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ID PMID Title PublicationDate abstract
21324345 Basic aminopeptidase activity is an emerging biomarker in collagen-induced rheumatoid arth 2011 Apr 11 The objective of this study was to investigate the catalytic activity of basic aminopeptidase (APB) and its association with periarticular edema and circulating tumor necrosis factor (TNF)-alpha and type II collagen (CII) antibodies (AACII) in a rat model of rheumatoid arthritis (RA) induced by CII (CIA). Edema does not occur in part of CII-treated, even when AACII is higher than in control. TNF-alpha is detectable only in edematous CII-treated. APB in synovial membrane is predominantly a membrane-bound activity also present in soluble form and with higher activity in edematous than in non-edematous CII-treated or control. Synovial fluid and blood plasma have lower APB in non-edematous than in edematous CII-treated or control. In peripheral blood mononuclear cells (PBMCs) the highest levels of APB are found in soluble form in control and in membrane-bound form in non-edematous CII-treated. CII treatment distinguishes two categories of rats: one with arthritic edema, high AACII, detectable TNF-alpha, high soluble and membrane-bound APB in synovial membrane and low APB in the soluble fraction of PBMCs, and another without edema and with high AACII, undetectable TNF-alpha, low APB in the synovial fluid and blood plasma and high APB in the membrane-bound fraction of PBMCs. Data suggest that APB and CIA are strongly related.
21833530 Is Still's disease still one disease? A case of Adult-onset Still's disease showing accumu 2012 Aug Adult-onset Still's disease (AOSD) is known as a systemic inflammatory disease of unknown etiology and pathogenesis, characterized by fever, skin eruptions, systemic organ involvement, and arthralgias. AOSD is difficult to diagnose because of its heterogeneous clinical manifestations and prevalence (although more prevalent in the young, onset of AOSD after the age of 60 has also been described), and absence of pathognomonic clinical features. The disease also lacks a specific diagnostic test. To date, association studies between AOSD and HLA loci have failed to indentify a genetic predisposition. The recent publication of entirely different PET-CT manifestations found in three patients who were supposed to have the same disease (AOSD), as well as the surprisingly different PET-CT images of our AOSD patient (accumulation in the carotids and large vessels of the legs), raises our suspicion that AOSD is actually not one entity but a constellation of disorders whose varying underlying pathologies are now being revealed by new imaging techniques.
22115327 Annual costs of tumor necrosis factor inhibitors using real-world data in a commercially i 2012 OBJECTIVE: To calculate annual cost per treated patient of tumor necrosis factor (TNF) inhibitors etanercept, adalimumab, and infliximab for common approved indications, based on actual TNF-inhibitor use in clinical practice. METHODS: Adults with ≥1 claim for etanercept, adalimumab, or infliximab between January 2005 and March 2009 were identified from the IMS LifeLink™ Health Plan Claims Database. Patients new to therapy or continuing therapy (i.e., a prior claim for a TNF-inhibitor) were analyzed separately. Included patients had been enrolled from 180 days before the first TNF-inhibitor claim (index date) through 360 days after the index date and had a diagnosis during the pre-index period for rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Patients with Crohn's disease, ulcerative colitis, or juvenile idiopathic arthritis were excluded. Annual costs were calculated using wholesale acquisition costs for the TNF-inhibitor and Medicare Physician Fee Schedule for drug administration. Costs from restarting or switching TNF-inhibitor therapy during the first year were included. RESULTS: A total of 27,704 patients (11,528 new, 16,176 continuing) had claims for etanercept, adalimumab, or infliximab, most commonly (65%) for treatment of rheumatoid arthritis. The most commonly used agent was etanercept (14,777 patients; 53%), followed by adalimumab (6862 patients; 25%) and infliximab (6065 patients; 22%). Annual cost per treated patient was etanercept $14,873, adalimumab $17,766, and infliximab $21,256 across all indications. Annual cost per treated patient by disease was (etanercept/adalimumab/infliximab): rheumatoid arthritis ($14,314/$17,700/$20,390), psoriasis ($17,182/$17,682/$23,935), psoriatic arthritis ($15,030/$18,483/$24,974), and ankylosing spondylitis ($14,254/$16,925/$23,056). New and continuing patients showed similar results, with etanercept having the lowest costs. LIMITATIONS: This analysis is limited to three TNF-inhibitors and a US managed-care population. CONCLUSIONS: Based on this analysis of real-world use of TNF-inhibitors among patients in nationwide clinical practice settings, the annual TNF-inhibitor cost per treated patient was lowest for etanercept across all indications.
22392992 Chemokine receptor CXCR3 agonist prevents human T-cell migration in a humanized model of a 2012 Mar 20 The recruitment of T lymphocytes during diseases such as rheumatoid arthritis is regulated by stimulation of the chemokine receptors expressed by these cells. This study was designed to assess the potential of a CXCR3-specific small-molecule agonist to inhibit the migration of activated human T cells toward multiple chemokines. Further experiments defined the molecular mechanism for this anti-inflammatory activity. Analysis in vitro demonstrated agonist induced internalization of both CXCR3 and other chemokine receptors coexpressed by CXCR3(+) T cells. Unlike chemokine receptor-specific antagonists, the CXCR3 agonist inhibited migration of activated T cells toward the chemokine mixture in synovial fluid from patients with active rheumatoid arthritis. A humanized mouse air-pouch model showed that intravenous treatment with the CXCR3 agonist prevented inflammatory migration of activated human T cells toward this synovial fluid. A potential mechanism for this action was defined by demonstration that the CXCR3 agonist induces receptor cross-phosphorylation within CXCR3-CCR5 heterodimers on the surface of activated T cells. This study shows that generalized chemokine receptor desensitization can be induced by specific stimulation of a single chemokine receptor on the surface of activated human T cells. A humanized mouse model was used to demonstrate that this receptor desensitization inhibits the inflammatory response that is normally produced by the chemokines present in synovial fluid from patients with active rheumatoid arthritis.
27790015 Goals for rheumatoid arthritis: treating to target or treating to prevent? 2012 Although treat-to-target goals for rheumatoid arthritis (RA) have been well-established through several guidelines in recent years, concerns regarding treat-to-prevent goals for RA remain unclear. RA patients are typically subjected to over- or under-treatment because it is difficult for clinicians to determine the prognosis of RA patients. This typically results in failure to select and identify patient subsets that should receive monotherapy or combination therapy to treat early RA. Understanding treat-to-prevent goals, as well as unfavorable prognoses, risk factors, and prediction methods for RA, is therefore critical for making treatment decisions. Rapid radiographic progression plays a central role in contributing to other composite RA indices, so this may be the best method for defining treat-to-prevent goals for RA. Accordingly, risk factors of rapid radiographic progression have been defined and two prediction models were retrospectively derived based on clinical trial data. Additional studies are required to develop risk models that can be used for accurate predictions.
22622610 Patient's perception of quality patient--provider communication. 2012 May PURPOSE: To develop a model of patients' perception of quality patient-healthcare provider communication. METHODS/SAMPLE: Fifteen patients with rheumatoid arthritis participated in in-depth, audiorecorded interviews. Following transcription verification, interviews were analyzed using constant comparative analysis to identify primary themes and develop a model of patients' perception of quality patient-healthcare provider communication. FINDINGS: The participants described a multifaceted, dynamic process of quality patient-healthcare provider communication involving the interrelationship between appropriate time and 4 key communication exchanges: patient honesty when explaining symptoms, patients asking questions and offering opinions, healthcare providers asking questions and offering opinions, and healthcare providers disseminating information. CONCLUSION: By understanding patient-healthcare provider communication from the patient perspective within the rubric of this model, healthcare providers can adapt interactions with patients with rheumatoid arthritis to incorporate dimensions of the exchange that their patients feel create effective communication.
21841737 [Synovial lipoma arborescens]. 2011 Apr Synovial lipoma arborescens is a rare and benign intra-articular pathology, of unknown etiology, characterized by a villous and lipomatous proliferation of synovial tissue. It presents with atypical clinical manifestations, usually located in the knee, represented as recurrent joint effusions and painless swelling joint. The magnetic resonance is the most specific test and can often even avoid the synovial biopsy. We related the case of a female patient with mechanical pain in the knee with indolent evolution for 18 years, clinical and radiological compatible with osteoarthritis. With the finding of a localized unilateral increase of the suprapatellar bursa without perceptible joint effusion and ultrasonographic aspect of an exuberant nodular synovitis, the possibility of villonodular pigmented synovitis had to be discarded by synovial biopsy. Even after this procedure, her diagnosis was not clear, being reported to rheumatology evaluation due to histopathology findings confused with rheumatoid arthritis. The set of clinical, laboratory, magnetic resonance and histological review of synovial tissue confirmed the diagnosis of synovial lipoma arborescens, excluding the possibility of rheumatoid arthritis.
21629480 Spontaneous rupture of the extensor pollicis longus tendon in a tailor. 2011 Jun A spontaneous rupture of the extensor pollicis longus (EPL) tendon is associated with rheumatoid arthritis, fractures of the wrist, systemic or local steroids and repetitive, and excessive abnormal motion of the wrist joint. The authors encountered a case of a spontaneous rupture of the EPL tendon. The patient had no predisposing factors including trauma or steroid injection. Although the patient had a positive rheumatoid factor, he did not demonstrate other clinical or radiological findings of rheumatoid arthritis. During surgery, the EPL tendon was found to be ruptured at the extensor retinaculum (third compartment). Reconstruction of the extensor tendon using the palmaris longus tendon was performed. At the 18-month follow-up, the patient showed satisfactory extension of the thumb and 40° extension and flexion at the wrist.
22771273 Frequency of complications and usefulness of the minor salivary gland biopsy. 2012 Sep Findings of specific antibodies and histopathology data are essential for the diagnosis of Sjögren syndrome (SS). Although the minor salivary gland biopsy (MSGB) is technically simple, it needs to be performed in a medical institution to avoid complications. OBJECTIVE: To determine the frequency of complications and the usefulness of this technique. MATERIALS AND METHODS: Patients who underwent a minor salivary gland biopsy for a possible diagnosis of SS at Rivadavia Hospital between October 2007 and May 2010 where included. The patients were seen a week and a month after the procedure for follow up. RESULTS: Frequency of acute complications (n=186): 15 patients; 8.1%, 95% CI: 4.7-13.2 (Bleeding 7.5%, syncope 3.2%, hematoma 2.7%. No accidents occurred). Medium term complications (n=164): 16 patients: 9.75%, 95% CI: 5.9-15.6 (pain 7.32%, inflammation 3.66%, sensitivity disorders 3.05%, granuloma 1.22%,). No infections or suture dehiscence occurred. Microscopic results: 154 biopsy reports were received: glandular 90.9%, 95% CI: 85-95 (typical, sialadenitis, grade III and IV infiltration). CONCLUSIONS: MSGB has very low frequency of medium term and acute complications and it has high usefulness.
22567482 Pseudoseptic arthritis: a case series and review of the literature. 2011 Purpose. Pseudoseptic arthritis is an acute inflammatory monoarthritis with a sterile synovial gram stain and culture. Pseudoseptic arthritis has been previously described in the literature in a variety of settings including rheumatoid arthritis and microcrystalline disease. Despite pseudoseptic arthritis being a described entity, there is little published data on this topic with no published reports since 1992. Methods. This paper was a retrospective chart review over a 20-year period that identified all rheumatology inpatient consultations at our tertiary rural hospital for pseudoseptic arthritis. Results. We identified 10 patients with pseudoseptic arthritis and presented 5 of those cases in this paper. Majority of these patients had known autoimmune inflammatory arthritis or microcrystalline inflammatory arthritis. Conclusion. Pseudoseptic arthritis is a syndrome that should be in the differential diagnosis with patients with long standing inflammatory condition who present with an acute monoarthritis with no known bacterial source for septic arthritis.
22772886 [Rheumatic joint disease in childhood and adolescence ]. 2012 Jul Rheumatic joint disease in childhood and adolescence is relatively rare. In the general population, 1 child with juvenile arthritis accounts for 100 adult patients with rheumatoid arthritis. At disease onset 50% of affected children are between 2 and 6 years of age. Symptoms are often subtle and pain is usually not the leading symptom. Early treatment of juvenile arthritis is essential in order to prevent long-term sequelae in affected children. Many children are introduced to a pediatric rheumatologist only with considerable delay. Therapy is based on NSAIDs, intra-articular steroid injections, and immunosuppressive drugs. In severe cases patients are treated with biologics. Physical and occupational therapy are important supportive measures in the treatment.
21362782 Composite Measures in Psoriatic Arthritis: a report from the GRAPPA 2009 annual meeting. 2011 Mar A composite measure is one way of incorporating an assessment of all relevant clinical outcomes into one single measure. By definition it incorporates several dimensions of disease status often by combining these different domains into a single score. Such instruments are well established in rheumatoid arthritis (RA), and these RA-specific measures have successfully been adopted for use in clinical trials involving patients with psoriatic arthritis (PsA). However, the need for a more PsA-specific composite measure has led to a number of proposals, which, for the large part, incorporate only peripheral articular disease activity. New indices that combine the diverse clinical manifestations of PsA are now under development. These issues were discussed at the 2009 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) in Stockholm, Sweden, and are summarized here.
21289422 [Animal models for bone and joint disease. CIA, CAIA model]. 2011 Feb The collagen-induced arthritis (collagen-induced arthritis, CIA) is an autoimmune arthritis that resembles rheumatoid arthritis (RA) in many ways, therefore it has been used most commonly as a model of RA. CIA is induced by immunization with an emulsion of complete Freund's adjuvant (CFA) and type II collagen (C II ) . Collagen antibody-induced arthritis (CAIA) is induced by the administration of a cocktail of monoclonal antibodies recognizing conserved epitopes located within the CB11 fragment. CAIA offers several advantages over CIA, including rapid disease onset, high uptake rate, and the capacity to use genetically modified mice, such as transgenics and knockouts.
21768392 Peptides targeting inflamed synovial vasculature attenuate autoimmune arthritis. 2011 Aug 2 Autoimmune diseases, such as rheumatoid arthritis, frequently target one major tissue/organ despite the systemic nature of the immune response. This is particularly perplexing in the case of ubiquitously distributed antigens invoked in arthritis induction. We reasoned that selective targeting of the synovial joints in autoimmune arthritis might be due in part to the unique attributes of the joint vasculature. We examined this proposition using the adjuvant-induced arthritis model of human rheumatoid arthritis, and profiled the synovial vasculature using ex vivo and in vivo screening of a defined phage peptide-display library. We identified phage that preferentially homed to the inflamed joints. The corresponding synthetic peptides showed binding to the joint-derived endothelial cells, as well as specificity in inhibiting binding of the respective phage to the synovial vasculature. Intriguingly, the treatment of arthritic rats with one such peptide resulted in efficient inhibition of the progression of arthritis. The suppression of arthritis was attributable in part to the peptide-induced reduction of T-cell trafficking into the joints and the inhibition of angiogenesis. This peptide differed in sequence, in receptor binding specificity, and in angiogenesis/inflammation-related cell signaling from the previously characterized arginine-glycine-aspartic acid-containing peptide. Thus, our study reveals joint-homing peptides that can be further exploited for the selective delivery of antiarthritic agents into the inflamed joints to enhance their efficacy while reducing systemic toxicity, and also for examining intricacies of the pathogenesis of arthritis. This approach can be customized for application to other organ-specific autoimmune diseases as well.
22823586 MiR-146a polymorphism is associated with asthma but not with systemic lupus erythematosus 2012 Oct Extensive research has shown that aberrant expression of microRNAs (miRNAs) plays an important role in innate and adaptive immune responses. The rs2910164 polymorphism has been identified as a functional variant, which affects the transcription and expression level of miR-146a and, thereby, contributes to the pathogenesis of several inflammatory and autoimmune diseases. To investigate whether the rs2910164 G/C polymorphism was associated with asthma, systemic lupus erythematosus (SLE) or juvenile rheumatoid arthritis (JRA), we performed an association study in a pediatric Mexican cohort. We included 979 pediatric patients (asthma: 402, SLE: 367 and JRA: 210) and 531 control subjects without inflammatory or immune diseases. Genotyping was performed using the 5' exonuclease technique. The genotype distribution of the rs2910164 polymorphism was in Hardy-Weinberg equilibrium in each group. No significant differences were detected in the distribution of this polymorphism between cases and controls (P = 0.108, 0.609 and 0.553 for subjects with asthma, JRA and SLE, respectively). However, stratification by gender showed a statistically significant difference between asthmatic and control females, where the C allele was significantly associated with protection to asthma (odds ratio = 0.694, 95% confidence interval 0.519-0.929, P = 0.0138). Our results provide evidence that rs2910164 may play a role in the susceptibility to childhood-onset asthma, but not SLE or JRA in Mexicans. Further association studies may contribute to determining the role of miR-146a single-nucleotide polymorphisms in immune-mediated diseases.
22338608 HMOX1 promoter (GT)n polymorphim is associated with childhood-onset systemic lupus erythem 2012 Mar OBJECTIVES: The heme oxigenase 1 (HO-1), a rate-limiting enzyme for heme degradation, is an important cytoprotective protein. Transcriptional activity of HO-1 coding gene (HMOX1) can be regulated by the presence of a dinucleotide repeat polymorphism (GT)n at its promoter region. Accordingly, length of (GT)n repeat has been associated with susceptibility to several diseases. We investigated whether the HMOX1 (GT)n polymorphism was associated with childhood-onset systemic lupus erythematosus (SLE) and juvenile rheumatoid arthritis (JRA) susceptibility. METHODS: We studied 207 and 333 unrelated Mexican patients with JRA and childhood-onset SLE, respectively. The control population consisted of 653 individuals ethnically matched with cases. The HMOX1 (GT)n polymorphism was genotype by PCR and fluorescence technology. RESULTS: We found 27 different alleles, with the 22 and 29 repeats as the most common alleles. Distribution of short allele (n<25) and SS genotype was not statistically associated with JRA subjects. Interestingly, the frequency of both short allele and SS genotype was significantly associated with SLE susceptibility (OR=1.47, 95%CI [1.14-1.89], p=0.002; and OR=2.79, 95%CI [1.24-6.24], p=0.01, respectively). CONCLUSIONS: The distribution pattern of HMOX1 (GT) alleles was different in the Mexican population than those reported elsewhere. Our results suggest that HMOX1 (GT)n polymorphism was associated with susceptibility to childhood-onset SLE but not with JRA in Mexican individuals.
23070121 Juvenile rheumatoid arthritis and asthma, but not childhood-onset systemic lupus erythemat 2013 Apr A regulatory single nucleotide polymorphism located in the 5' region (-169T/C) of the Fc receptor-like 3 (FCRL3_3) gene has been associated with both susceptibility and protection in immune diseases. This case-control study aimed to evaluate the association between FCRL3 polymorphisms and juvenile rheumatoid arthritis (JRA), asthma, and childhood-onset systemic lupus erythematosus (SLE) in a Mexican population. We performed PCR-based genotyping to identify four FCRL3 single nucleotide polymorphisms (FCRL3_3 to FCRL3_6) in patients with JRA (n=202), asthma (n=239), or childhood-onset SLE (n=377), and healthy controls (n=400). The case-control analysis showed a male-gender dependent association between the FCRL3_3C, FCRL3_5C, and FCRL3_6A alleles and either JRA (OR=0.57, p=0.003; OR=0.55, p=0.002; OR=0.53, p=0.0007, respectively) or asthma (OR=0.72, p=0.04; OR=0.74, p=0.05; OR=0.70, p=0.02, respectively). As expected, minor alleles of these SNPs with the CGCA haplotype were also significantly associated with JRA (OR=0.35, p=0.00005) and asthma (OR=0.61, p=0.007). We found no association between FCRL3 SNPs or haplotypes and childhood-onset SLE. These results supported the notion that FCRL3 is involved in the etiology of several immune diseases. Our results also suggested that SNPs located in the FCRL3 gene were protective against JRA and asthma in male Mexican patients.
25379304 Effective treatment of rheumatoid arthritis-associated interstitial lung disease by B-cell 2012 Rheumatoid arthritis- (RA-) associated interstitial lung disease (RA-ILD) is the extra-articular complication with most adverse impact on the quality of life and survival in RA patients. However, treatment options are limited and controlled studies are lacking. Here, we present the case of a 66-year-old patient suffering from severe RA-ILD, which has been successfully treated with Rituximab (RTX). After failure of conventional DMARD therapy, our patient showed sustained improvement of clinical pulmonary parameters as well as joint inflammation following B-cell depletion with RTX. The six-minute-walk test improved from 380 meters to 536 meters and the forced vital capacity from 2.49 liters to 3.49. The disease activity score could be reduced from 7.7 to 2.8. Therefore, RTX might be considered as an alternative treatment for RA-ILD in patients not responding to conventional DMARD therapy.
22876244 Effect of Arthritic Synovial Fluids on the Expression of Immunomodulatory Factors by Mesen 2012 BACKGROUND: In diseased joints, the catabolic environment results in progressive joint damage. Mesenchymal stem cells (MSCs) can have immunomodulatory effects by secreting anti-inflammatory factors. To exert these effects, MSCs need to be triggered by pro-inflammatory cytokines. To explore the potential of MSCs as a treatment for diseased joints, we studied the effect of synovial fluid (SF) from donors with different joint diseases and donors without joint pathology on the immunomodulatory capacities of human MSCs in vitro. We hypothesized that SF of diseased joints influences the immunomodulatory effects of MSCs. MATERIALS AND METHODS: MSCs were cultured in medium with SF of six osteoarthritis (OA) or six rheumatoid arthritis (RA) donors and three donors without joint pathology were used as control. Gene expressions of IL-6, HGF, TNFa, TGFb1, and indoleamine 2,3-dioxygenase (IDO) were analyzed. l-kynurenine concentration in conditioned medium (CM) by MSCs with SF was determined as a measure of IDO activity by MSCs. Furthermore, the effect of CM with SF on proliferation of activated lymphocytes was analyzed. RESULTS: Addition of SF significantly up-regulated the mRNA expression of IL-6 and IDO in MSCs. SF(OA) induced significantly higher expression of IDO than SF(control), although no difference in IDO activity of the MSCs could be shown with a l-kynurenine assay. Medium conditioned by MSCs with SF(OA or RA) suppressed activated lymphocyte proliferation in vitro more than medium conditioned by MSCs without SF or with SF(control). DISCUSSION: SF can influence the expression of genes involved in immunomodulation by MSCs and the effect on lymphocyte proliferation. We found indications for disease-specific differences between SFs but the variation between donors, even within one disease group was high. These data warrant further research to examine the potential application of MSC therapy in arthritic joints.
28083160 International Variation in the Usage of Medicines: A Review of the Literature. 2011 Spring This article describes a review of the published and grey literature on international variation in the use of medicines in six areas (osteoporosis, atypical anti-psychotics, dementia, rheumatoid arthritis, cardiovascular disease/lipid-regulating drugs (statins), and hepatitis C). We identify three broad groups of determinants of international variation in medicines use: (1) Macro- or system level factors: Differences in reimbursement policies, and the role of health technology assessment, were highlighted as a likely driving force of international variation in almost all areas of medicines use reviewed. A related aspect is patient co-payment, which is likely to play an important role in the United States in particular. The extent to which cost-sharing policies impact on overall use of medicines in international comparison remains unclear. (2) Service organisation and delivery: Differences in access to specialists are a likely driver of international variation in areas such as atypical anti-psychotics, dementia, and rheumatic arthritis, with for example access to and availability of relevant specialists identified as acting as a crucial bottleneck for accessing treatment for dementia and rheumatoid arthritis. (3) Clinical practice: Studies highlighted the role of variation in the use and ascertainment methods for mental disorders; differences in the use of clinical or practice guidelines; differences in prescribing patterns; and reluctance among clinicians in some countries to take up newer medicines. Each of these factors is likely to play a role in explaining international variation in medicines use, but their relative importance will vary depending on the disease area in question and the system context.