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ID PMID Title PublicationDate abstract
23188202 Hearing impairment in a tertiary-care-level population of Mexican rheumatoid arthritis pat 2012 Dec OBJECTIVES: The objectives of this study were to assess characteristics of hearing impairment (HI) in Mexican Mestizo patients with rheumatoid arthritis. METHODS: One hundred thirteen consecutive patients (101 women, aged 43.3 ± 13.1 years) without previously identified HI diagnosis had a structured interview and complete rheumatic and audiologic evaluations, which included at least a pure-tone audiometry and standard and high-frequency tympanometry. Hearing impairment was defined if the average thresholds for at least 1 of low-, mid-, or high-frequency ranges were 25-dB hearing level or greater in 1 ear (unilateral) or both ears (bilateral). Hearing impairment was classified as mild or moderate/severe. Appropriate statistics, multivariate analysis, and receiver operating characteristic curves were used. RESULTS: Hearing impairment was detected in 27 patients (24%), was sensorineural-type HI in 25 (93%), bilateral in 14 (52%), and mild in 20 of them (74%). Normal tympanograms (type A) were found in 93 patients (82%), although high-frequency tympanometry was abnormal in 80 patients (71.4%). Patients with HI were significantly older (51.8 ± 14.1 vs. 40.7 ± 11.7 years, P ≤ 0.001), had more frequent rheumatoid nodules (37% vs. 12.8%, P = 0.001), and had more (median [range]) comorbidities per patient (2 [1-2] vs. 1 [0-2], P = 0.03). Multivariate analysis showed that HI was significantly associated to age (odds ratio, 1.1; 95% confidence interval, 1.03-1.15; P ≤ 0.001). The best cutoff level for HI was 50 years of age and increased to 59 years for moderate/severe HI. CONCLUSIONS: A significant proportion of Mexican Mestizo outpatients with rheumatoid arthritis had previously undiagnosed HI, mainly of sensorineural type, of mild severity, and bilateral. Older age was the only prognosticator of HI.
22467920 Treating rheumatoid arthritis to target: a Canadian physician survey. 2012 May OBJECTIVE: To assess agreement and application of Treat to Target (T2T) recommendations in Canadian practice. METHODS: A survey of Canadian rheumatologists was conducted on the recommendations of T2T, an international initiative toward reaching specific therapeutic goals in rheumatoid arthritis. Agreement with each recommendation was measured on a 10-point Likert scale (1 = fully disagree, 10 = fully agree). A 4-point Likert scale (never, not very often, very often, always) assessed application of each recommendation in current practice. Responders who answered "never" or "not very often" were asked whether they were willing to change their practice according to the particular recommendation. RESULTS: Seventy-eight rheumatologists responded (24% of the 330 who were contacted). The average agreement scores ranged from 6.92 for recommendation #5 (the frequency of measures of disease activity) to 9.10 for recommendation #10 (the patient needs to be involved in the decision-making process). A majority of participants indicated that they apply the T2T recommendations in their practice. Recommendations dealing with frequency of visits and the use of composite measures received the highest number of "never" or "not very often" responses. Busy practices and lack of confidence in composite outcome measures were the main reasons for objections to certain components of the recommendations. CONCLUSION: Although a majority of Canadian rheumatologists agreed with and supported the T2T recommendations, there was resistance toward specific aspects of these recommendations. Efforts are needed to better understand the reasons behind identified disagreements. Action plans to encourage the application of T2T recommendations in Canada are in development.
21722499 Greater remission rates in patients with early versus long-standing disease in biologic-na 2011 May OBJECTIVES: Current aim of rheumatoid arthritis (RA) treatment is to achieve remission in as many patients as possible. Rates of remission and clinical outcomes after treatment with abatacept in biologic-naive rheumatoid arthritis (RA) patients with early disease and an inadequate response to methotrexate (MTX) versus patients with ≥ 10 years of disease were assessed. METHODS: Data from two trials assessing the efficacy of abatacept in MTX inadequate responders were pooled for this exploratory post hoc analysis. Patients with disease duration of ≤ 2 years at baseline (early disease), originally assigned to an abatacept approximately 10 mg/kg treatment arm and entered into a long-term extension (LTE), were compared with patients with ≥ 10 years of disease (long-standing RA). Remission, DAS28-CRP, ACR 70 responses and the Routine Assessment of Patient Index Data 3 (RAPID3), improvement in physical function as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: Twenty-three percent of these patients (n=108) had early disease. A higher percentage of patients with early disease achieved DAS28-CRP remission versus patients with long-standing disease (35.2% vs. 19.4% at year 1, p<0.01; 46.0% vs. 30.9% at year 3, p<0.05). In addition, a higher percentage of the subgroup with early RA achieved ACR70 responses. More patients with early RA had a meaningful improvement in their HAQ-DI (75.2% vs. 60.4%; p<0.05) and RAPID3 scores at one year (mean changes from baseline of -9.6 vs. -8.1; p=0.009). CONCLUSIONS: These data provide additional support for the possible use of abatacept in biologic-naive patients who have had inadequate response to MTX, earlier in their disease course.
21467708 Fatal acute pancreatitis associated with reactive AA amyloidosis in rheumatoid arthritis w 2011 We report three cases of fatal pancreatitis associated with systemic AA amyloidosis in rheumatoid arthritis (RA). All of the patients showed end-stage renal failure, and hemodialysis was introduced during the course of treatment. Autopsy was performed on two of the three patients, and this revealed amyloid deposition on the vascular walls in the pancreas. It was strongly suggested that the acute pancreatitis in all three patients was attributable to deposition of amyloid in vascular and pancreatic tissues. Acute pancreatitis is considered to be a rare complication of end-stage amyloidosis associated with RA, and is frequently fatal. It is important to treat RA patients intensively to avoid such deposition of amyloid.
22881230 Novel adipokine fibroblast growth factor 21 is increased in rheumatoid arthritis. 2012 Fibroblast growth factor-21 (FGF-21) has been recently characterized as a new adipokine. The aim of this study was to assess FGF-21 levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationship between FGF-21, disease activity and metabolic status. The levels of FGF-21 in serum and synovial fluid samples from 38 patients with RA and 42 control individuals with OA were determined by ELISA. Patients were assessed for disease activity using the disease activity score (DAS28), a serum glucose and lipid profile. Age, sex and BMI-adjusted FGF-21 levels in the serum (p=0.024) and synovial fluid (p=0.010) samples were significantly higher in patients with RA when compared with OA. The levels of FGF-21 in the serum significantly correlated with the levels in the synovial fluid. Serum and synovial fluid FGF-21 levels adjusted for confounders correlated positively with C-reactive protein. The levels of FGF-21 were positively correlated with BMI in patients with RA; however, the levels were not associated with disease activity or lipid profiles. Furthermore, serum FGF-21 levels were significantly higher in seropositive compared with seronegative RA patients. This work shows that patients with seropositive RA have increased levels of FGF-21. The results suggest that FGF-21 is related to BMI but not disease activity or lipid profiles in patients with RA.
21949702 PTPN22 1858C>T polymorphism distribution in Europe and association with rheumatoid arthrit 2011 OBJECTIVE: The PTPN22 rs2476601 polymorphism is associated with rheumatoid arthritis (RA); nonetheless, the association is weaker or absent in some southern European populations. The aim of the study was to evaluate the association between the PTPN22 rs2476601 polymorphism and RA in Italian subjects and to compare our results with those of other European countries, carrying out a meta-analysis of European data. METHODS: A total of 396 RA cases and 477 controls, all of Italic ancestry, were genotyped for PTPN22 rs2476601 polymorphism. Patients were tested for autoantibodies positivity. The meta-analysis was performed on 23 selected studies. RESULTS: The PTPN22 T1858 allele was significantly more frequent in RA patients compared to controls (5.7% vs. 3.7%, p = 0.045). No clear relationship arose with the autoantibodies tested. The 1858T allele frequency in Italian RA patients was lower than the one described in northern European populations and similar to the frequency found in Spain, Turkey, Greece, Tunisia. A clear-cut North-South gradient arose from the analysis. CONCLUSIONS: The PTPN22 T1858 allele is associated with RA in the Italian population. A North-South gradient of the allele frequency seems to exist in Europe, with a lower prevalence of the mutation in the Mediterranean area.
22166255 Aggressive therapy in patients with early arthritis results in similar outcome compared wi 2012 Apr OBJECTIVE: To compare the effects of aggressive tight control therapy and conventional care on radiographic progression and disease activity in patients with early mild inflammatory arthritis. METHODS: Patients with two to five swollen joints, Sharp-van der Heijde radiographic score (SHS) <5 and symptom duration ≤2 years were randomized between two strategies. Patients with a definite non-RA diagnosis were excluded. The protocol of the aggressive group aimed for remission (DAS < 1.6), with consecutive treatment steps: MTX, addition of adalimumab and combination therapy. The conventional care group followed a strategy with traditional DMARDs (no prednisone or biologics) without DAS-based guideline. Outcome measures after 2 years were SHS (primary), remission rate and HAQ score (secondary). RESULTS: Eighty-two patients participated (60% ACPA positive). In the aggressive group (n = 42), 19 patients were treated with adalimumab. In the conventional care group (n = 40), 24 patients started with hydroxychloroquin (HCQ), 2 with sulfasalazine (SSZ) and 14 with MTX. After 2 years, the median SHS increase was 0 [interquartile range (IQR) 0-1.1] and 0.5 (IQR 0-2.5), remission rates were 66 and 49% and HAQ decreased with a mean of -0.09 (0.50) and -0.25 (0.59) in the aggressive and conventional care group, respectively. All comparisons were non-significant. CONCLUSION: In patients with early arthritis of two to five joints, both aggressive tight-control therapy including adalimumab and conventional therapy resulted in remission rates around 50%, low radiographic damage and excellent functional status after 2 years. However, full disease control including radiographic arrest in all patients remains an elusive target even in moderately active early arthritis. Trial registration. Dutch Trial Register, http://www.trialregister.nl/, NTR 144.
22806421 Long-term therapeutic effects and safety of tacrolimus added to methotrexate in patients w 2013 Apr To assess the long-term safety and efficacy of tacrolimus (TAC) used in combination with oral methotrexate (MTX) in patients with rheumatoid arthritis (RA) whose disease remains active despite treatment with MTX alone. The clinical courses of 24 RA patients who received TAC added to MTX from a single center were analyzed retrospectively. The disease activity was evaluated by the DAS28-ESR(3) every 12 months after the addition of TAC, and side effects were evaluated for 3 years. At 3 years after starting the treatment, TAC was still being used by 19 patients (79 %). The causes of discontinuation were an inadequate response (3 cases), oral ulcers and elevation of creatinine (1 case), and worsening of interstitial pneumonia (1 case). No death was registered. The DAS28-ESR(3) was decreased from 4.81 to 3.41 after 3 years of treatment. The doses of prednisolone were decreased from 5.1 mg/day to 3.2 mg/day after 3 years. In patients whose active RA persists despite treatment with MTX, TAC in combination with MTX is safe and well tolerated and provided clinical benefit for a long time in this single-center retrospective study. Further studies are required to confirm the safety and efficacy of this combination therapy.
21288417 High rate of osteolytic lesions in medium-term followup after the AES total ankle replacem 2011 Feb BACKGROUND: Some previous studies have shown a high percentage of early-onset and rapidly progressing osteolysis associated with total ankle arthroplasty (TAA) by the Ankle Evolutive System (AES). The purpose of our study was to analyze medium-term results at our institution. MATERIALS AND METHODS: Altogether 38 TAAs using AES prostheses were carried out between 2003 and 2007. Diagnoses were rheumatoid arthritis (71%), post-traumatic and idiopathic osteoarthritis (29%). The mean age was 54 years, followup 28 months. Tibial and talar components had hydroxyapatite coating on metal (Co-Cr) components (HA-coated). Since 2005 the design was changed and components were porous coated with titanium and hydroxyapatite (dual-coated). RESULTS: Two-year survival was 79% (95% CI: 56 to 98). At followup 34 (89%) primary tibial and talar components were preserved. In 19 (50%) TAAs osteolysis (more than or equal to 2 mm) occurred in the periprosthetic bone area and in nine (24%) comprised large "cyst-like osteolysis''. In HA-coated prostheses radiolucent lines (less than or equal to 2 mm) or osteolysis (more than or equal to 2 mm) were detected in 11 (100%) cases and in dual-coated prostheses in 19 (74%) (p = 0.08). On the other hand there was more large "cyst-like osteolysis'' around the dual-coated prosthesis and lesions were larger (p = 0.017). In rheumatoid arthritis osteolysis was detected in 14 (52%) and large "cyst-like osteolysis'' in seven (26%) prostheses and in the group of traumatic and idiopathic osteoarthritis in six (55%) and two (18%), respectively. CONCLUSION: This study showed a high frequency of osteolysis in medium-term followup after the AES ankle replacement. The outcome was not sufficiently beneficial and we have discontinued use of this prosthesis.
22177419 Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated wit 2011 INTRODUCTION: As a group, rheumatoid arthritis (RA) patients exhibit increased risk of infection, and those treated with anti-tumor necrosis factor (TNF) therapy are at further risk. This increased susceptibility may result from a compromised humoral immune response. Therefore, we asked if short-term effector (d5-d10) and memory (1 month or later) B cell responses to antigen were compromised in RA patients treated with anti-TNF therapy. METHODS: Peripheral blood samples were obtained from RA patients, including a subset treated with anti-TNF, and from healthy controls to examine influenza-specific responses following seasonal influenza vaccination. Serum antibody was measured by hemagglutination inhibition assay. The frequency of influenza vaccine-specific antibody secreting cells and memory B cells was measured by EliSpot. Plasmablast (CD19+IgD-CD27hiCD38hi) induction was measured by flow cytometry. RESULTS: Compared with healthy controls, RA patients treated with anti-TNF exhibited significantly decreased influenza-specific serum antibody and memory B cell responses throughout multiple years of the study. The short-term influenza-specific effector B cell response was also significantly decreased in RA patients treated with anti-TNF as compared with healthy controls, and correlated with decreased influenza-specific memory B cells and serum antibody present at one month following vaccination. CONCLUSIONS: RA patients treated with anti-TNF exhibit a compromised immune response to influenza vaccine, consisting of impaired effector and consequently memory B cell and antibody responses. The results suggest that the increased incidence and severity of infection observed in this patient population could be a consequence of diminished antigen-responsiveness. Therefore, this patient population would likely benefit from repeat vaccination and from vaccines with enhanced immunogenicity.
22507725 Total elbow replacement with the Coonrad-Morrey prosthesis: our medium to long-term result 2012 Apr INTRODUCTION: Semiconstrained total elbow replacement is now a well recognised and reliable surgical option for advanced elbow disease, mainly rheumatoid arthritis. METHODS: We report a retrospective analysis of 31 primary total elbow replacements in 28 patients with a mean follow-up duration of 55 months. The mean age of the patients was 65 years. The indications included 27 cases of rheumatoid arthritis, 3 fractures and 1 case of osteoarthritis. Twenty-one elbows in nineteen patients were assessed using the Mayo elbow performance score (MEPS) in a special follow-up clinic. In the other nine patients (ten elbows), the assessment was carried out with case notes and x-rays. RESULTS: The mean pre-operative MEPS in the 21 elbows recalled was 40. This improved to 89 post-operatively (range: 55-100). Sixteen of the twenty-one elbows were considered excellent, two good, two fair and one poor. The range of movement was recorded in eight of the other ten elbows and the mean was 98°. At the last follow-up visit, x-rays were normal in 23 elbows although the ulnar component was loose in 3, the humeral component loose in 2. There were also two cases of non-union of the medial epicondyle and one patient had mild heterotopic ossification. Complications included one infection, which needed irrigation and debridement with a satisfactory final result, and two cases of ulnar nerve palsy/neurapraxia. Two elbows were considered failures due to severe pain caused by prosthetic loosening. These were referred for revision surgery. CONCLUSIONS: Excellent pain relief and good function can be achieved in the medium and long term with the Coonrad-Morrey-semiconstrained total elbow replacement prosthesis in patients with severe destructive elbow arthropathy.
21617554 Double-blind, randomized, controlled, pilot study comparing classic ayurvedic medicine, me 2011 Jun OBJECTIVE: To compare classic Ayurveda, methotrexate (MTX), and their combination in a double-blind, randomized, double-dummy, pilot trial in rheumatoid arthritis (RA) for 36 weeks. METHODS: Forty-three seropositive RA patients by American College of Rheumatology (ACR) criteria with disease duration of less than 7 years were assigned to the following treatment groups: MTX plus Ayurvedic placebo (n = 14), Ayurveda plus MTX placebo (n = 12), or Ayurveda plus MTX (n = 17). Outcomes included the Disease Activity Score (DAS28-CRP), ACR20/50/70, and Health Assessment Questionnaire--Disability Index. All measures were obtained every 12 weeks for 36 weeks. Analyses included descriptive statistics, analysis of variance, χ², or Student t test. The unique features of this study included the development of placebos for each Ayurvedic pharmacological dosage form and individualization of Ayurvedic therapy. RESULTS: All groups were comparable at baseline in demographics and disease characteristics. There were no statistically significant differences among the 3 groups on the efficacy measures. ACR20 results were MTX 86%, Ayurveda 100%, and combination 82%, and DAS28-CRP response were MTX -2.4, Ayurveda -1.7, and combination -2.4. Differences in adverse events among groups were also not statistically significant, although the MTX groups experienced more adverse event (MTX 174, Ayurveda 112, combination 176). No deaths occurred. CONCLUSIONS: In this first-ever, double-blind, randomized, placebo-controlled pilot study comparing Ayurveda, MTX, and their combination, all 3 treatments were approximately equivalent in efficacy, within the limits of a pilot study. Adverse events were numerically fewer in the Ayurveda-only group. This study demonstrates that double-blind, placebo-controlled, randomized studies are possible when testing individualized classic Ayurvedic versus allopathic treatment in ways acceptable to western standards and to Ayurvedic physicians. It also justifies the need for larger studies.
22068352 Antibodies to mutated citrullinated vimentin in patients with chronic hepatitis C virus ge 2012 Nov One of the extra-hepatic manifestations of hepatitis C virus (HCV) infection is polyarthritis that mimics rheumatoid arthritis (RA). Anti-mutated citrullinated vimentin (MCV) was recently introduced in the diagnostic workup of RA, but its exact role in HCV infection and its related arthropathy is still unclear. The aim of the study is to determine the prevalence of anti-MCV antibodies in HCV-infected patients with or without articular involvement, and to investigate whether anti-MCV antibodies have an additional role to anticyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) in differentiating patients with RA from patients with HCV-related arthropathy. Fifty-five HCV-infected patients (HCV RNA positive) and 30 RA patients (fulfilling the American College of Rheumatology classification criteria for RA and negative for HCV) were included. Anti-MCV antibodies, anti-CCP antibodies, RF and cryoglobulins were measured. Articular involvement in hepatitis C patients was evaluated. Articular involvement was detected in 30/55 (54.5%) of HCV-infected patients. The most frequent pattern was symmetric polyarthralgias and the most frequent joints to be involved were the wrists, metacarpophalangeal joints, shoulders and knees. In HCV arthropathy, anti-MCV was positive in 9/30 (30%), anti-CCP in 0% and RF in 22/30 (73.3%). Whereas, in chronic HCV without arthropathy, anti-MCV was positive in 8 patients (32%), anti-CCP in one patient (4%) and RF in 23/25 (92.0%). There was no significant difference between the two HCV groups as regards the frequencies of anti-MCV (P = 0.89), anti-CCP (P = 0.93) and RF (P = 0.15). In RA, anti-MCV was positive in 93.3% anti-CCP in 96.7% and RF in 86.7%. There was no significant difference in RF between RA and HCV arthropathy (P = 0.33). Meanwhile, there was a highly significant difference between both groups regarding anti-MCV and anti-CCP (P < 0.0001 for each). The sensitivity of anti-MCV, anti-CCP and RF for RA was 93.3, 96.7 and 86.7%, respectively. Whereas their specificity was 69.1, 98.2 and 18.2%, respectively. In addition, the mean levels of anti-MCV and anti-CCP were significantly increased in RA than in all HCV patients (P = 0.038 and P < 0.0001, respectively). Meanwhile, there were no significant differences in mean levels of anti-MCV and anti-CCP between HCV patients with arthropathy and those without arthropathy (P = 0.11 and P = 0.73, respectively). Also, there were no differences in mean RF between both HCV groups. There was a significant positive correlation between anti-MCV and anti-CCP levels in patients with HCV-related arthropathy (r = 0.39, P = 0.032) and in those without arthropathy (r = 0.578, P = 0.002). Cryoglobulins were detected in 7/30 HCV-related arthropathy (23.3%) and were positively correlated with anti-MCV(r = 0.485, P = 0.007). Anti-CCP still attains the major role in differentiating RA from HCV arthropathy. Anti-MCV seems to play no additional role in this aspect. The role of mutation of vimentin in the pathogenesis of HCV arthropathy is not as clear as it is for RA and needs further investigation.
22507342 Similar serum levels of IL-6 and its soluble receptors in patients with HCV-related arthri 2012 Jan The high serum levels of Interleukin-6 (IL-6) and its soluble receptors (sIL-6r and sgp130), described in the course of Rheumatoid Arthritis (RA), have been linked to the enhanced activity of this cytokine in this disorder. In this study, the serum concentrations of IL-6 and its soluble receptors were determined in a group of patients with HCV-related arthritis (HCVrA), a condition resembling RA in several aspects, and then compared to those found in a sample of subjects affected by RA. Twenty-one patients with HCVrA, 24 patients with RA and 20 healthy subjects (control group) were examined. Different ELISA methods were used for determination of serum concentrations of IL-6, sIL-6r and sgp130. Increased IL-6 serum levels were found in 15 (71 %) of the patients with HCVrA and in 16 (62 %) of those with RA. Eight (38 %) of the patients with HCVrA and 11 (46%) of those with RA denoted high levels of sIL-6r, while sgp130 levels were elevated in 21 (76%) of the patients with HCVrA and in 16 (69%) of those with RA. A significant difference between the median values of sIL-6r and sgp130 levels in the two groups of patients versus controls was found. A mild correlation of these parameters with RF levels was detected in the RA group. Furthermore, in HCVrA patients the serum levels of IL-6, sIL-6r and sgp130 appeared unrelated to HCV viraemia and to levels of transaminases. The enhanced serum levels of IL-6 in HCVra patients indicate an increased synthesis and hyperactivity of this cytokine in HCVrA, and the substantial similarity of the behaviour of IL-6 and its serum receptors in the two groups of patients suggests common mechanisms with RA, in which the function of I L-6 is central.
21460598 Epigenetics and autoimmunity, with special emphasis on methylation. 2011 Epigenetics signifies stable and heritable changes in gene expression without changes in the genetic code. There is a wealth of emerging evidence for such processes in promoting autoimmunity. The first clue is that inhibition of DNA methyl transferases (DNMTs) induces systemic lupus erythematosus (SLE) in animals. Similar immune-mediated disorders have been generated by injecting normal T cells incubated with DNMT inhibitors into healthy mice. Further, monozygotic twins display differences in DNA methylation that parallel discordances in SLE. Moreover, defects in DNA methylation characterize lymphocytes from SLE, synoviocytes from rheumatoid arthritis, and neural cells from multiple sclerosis patients. It has also been shown that DNA hypomethylation of T and B cells correlates with reduced DNMT efficacy and histone acetylation in SLE. Once a gene promoter has been demethylated, the gene recovers its capacity to be transcribed, e.g., genes for cytokines, activation receptors on cells, and endogenous retroviruses. This outcome has been associated with a blockage of the Erk pathway and/or a growth arrest at the G0/G1 interface of the cell cycle. Of importance is the fact that these changes can be reversed. For example, blockade of the interleukin-6 autocrine loop in SLE B cells restores DNA methylation status, thus opening new perspectives for therapy.
20724311 Multinational evidence-based recommendations on how to investigate and follow-up undiffere 2011 Jan OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.
22185187 Tuberculous scleritis in a patient with rheumatoid arthritis. 2012 Feb Scleritis is an ocular inflammatory disorder commonly associated with systemic autoimmune diseases. We report a case of nodular scleritis with an etiological diagnosis of tuberculosis wherein diagnosis was possible only after histopathological examination of the enucleated eye. METHOD OF STUDY: A 52 year female patient was referred as a case of nodular scleritis not responding to topical and oral anti-inflammatory agents. She was being treated with immunosuppressives for rheumatoid arthritis by her rheumatologist. Scleritis improved initially but worsened in few months with development of complications. Eye was enucleated and histopathological examination revealed tuberculous bacilli in retinal pigment epithelial cells. CONCLUSION: Infective scleritis should be suspected in cases of scleritis which progress despite treatment. Reactivation of latent Mycobacterium tuberculosis may occur especially in patients on long term systemic immunosuppressive treatment. Early detection and aggressive treatment is necessary for preventing morbidity or mortality due to these infections.
21593236 Distinct effects of anti-tumor necrosis factor combined therapy on TH1/TH2 balance in rheu 2011 Jul The immune balance in patients with rheumatoid arthritis (RA), a disease characterized by TH1 dominance, treated by the preferred combined anti-tumor necrosis factor (anti-TNF) and methotrexate (MTX) therapy was evaluated by assessing the chemokine and cytokine receptors as well as apoptosis induction. A meta-analysis of combined therapy by TNF blockers and MTX in 15 RA patients, MTX monotherapy in 20 RA patients, and 11 diagnosed but untreated RA patients was performed by assessing several immune markers in the whole lymphocyte population, as well as in specific CD4 cells, by both flow cytometry and image analysis. A significant downregulation of CXCR3 and IL-12 receptors (both TH1 markers) and a significant increase in the chemokine receptor CCR4 and, to a lesser extent, IL-4R (both TH2 markers) were found; a particularly marked increase was found in patients treated by combined therapy. This phenomenon was pronounced in CD4 cells and was accompanied by a high proportion of apoptotic cells. The therapeutic effect of MTX and TNF blockers may be due to apoptosis induction in lymphocytes infiltrating from the inflammation site and restoring the TH1/TH2 balance.
21916920 IgG rheumatoid factors against the four human Fc-gamma subclasses in early rheumatoid arth 2012 Jan Rheumatoid factor (RF), i.e. a family of autoantibodies against the Fc part of IgG, is an important seromarker of rheumatoid arthritis (RA). Traditional particle agglutination without disclosing the antibody isotype remains the predominating diagnostic method in clinical routine. Although IgG-RF attracts pathogenic interest, its detection remains technically challenging. The present study aimed at developing a set of tests identifying IgG-RFs directed against the four IgG subclasses. IgG-RF against either subclass of human IgG-Fc were analysed with four novel enzyme-linked immunosorbent assays (ELISAs) utilizing four recombinant human Fc-gamma fragments (hIgG1-4) as sources of antigen. Sera from 40 patients with recent onset RA (20 seropositive and 20 seronegative by IgM-RF and IgA-RF-isotype-specific ELISA) were analysed. Sera from 20 healthy blood donors served as reference. Among the IgM-/IgA-RF-positive RA-sera, IgG-RF was found directed against hIgG1 and hIgG2, but not against hIgG3 or hIgG4. Significant correlations were seen between IgG-RF against hIgG2-Fc and IgM-RF (r = 0.666) levels. Further prospective studies are warranted to elucidate any correlation to disease course and outcome.
22875826 The outsiders: emerging roles of ectonucleotidases in inflammation. 2012 Aug 8 Research on the biological roles of ectonucleoidases has revealed that CD73, an ecto-5 nucleotidase, plays a special role in the extracellular conversion of adenosine monophosphate to adenosine--specifically, as a checkpoint that determines whether the extracellular environment is proinflammatory (characterized by adenosine 5'-triphosphate-mediated responses) or anti-inflammatory (adenosine-mediated responses). Inactivating or inhibiting CD73 attenuates the extracellular formation of adenosine, exacerbating the severity of various inflammatory diseases. In this issue of Science Translational Medicine, Flögel and colleagues showed that CD73 can be pharmacologically exploited to convert an inactive adenosine precursor to an active, anti-inflammatory adenosine analog. In addition to attenuating inflammation associated with collagen-induced arthritis in a mouse model, this prodrug approach was site-selective, because the metabolic conversion relies on CD73, which is up-regulated in the inflammatory locus (the joint).