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

ID PMID Title PublicationDate abstract
11723281 Onset of multiple sclerosis associated with anti-TNF therapy. 2001 Nov 27 Therapies aimed at inhibiting tumor necrosis factor (TNF), a proinflammatory cytokine implicated in autoimmune disease are effective, especially for rheumatoid arthritis. We report a patient with new onset MS closely associated with the initiation of anti-TNF therapy for juvenile rheumatoid arthritis. It is possible that the inhibition of TNF triggered MS in this individual.
10493689 Resting energy expenditure and nutritional status in children with juvenile rheumatoid art 1999 Sep OBJECTIVE: Undernutrition is frequently encountered in children with juvenile rheumatoid arthritis (JRA). We assessed resting energy expenditure (REE) in relation to nutritional status and body composition in patients with JRA. METHODS: We selected 33 children (age 6 to 18 yrs) with JRA (13 oligoarticular, 10 polyarticular, 10 systemic JRA) and 17 controls matched for age and sex. Nutritional status was assessed for height, weight, and fat-free mass (FFM), and REE was measured with indirect calorimetry. RESULTS: Nutritional status in the patients with systemic JRA was diminished compared to the controls for height (140 vs. 159 cm; p<0.01) and FFM (28 vs. 38 kg; p = 0.03). Oligo and polyarticular patients with JRA had normal height and FFM. No significant differences existed in crude REE among the groups. However, after correcting REE for body weight and FFM, the patients with systemic JRA, compared to controls, had 18% higher REE per kg body weight (159 vs. 134 kJ/kg/day; p<0.01) and 21% higher REE per kg FFM (196 vs. 162 kJ/kg/day; p<0.01). Oligo and polyarticular JRA patients had 8% increased values for REE per kg body weight or FFM, but these differences were not statistically significant. CONCLUSION: Patients with systemic JRA show stunting, low FFM, and a significantly increased REE when nutritional status is taken into account. These data suggest that assessment of individual energy requirements should include correction for fat-free mass in the treatment of malnutrition in patients with systemic JRA.
10857800 Polymorphism at NRAMP1 and D2S1471 loci associated with juvenile rheumatoid arthritis. 2000 Jun OBJECTIVE: To examine the role of NRAMP1 in susceptibility to juvenile rheumatoid arthritis (JRA). METHODS: DNA from 119 JRA patients (72 pauciarticular, 47 polyarticular) and 111 healthy controls from Latvia was genotyped for a functional repeat polymorphism in the promoter of NRAMP1 and a linked (<150 kb) microsatellite D2S1471. The findings were compared with those from HLA-DQ alleles typed previously. Chi-square analyses were performed using the Mantel-Haenszel test and stratification according to pure Latvian or pure Russian descent. Haplotype analysis was performed using the Associate program to implement the expectation-maximization algorithm based on the gene-counting technique. RESULTS: Allele 3 at NRAMP1 conferred increased risk (odds ratios [ORs] 2.26, 2.31, and 2.19; P = 0.0006, 0.003, and 0.019) of disease in the JRA, pauciarticular, and polyarticular patient groups, respectively. Allele 2 conferred protection (OR 0.44, 0.43, and 0.46). Alleles at D2S1471 that conferred susceptibility (6 and 12) or protection (11) did so only when on a haplotype with alleles 3 or 2, respectively, at NRAMP1. Allele 3 at NRAMP1 was additive with HLA-DQ7 for susceptibility (OR 3.71, 3.71, and 4.02), and allele 2 at NRAMP1 was additive with HLA-DQ5 for protection (OR 0.19, 0.08, and 0.12). CONCLUSION: The NRAMP1 allele conferring susceptibility to JRA drives high levels of NRAMP1 expression, while the allele associated with protection drives low levels. These 2 alleles are inversely associated with susceptibility to infectious disease, consistent with their maintenance in populations through balancing selection.
10421569 Autoimmunity: Another pathway towards arthritis. 1999 Jul 15 A new pathway leading to arthritis has been revealed by the discovery that antibodies specific for a ubiquitously expressed antigen are able to transfer a severe arthritic phenotype in mice. This new model will be useful for further analyses of the different pathways involved in rheumatoid arthritis.
11080999 Decreased physical function in juvenile rheumatoid arthritis. 1999 Oct OBJECTIVE: To assess the extent of physical disability in juvenile rheumatoid arthritis (JRA), classified according to subtype, and whether synovitis or flexion contractures are present on examination. METHODS: This retrospective study included 88 JRA patients and 50 controls without musculoskeletal disease. The outcome measure was the disability index (DI) derived from the Childhood Health Assessment Questionnaire (CHAQ). RESULTS: DI scores for JRA patients with synovitis (mean 0.49, range 0-1.88) and without synovitis (mean 0.37, range 0-1.75) were significantly higher (P < 0.001 for both groups) than for controls (mean 0.06, range 0-0.75, P < 0.001), but not significantly different from one another. Similarly, DI scores for JRA patients with and without any flexion contractures were higher than for controls, but not significantly different from one another. DI scores for JRA patients with both synovitis and flexion contractures were significantly higher than DI scores for JRA patients with neither, but were not distinguishable from JRA patients with synovitis only or flexion contractures only. Likewise, DI scores for JRA patients lacking synovitis and flexion contractures were not significantly different than those for JRA patients with one or the other. DI scores for systemic and polyarticular patients were higher than for pauciarticular patients, and DI scores for all 3 subtypes were higher than for controls. CONCLUSION: Our findings suggest that many JRA patients, including those with pauciarticular JRA, have problems with physical function, even when synovitis and flexion contractures are not present. Further attention and research is needed to elucidate the causes or origins of disability in JRA patients with seemingly well-controlled disease. We recommend that health status instruments like the CHAQ be more widely used for JRA patients to complement other assessments, especially in planning occupational and physical therapy.
10518958 [Adult-onset Still's disease. Report of 5 cases]. 1999 Apr The authors report 5 cases of Still's disease in adults whose symptoms were mainly characterised by high fever, transient exanthema, polyarthralgia and/or polyarthritis, lymphoadenomegaly, splenomegaly and neutrophil leukocytosis. Assays for leukocytosis were positive, as were those for inflammatory markers and serum ferritin was also high in all 3 patients in which it assayed. On the contrary, serum ferritin latex test, Waaler-Rose reaction and all other tests commonly used to diagnose long-term fevers were all negative. All the subjects examined recovered after prolonged steroid therapy. Only one patient reported severe sequelae in the hip joints and subsequently underwent bilateral hip replacement surgery.
10711510 Overview of the radiology of juvenile idiopathic arthritis (JIA). 2000 Feb Plain films remain the basic tool for diagnosis and follow-up evaluation of juvenile idiopathic arthritis (JIA). In this paper, we review the new classification of JIA: systemic arthritis. oligoarthritis (persistent), oligoarthritis (extended), polyarticular arthritis (rheumatoid factor negative), polyarticular arthritis (rheumatoid factor positive), enthesitis-related arthritis, psoriatic arthritis and unclassified arthritis. We will also review regional abnormalities of three stages: an early stage, an intermediate stage, a late stage, as well as the differential diagnosis.
9458222 Interleukin 1beta mediated calciotropic activity in serum of children with juvenile rheuma 1998 Jan OBJECTIVE: To detect the presence and source of calciotropic activity in the serum of children with juvenile rheumatoid arthritis (JRA). METHODS: Metabolic evaluation of an adolescent with polyarticular JRA and hypercalcemia/hypercalciuria included testing with a bone disc bioassay. The bioassay detects calciotropic activity (increased bone resorption or reduced bone formation) in serum. Interleukin 1 receptor antagonist (IL-1RA) was added to patient sera to test the role of IL-1beta. The results in this index case prompted additional study in 9 children with JRA. Correlation of calciotropic activity with disease activity score, erythrocyte sedimentation rate (ESR), and urinary calcium excretion was by Spearman rank correlation. RESULTS: Calciotropic activity was found in 2 consecutive samples from the index patient. This activity was eliminated by addition of IL-1RA (p < 0.001 compared to serum alone). Testing of the other 9 children showed calciotropic activity at least once in 7/9 and 10/15 samples studied. Addition of IL-1RA completely (6/8) or partially (2/8) neutralized calciotropic activity (p < 0.001 compared to serum alone) in the specimens available for testing. Calciotropic activity did not significantly correlate with disease activity score, ESR, or urine calcium. CONCLUSION: Our data indicate the presence of IL-1beta mediated calciotropic activity in the sera of children with JRA, and suggest a role for IL-1beta in JRA associated osteopenia.
9045866 Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-li 1997 Feb 15 Stunted growth is a major complication of chronic inflammation and recurrent infections in children. Systemic juvenile rheumatoid arthritis is a chronic inflammatory disorder characterized by markedly elevated circulating levels of IL-6 and stunted growth. In this study we found that NSE/hIL-6 transgenic mouse lines expressing high levels of circulating IL-6 since early after birth presented a reduced growth rate that led to mice 50-70% the size of nontransgenic littermates. Administration of a monoclonal antibody to the murine IL-6 receptor partially reverted the growth defect. In NSE/hIL-6 transgenic mice, circulating IGF-I levels were significantly lower than those of nontransgenic littermates; on the contrary, the distribution of growth hormone pituitary cells, as well as circulating growth hormone levels, were normal. Treatment of nontransgenic mice of the same strain with IL-6 resulted in a significant decrease in IGF-I levels. Moreover, in patients with systemic juvenile rheumatoid arthritis, circulating IL-6 levels were negatively correlated with IGF-I levels. Our findings suggest that IL-6-mediated decrease in IGF-I production represents a major mechanism by which chronic inflammation affects growth.
9493534 Results of 2-stage reimplantation for infected total knee arthroplasty. 1998 Jan Optimum treatment of the infected total knee arthroplasty has not been clearly established. To clarify the efficacy of two-stage reimplantation, experience with 66 infected total knee arthroplasties in 64 patients who had been treated with 2-stage reimplantation total knee arthroplasty between September 1980 and October 1993 was reviewed. Of these, 55 knees in 54 patients were available for follow-up examinations at an average of 61.9 months (range, 28-146 months). The initial diagnoses were rheumatoid arthritis (14 knees) and osteoarthritis (41 knees). Reimplantation was successful in 80.0% of knees with low-virulence organisms (coagulase-negative Staphylococcus, Streptococcus), 71.4% with polymicrobial organisms, and 66.7% with high-virulence organisms (methicillin-resistant Staphylococcus aureus). Reimplantation was successful in 82% of patients with osteoarthritis and in 54% of patients with rheumatoid arthritis (P = .024). The success rate was 92% if infection occurred after primary arthroplasty but only 41% if after multiple previous knee operations (arthroscopy, osteotomy, or revision total knee arthroplasty) (P < .001).
11215160 [A case with juvenile rheumatoid arthritis who developed cerebral vasculitis and venovascu 2000 Oct On November, 1997, a 15-year-old boy visited our hospital because of headache, fever and arthralgia. He was treated with 5 mg/day of prednisolone thereafter. On October 21, 1998, he was admitted because of remittent fever and multiple arthralgia and diagnosis of juvenile rheumatoid arthritis (JRA) was made. He was also found to have hypertension of 210/110 mmHg, and soon developed ptosis of the eye, facial paresis and perceptive deafness of the right side. Cerebrospinal fluid showed protein of 98 mg/dl and mildly elevated IgG, IgA and IgM levels with normal cell count. Brain MRI examination revealed multiple cerebral lesions in the frontal, parietal and cerebellar areas on the right, whose cause was thought to be vasculitis. Renal angiography demonstrated a right renal artery stenosis, compatible with renovascular hypertension. He was treated with 60 mg of prednisolone per day, which brought about a satisfactory improvement of the above rheumatic and neurologic signs. On November 17, 1998, he received a follow-up study of MRI, which failed to show any cerebral lesions, supporting the effectiveness of prednisolone. An angiotensin converting enzyme inhibitor successfully normalized hypertension and renin activity in serum, although renal blood flow did not increase.
11123018 Cytokines and the immunopathology of the spondyloarthropathies. 1999 Oct In contrast to rheumatoid arthritis (RA), the triggering antigens are known in reactive arthritis (ReA) and Lyme arthritis. Thus, in these arthritides the antigen-specific T-cell response can be investigated in much detail and lessons possibly learned for other spondyloarthropathies (SpA) such as ankylosing spondylitis (AS) where T cells may well also play an important role in the pathogenesis. This article focusses on the immunopathology of the SpA, ReA, and AS with special reference to T cells and cytokines.
10990175 Update in Sjögren syndrome. 2000 Sep Sjögren syndrome (SS), the second most common autoimmune rheumatic disease, refers to keratoconjunctivitis sicca and xerostomia resulting from immune lymphocytes that infiltrate the lacrimal and salivary glands. However, differential diagnosis remains confusing due to the high prevalence of vague symptoms of dryness, fatigue, and myalgias in the general population. The problems of diagnosis are further compounded by the finding of "positive" antinuclear antibodies in a high percent of the general population. Unless minor salivary gland biopsies are read by experienced observers, nonspecific changes of sialadenitis are frequently confused with the focal lymphocytic infiltrates that are characteristic of SS. The distinction between fibromyalgia patients with low titer antinuclear antibodies and primary SS remains difficult. Even in patients fulfilling strict criteria for SS, the genomic search for critical genes has proven difficult due to the multigenic pattern of inheritance and strong role of currently undefined environmental factors. No single environmental factor has been detected in the majority of SS patients. SS-like syndrome has been detected in certain patients with HTLV-1 and hepatitis C infection, providing clues to pathogenesis. Even in SS patients with marked sicca symptoms, minor salivary gland biopsy shows that almost 50% of glandular cells are still detected on biopsy. These results imply the importance of immune factors such as cytokines and autoantibodies in decreasing neuro-secretory circuits and induction of glandular dysfunction. Of potential importance, an antibody against muscarinic M3 receptor that can decrease secretory function when injected into rodents is frequently found in the sera of SS patients. Newly developed topical and oral therapies can ease the oral and ocular dryness. Orally administered agonists of the muscarinic M3 receptor (pilocarpine and cevimeline) have recently been approved by the US Food and Drug Administration to increase salivary secretion. Topical ocular use of low-dose corticosteroids or cyclosporin may decrease conjunctival surface inflammation. In a Phase II double-blind study, orally administered interferon alpha (150 U) led to improved saliva flow and symptoms. In pregnant patients with evidence of fetal distress, oral dexamethasone is preferred because this agent crosses the placenta effectively. In animal models, antagonists of tumor necrosis factor and inhibitors of de novo pyrimidine synthesis appear promising.
11393497 Incidence of physician-diagnosed primary Sjögren syndrome in residents of Olmsted County, 2001 Jun OBJECTIVES: To estimate the incidence of physician-diagnosed primary Sjögren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients. PATIENTS AND METHODS: We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk. RESULTS: Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia. CONCLUSIONS: The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.
17344708 The prevalence of rheumatoid arthritis in the Qassim region of Saudi Arabia. 1998 BACKGROUND: Although rheumatoid arthritis (RA) of varying degrees of severity has been seen in our clinics, there is no statistical evidence of the magnitude of the problem in Saudi nationals. We conducted this study to determine the prevalence of RA in the Al Qassim Region of Saudi Arabia. PATIENTS AND METHODS: Five thousand eight hundred and ninety-one Saudi adults, aged 16 years and over, were studied in a house-to-house survey in the Al Qassim Region. RESULTS: Of the 5891 adults studied, 13 cases of RA were identified, using the criteria set for the diagnosis of RA by the American College of Rheumatology. Thirty-five percent of our patients showed positive rheumatoid factor. CONCLUSION: The prevalence of RA in Al Qassim was estimated at 2.2 per thousand people. It was also noted that the prevalence of the disease increased with age, and that it was more common in females.
10833937 [Classification of idiopathic juvenile arthritis]. 2000 Feb 10 We present a review of the criteria for the classification of juvenile arthritides. Historical aspects, the present situation and proposals for new criteria are outlined. The most commonly used classification criteria today are the European juvenile chronic arthritis criteria (JCA), the European League Against Rheumatism (EULAR) criteria, and the American juvenile rheumatoid arthritis (JRA), the American Rheumatoid Association (ARA) criteria. They differ in nomenclature and have different inclusion and exclusion demands. This has made it difficult to compare studies using different criteria. Neither of them can define homogeneous subgroups of disease. The most recent proposal for new classification criteria of juvenile arthritides is that of the International League Against Rheumatism, ILAR. They are primarily designed to define homogeneous subgroups of disease. The goal is also to obtain an international consensus. Advantages and disadvantages are discussed in this article. The criteria have not yet been validated, and should not be used by clinicians until they have been approved by the international scientific society. We also present guidelines recommended for the classification of juvenile arthritis in Norway today. We recommend using the term juvenile arthritis. Disease duration of arthritis must be at least six weeks. A diagnosis of arthritis should not be made on painful and restricted joint movement alone, as is the case in both the EULAR and ARA criteria today, but at least be based on definite swelling of joints verified by either clinical examination and/or by imaging techniques such as ultrasound, X-ray or EMR.
9764301 Rheumatoid nodules of the larynx. 1998 Jun A 67-year-old woman with rheumatoid arthritis was hospitalized because of dysphagia and severe nodulosis. Over a two-year period the patient had been treated with methotrexate. A computed tomography (CT) scan of the neck showed a 2 x 2 cm large tumour behind the top left lateral thyroid cartilage. A biopsy taken during direct laryngoscopy showed it was a rheumatic nodule. Treatment with colchicine reduced the patient's dysphagia. As methotrexate is used increasingly in the treatment of rheumatoid arthritis and as this particular drug causes rheumatic nodules in five to 10 per cent of the patients, it must be foreseen that the incidence of nodules in the upper airways will increase.
10025145 [Pseudophakia in children with juvenile arthritis]. 1998 Dec BACKGROUND: Cataract secondary to juvenile rheumatoid arthritis is a severe, vision-threatening complication in early childhood. Intraocular lens implantation is controversial. The follow-up of four pseudophakic eyes of three patients and their perioperative therapeutic regimen were retrospectively analyzed. Early and late postoperative complications are reported. PATIENTS AND METHODS: Both girls had lens aspiration and posterior lens implantation at the ages of 6 and 12 years, the boy at the age of 10 and 14 years. All patients had relapsing anterior uveitis. The follow-up time was 3 years (1-6 years). One girl was diagnosed with sarcoidosis, causing juvenile arthritis. Both girls had perioperative methothrexate and prednisolone therapy. The boy had azathioprine therapy at the time of his first cataract surgery; later he had no systemic therapy. Both girls' intraocular lenses were implanted at different eye hospitals. RESULTS: Both girls had severe inflammatory reactions after surgery. At the hospitals both eyes had surgical revision for iris capture. In one case this was combined with exchanging the intraocular lens. Iris capture persisted for this eye and later vitrectomy with silicone oil filling was necessary to delay phthisis, resulting in amaurosis. For two pseudophakic eyes vitrectomy was necessary later because of severe vitreous opacities, but visual acuity was severely diminished by chronic cystoid macular edema and epiretinal membranes. The boy developed in his second eye intermittent iris bombata and persistent secondary glaucoma, visual acuity was stabilized at 0.5. CONCLUSIONS: Secondary cataract due to juvenile rheumatoid arthritis or sarcoidosis is a difficult situation for phacoemulsification with intraocular lens implantation in children. For severe inflammatory complications intense local and systemic anti-inflammatory therapy is mandatory. Visual prognosis is reduced for the uveitic posterior segment and glaucoma complications. IOL implantation can be recommended for only a very few patients.
17984875 The Rheumatoid hip. 2000 Dec 30 Rheumatoid Arthritis (RA) is among the most common systemic diseases of connective tissue, affecting 1,5% of the population. In recent years about 30 000 new cases of RA have been reported annually. The rheumatoid process has a progressive course, leading to system-wide destruction of bones and joints, along with damage to many other organs and systems. The treatment team involved in managing cases of RA must be composed of specialists from many different fields: orthopedic surgeons, rheumatologists, physiotherapists, social workers, occupational therapists, and visiting nurses.
The treatment goal is to improve the patient's quality of life, to reduce or eliminate pain, and in the most severe cases to facilitate nursing care. In the surgical treatment of these patients the procedures used include synovectomy, joint debridement, soft tissue relaxation operations, arthrodesis, osteotomy, resection arthroplasty, and joint replacement. Among the more than 100 known connective tissue diseases, the hip joint is most commonly involved in cases of rheumatoid arthritis and ankylosing spondylitis. In cases of substantial destruction of the hip, the treatment of choice is joint replacement. Both cemented and cementless prostheses are used in the treatment of RA patients, depending on the surgeon's experience and the patient's age, general clinical status, and the quality of the bone tissue. Postoperative treatment in these patients does not differ from the generally accepted standards for the treatment of degenerative diseases. Based on the author's own experience in the Rheumatoorthopedic Department at the Institute of Rheumatology, it can safely be stated that hip joint replacement is a valuable and well tested method in the treatment of destructive changes to the hip joints in RA patients.
10981654 A case of adult-onset Still's disease complicated by non-Hodgkin's lymphoma. 2000 Left cervical lymphadenopathy developed in a 50-year-old male who had a history of adult-onset Still's disease for the preceding 18 months. Still's disease is characterized by rash, fever, and leukocytosis. Lymphadenopathy has been reported in about 60% of the patients, and most histopathologic studies have shown non-specific reactive hyperplasia. However, in this case, an open biopsy of the cervical node revealed a histology of diffuse large B-cell lymphoma. The B-cell malignant lymphoma that developed may have resulted from a sequential progression of a previous stage of benign lymphoproliferative lesion. Our case suggests that the pathophysiology of adult-onset Still's disease involves the stimulation of lymphoid systems to the point of progression towards lymphoma. Malignant lymphoma should be added to the list of life-threatening complications which, although rare, are associated with this disease.