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ID PMID Title PublicationDate abstract
19728558 Beneficial effects of cellular stress response in traditional spa treatment of rheumatoid 2009 Patients with rheumatoid arthritis often conduct bathing in hot mineral water with a high concentrations of sulfate compounds in the water and ambient air. We investigated the effect of hyperthermia and sulfur as possible stress factors at transcriptional level in several proinflammatory genes in fibroblast like synoviocytes. We mimicked the classical balneological treatment. Cells were exposed to 30 minutes of hyperthermia (41-42 degrees C) or sulfur (2 mM NaHS). Indeed, both factors were acting as stressors, inducing a profound expression of heat shock protein 70 (HSP70). Stimulation of the cells with IL1beta induced a series of proinflammatory genes (IL1alpha, IL1beta, TNFalpha, IL8, monocyte chemoattractant peptide-1 and COX-2), but if the cells were treated with hyperthermia prior to IL1beta expression, gene expressions were significantly decreased up to 8 h. Treatment with sulfur alone induced expression of observed genes up to 12 h. We may conclude that hyperthermia as a balneological mean has indeed a protective effect on cells, but sulfur, which at first we considered as an antiinflammatory mean, had actually an opposite effect and induced expression of proinflammatory genes. Our data confirmed that the effect of hyperthermia as balneological mean treatment is beneficial, but sulfur treatment must be taken in reconsideration.
20003278 A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone 2009 INTRODUCTION: Osteoclasts play a key role in the pathogenesis of bone erosion and systemic bone mass loss during rheumatoid arthritis (RA). In this study, we aimed to determine the effect of methotrexate (MTX) and zoledronic acid (ZA), used alone or in combination, on osteoclast-mediated bone erosions and systemic bone mass loss in a rat model of collagen induced arthritis (CIA). We hypothesized that MTX and ZA could have an additive effect to prevent both bone erosion and systemic bone loss. METHODS: Arthritis was induced in 64 female Sprague-Dawley rats. After the clinical onset of CIA, rats were assigned to treatment with MTX (1 mg/kg/week), ZA (100 microg/kg twice weekly), both treatments at the same regimens, or vehicle. Arthritis score and paw thickness were recorded twice weekly. The rats were sacrificed on D28 and hind paws were removed for radiographic, histological and immunohistochemical analysis. The effects of treatments on osteoclastogenesis were determined by Tartrate resistant acid phosphatase (TRAP) staining. Micro-CT of the tibia was carried out for histomorphometric analysis. Bone mass density was evaluated by densitometry. RESULTS: MTX significantly decreased the severity of CIA, whereas ZA slightly exacerbated it. When these two drugs were used in combination, MTX prevented the pro-inflammatory effect of ZA. The combination of ZA with MTX was more effective than MTX alone for reducing structural joint damage with a dramatic decrease of osteoclasts' number in the eroded joints. However, MTX alone also significantly reduced the number of osteoclasts and the number of CD68+ mononuclear cells. ZA alone, or ZA with MTX, significantly increased the systemic bone mass density measured by densitometry and bone volume on histomorphometric analysis. CONCLUSIONS: A combination of MTX and ZA prevented both bone erosion and systemic bone loss in a rat model of arthritis. Both treatments independently decreased the number of osteoclasts in the eroded joint. However, while MTX probably acts mainly through a decrease of inflammation, ZA has a direct effect on osteoclasts, allowing a dramatic down-regulation of these cells in inflamed joints. These two different mechanisms of action provide support for the use of a combination of these two drugs to improve the prevention of structural joint damage in RA.
19602788 Inflammatory cells in lung disease associated with rheumatoid arthritis. 2009 OBJECTIVE: Rheumatoid arthritis (RA) is associated with numerous pulmonary manifestations. However, the inflammatory mechanism remains undetermined. We studied the features of inflammatory cells in bronchoalveolar lavage (BAL) fluid and biopsy lung tissue from patients with RA-associated lung disease. METHODS: BAL findings were statistically compared between diseases. We divided RA patients into two groups, airway lesion group (AW) and interstitial lesion group (INT) according to predominant HRCT findings and compared the BAL findings. We immunohistochemically stained lung tissue for CD4, CD8, CD20, and CD163 and counted the immunopositive cells in five different regions. PATIENTS: Twenty patients fulfilling the Japanese criteria for RA, 13 patients with systemic sclerosis (SSc), and 21 patients with polymyositis and dermatomyositis (PM-DM) with pulmonary disease detected by high-resolution CT (HRCT) were enrolled in this study. RESULTS: As for BAL in RA, we found a lower lymphocyte frequency with higher CD4/8 ratio compared with PM-DM and a higher neutrophil percentage than both PM-DM and SSc. Nine and eleven patients with RA were classified into AW and INT groups, respectively. BAL findings did not differ between the two groups. Immunohistochemically, most CD4(+) and CD20(+) lymphocytes were accumulated in lymphoid follicles and in the alveolar wall and T-lymphocytes; in particular CD8(+) lymphocytes were predominant in lung interstitium. CONCLUSION: These results suggest that 1) neutrophils may play an important role, 2) the inflammatory mechanism may be similar between airway lesion and interstitial pneumonia, and 3) CD8(+) lymphocytes may be major inflammatory cells in lung interstitium in RA-associated interstitial lung disease.
19734739 Polyarticular lipoma arborescens with inflammatory synovitis. 2009 Sep Lipoma arborescens is a rare clinical condition characterized by mono or biarticular involvement of large joints, such as knees, hips, ankles, elbows, and shoulders. The aim of this case report is to describe an unusual case of lipoma arborescens affecting multiple large joints, mimicking rheumatoid arthritis. The patient, a 29-year-old woman had a history of intermittent arthritis of the wrists, knees, and ankles for at least 12 years. With the diagnosis of rheumatoid arthritis she had been on methotrexate (7.5 mg/wk) for the last 6 months along with different nonsteroidal anti-inflammatory drugs, without benefit. On physical examination a discreet joint swelling of the knees without effusion, gluteal muscle atrophy, and limited hip movements were observed. Laboratory tests presented normal acute phase reactants of inflammation as well as the rheumatoid factor, CK, and negative results for antinuclear, anti-DNA, anti-SSA/Ro, and anti-CCP (ELISA) antibodies. Magnetic resonance imaging of the knees and hips showed articular effusion and synovitis, and a pattern of lipoma arborescens. The histopathologic study confirmed the diagnosis. Knee arthroscopic synovectomy brought some improvement to joint mobility and pain.Although rare, this condition must be remembered in the presence of inflammatory arthropathy, particularly in the absence of response to clinical treatment, and absence of rheumatoid factor and anti-CCP antibodies, since the therapeutic strategy is radically different.
22766573 A case of severe staphylococcal septicaemia: septic arthritis and a mediastinal abscess fo 2010 Aug 19 This highly unusual case illustrates how a potentially life-threatening complication may develop insidiously in the context of immunosuppression. A 46-year-old woman presented with increasing malaise and a marked inflammatory response in the context of immunosuppressive therapy for rhueumatoid arthritis. On the basis of microbiological findings, the patient was treated for systemic staphylococcal infection with a prolonged antibiotic course. In addition, incision and drainage procedures were performed on associated, non-resolving abscesses at various sites. One particular lesion in the breast was slow to heal and was monitored with ultrasound imaging. Subsequent cross-sectional imaging revealed that this was, in fact, a large mediastinal abscess, eroding the manubrium and lying within close proximity of the aorta. The patient was eventually referred to a cardiothoracic unit for complete evacuation of this lesion. Following a prolonged illness and treatment period, the patient recovered well and successfully resumed employment.
20831200 Syntheses of click PEG-dexamethasone conjugates for the treatment of rheumatoid arthritis. 2010 Oct 11 A novel linear multifunctional polyethylene glycol (PEG)-dexamethasone (Dex) conjugate (click PEG-Dex) was synthesized using facile Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (a click reaction). Dex was conjugated to the click PEG via an acid-labile hydrazone bond to allow the drug release in a pathophysiological environment. To evaluate click PEG's potential as a versatile drug delivery platform, the click PEG-Dex conjugates were tested in an adjuvant-induced arthritis (AA) rat model. In vivo optical imaging data confirmed the arthrotropism of the conjugates in the arthritic rats. A long-term treatment study revealed that a single click PEG-Dex conjugate administration provided sustained (>15 days) amelioration of ankle joint inflammation to the AA rats. Treatment with an equivalent dose of dexamethasone phosphate sodium (free Dex) only provided temporal resolution of the arthritis, which recurred upon treatment withdrawal. Further histological and bone mineral density comparison between the ankle joints from both click PEG-Dex and free Dex treatment groups confirmed the superior anti-inflammatory and disease modifying effects of the novel polymer-drug conjugates.
21082959 Autologous hematopoietic stem cell transplantation in autoimmune diseases. 2009 Dec The term 'autoimmune diseases' encompasses a spectrum of diseases whose clinical manifestations and, possibly, biological features vary widely. The results of conventional treatment are considered unsatisfactory in aggressive forms, with subsets of patients having short life expectancies. Relying on wide experimental evidence and more feeble clinical data, some research groups have used autologous hematopoietic stem cell transplantation (HSCT) in the most disabling autoimmune diseases with the aim of resetting the patient's immune system. Immunoablative conditioning regimens are preferred over their myeloablative counterparts, and some form of in vivo and/or ex vivo T-cell depletion is generally adopted. Despite 15 years' experience, published controlled clinical trials are still lacking, with the evidence so far available coming from pilot studies and registry surveys. In multiple sclerosis, clinical improvement, or at least lasting disease stabilization, can be achieved in the majority of the patients; nevertheless, the worst results are observed in patients with progressive disease, where no benefit can be expected from conventional therapy. Concerning rheumatologic diseases, wide experience has been acquired in systemic sclerosis, with long-term improvements in cutaneous disease being frequently reported, although visceral involvement remains unchanged at best. Autografting has proved to be barely effective in rheumatoid arthritis and quite toxic in juvenile idiopathic arthritis, whereas it leads to clinical remission and the reversal of visceral impairment in the majority of patients with systemic lupus erythematosus. A promising indication is Crohn's disease, in which long-term endoscopic remission is frequently observed. Growing experience with autologous HCST in autoimmune diseases has progressively reduced concerns about transplant-related mortality and secondary myelodysplasia/leukemia. Therefore, a sustained complete remission seems to be within the reach of autografting in some autoimmune diseases; in others, the indications, risks and benefits of autografting need to be better defined. Consequently, the search for new drugs should also be encouraged.
18980958 Polymyalgia rheumatica can be distinguished from late onset rheumatoid arthritis at baseli 2009 Feb OBJECTIVE: To describe the pattern of arthropathy and HLA-DRB1 alleles associated with PMR in order to develop a diagnostic algorithm that could help distinguish PMR and RF-negative (RF -ve) late-onset RA (LO-RA) at presentation. METHODS: This was a prospective study of all patients presenting with PMR or LO-RA over a 10-yr period to one physician. Demographic, clinical and laboratory data were collected at presentation and during a minimum of 5 yrs of follow-up. The accuracy of the initial diagnosis was systematically reviewed. RESULTS: One hundred and forty-two patients with LO-RA, 147 with PMR and 42 with PMR + TA were studied. Peripheral synovitis was observed in 23% of the PMR patients. In comparison with RF -ve LO-RA, PMR patients were younger (P < 0.001), myalgia more frequent [100 vs 16% (P < 0.001)] and arthritis of PIP, MCP and wrist were less frequent (P < 0.001). The combination of wrist + MCP/PIP or wrist + PIP + MCP were highly suggestive of RF -ve LO-RA (P < 0.001). HLA-DRB1*0101/0102 and *0401 were significantly increased in PMR patients compared with healthy controls. Plasma viscosity and arthritis in the wrist, in combination with at least one MCP or PIP joint at disease onset, were predictive of whether a non-erosive RF -ve patient would ultimately be diagnosed as having RF -ve LO-RA or PMR (+/-/arthritis). CONCLUSION: Our longitudinal follow-up data were consistent with RF -ve LO-RA being a separate disease entity to PMR despite some phenotypic and immunogenetic similarities at disease onset. A diagnostic algorithm was derived using baseline clinical features to predict the final diagnosis of RF -ve, non-erosive patients.
19519585 Bench to bedside of CTLA-4: a novel immuno-therapeutic agent for inflammatory disorders. 2009 Jun Co-stimulatory molecules are antigen-independent generators of secondary signals which aid in maintaining the homeostasis of the immune system. CTLA-4 is one among extensively studied co-stimulatory molecules which down-regulate immune response. The attributes of immunosuppressive qualities and capacity to induce tolerance have made its recognition as a potential immuno-therapeutic agent for autoimmune mediated inflammatory disorders. In 2007, European Medical Drug Agency (EMEA) has approved administration of CTLA-4Ig (commercial name: Orencia; generic name: Abatacept), as a mean for co-stimulation blockade, for treating patients with rheumatoid arthritis. This review is focused on working mechanism of CTLA-4 from its recognition (bench) to its usage as a potential therapeutic agent (bedside) for several inflammatory diseases. The efficacious aspects of chimeric CTLA-4 in phase I, II and III clinical trials for rheumatoid arthritis, psoriasis, multiple sclerosis are concisely described. This article highlights recent patents and the future usage of co-stimulatory molecules as a therapeutic agent providing a promising immuno-modulatory approach in regulating inflammation.
19703021 Increased expression of activation-induced cytidine deaminase is associated with anti-CCP 2009 Sep Rheumatoid arthritis (RA) is associated with higher levels of autoantibodies and IL-17. Here, we investigated if ectopic lymphoid follicles and peripheral blood mononuclear cells (PBMCs) from RA patients exhibit increased activation-induced cytidine deaminase (AID), and if increased AID is correlated with serum levels of autoantibodies and IL-17. The results of immunohistochemical staining showed that organized AID(+) germinal centres were observed in six of the 12 RA synovial samples, and AID(+) cells were found almost exclusively in the B-cell areas of these follicles. Aggregated but not organized lymphoid follicles were found in only one OA synovial sample without AID(+) cells. Significantly higher levels of AID mRNA (Aicda) detected by RT-PCR were found in the PBMCs from RA patients than PBMCs from normal controls (P < 0.01). In the PBMCs from RA patients, AID was expressed predominately by the CD10(+)IgM(+)CD20(+) B-cell population and the percentage of these cells that expressed AID was significantly higher than in normal controls (P < 0.01). AID expression in the PBMCs correlated significantly and positively with the serum levels of rheumatoid factor (RF) (P
19196728 Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthr 2010 Mar OBJECTIVES: Th17 cells are an effector T-cell population that plays a role in chronic inflammatory conditions and is dependent on IL-23 for their survival and expansion. More recently, a genetic association was discovered between polymorphisms in the gene coding for the IL-23 receptor and spondyloarthritis. This study aimed to evaluate the role of Th17-associated cytokines in spondyloarthritis pathogenesis by measuring their levels in the joints and circulation as well as correlating them with disease activity parameters. METHODS: Paired synovial fluid (SF), serum and synovial biopsies were obtained from 30 non-PsA (psoriatic arthritis) spondyloarthritis, 22 PsA and 22 rheumatoid arthritis (RA) patients. IL-17, IL-23 and CCL20 were measured by ELISA in the SF and serum of patients and correlated with systemic and local parameters of disease activity. RESULTS: Concentrations of CCL20, a major Th17-attracting chemokine, tended to be higher in the joints of RA than in spondyloarthritis patients. Interestingly, levels of CCL20 were markedly higher in SF as opposed to serum. In addition, there was a remarkable association between the expression of the Th17 cytokine system and the presence of intimal lining layer hyperplasia in RA. Also in the serum, there was a tendency for higher IL-23 levels in RA, which correlated strongly with disease activity parameters. CONCLUSIONS: Th17-related cytokines are expressed in joints of spondyloarthritis as well as RA patients. IL-23 levels, however, correlate with disease activity parameters in RA only. These results point towards a differential regulation of the Th17 cytokine system in spondyloarthritis compared with RA.
20553587 Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TEN 2010 INTRODUCTION: The single nucleotide polymorphism (SNP) rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster has been associated with rheumatoid arthritis (RA). Other variants within this cluster, including rs17388568 that is not in linkage disequilibrium (LD) with rs6822844, and rs907715 that is in moderate LD with rs6822844 and rs17388568, have been associated with a number of autoimmune phenotypes, including type 1 diabetes (T1D). Here we aimed to: one, confirm at a genome-wide level of significance association of rs6822844 with RA and, two, evaluate whether or not there were effects independent of rs6822844 on RA at the KIAA1109-TENR-IL2-IL21 locus. METHODS: A total of 842 Australasian RA patients and 1,115 controls of European Caucasian ancestry were genotyped for rs6822844, rs17388568 and rs907715. Meta-analysis of these data with published and publicly-available data was conducted using STATA. RESULTS: No statistically significant evidence for association was observed in the Australasian sample set for rs6822844 (odds ratio (OR)=0.95 (0.80 to 1.12), P=0.54), or rs17388568 (OR=1.03 (0.90 to 1.19), P=0.65) or rs907715 (OR=0.98 (0.86 to 1.12), P=0.69). When combined in a meta-analysis using data from a total of 9,772 cases and 10,909 controls there was a genome-wide level of significance supporting association of rs6822844 with RA (OR=0.86 (0.82 to 0.91), P=8.8x10(-8), P=2.1x10(-8) including North American Rheumatoid Arthritis Consortium data). Meta-analysis of rs17388568, using a total of 6,585 cases and 7,528 controls, revealed no significant association with RA (OR=1.03, (0.98 to 1.09); P=0.22) and meta-analysis of rs907715 using a total of 2,689 cases and 4,045 controls revealed a trend towards association (OR=0.93 (0.87 to 1.00), P=0.07). However, this trend was not independent of the association at rs6822844. CONCLUSIONS: The KIAA1109-TENR-IL2-IL21 gene cluster, that encodes an interleukin (IL-21) that plays an important role in Th17 cell biology, is the 20th locus for which there is a genome-wide (P
19690864 Fc receptor-like 3 -169 C/T polymorphism and RA susceptibility: a meta-analysis. 2010 May The Fc receptor-like 3 (FCRL3) -169 C/T polymorphism has been reported to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but with inconsistent results. The aim of this study was to explore whether the FCRL3 -169 C/T polymorphism confers susceptibility to RA and SLE. The authors conducted a random effect meta-analysis on the associations between the C/C (recessive effect) or C/C + C/T (dominant effect) genotype or the allele C of the FCRL3 -169 polymorphisms and RA or SLE in different populations. In total, 15 separate comparisons, 12 for RA and 3 for SLE, drawn from nine European and six Asian population samples were included in this meta-analysis. No association between RA and the FCRL3 C allele was found for all study subjects (OR = 1.064, 95% CI = 0.987-1.146, p = 0.107). However, stratification by ethnicity indicated that the FCRL3 C allele was significantly associated with RA in Asians (OR = 1.203, 95% CI = 1.097-31.319, p < 0.001). Conversely, no association was detected for this allele and RA in Europeans (OR = 0.997, 95% CI = 0.931-1.068, p = 0.933). The ORs for the C/C + C/T and C/C genotypes in these ethnic groups showed the same trends as the FCRL3 C allele. An association between SLE and the FCRL3 -169 A allele was found in all study subjects (OR = 1.115, 95% CI = 1.003-1.240, p = 0.043), but meta-analysis excluding studies with controls not in HWE did not show the association. This meta-analysis suggests that the FCRL3 -169 C/T polymorphism is a significant risk factor for RA in Asians, but not in Europeans.
20166872 The type I IFN system in rheumatoid arthritis. 2010 Apr Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterized by joint inflammation, immune cell infiltration of the synovia, and cartilage/bone destruction. Despite noteworthy progress in the treatment of RA in recent years, many patients remain refractory to current therapeutic strategies that target either the adaptive immune system or mediators of the innate system. Type I interferons (IFNs) play a significant role in regulation of the innate immune system, originally being discovered as part of intracellular immune defence against viral infection. IFNs are pleiotropic cytokines, mediating both immunostimulatory and immunosuppressive effects. IFN-alpha and beta have been detected in RA synovial fluid and tissue and subsequent therapeutic approaches using type I IFN in murine models of arthritis and in human RA have produced different and controversial results. Great interest has been directed toward principally plasmacytoid dendritic cells (pDCs), although also toward myeloid dendritic cells, as sources of type I IFN. Furthermore, manipulation of DC populations in murine RA models demonstrated that pDCs could suppress the development of arthritis and autoimmunity and may offer an attractive therapy for T-cell-mediated autoimmune diseases. Finally, dendritic cells (DCs) are vehicles for the delivery of therapeutic vaccines, and clinical trials are ongoing in RA with "tolerogenic" DC populations. Further, studies on animal models of RA will elucidate how IFN and DCs contribute to the establishment of autoimmune arthritis and the potential for manipulation of these cell populations and products to re-establish the immune tolerance.
20525329 TRPM3 channel stimulated by pregnenolone sulphate in synovial fibroblasts and negatively c 2010 Jun 4 BACKGROUND: Calcium-permeable channels are known to have roles in many mammalian cell types but the expression and contribution of such ion channels in synovial cells is mostly unknown. The objective of this study was to investigate the potential relevance of Transient Receptor Potential Melastatin 3 (TRPM3) channel to fibroblast-like synoviocytes (FLSs) of patients with rheumatoid arthritis. METHODS: The study used RT-PCR and immunofluorescence to detect mRNA and protein. Intracellular calcium measurement detected channel activity in a FLS cell-line and primary cultures of FLSs from patients with rheumatoid arthritis. Enzyme-linked immunosorbent assays measured hyaluronan. RESULTS: Endogenous expression of TRPM3 was detected. Previously reported stimulators of TRPM3 sphingosine and pregnenolone sulphate evoked sustained elevation of intracellular calcium in FLSs. The FLS cell-line showed an initial transient response to sphingosine which may be explained by TRPV4 channels but was not observed in FLSs from patients. Blocking antibody targeted to TRPM3 inhibited sustained sphingosine and pregnenolone sulphate responses. Secretion of hyaluronan, which contributes adversely in rheumatoid arthritis, was suppressed by pregnenolone sulphate in FLSs from patients and the effect was blocked by anti-TRPM3 antibody. CONCLUSIONS: The data suggest that FLSs of patients with rheumatoid arthritis express TRPM3-containing ion channels that couple negatively to hyaluronan secretion and can be stimulated by pharmacological concentrations of pregnenolone sulphate.
20650613 A prospective analysis of anti-desmoglein antibody profiles in patients with rheumatoid ar 2010 Sep BACKGROUND: Drug-induced pemphigus is mainly caused by drugs containing sulfhydryl (thiol) groups in their molecules. OBJECTIVES: To understand the serial alteration of anti-desmoglein (Dsg) antibody profile in patients with rheumatoid arthritis (RA) receiving thiol compounds. METHODS: Anti-Dsg1 or -Dsg3 antibodies were analysed twice in a 1.6-year interval, in the same series of RA patients. RESULTS: Eleven of 204 serum samples (5.4%) and 6 of 139 samples (4.3%) from the same RA group showed a positive reaction against Dsg1 or Dsg3 in the first and second screening tests, respectively. The positive rates were higher than those in patients with collagen diseases including systemic lupus erythematosus, Sjögren syndrome, mixed connective tissue disease, and systemic sclerosis. In comparison with the results in the first and second screening tests, one RA patient newly gained anti-Dsg3 antibody, and at least 4 patients lost the antibodies in 1.6 years. Three patients produced antibodies to Dsg1 and/or Dsg3 in a similar fashion as did in the first screening tests. Only one RA serum sample exhibited an intercellular reactivity to human skin or monkey esophagus by immunofluorescence, and another sample bound to a 130 kDa protein suggestive of Dsg3 by immunoblotting. Most anti-Dsg antibodies in RA patients recognized EDTA-resistant epitopes of Dsg different from EDTA-sensitive epitopes recognized by pemphigus sera. CONCLUSION: RA patients receiving any of the thiol compounds may gain autoantibodies to non-conformational epitopes of either Dsg1 or Dsg3, and that such autoantibodies alone are not capable of inducing acantholysis.
21068093 Prediction of MRI erosive progression: a comparison of modern imaging modalities in early 2011 Jan OBJECTIVES: To examine the associations between modern imaging modalities and joint damage measured as 1-year MRI erosive progression, in early rheumatoid arthritis (RA) patients. METHODS: 84 RA patients with disease duration of less than 1 year were included in this inception cohort. Patients were evaluated at baseline, 3, 6 and 12 months by core measures of disease activity, MRI and ultrasound grey-scale (USGS) of inflammation, conventional radiography and digital x-ray radiogrammetry (DXR) bone mineral density (BMD) of cortical hand bone. RESULTS: 53 of the 79 patients (67%) who completed the follow-up had MRI erosive progression (dependent variable). USGS and MRI bone marrow oedema (BME) were in multivariate analyses independent predictors of 1-year MRI erosive progression. There was a trend towards higher MRI synovitis score and 3-month DXR BMD loss in patients developing MRI erosions. On an individual level, USGS inflammation, MRI synovitis and MRI BME also somewhat better predicted outcome than rheumatoid factor, anticitrullinated protein antibodies and disease activity score 28. CONCLUSIONS: USGS inflammation and MRI BME were independent predictors of MRI erosive progression in early RA patients on a group level. The exact prognosis of the individual patients could not be determined by imaging alone.
21108178 Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for 2011 Jan Tocilizumab is a monoclonal antibody against human interleukin-6 receptor which blocks the binding of interleukin-6 to its receptor. Tocilizumab is effective for the treatment of inflammatory disorders including rheumatoid arthritis. We report a case of multiple ulcers in the small and large intestines, which occurred during tocilizumab therapy. A 57-year-old woman started to use tocilizumab for rheumatoid arthritis. Three months later, she complained of hematochezia. Double-balloon endoscopy revealed multiple small aphthoid ulcers in the small and large intestines. One month after the woman had recovered, she was given tocilizumab again. The woman had hematochezia and abdominal pain again 2 weeks later. Colonoscopy revealed multiple round, discrete punched-out ulcers in the terminal ileum, and vast deep ulcers from the cecum to the descending colon. Bioptic histopathology and cultivation showed non-specific findings. Six weeks after discontinuation of tocilizumab, ulcers in the small and large intestine dramatically improved, leaving ulcer scars. This disease course and the results of examination made us strongly suspect that tocilizumab induced multiple ulcers in the small and large intestines. Interleukin-6 is a pleiotropic cytokine and involved in intestinal mucosal wound healing as well as in inflammatory processes. It is possible that tocilizumab inhibited tissue repair of the intestine and caused intestinal ulcers.
20163024 [Two cases of tuberculosis after treatment of rheumatoid arthritis with infliximab]. 2010 Jan We report two cases of tuberculosis (TB) after treatment with infliximab (IFX) for rheumatoid arthritis (RA). The first case, a 69-year-old woman with RA, developed miliary TB with acute respiratory distress syndrome 21 months after initiation of IFX therapy. Sputum samples revealed smears and cultures positive for Mycobacterium tuberculosis and also positive polymerase chain reaction for TB (PCR-TB); in addition urine samples were smear-negative and culture-positive for TB. She was treated with corticosteroid pulse therapy and anti-tuberculosis drugs, and recovered. The second case, a 51-year-old man with RA, had had contact with a tuberculosis patient four years after initiation of IFX therapy. One year later, he developed pulmonary and pleural tuberculosis. Mycobacterium tuberculosis was detected in the bronchial lavage fluid and pleural effusion (smear-negative and culture- and PCR-TB positive). He clinically improved by treatment with anti-tuberculosis drugs. In both cases, the enzyme-linked immunosorbent spot (ELISPOT) tests revealed positive responses although the QuantiFERON TB-2G tests were not positive. We suggest that the ELISPOT test may be useful as a supportive diagnostic tool for tuberculosis in immunocompromised conditions including RA treated with a tumor necrosis factor-alpha (TNF-alpha) inhibitor.
19095171 Comparison of perioperative complications in patients with and without rheumatoid arthriti 2009 Jan Total elbow replacement is a well-recognized surgical treatment for patients with advanced rheumatoid arthritis (RA) of the elbow. At present, there is minimal literature outlining the perioperative complications associated with total elbow replacement. We endeavored to identify complication rates and hospital disposition differences between patients with and without RA who received a total elbow replacement. Data from the Nationwide Inpatient Sample was used to capture 3,617 patients who received a total elbow arthroplasty between 1988-2005. Of these, 888 had a primary diagnosis of RA and were compared against patients without RA. Analyses addressed perioperative complications and hospital disposition factors, such as charges and length of stay. Overall complication rates were very low with only 2 variables, respiratory complications (P = .01) and renal failure (P = .04) demonstrating significantly worse outcomes in patients without RA (P = .01). Patients without RA had also had longer lengths of stay (P < 0.01). There were 9 reported perioperative deaths. The findings suggest that the perioperative complications of a total elbow replacement for all patients studied are few and that outcomes in patients with RA are nearly equivalent to those in patients without RA.