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ID PMID Title PublicationDate abstract
21157511 Cytotoxic T lymphocyte-Associated Antigen +49G Variant Confers Risk for Anti-CCP- and Rheu 2010 Controversial observations have been published on the association of the cytotoxic T lymphocyte associated antigen gene's variants with rheumatoid arthritis (RA). After genotyping 428 patients and 230 matched controls, the prevalence of the CT60(∗)G allele was more frequent in RF- and/or anti-CCP-seropositive RApatients, compared to the healthy controls (P < .001). Regression analysis revealed that the CT60(∗)G allele is a possible predisposing factor for RA in these subgroups. No accumulation of the +49(∗)G allele was found among patients, and this variant was not found to correlate with RA. Assaying the possible genotype variations, the +49(∗)G-CT60(∗)G allelic combination was accumulated in seropositive RA-subtypes, and was associated with the risk of RA (OR = 1.73, P = .001 for the whole RA-population). Although the +49(∗)G allele did not mean a predisposition to RA alone, in combination with CT60(∗)G it, also conferred risk, suggesting that the +49A/G variant is associated with the risk of RA only in certain haplotypes.
20155432 Successful treatment of severe nodular scleritis with adalimumab. 2010 May Ocular features may occur in longstanding rheumatoid arthritis. Among them, scleritis represents the most frequent manifestation of ophthalmologic rheumatoid disease. There are three types of anterior scleritis: diffuse, nodular, and necrotizing with and without inflammation (scleromalacia perforans). Nodular scleritis is the second cause of anterior scleritis representing 20% of all types of scleritis. The conventional treatment of nodular scleritis consists in topical steroids and DMARDS. In severe cases, the therapy with immunosuppressive agents to avoid complications is necessary. We describe a 46-year-old woman presented right nodular scleritis with rheumatoid arthritis. She was treated initially with topical steroids and DMARDs but was unable to received systemic steroids due to left open angle glaucoma in the opposite eye. After an ocular exacerbation, we initiated adalimumab with complete resolution of nodular scleritis. This is the first report of adalimumab in the treatment of nodular scleritis. Adalimumab could be a good alternative in patients with severe nodular scleritis who fail to have conventional treatment with DMARDs and unable to receive systemic steroids.
19784703 Complementary and alternative medicine in rheumatoid arthritis: no longer the last resort! 2010 Feb Complementary and alternative medicine (CAM) has become popular with consumers worldwide and accounts for significant private and public health expenditures. According to earlier reports, the prevalence of CAM use by rheumatoid arthritis (RA) patients in the United States is anywhere between 28% and 90%. Extensive use among RA patients and the limited knowledge among physicians had confirmed the need to evaluate the increasing prevalence of various CAM modalities. The primary aim of this study was to identify the incidence of CAM usage among our RA patients. Additionally, we aimed to correlate patient demographics and disease characteristics with the use of specific CAM modalities. An analysis of data extracted from our institution's RA longitudinal registry was performed. The patients were asked to select from a list the modalities they were currently using and/or had used in the past. Of patients, 75.9% reported current or past use of CAM with >10% using 12 different modalities. Nutritional supplements and touch therapies were the most widely used overall, with mind-body therapies more prevalent among younger patients. CAM users were found to have more extra-articular manifestations and fewer comorbidities than non-CAM users. The use of CAM among RA patients is widespread with a broad spectrum of CAM modalities being used in early stages of the disease, frequently in conjunction with mainstream conventional treatments. Therefore, CAM may no longer be considered the rheumatoid patients' last resort.
20039431 ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces sustained ame 2010 Jan OBJECTIVE: To assess the therapeutic potential of anti-CD3 monoclonal antibodies (mAb) for rheumatoid arthritis, using collagen-induced arthritis as an animal model. METHODS: Arthritis was induced in DBA/1 mice by immunization with type II collagen. After disease onset, a single injection of anti-CD3 mAb (20 microg/mouse) was administered, and arthritis severity was monitored over a 10-day period. RESULTS: Anti-CD3 mAb treatment resulted in a sustained reduction in disease activity, which was associated with an increase in the proportion of naturally occurring CD4+CD25+FoxP3+ regulatory T (Treg) cells and the generation of a population of CD8+CD25+FoxP3+ Treg cells. Anti-CD3 mAb treatment did not alter the capacity of CD4+ Treg cells to suppress effector T cell proliferation and interferon-gamma (IFNgamma) production in vitro. However, CD4+ Treg cells from both anti-CD3 mAb-treated and control mice were unable to suppress interleukin-17 (IL-17) production. In contrast, CD8+ Treg cells induced by anti-CD3 therapy suppressed IL-17 production as well as CD4+ T cell proliferation and IFNgamma production. CONCLUSION: These results show that anti-CD3 mAb treatment has important therapeutic potential for rheumatoid arthritis and has the capacity to generate antiarthritic CD8+ Treg cells and expand the relative numbers of CD4+ Treg cells.
19368720 Evaluation of anti-IL-6 monoclonal antibody therapy using murine type II collagen-induced 2009 Apr 15 Interleukin-6 is a multifunctional cytokine that is critical for T/B-cell differentiation and maturation, immunoglobulin secretion, acute-phase protein production, and macrophage/monocyte functions. Extensive research into the biology of IL-6 has implicated IL-6 in the pathophysiology and pathogenesis of RA. An anti-murine IL-6 mAb that neutralizes mouse IL-6 activities was tested in animal model of collagen-induced arthritis. Prophylactic treatment with anti-IL-6 mAb significantly reduced the incidence and severity of arthritis compared to control mAb treated mice. The mitogenic response of B and T cells isolated from the lymph nodes of anti-IL-6 treated mice was significantly reduced compared to cells isolated from control mAb treated mice. The overall histopathology score for paws from the anti-IL-6 treated mice was significantly reduced when compared to paws from mice treated with control mAb, including both inflammatory (synovitis and pannus) and erosive (erosions and architecture) parameters. Reduced loss of cartilage matrix components was also observed in the anti-IL-6 treated mice. Collectively, these data suggest that IL-6 plays a major role in the pathophysiology of rheumatoid arthritis, and thus support the potential benefit of anti-IL-6 mAb treatment in rheumatoid arthritis patients.
19693641 Psoriatic arthritis and chronic lymphoedema: treatment efficacy by adalimumab. 2009 Nov Lymphoedema is a rare complication of psoriatic arthritis (PsA) and inflammatory joint disease, with no response noted to disease-modifying drugs. However, reports are emerging of a beneficial effect on lymphoedema in patients treated with tumor necrosis factor-alpha antagonists for PsA (Etanercept), rheumatoid arthritis (Etanercept) and ankylosing spondylitis (Infliximab). We describe a psoriatic arthritis patient whose lymphoedema greatly improved following commencement of adalimumab.
18980853 Sternoclavicular septic arthritis in a previously healthy patient: a case report and revie 2009 May Sternoclavicular septic arthritis is an unusual event in healthy patients. Cases have been reported in diabetes mellitus patients, intravenous drug abusers and patients affected by rheumatoid arthritis. We report a case of this unique infection that occurred in a patient who was not at risk of septic arthritis. Through this case and a review of the literature, we discuss the difficulty of diagnosing this disorder, and the consequences of delayed treatment in terms of life-threatening outcomes and therapeutic options.
18835272 Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regu 2009 Mar Various experimental and epidemiological studies have demonstrated that helminth infections affect outcomes of allergic or autoimmune disorders. Here, we examined the effects of Schistosoma mansoni infection on mouse collagen-induced arthritis, one of the most widely used animal models for rheumatoid arthritis. Male DBA/1 mice were infected with S. mansoni 2 weeks prior to being immunized with type II collagen (IIC). Cytokine mRNA expression in mouse paws, cytokine production by ConA-stimulated spleen cells, and anti-IIC antibodies were evaluated in addition to the severity of arthritis. S. mansoni infection significantly reduced the severity of arthritis. Anti-IIC IgG and IgG2a levels were lower in infected than uninfected mice. With regard to cytokine producing potentials in the infected mice, the down-regulation of Th1 (IFNgamma) and pro-inflammatory cytokines (TNFalpha and IL-17A), and up-regulation of Th2 (IL-4) and an anti-inflammatory cytokine (IL-10) were observed.In addition, real-time PCR revealed that the augmentation of pro-inflammatory mediators such as IL-1 beta, IL-6 and receptor activator of NFkappaB ligand in inflamed paws was abrogated by S. mansoni infection [corrected]. In conclusion, schistosome infection reduced the severity of autoimmune arthritis via systemic and local suppression of pro-inflammatory mediators, suggesting the potential of parasite-derived materials as therapeutic agents against rheumatoid arthritis.
27022536 EVALUATION OF THE CERVICAL SPINE AMONG PATIENTS WITH RHEUMATOID ARTHRITIS. 2010 Mar OBJECTIVE: To evaluate the prevalence of cervical spine abnormalities among patients with rheumatoid arthritis and correlate the imaging findings with the clinical state. METHODS: A cross-sectional study on 35 patients was carried out at the School of Medicine of the Federal University of Goiás (UFG) in 2004. The following were evaluated: age, use of medications and the clinical picture of pain and neurological characteristics. The erythrocyte sedimentation rate (ESR) and rheumatoid factor were tested, and radiographs of the cervical spine were produced in anteroposterior, lateral and dynamic views. To evaluate the influence of the variables on the emergence of instabilities, univariate and multivariate logistic regression tests were used (p < 0.05). RESULTS: Among the 35 patients evaluated, 13 (37.1%) presented a stable cervical spine. Out of the 22 patients with instability, six presented more than one type. Atlantoaxial instability was found in 15 patients, with a mean anterior atlantodental distance of 3.40 mm in the neutral lateral radiographic view and 6.54 mm in the lateral view with flexion. Basilar invagination was found in five patients and subaxial subluxation in seven patients. Two thirds of the asymptomatic patients had instabilities. Bicipital hyperreflexia presented statistically significant correlations with atlantoaxial instability (p = 0.024) and subaxial instability (p = 0.01). Age at diagnosis correlated with subaxial instability (p = 0.02). CONCLUSIONS: The prevalence of cervical instability was 62.9 % (22/35). The most frequent instabilities were: atlantoaxial subluxation (42.9 %), subaxial subluxation (20%) and basilar invagination (14.3%). The correlation between instabilities and clinical signs and symptoms was poor. The patients with subaxial subluxation presented disease onset at a younger age. Dynamic radiography was important for diagnosing atlantoaxial subluxation.
19519924 Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheuma 2009 Epidemiology is the study of the distribution and determinants of disease in human populations. Over the past decade there has been considerable progress in our understanding of the fundamental descriptive epidemiology (levels of disease frequency: incidence and prevalence, comorbidity, mortality, trends over time, geographic distributions, and clinical characteristics) of the rheumatic diseases. This progress is reviewed for the following major rheumatic diseases: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriatic arthritis, osteoarthritis, systemic lupus erythematosus, giant cell arteritis, polymyalgia rheumatica, gout, Sjögren's syndrome, and ankylosing spondylitis. These findings demonstrate the dynamic nature of the incidence and prevalence of these conditions--a reflection of the impact of genetic and environmental factors. The past decade has also brought new insights regarding the comorbidity associated with rheumatic diseases. Strong evidence now shows that persons with RA are at a high risk for developing several comorbid disorders, that these conditions may have atypical features and thus may be difficult to diagnose, and that persons with RA experience poorer outcomes after comorbidity compared with the general population. Taken together, these findings underscore the complexity of the rheumatic diseases and highlight the key role of epidemiological research in understanding these intriguing conditions.
21122546 A case of Crohn's disease complicated by adult onset Still's disease. 2010 Oct Arthritis and arthralgia are the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD), occurring in up to a third of patients. These may affect the peripheral or axial skeletal system and may or may not reflect disease activity. As a result, it is challenging to identify an alternative diagnosis to account for joint manifestations in the setting of IBD. We describe a case of a 30 year old woman with quiescent Crohn's colitis who presented with 2 weeks of fever, flitting arthralgia, a sore throat and a nocturnal rash on her thighs. She denied any gastrointestinal symptoms to suggest a flare up of IBD. Investigations revealed a neutrophilia and a markedly elevated serum ferritin. The patient met all four major and several minor Yamaguchi criteria for Adult Onset Still's Disease (AOSD). She was treated with corticosteroids and analgesia with resolution of her symptoms and normalisation of her biochemical markers. While joint manifestations are the most common extra-intestinal symptoms of Inflammatory Bowel Disease, atypical presentations should raise the concern of an additional diagnosis. This case represents a rare presentation of Crohn's disease complicated by AOSD.
21218013 Pathogenesis and clinical manifestations of juvenile rheumatoid arthritis. 2010 Nov Juvenile rheumatoid arthritis (JRA) is the most common rheumatic childhood disease; its onset is before 16 years of age and it persists for at least 6 weeks. JRA encompasses a heterogeneous group of diseases that is classified according to 3 major presentations: oligoarthritis, polyarthritis, and systemic onset diseases. These presentations may originate from the same or different causes that involve interaction with specific immunogenetic predispositions, and result in heterogeneous clinical manifestations. An arthritic joint exhibits cardinal signs of joint inflammation, such as swelling, pain, heat, and loss of function; any joint can be arthritic, but large joints are more frequently affected. Extra-articular manifestations include high fever, skin rash, serositis, and uveitis. The first 2 types of JRA are regarded as T helper 1 (Th1) cell-mediated inflammatory disorders, mainly based on the abundance of activated Th1 cells in the inflamed synovium and the pathogenetic role of proinflammatory cytokines that are mainly produced by Th1 cell-stimulated monocytes. In contrast, the pathogenesis of systemic onset disease differs from that of other types of JRA in several respects, including the lack of association with human leukocyte antigen type and the absence of autoantibodies or autoreactive T cells. Although the precise mechanism that leads to JRA remains unclear, proinflammatory cytokines are thought to be responsible for at least part of the clinical symptoms in all JRA types. The effectiveness of biologic therapy in blocking the action of these cytokines in JRA patients provides strong evidence that they play a fundamental role in JRA inflammation.
20018013 Power of selective genotyping in genome-wide association studies of quantitative traits. 2009 Dec 15 The selective genotyping approach in quantitative genetics means genotyping only individuals with extreme phenotypes. This approach is considered an efficient way to perform gene mapping, and can be applied in both linkage and association studies. Selective genotyping in association mapping of quantitative trait loci was proposed to increase the power of detecting rare alleles of large effect. However, using this approach, only common variants have been detected. Studies on selective genotyping have been limited to single-locus scenarios. In this study we aim to investigate the power of selective genotyping in a genome-wide association study scenario, and we specifically study the impact of minor allele frequency of variants on the power of this approach. We use the Genetic Analysis Workshop 16 rheumatoid arthritis whole-genome data from the North American Rheumatoid Arthritis Consortium. Two quantitative traits, anti-cyclic citrullinated peptide and rheumatoid factor immunoglobulin M, and one binary trait, rheumatoid arthritis affection status, are used in the analysis. The power of selective genotyping is explored as a function of three parameters: sampling proportion, minor allele frequency of single-nucleotide polymorphism, and test level. The results show that the selective genotyping approach is more efficient in detecting common variants than detecting rare variants, and it is efficient only when the level of declaring significance is not stringent. In summary, the selective genotyping approach is most suitable for detecting common variants in candidate gene-based studies.
21134433 Ex vivo and in vivo effect of Chinese herbal pill Yi Shen Juan Bi (YJB) on experimental ar 2011 Mar 8 AIM OF THIS STUDY: Chinese herbal pill Yi Shen Juan Bi (YJB), which is a compound herbal drug, has traditionally been used as an anti-rheumatic drug in Chinese local clinics. Thus, we investigated the therapeutic effect of the YJB in rheumatoid arthritis (RA), using Freund's complete induced adjuvant arthritis (AA) in rat model. METHODS: For that purpose, macrophage derived cytokine tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) were measured in ex vivo by enzyme linked immunosorbent assay (ELISA). We also assayed the effect of YJB on peritoneal macrophage derived nitric oxide (NO) in ex vivo by Griess reaction. Prostaglandin E (PGE) in metapedes was assayed by ultraviolet spectrophotometer method. Further synovial Bax level was examined by Western blot analysis. RESULTS: YJB significantly decreased the production of peritoneal macrophages derived TNF-α, IL-1 and NO. YJB also significantly decreased prostaglandin E (PGE) and upregulated the Bax expression in AA rat's synovium. CONCLUSION: YJB is a potential anti-rheumatic agent targeting the inflammatory and immunomodulatory response of macrophages while down regulating the PGE and up-regulating the pro-apoptotic Bax expression. Such characteristics of YJB on AA may be advantageous to the treatment of clinical rheumatoid arthritis.
20961790 Current treatments for juvenile idiopathic arthritis. 2010 Dec Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, most of which differ from the main adult-onset inflammatory joint diseases. Nonsystemic forms of JIA (oligoarthritis, polyarthritis with or without rheumatoid factors, and spondyloarthropathies) are managed similarly to adult-onset rheumatoid arthritis or spondylarthritis, with a few differences. More specifically, JIA-associated chronic uveitis may require the use of biotherapies that remain experimental in JIA, such as monoclonal antibodies to TNFα or abatacept. International networks have enabled therapeutic trials of medications targeting TNFα alpha, interleukin (IL)-1, IL-6, or T-cell co-stimulation (abatacept). Systemic-onset JIA (also called childhood-onset Still's disease) raises specific treatment challenges and may require treatment with IL-1 antagonists, tocilizumab, or even thalidomide; as a very last resort, intensive immunosuppressant therapy with autologous hematopoietic stem-cell transplantation may be considered. Close monitoring of growth velocity and bone mass accrual is in order, and some patients require additional medications such as growth hormone. Patients with JIA should be managed in specialized centers that have coordinated chains of care for the entire pediatric period and into adulthood. In addition, the use in pediatric patients of recently introduced treatments requires close monitoring for long-term side effects.
20237930 Successful treatment with intravenous immunoglobulin of severe thrombocytopenia complicate 2012 May Sjogren's syndrome (SS) is a systemic autoimmune disease characterized by xerophthalmia, xerostomia and extraglandular manifestations. Anemia, leukopenia, thrombocytopenia and lymphoproliferative disorders, including lymphoma are well-known extraglandular, hematological complications of SS. We report here a rare case of patient with primary SS who developed pancytopenia with severe thrombocytopenia as an initial manifestation and successfully treated with IV immunoglobulin (IVIG). The present case suggests that pancytopenia with severe thrombocytopenia can be a difficult-to-treat abnormality, and initial manifestation of primary SS and IVIG might be an effective treatment for severe thrombocytopenia refractory to high-dose steroid in primary SS.
21173564 [A case of pseudomembranous colitis in a juvenile rheumatoid arthritis patient taking meth 2010 Dec Pseudomembranous colitis is mainly caused by antibiotics and Clostridium difficile infection. But conditions such as gastrointestinal surgery, antacid medication, anti-neoplastic agent or immunosuppressive agent which influences the normal flora of colon can induce colitis without the administration of any antibiotics. We experienced a 13 year-old male who was taking low-dose methotrexate for juvenile rheumatoid arthritis complained diarrhea and abdominal pain for 3 weeks. Sigmoidoscopic findings revealed diffuse patch yellowish pseudomembranes on the rectum. Histologic finding was compatible to pseudomembranous colitis. His symptom was improved after stop taking methotrexate and the administration of metronidazole. If a patient treated with immunosuppressive agents or antineoplastic agents complains diarrhea, fever or abdominal pain and has not improved with conservative care, pseudomembranous colitis should be taken into account as a differential diagnosis and prompt treatment is required for better prognosis.
20453189 Adult-Onset Still Disease (AOSD). 2010 May Adult-onset Still disease (AOSD) is an uncommon clinical entity that predominantly affects young adults. One of the most common presentations of the disease is fever of unknown origin. Early diagnosis can be difficult because fever of unknown origin is more commonly seen with other conditions such as malignancy or infection. Ambiguity in presentation and lack of serologic markers make diagnosis difficult. We describe here an 18-year-old African-American man who presented with fever, sore throat, and arthritis at initial admission, with serology positive for both Mycoplasma pneumonia and Epstein-Barr infection. The patient was discharged without improvement. He was then readmitted with persistence of initial symptoms and, at that stage, he fulfilled the proposed diagnostic criteria of AOSD. The purpose of this case report is to describe the triggering infections that can initially mislead diagnosis and to review the literature about AOSD from a primary care perspective.
20195880 Juvenile idiopathic arthritis among Nigerians: a case study. 2010 Jul Juvenile idiopathic arthritis (JIA) has rarely been reported among Black Africans. This retrospective case study was part of an audit of cases presenting to a private practice rheumatology clinic in Lagos, Nigeria. The objective of this study was to determine the clinical, laboratory, and radiographic features of patients with JIA, as well as to highlight their management. A total of 23 cases (F-16:M-7) were seen over an 8.5-year period. Polyarticular presentation was the commonest while systemic onset was the least. The mean age at presentation was 12.7 years. Most of the patients presented late with mean of 3.7 years before presentation. The knees and ankles were most commonly involved. ESR was elevated in most of the cases. Rheumatoid factor and Antinuclear antibodies were invariably negative. Treatments were with standard drugs. Although JIA is uncommonly seen in our population, the clinical and laboratory features are similar as elsewhere, though there are some differences.
19481238 Nerve growth factor in rheumatic diseases. 2010 Oct OBJECTIVES: The nervous system modulates the immune response in many autoimmune syndromes by neurogenic inflammation. One of the pivotal mediators is nerve growth factor (NGF), which is known for its effects on neuronal survival and growth. There is considerable evidence that NGF acts as an important mediator of many immune responses. This article reviews the role of NGF in rheumatic diseases and strategies for potential therapeutic interventions. METHODS: We conducted a database search using Medline and Medpilot. Eight hundred abstracts containing the keyword NGF and 1 of the following terms were reviewed: arthritis, neurogenic inflammation, rheumatoid arthritis, osteoarthritis, collagen arthritis, arteritis, psoriasis, psoriatic arthritis, Sjogren syndrome, systemic lupus erythematosus, gout, osteoporosis, lower back pain, lumbar disc herniation, nerve root compression, spondyloarthritis, spondylarthropathy, algoneurodystrophy, fibromyalgia, Kawasaki syndrome, polyarteritis nodosa, cytokine, vasculitis, pain, therapy, and antagonist. Articles were analyzed based on relevance and content. Most clinical trials and studies with human specimens were included. Studies with experimental animal models were selected if they contained relevant data. RESULTS: NGF is overexpressed in many inflammatory and degenerative rheumatic diseases. Concentrations differ to some extent and sometimes even show contradictory results. NGF is found in serum, synovial fluid, and cerebrospinal fluid, and tissue specimens. NGF concentrations can be correlated with the extent of inflammation and/or clinical activity in many conditions. In rheumatoid arthritis, NGF levels are significantly higher as compared with osteoarthritis. CONCLUSIONS: NGF is a significant mediator and modulator of inflammation. NGF sometimes shows detrimental and sometimes regenerative activity. These findings indicate potential therapeutic interventions using either NGF antagonists or recombinant NGF.