of chronic rheumatic and non-rheumatic joint diseases. We would like to propose a histological graduation scheme ("synovialitis score"), which is applicable to all forms of synovitis, irrespective of its etiology. This score evaluates the three compartments of chronic synovialitis [enlargement of lining cell layer, activation of synovial stroma (i. e. resident cells), leukocytic infiltrate] semiquantitatively (from 0=absent to 3=strong). Each compartment is graded separately, and the sum resembles the synovialitis score, which is interpreted as follows: 0-1: no synovialitis, 2- 3: slight synovialitis, 4-6: moderate synovialitis, 7-9: strong synovialitis (for sample photos see also www.charite.de/ch/patho/Webpage/pages/forschung/arbeitsgruppen/ag-krenn/index.htm). A total of 483 synovial specimens (resections n=462, biopsies n=21) were graded by two independent observers. Clinical diagnoses were osteoarthrosis (OA; n=153), posttraumatic arthritis (PtA; n=31), rheumatoid arthritis (RA; n=239), psoriatic arthritis (PsA; n=32), reactive arthritis (ReA; n=7), and controls (Co, n=21) from necropsies of patients without joint damage. The correlation between two observers was high (p<0.001). The correlation coefficient between the different samples from the same joint in n=112 cases was between 0.86 and 0.95. Median synovialitis scores when correlated with clinical diagnoses were: Co 0.5, OA 2, PtA 3, PsA 3, ReA 4, RA 5. The differences in scores between Co and all other groups were highly significant (p<0.001). A synovialitis score of 4 points and more was strongly associated with rheumatic joint diseases (sensitivity 73%, specificity 86%). Validation of the synovialitis score by gene expression data showed good correlations for the lining cell enlargement with MMP1 (0.685), for the leukocytic infiltrate with CD3 (0.754) and CD138 (0.744) and for the stroma activation with CD14 (0.744). The proposed synovialitis score is based on well definable histopathologic criteria and contributes to the diagnosis of rheumatic and non-rheumatic joint diseases.
16669473 The comprehensive evaluation of temporomandibular disorders seen in rheumatoid arthritis. 2006 Mar BACKGROUND: We studied clinical signs and symptoms of temporomandibular disorders and radiological changes in the temporomandibular joint from patients with rheumatoid arthritis (RA) compared to patients with myofascial pain dysfunction of the temporomandibular system and control patients to evaluate clinical and radiological relationships. METHODS: A cross-sectional, controlled, clinical and radiological study was planned and 99 subjects (69 patients and 30 controls) were included in the study. RESULTS: Twenty-three patients with RA (69.7 per cent) had painful temporomandibular joint. Fifty-five per cent had myofascial pain dysfunction according to the research diagnostic criteria for temporomandibular disorders (TMD). Nearly all of our patients with RA (93.9 per cent) had symptoms, and almost all of them had positive findings of TMD in high resolution computed tomography. Condylar head resorption, joint space narrowing and degeneration were statistically more prominent features in patients with rheumatoid arthritis compared with controls (p < 0.05). The pain score on active palpation correlated with the number of the mandibular subchondral cysts on high resolution computed tomography (r = 0.6, p < 0.05). CONCLUSION: Although the myofascial pain of the temporomandibular system is an important cause of pain in rheumatoid arthritis, prospective controlled studies are needed to develop effective therapeutic strategies for these patients.
16225377 Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. 2005 Infliximab (Remicade) is a chimeric monoclonal antibody against tumour necrosis factor (TNF)-alpha that has shown efficacy in Crohn's disease and rheumatoid arthritis with a disease-modifying activity and rapid onset of action. It is administered intravenously, generally in a schedule with initial infusions at 0, 2 and 6 weeks, followed by administration once every 8 weeks. Infliximab is effective in the treatment of patients with moderately to severely active Crohn's disease with an inadequate response to other treatment options or those with fistulising disease. In combination with methotrexate, infliximab reduced signs and symptoms and delayed disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease. The drug was generally well tolerated. Recrudescence of tuberculosis infection and worsening of heart failure and demyelinating disease are among some of the concerns with anti-TNFalpha therapy, requiring cautious use of these agents in high-risk patients. Current data suggest that infliximab may be cost effective, especially when long-term clinical outcomes and burden of the diseases are taken into account. More robust, prospective pharmaco-economic studies are required to better ascertain the cost effectiveness of infliximab. Direct head-to-head comparative trials of infliximab with other biological agents are not yet available and would be helpful in determining with greater certainty the place of infliximab in the management of these diseases. Nonetheless, infliximab, like other biological agents, is a valuable treatment option in patients with moderately to severely active Crohn's disease (including fistulising disease) or rheumatoid arthritis (including early disease).
16728461 Detailed analysis of the cell infiltrate and the expression of mediators of synovial infla 2006 Dec BACKGROUND: The synovial tissue is a primary target of many inflammatory arthropathies, including psoriatic arthritis (PsA). Identification of proinflammatory molecules in the synovium may help to identify potentially therapeutic targets. OBJECTIVE: To investigate extensively the features of cell infiltration and expression of mediators of inflammation and joint destruction in the synovium of patients with PsA compared with patients with rheumatoid arthritis matched for disease duration and use of drugs. METHODS: Multiple synovial tissue biopsy specimens were obtained by arthroscopy from an inflamed joint in 19 patients with PsA (eight oligoarthritis, 11 polyarthritis) and 24 patients with rheumatoid arthritis. Biopsy specimens were analysed by immunohistochemistry to detect T cells, plasma cells, fibroblast-like synoviocytes, macrophages, proinflammatory cytokines, matrix metalloproteinases and tissue inhibitor metalloproteinase-1, adhesion molecules and vascular markers. Stained sections were evaluated by digital image analysis. RESULTS: The synovial infiltrate of patients with PsA and rheumatoid arthritis was comparable with regard to numbers of fibroblast-like synoviocytes and macrophages. T cell numbers were considerably lower in the synovium of patients with PsA. The number of plasma cells also tended to be lower in PsA. The expression of tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, IL6 and IL18 was as high in PsA as in rheumatoid arthritis. The expression of matrix metalloproteinases, adhesion molecules and vascular markers was comparable for PsA and rheumatoid arthritis. CONCLUSION: These data show increased proinflammatory cytokine expression in PsA synovium, comparable to results obtained for rheumatoid arthritis, and support the notion that, in addition to TNFalpha blockade, there may be a rationale for treatments directed at IL1beta, IL6 and IL18.