Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
20689426 Neurological manifestations of primary Sjogren's syndrome. 2010 Oct PURPOSE OF REVIEW: This review summarizes our current understanding of the neurological manifestations of primary Sjogren's syndrome (PSS), their pathophysiology, and treatment. RECENT FINDINGS: Prevalence of neurological manifestations in PSS varies widely from 10 to 60%, with pure or predominantly sensory polyneuropathies as the most common neurologic manifestation (e.g. sensory ataxic or small fiber sensory painful neuropathy). Mononeuropathy multiplex, polyradiculopathy, symptomatic dysautonomia, cranial neuropathy, myopathy, and central nervous system involvement are less common. PSS-associated sensory neuropathy is often the presenting feature of Sjogren's syndrome and, therefore, a high index of suspicion is required, particularly in female patients with nonlength-dependent, painful, or ataxic sensory neuropathies or those with trigeminal sensory and autonomic involvement. The pathophysiological basis of PSS-associated neuropathy is still unclear. Dorsal root ganglionitis and peripheral nerve vasculitis have been observed on histological examination of biopsy and autopsy samples. A few studies have explored the fundamental role of humoral autoimmune mechanisms. Small, uncontrolled, treatment trials with numerous immunomodulatory agents have reported variable benefit in PSS-associated neuropathy, particularly corticosteroids for mononeuritis multiplex and intravenous immunoglobulin for small fiber or sensory ataxic neuropathy. SUMMARY: The clinical and histological spectrum of neurological manifestations of Sjogren's syndrome is becoming clear. The field needs further exploration of basic neuroimmunological mechanisms of neural injury, and controlled treatment trials.
20560455 [IgG4-related systemic disease/systemic IgG4-related disease]. 2010 May IgG4-related systemic disease/systemic IgG4-related disease has been established as a new systemic disease entity. It is characterized by high serum IgG4 concentrations and abundant IgG4-bearing plasma cell infiltration in the involved organs. The chronic inflammation can attack lacrimal glands, salivary glands, the thyroid, lung, pancreas, kidney, and prostate. The concept includes Mikulicz's disease, Riedel's thyroiditis, pulmonary fibrosis, pulmonary pseudotumor, autoimmune pancreatitis, a part of tubulointerstitial nephritis, and chronic prostatitis. It is important to note that these lesions can occur at different times and sites. So, it is necessary to reconfirm the disease definition and entity in each specialized field. The diagnosis of this disease is confirmed by the above serological and histopathological characteristics. There are clinical diagnostic criteria of Mikulicz's disease (the Japanese Medical Society for Sjögren's Syndrome) and autoimmune pancreatitis (the Japanese Ministry of Health, Labour and Welfare, and the Japan Pancreas Society). They are convenient and useful. Glucocorticoid improves the physical abnormalities, and the initial dose of prednisolone is 30 mg/day, tapered in 5-mg reductions every two weeks. Nevertheless, there are some cases unable to achieve complete remission.
19838717 [Adult-onset Still's disease, Schnitzler syndrome, and autoinflammatory syndromes in adult 2009 Nov Adult-onset Still's disease (AoSD), Schnitzler syndrome, and cases of adult-onset autoinflammatory syndromes [10-15% of cases of familial Mediterranean fever (FMF) and tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS)] are characterized by a genetic predisposition, with increased interleukin (IL)-1beta and IL-18 production and TNF-alpha signaling, respectively. As a result, periodic fever and inflammation at barrier tissues (synovial tissues, serous membranes, and the skin) are encountered in such patients. Pathophysiological insights into these diseases have renewed interest in research on IL-1beta in rheumatic diseases and have opened new therapeutic avenues. Recently published studies have shown that patients with Schnitzler syndrome, methotrexate-refractory AoSD, and colchicine-refractory FMF or contraindications to colchicines in FMF respond well to treatment with the soluble IL-1 receptor antagonist anakinra. For TRAPS patients, the p75 TNF-alpha receptor/Fc-IgG1 fusion protein etanercept is the treatment of first choice.
20017985 Adjusting for HLA-DRbeta1 in a genome-wide association analysis of rheumatoid arthritis an 2009 Dec 15 BACKGROUND: There is a long-established association between rheumatoid arthritis and HLA-DRbeta1. The shared epitope (SE) allele is an indicator of the presence of any of the HLA-DRbeta1 alleles associated with RA. Other autoantibodies are also associated with RA, specifically rheumatoid factor IgM (RFUW) and anti-cyclic citrullinated peptide (anti-CCP). METHODS: Using the Genetic Analysis Workshop 16 North American Rheumatoid Arthritis Consortium genome-wide association data, we sought to find non-HLA-DRbeta1 genetic associations by stratifying across SE status, and using the continuous biomarker phenotypes of RFUW and anti-CCP. To evaluate the binary RA phenotype, we applied the recently developed FP test and compared it to logistic regression or a genotype count-based test. We adjusted for multiple testing using the Bonferroni correction, the Q value approach, or permutation-based p-values. A case-only analysis of the biomarkers RFUW and anti-CCP used linear regression and ANOVAs. RESULTS: The initial genome-wide association analysis using all cases and controls provides substantial evidence of an association on chromosomes 9 and 2 within the immune system-related gene UBXD2. In SE-positive subjects, many single-nucleotide polymorphisms were significant, including some on chromosome 6. Due to very few SE negative cases, we had limited power to detect associations in SE negative subjects. We were also unable to find genetic associations with either RFUW or anti-CCP. CONCLUSION: Our analyses have confirmed previous findings for genes PTPN22 and C5. We also identified a novel candidate gene on chromosome 2, UBXD2. Results suggest FP test may be more powerful than the genotype count-based test.
19949123 Clinical and radiological follow-up of the Aequalis third-generation cemented total should 2009 Dec There are no long-term published results on the survival of a third-generation cemented total shoulder replacement. We describe a clinical and radiological study of the Aequalis total shoulder replacement for a minimum of ten years. Between September 1996 and May 1998, 39 consecutive patients underwent a primary cemented total shoulder replacement using this prosthesis. Data were collected prospectively on all patients each year, for a minimum of ten years, or until death or failure of the prosthesis. At a follow-up of at least ten years, 12 patients had died with the prosthesis intact and two had emigrated, leaving 25 available for clinical review. Of these, 13 had rheumatoid arthritis and 12 osteoarthritis. One refused radiological review leaving 24 with fresh radiographs. Survivorship at ten years was 100% for the humeral component and 92% for the glenoid component. The incidence of lucent lines was low. No humeral component was thought to be at risk and only two glenoid components. The osteoarthritic group gained a mean 65 degrees in forward flexion and their Constant score improved by a mean 41.4 points (13 to 55). The rheumatoid group gained a mean of 24 degrees in flexion and their Constant score improved by 29.4 points. This difference may have been due to failure of the rotator cuff in 75% of the patients with rheumatoid arthritis. Thus a third-generation total shoulder replacement gives an excellent result in patients with osteoarthritis and an intact rotator cuff. Patients with rheumatoid arthritis have a 75% risk of failure of the rotator cuff at ten years.
20457424 Nutritional status and clinical characteristics in children with juvenile rheumatoid arthr 2010 Apr BACKGROUND/PURPOSE: The aim of the study was to investigate the clinical characteristics and nutritional status of juvenile rheumatoid arthritis (JRA) in Taiwanese children. METHODS: Fifty-three patients were included in this study. The disease subtype and patient characteristics were recorded. Body mass index (BMI) was determined. Seventy-five healthy age-matched children served as a control group. RESULTS: The inflammation parameters, including white blood cell count, platelet count, C-reactive protein, and erythrocyte sedimentation rate, were elevated in the systemic group. The BMI level of the JRA group was significantly lower than the control group (p = 0.006), especially in the male patients (p = 0.016) and when the patient age was greater than 4 (p = 0.011). The patients with oligoarticular onset JRA had significantly lower BMI compared with the healthy control group (p = 0.012). CONCLUSION: Nutritional status is often impaired in patients with JRA. The BMI of the JRA patients was lower than that of age-matched healthy children, especially in the male group, and when disease onset age was greater than 4. In our unselected sample, the most affected disease subtype was oligoarticular onset JRA.
21125169 Lepromatous leprosy associated with the use of anti-TNF α therapy: case report. 2010 May TNF blockers have been used in the treatment of several types of chronic inflammatory arthritis, especially rheumatoid arthritis. However, many doubts regarding the safety and high risk of infectious diseases in these patients remain. The main objective of this report was to present a case of lepromatous leprosy in a rheumatoid arthritis patient using TNF blockers. The development of adverse events should be rigorously observed, especially those related to infectious agents. Thus, appropriate investigation of skin lesions in patients receiving anti-TNFα therapy is recommended, as the initial clinical manifestation may be unusual, particularly in endemic regions in Brazil.
20013284 [Critical overview of outcome parameters for patients with primary Sjögren's syndrome]. 2010 Feb Not only in the context of clinical trials in particular, but also in daily clinical practice, outcome parameters or measuring instruments are essential to assess the efficacy of a therapeutic intervention, its influence on disease activity and potentially also to predict further disease course. Such criteria can assist in the identification of patient risk groups that may require special checkups or interventions. Moreover, these parameters should be reliable, objective and valid, e.g. to allow comparison of results from different studies. Therefore, outcome parameters need to be developed and/or validated in a targeted manner for individual diseases or investigations. To date, we have only limited therapeutic options for Sjögren's syndrome, a frequent systemic autoimmune disorder of unknown origin. Against the background of the new therapy approaches expected, this article provides a critical overview of available and newly developed outcome parameters for patients with Sjögren's syndrome.
19915763 [Adult Still's disease. A great simulator. Retrospective review of 20 patients]. 2009 Aug BACKGROUND: Adult Still's disease is an inflammatory disorder characterized by quotidian fevers, and an evanescent rash. Its presentation can be acute or subacute. AIM: To report our experience with Adult Still's disease. MATERIAL AND METHODS: Systematic retrospective review of medical records of nine men and 11 women aged between 17 and 57 years, with Still's disease, followed in two public hospitals of Metropolitan Santiago. RESULTS: Eighty percent of patients had a prior different diagnosis. All presented with fever and joint involvement. Eighty percent had malaise, 80% had odynophagia, 80% had an evanescent rash, 70% had myalgias, 50% had lymph node enlargement and 40% had splenomegaly. Laboratory showed leukocytosis in 80% and a high erythrocyte sedimentation rate in all. High ferritin levels were detected in 80%, and became an important diagnosis clue. Initial treatment was based on non steroidal antiinflammatory drugs, however 80% required steroids and 35% required methotrexate. Azathioprine, sulphalazine, hydroxychloroquine and leflunomide were used occasionally. Eleven patients had a single episode, nine had a relapsing disease and four had a chronic or persistent mode. CONCLUSIONS: Adult Still's disease must be suspected in patients with fever of unknown origin. An early diagnosis and adequate treatment of the disease are associated with a favorable evolution and prognosis.
20798946 Clinical features and hyperferritinemia diagnostic cutoff points for AOSD based on ROC cur 2012 Jan Hyperferritinemia has been reported in adult-onset Still's disease (AOSD). This study aims to investigate clinical features of AOSD in Chinese population and diagnostic value of different hyperferritinemia cutoff points based on ROC curve. A total of 48 patients from October 2002 to February 2007 diagnosed AOSD in the department of rheumatology, the first affiliated hospital of Sun Yat-set University were enrolled. A total of 86 patients mainly complaining fever >39°C for over one week and meeting Yamaguchi criteria but confirmed as non-AOSD by other serological or pathological tests were obtained from the same department as controls. Total serum ferritin levels were determined at the time of admission. Clinical features of AOSD in Chinese population were similar to previous studies. Significantly higher levels of total serum ferritin were presented in patients with AOSD (8100.7 ± 13678.5) compared with non-AOSD controls (448.3 ± 539.4) (P < 0.01). No differences were found in serum ferritin level between different categories of non-AOSD patients (P > 0.05). High value of area under receiver operating characteristic curve (ROC curve) suggested that ferritin was very predictive in AOSD diagnosis. Three cutoff points were picked based on clinical practice and ROC curve. Ferritin level ≥2,500 µg/L appeared to be highly specific for a diagnosis of AOSD, yet the low sensitivity may falsely ruled out patients with true AOSD. Hyperferritinemia ≥750 µg/L was seldom observed in inflammatory diseases or solid tumor. Hyperferritinemia ≥1,250 µg/L could mostly rule out other autoimmune diseases and hematologic diseases. Combined Yamaguchi criteria and hyperferritinemia gave better prediction for AOSD. In conclusion, different hyperferritinemia cutoff points observed in ROC curve help to optimize diagnostic and therapeutic strategy.
18839267 Multi-organ failure in adult onset Still's disease: a septic disguise. 2009 Jun The diagnosis of adult onset Still's disease is difficult in the absence of definite clinical and laboratory criteria. A delayed diagnosis of adult onset Still's disease was made in a 23-year-old female who developed multi-organ failure and disseminated intravascular coagulation with fingertip auto-amputation during a febrile illness considered septic due to the persistence of elevated serum procalcitonin concentration.
19802652 Ground-glass-like hepatocellular inclusions in the course of adult-onset Still's disease. 2010 Feb Ground-glass hepatocytes are the cardinal biopsy feature of chronic hepatitis B virus (HBV) infection and may also be present in other specific conditions, including Lafora's disease, cyanamide aversion therapy for alcohol use, patients with transplantation, uremia, and metabolic disorders. In this report, we present the case of a patient with adult-onset Still's disease who underwent percutaneous liver biopsy, which revealed ground-glass-like cytoplasmic inclusions and which is a very unusual finding.
20045371 Anti-IL-1 molecules: new comers and new indications. 2010 Mar The interleukin 1 family is composed by the interleukin 1 (IL-1) and its natural occurring inhibitor, the interleukin 1 receptor antagonist (IL-1Ra). The role of both molecules in rheumatoid arthritis has been widely established, and in this sense new molecules blocking IL-1 actions are under investigation. Anakinra is the recombinant form of IL-1Ra, and has proven to be well tolerated and indicated in the treatment of rheumatoid arthritis. Nevertheless, other molecules such as mAb anti-IL-1 and IL-1 Trap are being developed. Moreover, the recent relation of IL-1 in the inflammasome and pathways of innate immunity has lead to new indications of anti-IL-1 molecules, especially in the autoinflammatory syndromes as well as in other inflammatory diseases. Herein we have performed a review of the literature, limited to English language journals (PUBMED search: combination of descriptors IL-1 and anakinra, systemic juvenile idiopathic arthritis, adult's onset Still's disease, autoinflammatory syndromes, gout, pseudogout, ankylosing spondylitis, and systemic lupus erythematosus from January 1985-December 2008) emphasizing the possible new indications. Although sufficient data is not yet available to fully assess the efficacy and safety of anti-IL-1 molecules in patients with inflammatory disorders other than rheumatoid arthritis, new data is promising.
19040301 The mid-range of the adjusted level of ferritin can predict the chronic course in patients 2009 Jan OBJECTIVE: To find a measure that can predict the disease course in patients with adult onset Still's disease (AOSD). METHODS: We retrospectively investigated the medical records of 71 hospitalized patients with AOSD. Patients were divided according to chronic and nonchronic disease course. The initial laboratory results were defined as those at the time of admission, the extremely deviated laboratory results as the highest or the lowest results, and the adjusted laboratory results as area under the curve divided by the days of hospitalization. All measures were compared and the odds ratio (OR) for the chronic disease pattern was assessed. RESULTS: The mean age was 39.7+/-13.5 years and women accounted for 63 of the total 71 (88.7%). Thirty patients (42.3%) had self-limited disease, 9 (12.7%) intermittent disease, and 23 (32.4%) the chronic disease pattern (32.4%). Nine patients (12.7%) died. The initial levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ferritin, the highest levels of lactate dehydrogenase (LDH) and ferritin, and the adjusted level of ferritin in patients with chronic disease were significantly higher than those with nonchronic disease. Among them, only the middle range of the adjusted ferritin level (784.1-4120.0 ng/ml) was found to have a significant predictive value for the chronic disease pattern (OR 81.7, p=0.007). CONCLUSION: A novel measure, the adjusted level of ferritin during the first hospitalization, might be useful to predict progression to chronic disease in patients with AOSD.
19208566 Sensitivity of the classification of psoriatic arthritis criteria in early psoriatic arthr 2009 Feb OBJECTIVE: To determine the sensitivity of the CASPAR criteria in patients with early psoriatic arthritis (PsA). METHODS: Consecutive patients with a clinical diagnosis of PsA and a disease duration < 12 months were enrolled for study. The proportion of patients meeting the criteria (i.e., the sensitivity) was determined. RESULTS: Forty-four patients with early PsA (23 women, 21 men; mean age 51 yrs, range 16-90) were enrolled. Mean disease duration (+/- SD) was 15.8 +/- 14.3 weeks (range 0.1-50.9 wks). Thirty-four patients satisfied the criteria at the first visit (sensitivity 77.3%). Most patients met the skin and laboratory criterion, i.e., they were rheumatoid factor-negative, while only 2 satisfied the radiologic criterion. CONCLUSION: Our findings suggest a less satisfactory performance of the CASPAR criteria when applied in early PsA. Lower sensitivity could mainly depend on the small proportion of patients fulfilling the radiologic criterion.
20376668 Cholecystokinin octapeptide exerts its therapeutic effects on collagen-induced arthritis b 2011 Oct The purpose of this study was to evaluate the potential therapeutic effect of cholecystokinin octapeptide (CCK-8) on collagen-induced arthritis (CIA), an accepted murine experimental disease model with diverse histopathological features similar to human rheumatoid arthritis (RA). CIA was induced in DBA/1J mice by immunization with chicken collagen type II (CII). CCK-8 at different doses was intraperitoneally administered daily for 1 week. Mice treated with CCK-8 at doses of 5 and 10 nmol but not 1 nmol displayed much delayed onset of CIA and significantly lower incidence and decreased severity of arthritis. CCK-8 treatment significantly reduced the production of cytokines (IL-17, IL-23, IL-6 and TNF-α) and chemokines monocyte chemoattractant protein 1 in the joints of arthritic mice or in synovial cell culture supernatant, and increased the levels of IFN-γ and TGF-β. T cells from CCK-8 treated mice proliferated much less, produced low level of IL-17 and high levels of IFN-γ and TGF-β. Moreover, CCK-8 treated mice showed lower levels of CII-specific IgG, particularly that of IgG2a, in sera than those from control mice. These results indicate that CCK-8 is effective in suppressing both inflammatory and Th17 responses in CIA. CCK-8 may represent a new therapeutic modality for rheumatoid arthritis.
20120827 Improving recognition of psoriatic arthritis. 2009 Dec Psoriatic arthritis (PsA) is a common form of inflammatory arthritis but is underdiagnosed. Psoriasis affects over 1.5% of the UK population. Around 15% of these patients will be diagnosed with PsA, but up to 40% may have evidence of arthritis if reviewed thoroughly. PsA can be difficult to diagnose as patients present with a variety of different patterns of arthritis. Most patients with PsA have relatively mild skin psoriasis, but some have more significant disease. Only 10-20% develop arthritis before their skin disease. Many patients have mild skin psoriasis that they are unaware of, or have not had diagnosed. Joint involvement is far more variable in PsA, compared with rheumatoid arthritis, and patients may present with: monoarthritis; oligoarthritis; involvement of the distal interphalangeal joints; a rheumatoid arthritis-like picture with multiple joints involved including the small joints in the hand or axial disease producing symptoms similar to ankylosing spondylitis. Features such as dactylitis (uniform sausage-like swelling of the whole digit either finger or toe) and enthesitis (inflammation at the sites of muscle or tendon attachment to bone) may also help diagnose PsA. Skin disease is present in the majority of patients although not all. Hidden areas for psoriasis include: behind the ears; at the top of the natal cleft and around the umbilicus. Larger joints, particularly the knees, can develop very big effusions causing obvious swelling. Areas to test for enthesitis should include the Achilles tendon, plantar fascia, costochondral joints and the elbow. Patients with suspected PsA should be referred promptly to a rheumatologist for further assessment and treatment. Diagnosis of PsA can be made on clinical grounds but blood tests and radiographs are performed routinely to aid diagnosis. Initial therapy for PsA should include NSAIDs to ease pain and stiffness. Local injections of corticosteroids are recommended for peripheral arthritis (given IA) and dactylitis (usually by injection into the flexor tendon or adjacent joints). DMARDs are routinely used to treat all aspects of psoriatic disease, except spinal disease, and prescribing should be initiated by a specialist.
20224509 Efalizumab-induced inflammatory polyarthritis: what are the implications? 2010 Apr A 49-year-old female was started on efalizumab for severe psoriasis. Three weeks later, she developed rapidly progressive inflammatory polyarthritis associated with high titers of both rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) antibody. To our knowledge, this is the first reported case of efalizumab-induced anti-CCP-positive rheumatoid arthritis (RA). The polyarticular form of psoriatic arthritis (PsA) is associated with HLA-DR4, an antigen also associated with RA, and the presence of shared epitope alleles in PsA patients correlates with erosive disease, indicating a possible common mechanism of disease. CD4 T-cells play a prominent role in the pathogenesis of RA and PsA. Efalizumab theoretically modulates that role, appearing clinically to precipitate arthritis in a subset of PsA patients. On April 8, 2009, the makers of efalizumab announced a phased voluntary withdrawal of the drug from the US market because of progressive multifocal leukoencephalopathy cases. Further research using animal models of inflammatory polyarthritis is needed to determine the exact relationship between efalizumab and inflammatory arthritis, as well as to further explore the apparent connection between the inflammatory polyarticular form of PsA and RA.
19863773 Rheumatoid arthritis: GWAS or TMI? 2009 Oct 27 Genome-wide association studies are the most comprehensive and straightforward approach to teasing out the identity of genetic polymorphisms associated with any given disease or characteristic. With the availability of DNA banks from large cohorts of ethnically matched patients and healthy individuals it is now possible to define even marginal genetic associations between genetic polymorphisms and diseases. As increasing numbers of these studies are carried out and as associations with smaller and smaller risks are identified, there is the growing concern that the findings will be of increasingly marginal value. Thus, the glut of new genetic associations is rapidly overwhelming our interest in the results, a situation that could be described as TMI (too much information). Recent genetic association studies in rheumatoid arthritis suggest that we may be approaching the TMI stage of genome-wide association studies.
21794573 [Interleukin 6 in the physiopathology of rheumatoid arthritis]. 2009 Feb Interleukin (IL) 6 was identified in 1986 as a factor produced by T lymphocytes, that mediates growth and immunoglobulin synthesis on B lymphocytes. IL-6 is a member of a large cytokine family sharing a gp130 membrane receptor. This receptor mediates specific Jak/STAT3 activation, which induces widespread expression of pro-inflammatory and immunoregulatory genes. IL-6 mediates potent systemic responses, in organs distant from its local inflammatory sources, in a prominent fashion compared to other cytokines. Most specific effects involve hematopoiesis and hepatic acute phase reactants synthesis. IL-6 became a rheumatoid arthritis (RA) target due to its pro-inflammatory and joint destructive potential, as well as its participation in T and B immunoregulation. The therapeutic success of tocilizumab has confirmed IL-6 as an RA target. Although additional studies on the participation of IL-6 in RA physiopathology are needed, a number of indirect data point to a relevant position in this setting.