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ID PMID Title PublicationDate abstract
25674479 Rituximab for pulmonary lymphomatoid granulomatosis which developed as a complication of m 2014 We report the case of a patient with Rheumatoid Arthritis [RA] presenting with clinical-pathological and radiological features of Pulmonary Lymphomatoid Granulomatosis (PLG). This is a rare lung disorder characterized by multiple nodular lesions with lymphocytic invasion of vascular walls. We present one such case of PLG secondary to Methotrexate and Azathioprine therapy, who was successfully treated with Steroids and Rituximab. We wish to highlight the importance of lung biopsy in the diagnosis and the use of rituximab as a treatment modality for RA as well as PLG.
25232525 Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/cli 2014 Sep 18 Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the Janus kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway. The orally administered small molecule inhibitor, tofacitinib, is the first drug to target the JAK/STAT pathway for entry into the armamentarium of the medical therapy of rheumatoid arthritis. The introduction of tofacitinib into general rheumatologic practice coupled with increasing understanding that additional cellular signal transduction pathways including the mitogen-activated protein kinase and phosphatidylinositide-3-kinase/Akt/mammalian target of rapamycin pathways as well as spleen tyrosine kinase also contribute to immune-mediated inflammatory in rheumatoid arthritis makes it likely that further development of orally administered protein kinase small molecule inhibitors for rheumatoid arthritis will occur in the near future.
24746812 Repair of radiographic hip joint in juvenile rheumatoid arthritis patients treated with et 2014 Oct For patients suffering from rheumatoid arthritis (RA), structural damage, i.e. bone erosion and joint space narrowing, is a major factor leading to functional disability. Negative radiographic progression has been shown in joints, especially in RA patients treated with tumor necrosis factor alpha (TNFα) inhibitors in combination with methotrexate. Bone erosion repair in small joints have been observed but only one study selected large weight-bearing joints. We reported 2 cases of patients with severe seropositive juvenile RA who shown improvement of joint space narrowing and subchondral erosion in hip joint when treated with etanercept in combination with methotrexate for at least 1year. Two Japanese cases were also published but with different TNF inhibitors. The mechanisms of bone erosion or joint space narrowing repair are unclear. One study investigated whether bone erosions in rheumatoid arthritis patients show evidence of repair in metacarpophalangeal joints when treated with TNF inhibitors and MTX. These results suggested that repair in RA emerged from the bone marrow and the endosteal lining rather than the periosteal compartment. No study investigated joint space narrowing repair in hip joint in rheumatoid arthritis patients. Larger studies needed to confirm joint space narrowing improvement in hip joint in patients treated with TNF inhibitors and to explain the mechanisms of repair.
25453756 A role for noncoding variation in schizophrenia. 2014 Nov 20 A large portion of common variant loci associated with genetic risk for schizophrenia reside within noncoding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from the human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci for a potential functional role, based on colocalization of a risk SNP, eQTL, and regulatory element sequence. We identified potential physical interactions of noncontiguous proximal and distal regulatory elements. This was verified in prefrontal cortex and -induced pluripotent stem cell-derived neurons for the L-type calcium channel (CACNA1C) risk locus. Our findings point to a functional link between schizophrenia-associated noncoding SNPs and 3D genome architecture associated with chromosomal loopings and transcriptional regulation in the brain.
24265892 Gamma-irradiated liposome/noisome and lipogelosome/niogelosome formulations for the treatm 2013 Jun Treatment of rheumatoid arthritis by intraarticular administration of anti-inflammatory drugs encapsulated in drug delivery systems, such as liposomes/niosomes and lipogelosomes/niogelosomes, prolongs the residence time of the drugs in the joint. It was therefore anticipated that liposome/niosome entrapment would enhance the efficacy of drugs in the inflammatory sides. Liposomes are good candidates for the local delivery of therapeutic agents, such as diclofenac sodium (DFNa), for intraarticular delivery. Drugs for parenteral delivery must be sterile, and radiation sterilization is a method recognized by pharmacopoeias to achieve sterility of drugs. However, irradiation might also affect the performance of drug delivery systems. One of the most critical points is irradiation dose, because certain undesirable chemical and physical changes may accompany with the treatment, especially with the traditionally applied dose of 25 kGy. The present study aims to determine the effects of gamma irradiation on DFNa-loaded liposomes/niosomes and lipogelosomes/niogelosomes for the treatment of rheumatoid arthritis.
23843716 A Fatal Case of Relapsing Pneumonia Caused by Legionella pneumophila in a Patient with Rhe 2013 We present a rare fatal case of relapsing pneumonia caused by Legionella pneumophila in a patient with rheumatoid arthritis after only two injections of adalimumab. A 78-year-old Japanese woman with a 14-year history of rheumatoid arthritis was prescribed adalimumab because her disease activity remained high. However, 8 days after her second injection of adalimumab, she was admitted to our hospital and diagnosed with pneumonia caused by L. pneumophila. Following intravenous antibiotic therapy, she recovered completely from pneumonia and was discharged on day 10, but pneumonia relapsed, resulting in death 79 days after the first episode of pneumonia. L. pneumophila can lead to recurrence of pneumonia that can ultimately prove fatal, similar to the present case. A review of the pertinent literature is also presented.
23840942 The role of simvastatin in the therapeutic approach of rheumatoid arthritis. 2013 The pleiotropic effects of statins, especially the anti-inflammatory and immunomodulatory ones, indicate that their therapeutic potential might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders such as rheumatoid arthritis. Therefore, we undertook a prospective cohort study to evaluate the efficacy and safety of simvastatin used for inflammation control in patients with rheumatoid arthritis. One hundred patients with active rheumatoid arthritis divided into two equal groups (the study one who received 20 mg/day of simvastatin in addition to prior DMARDs and the control one) were followed up over six months during three study visits. The results of the study support the fact that simvastatin at a dose of 20 mg/day has a low anti-inflammatory effect in patients with rheumatoid arthritis with a good safety profile.
24167426 Predictors and effective factors on quality of life among Iranian patients with rheumatoid 2013 INTRODUCTION: Rheumatoid arthritis is a chronic autoimmune disorder that leads to joint swelling, stiffness, pain and progressive joint destruction. It is a common disease with prevalence of 1% worldwide that affecting all aspects of patients' lives. Therefore, this study was conducted to summarize and provide a clear view of quality of life among the patients in Iran through a literature review. METHODS: This study was conducted as a literature review over article published between 2000 to 2013, by using data bases comprise of Google scholar, Science Direct, Pubmed, IRANDOC, SID, Medlib, Magiran and by key words: "quality of life", "rheumatoid arthritis", "Iran" and their Persian equivalents. Finally 2065 articles assessed and according to the aim of the study are 11 studies synthesized. Extracted results first were summarized in Extraction Table, and then analyzed manually. RESULTS: In reviewed articles rheumatoid arthritis patients' quality of life was measured by using five different tools, the most important one of them was SF36 questionnaire. Among eight dimensions of SF36 questionnaire, the highest mean according included articles result was social functioning with average score of 63.4 and the lowest for physical limitation (physical role functioning) with score of 43. Overall, mean of eight dimensions was 52.47. The most important factors affecting quality of life were disease severity and pain, depression, income, educational, occupational status, married status, sign of disease, fatigue, anxiety and disease activity scores. CONCLUSION: The results of the study showed relatively low quality of life of rheumatoid arthritis patients in Iran. Empowering patients by participating them in service delivery process and decision making can improves quality of life and in this regard health care provider must be focused on patient self-care abilities and reinforcing this factor by training them.
24244814 Effects of Calcium Gluconate, a Water Soluble Calcium Salt on the Collagen-Induced DBA/1J 2013 Jul 30 This study examined the effects of calcium (Ca) gluconate on collagen-induced DBA mouse rheumatoid arthritis (CIA). A single daily dose of 200, 100 or 50 mg/kg Ca gluconate was administered orally to male DBA/1J mice for 40 days after initial collagen immunization. To ascertain the effects administering the collagen booster, CIA-related features (including body weight, poly-arthritis, knee and paw thickness, and paw weight increase) were measured from histopathological changes in the spleen, left popliteal lymph node, third digit and the knee joint regions. CIA-related bone and cartilage damage improved significantly in the Ca gluconate- administered CIA mice. Additionally, myeloperoxidase (MPO) levels in the paw were reduced in Ca gluconate-treated CIA mice compared to CIA control groups. The level of malondialdehyde (MDA), an indicator of oxidative stress, decreased in a dosedependent manner in the Ca gluconate group. Finally, the production of IL-6 and TNF-α, involved in rheumatoid arthritis pathogenesis, were suppressed by treatment with Ca gluconate. Taken together, these results suggest that Ca gluconate is a promising candidate anti-rheumatoid arthritis agent, exerting anti-inflammatory, anti-oxidative and immunomodulatory effects in CIA mice.
23362468 Regulation of bone destruction in rheumatoid arthritis through RANKL-RANK pathways. 2013 Jan 18 Recent studies have demonstrated that osteoclasts, the primary cells responsible for bone resorption, are mainly involved in bone and joint destruction in rheumatoid arthritis (RA) patients. Recent progress in bone cell biology has revealed the molecular mechanism of osteoclast differentiation and bone resorption by mature osteoclasts. We highlight here the potential role of the receptor activator of nuclear factor κB ligand (RANKL)-RANK pathways in bone destruction in RA and review recent clinical trials treating RA by targeting RANKL.
25558381 Staphylococcal enterotoxin C in synovial fluid of patients with rheumatoid arthritis. 2014 Oct BACKGROUND: In the previous studies using the commercial ELISA kit, the existence of staphylococcal superantigens has been reported in synovial fluid of patients with rheumatoid arthritis (RA). OBJECTIVES: This study aimed to design molecular methods to detect staphylococcal enterotoxin C in synovial fluid of patients with rheumatoid arthritis. MATERIALS AND METHODS: In this experimental study, Staphylococcus aureus strain producing enterotoxin C was used as the reference strain. The polymerase chain reaction (PCR) was set up by design a specific pair of primers. Besides bacterial culture, 50 synovial fluid samples of patients with rheumatoid arthritis were subjected to DNA extraction, and then PCR amplification was carried out according to the protocol. All samples were examined by ELISA method for enterotoxin C. The data were descriptively analyzed. RESULTS: The results of bacterial culture were negative for all samples. The results showed that 66% (33 cases) of samples contained entC gene and only 46% (23 cases) have also enterotoxin C. The interesting finding was that the results of ELISA and PCR were the same and have shown only 22 positive cases (44%samples) for staphylococcal enterotoxin C. CONCLUSIONS: Based on the findings of this study, S. aureus enterotoxin C (SEC) has been detected in synovial fluid of patients with rheumatoid arthritis by PCR and ELISA methods. These valuable findings may describe the exact etiology of the RA and as well as change the methods of its diagnosis and treatment. This is the first research, which has shown the staphylococcal entC gene in synovial fluid of RA patients. However, S. aureus strains can produce more than 20 types of enterotoxins. Therefore, its involvement on rheumatoid arthritis pathogenesis makes an important challenge in the future. In this regard, further investigation on the other enterotoxins is necessary.
25400373 Radiosynovectomy of the elbow joint synovitis in rheumatoid arthritis treated with Lutetiu 2014 Oct Rheumatoid arthritis is a chronic disease that is mainly characterized by asymmetric erosive synovitis, particularly affecting the peripheral joints. Radiation synovectomy or radiosynovectomy, also known as radiosynoviorthesis was first described in 1950's as a adjuvant treatment for rheumatoid arthritis. Radiosynovectomy is based on the irradiation of the joint synovium by the intra-articular administration of various β-emitting radiopharmaceuticals. Lu-177 has presence of gamma photons of imagable energy with low abundance which provides the additional benefit of carrying out simultaneous scintigraphy. We describe the first case report of use of Lu-177 hydroxylapatite particulates in a 35-year-old female patient who was presented with elbow joint synovitis due to rheumatoid arthritis.
24906639 Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on susceptibility and sub 2015 Nov BACKGROUND: Recently, our research group identified the non-deleted (functional) leucocyte immunoglobulin-like receptor A3 (LILRA3) as a new genetic risk for rheumatoid arthritis. OBJECTIVES: To further investigate whether the functional LILRA3 is a new susceptibility factor for other autoimmune diseases-for example, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). METHODS: The LILRA3 deletion polymorphism and its tagging single nucleotide polymorphism rs103294 were genotyped for 1099 patients with SLE, 403 patients with pSS and 2169 healthy controls. Association analyses were performed in whole dataset or clinical/serological subsets. The impact of LILRA3 on SLE activity and LILRA3 expression was evaluated. RESULTS: The functional LILRA3 conferred high susceptibility to both SLE (p=3.51×10(-7), OR=2.03) and pSS (p=1.40×10(-3), OR=2.32). It was associated with almost all the clinical/serological features in SLE, especially with leucopenia (p=4.09×10(-7), OR=2.19) and thrombocytopenia (p=1.68×10(-5), OR=1.70). In pSS, functional LILRA3 was specifically associated with leucopenia (p=4.39×10(-4), OR=3.25), anti-Ro/SSA-positive subphenotypes (p=4.54×10(-3), OR=2.34) and anti-La/SSB-positive subphenotypes (p=0.012, OR=2.49). Functional LILRA3 conferred higher disease activity in patients with SLE (p=0.044) and higher LILRA3 expression in both SLE (p=5.57×10(-8)) and pSS (p=1.49×10(-7)) than in controls. CONCLUSIONS: Functional LILRA3 is a new susceptibility factor for SLE and pSS. It highly predisposes to certain phenotypes such as leucopenia and thrombocytopenia in SLE, and may confer increased disease activity in SLE and a higher risk of leucopenia and autoantibody-positive subphenotypes in pSS.
23570499 A rare association of rheumatoid arthritis and primary biliary cirrhosis treated with ritu 2013 Apr 9 INTRODUCTION: Primary biliary cirrhosis is an autoimmune disease that tends to progress to fibrosis and cirrhosis with hepatic failure. Primary biliary cirrhosis is often associated with other non- hepatic autoimmune diseases. An association with rheumatoid arthritis has been suggested to coexist in 1.8% to 5.6% of patients with primary biliary cirrhosis, but data supporting this association are scarce. The etiologic and pathogenetic mechanisms are not yet fully understood and several factors have been implicated. The therapeutic management must consider the two pathologies. CASE PRESENTATION: We describe the case of a 60-year-old Moroccan woman with severe erosive rheumatoid arthritis and primary biliary cirrhosis treated with rituximab. During treatment, we observed a good clinical and biological response of her rheumatoid arthritis but persistent abnormal liver function tests. CONCLUSION: B cells seem to play a major role in the pathogenesis of both rheumatoid arthritis and primary biliary cirrhosis. Additional studies are necessary to better determine the therapeutic role of rituximab in both diseases.
24488421 Limitations in the classification of childhood-onset rheumatoid arthritis. 2014 Mar OBJECTIVE: Rheumatoid factor-positive polyarthritis (RF+ poly) is the juvenile idiopathic arthritis (JIA) category that resembles adult seropositive rheumatoid arthritis (RA). We studied children with RF+ and/or anticyclic citrullinated peptide antibody (anti-CCP)+ JIA to determine what proportion of those children meet International League of Associations for Rheumatology (ILAR) criteria for RF+ poly JIA and to assess for significant differences between children who meet RF+ poly criteria and those who are classified in other categories. METHODS: Charts of children with JIA who were RF+ and/or anti-CCP+ were reviewed. Children with RF+ poly JIA were compared to children in other categories. Statistical analysis was performed using chi-square, Fisher's exact test, and the Student's t-test. RESULTS: Of 56 children with RF+ and/or anti-CCP+ JIA, 34 (61%) met ILAR criteria for RF+ poly JIA. Twelve children had RF-/anti-CCP+ JIA with low anti-CCP titers. When these 12 children were excluded, there were few significant differences between children who met criteria for RF+ poly and those who were classified in other categories. The American College of Rheumatology/European League Against Rheumatism criteria for RA identified more RF+ children than did the ILAR RF+ poly classification (100% vs 77%). CONCLUSION: A number of children with RF+ arthritis were excluded from the RF+ poly JIA classification, though many demographic features and disease measures were similar to those of children who met criteria for RF+ poly JIA. We propose prioritization of RF/anti-CCP positivity over specific exclusions, along with inclusion of anti-CCP, in future revisions of the JIA classification criteria, to improve the sensitivity of diagnosing childhood-onset RA.
25232526 Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis. 2014 Sep 18 Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs (DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis (RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase (JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type I cytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb's mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaLs (ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.
24368945 Risk factors for asymptomatic ventricular dysfunction in rheumatoid arthritis patients. 2013 Objective. The aim of the study was to describe echocardiographic abnormalities in patients with rheumatoid arthritis, concurrent systemic comorbidities, rheumatologic clinical activity, serologic markers of rheumatoid arthritis, and inflammatory activity. Methods. In an observational, cross-sectional study, rheumatoid arthritis outpatients were included (n = 105). Conventional transthoracic echocardiographic variables were compared between patients with arthritis and non-RA controls (n = 41). For rheumatoid arthritis patients, articular activity and rheumatologic and inflammatory markers were obtained. Results. Ventricular dysfunction was found in 54.3% of the population: systolic (18.1%), diastolic (32.4%), and/or right (24.8%), with lower ejection fraction (P < 0.0001). Pulmonary hypertension was found in 46.9%. Other echocardiographic findings included increased left atrial diameter (P = 0.01), aortic diameter (P = 0.01), ventricular septum (P = 0.01), left ventricular posterior wall (P = 0.013), and right ventricular (P = 0.01) and atrial diameters compared to control subjects. Rheumatoid factor and anti-CCP antibodies levels were significantly elevated in cases with ventricular dysfunction. Angina and myocardial infarction, diabetes, and dyslipidemia were the main risk factors for ventricular dysfunction. Conclusions. Ventricular dysfunction is common in rheumatoid arthritis and associated with longer disease duration and increased serologic markers of rheumatoid arthritis. Screening for cardiac abnormalities should be considered in this kind of patients.
23493495 Significance of bone marrow edema in pathogenesis of rheumatoid arthritis. 2013 Jan Assessing the pathology of the synovium, its thickening and increased vascularity through ultrasound and magnetic resonance examinations (more often an ultrasound study alone) is still considered a sensitive parameter in the diagnosis of rheumatoid arthritis and in monitoring of treatment efficacy. Magnetic resonance studies showed that, aside from the joint pannus, the subchondral bone tissue constitutes an essential element in the development of rheumatoid arthritis. Bone marrow edema correlates with inflammation severity, joint destruction, clinical signs and symptoms of rheumatoid arthritis, and thus is considered a predictor of rapid radiological progression of the disease. The newest studies reveal that bone marrow edema may be a more sensitive indicator of the response to therapy than appearance of the synovium. Bone marrow edema presents with increased signal in T2-weighted images, being most visible in fat saturation or IR sequences (STIR, TIRM). On the other hand, it is hypointense and less evident in T1-weighted images. It becomes enhanced (hyperintense) after contrast administration. Histopathological studies confirmed that it is a result of bone inflammation (osteitis/osteomyelitis), i.e. replacememt of bone marrow fat by inflammatory infiltrates containing macrophages, T lymphocytes, B lymphocytes, plasma cells and osteoclasts. Bone marrow edema appears after a few weeks from occurrence of symptoms and therefore is considered an early marker of inflammation. It correlates with clinical assessment of disease activity and elevated markers of acute inflammatory phase, i.e. ESR and CRP. It is a reversible phenomenon and may become attenuated due to biological treatment. It is considered a "herald" of erosions, as the risk of their formation is 6-fold higher in sites where BME was previously noted.
27489657 Effect of correction of hindfoot valgus deformity on ankle joint pain relief in rheumatoid 2014 We often see painful ankle joint destruction with painful hindfoot valgus deformity in rheumatoid arthritis. Our policy in such cases has been to first correct the hindfoot deformity in the subtalar joint with fusion, but then ankle joint pain has been observed. Two women with rheumatoid arthritis underwent correction and fusion surgery for hindfoot valgus deformity. They had been using wheelchairs because of severe pain in the ankle joint and hindfoot despite extensive medical treatment. After surgery, both patients complained of no pain in the hindfoot. Furthermore, dramatic pain reduction in the ankle joint was also observed especially in a case without ankle joint instability. Consequently, the patients could walk without any support. Correction of valgus hindfoot deformity contributes to centralizing the weight-bearing line in the ankle joint, leading to ankle joint pain relief. It appears possible to preserve the ankle joint without additional ankle surgery even in rheumatoid arthritis cases, if ankle is stable.
23997576 Pharmacotherapy options in rheumatoid arthritis. 2013 Drugs form the mainstay of therapy in rheumatoid arthritis (RA). Five main classes of drugs are currently used: analgesics, non-steroidal anti-inflammatories (NSAIDs), glucocorticoids, nonbiologic and biologic disease-modifying antirheumatic drugs. Current clinical practice guidelines recommend that clinicians start biologic agents if patients have suboptimal response or intolerant to one or two traditional disease modifying agents (DMARDs). Methotrexate, sulfasalazine, leflunomide and hydroxychloroquine are the commonly used DMARDs. Currently, anti-TNF is the commonly used first line biologic worldwide followed by abatacept and it is usually combined with MTX. There is some evidence that tocilizumab is the most effective biologic as a monotherapy agent. Rituximab is generally not used as a first line biologic therapy due to safety issues but still as effective as anti-TNF. The long term data for the newer oral small molecule biologics such as tofacitinib is not available and hence used only as a last resort.