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ID PMID Title PublicationDate abstract
11751992 Fibroblast growth factor-2 determines severity of joint disease in adjuvant-induced arthri 2002 Jan 1 Rheumatoid arthritis (RA), a systemic inflammatory disease of unknown etiology, mainly affects synovial joints. Although angiogenic growth factors, including fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), may play a critical role in the development and progression of RA joint disease, little information is now available regarding their exact role in initiation and/or progression of RA. In this study, we show that both polypeptides were up-regulated in the rat joint synovial tissue of an adjuvant-induced model of arthritis (AIA), as well as human subjects with RA. FGF-2 overexpression via Sendai virus-mediated gene transfer significantly worsened clinical symptoms and signs of rat AIA, including hind paw swelling and radiological bone destruction, as well as histological findings based on inflammatory reaction, synovial angiogenesis, pannus formation, and osteocartilaginous destruction, associated with up-regulation of endogenous VEGF. FGF-2 gene transfer to non-AIA joints was without effect. These findings suggested that FGF-2 modulated disease progression, but did not affect initiation. Reverse experiments using anti-FGF-2-neutralizing rabbit IgG attenuated clinical symptoms and histopathological abnormalities of AIA joints. To our knowledge, this is the first report indicating direct in vivo evidence of disease-modulatory effects of FGF-2 in AIA, as probably associated with endogenous VEGF function. FGF-2 may prove to be a possible therapeutic target to treat subjects with RA.
12846052 Vitamin D receptor genotypes are not associated with rheumatoid arthritis or biochemical p 2003 May OBJECTIVE: Vitamin D is known to exert immunomodulatory effects. An overrepresentation of the b allele of the vitamin D receptor (VDR) has been detected in autoimmune diseases as type-1-diabetes and multiple sclerosis. VDR polymorphisms have been shown to influence bone metabolism and bone density. The aim of the present study was to examine the distribution of VDR alleles in German rheumatoid arthritis (RA) patients and their relation to bone turnover parameters. METHODS: 62 German RA patients were included and compared to 40 controls. Three VDR alleles were examined (Bsm I, Taq I and Fok I). In addition, serum intact osteocalcin (OC), parathyroid hormone, bone specific alkaline phosphatase (B-ALP), the carboxyterminal extension peptide of type I procollagen, 25-OH-vitamin D and urinary deoxypyridinoline (DPD) excretion were measured. Furthermore, C-reactive protein, erythrocyte sedimentation rate and rheumatoid factor were measured. RESULTS: We found a slightly higher frequency of the bB and tT-genotype in RA patients compared to controls, which was not statistically significant. OC and B-ALP were found to be significantly higher in RA patients with positive correlations between bone formation and resorption parameters indicating higher bone turnover in RA patients with maintained coupling. CRP in RA patients correlated with DPD and inversely with PTH. VDR genotype showed no association with bone turnover, family history or the presence of rheumatoid factor. CONCLUSIONS: Our results suggest that VDR polymorphisms do not play a major role in RA predisposition in Germans.
12579594 The assessment of rheumatoid arthritis and the acceptability of self-report questionnaires 2003 Feb 15 OBJECTIVE: To assess the acceptability of self-report questionnaires (SRQ) in clinical practice and to understand the value that rheumatologists give to various assessment methods in rheumatoid arthritis. METHODS: Rheumatologists who completed a training course in the use of SRQ in clinical trials and clinical practice used the SRQ in their practices. Six months later 221 rheumatologists completed a survey regarding their experiences in assessing rheumatoid arthritis and in the use of SRQ. RESULTS: Prior to the start of the program, 18% of rheumatologists used self-report questionnaires, 6 months later, 48% were using SRQ in their practices. Rheumatologists who did not use questionnaires placed less value on all assessment methods, and particularly on questionnaire assessments of function and pain. They also were more likely to report that questionnaires were difficult to use, not accepted by staff, were too long, and that they had limited staff. Rheumatologists who used the questionnaires reported none of these difficulties and were satisfied with the benefits provide by SRQ. When assessment measures were ranked, rheumatologist ranked ACR 20, radiography, and erythrocyte sedimentation rate/c-reactive protein as the least important in both clinical trials and in clinical practice, and they rated swollen and tender joint counts followed by SRQ as the most useful assessment tools. CONCLUSION: SRQ are well received by rheumatologists, and following a training program almost 50% continued to use SRQ in their practices. Those who used questionnaires were generally more positive about assessments and had little difficulty in the technical aspects of administration, scoring, and interpretation.
12867581 Serum cortisol reduction and abnormal prolactin and CD4+/CD8+ T-cell response as a result 2004 Jan OBJECTIVE: To investigate muscle energetics in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and measure serum cortisol, prolactin and CD4+/CD8+ T-cell levels during and after controlled exhaustive exercise. METHODS: Patients with RA (n = 7), patients with SLE (n = 6) and healthy individuals (HI) (n = 10) performed incremental cycle ergometry to the limit of tolerance. Ventilation, oxygen uptake (VO2) and carbon dioxide output were measured and the lactate threshold (LT) was estimated. Serum cortisol, prolactin, CD4+ and CD8+ lymphocyte subset levels were determined at baseline, peak exercise and 1 h after exercise. RESULTS: Exercise tolerance was reduced in patients with RA and patients with SLE, as reflected by peak VO2 and LT, but muscle energetics were not altered. In RA and SLE, there was significant reduction in cortisol levels at peak (-10%; P = 0.03) and post-exercise times (-36%; P = 0.05). Prolactin varied significantly at peak exercise in HI only (+60%; P = 0.05). There was a significant reduction in CD4+ T cells at peak exercise in RA (-15%; P = 0.02) and SLE patients (-8%; P = 0.04) and an increase after exercise in SLE patients (+11%; P = 0.03). In HI, CD8+ T cells increased significantly (+47%; P = 0.01) at peak exercise, but this was not found in RA and SLE patients. A significant reduction in CD8+ T cells was noted after exercise in SLE patients (-6%; P = 0.05). CONCLUSION: RA and lupus patients do not have significantly altered muscle energetics, but have abnormal cortisol, prolactin and CD4+/CD8+ T-cell responses to exercise. Further studies need to be carried out to evaluate whether short bouts of strenuous exercise have detrimental clinical effects.
12223980 Seronegative oligoarthritis: a 23-year follow-up study. 2002 Sep The aim of the study was to investigate the long-term outcome of non-specific seronegative oligoarthritis in adults. The study included 64 adult patients with recent (<6 months) seronegative oligoarthritis (rheumatoid factor negative, number of swollen joints 1-4 during the first 6 months). Follow-up examinations were carried out at onset and at 1, 3 and 8 years from entry. A total of 47 patients attended the 23-year follow-up. The endpoint outcome was good. Seven had mild erosions in the hands or feet. Only one patient with HLA-B27 developed bilateral sacroiliitis. Three patients had retired from work because of joint disease. The functional outcome of the patients analysed by HAQ was very good after 23 years: 0 in 33 and 0.1-0.9 in 12 of the 47 patients. Reclassification revealed a certain heterogeneity: one case each of rheumatoid arthritis, SLE and ankylosing spondylitis, two cases of post-traumatic arthritis, four of osteoarthrosis, and six of possible reactive arthritis. Out of the remaining 49 patients 15 were HLA-B27 positive and 16 had at least one of the psoriasis-related HLA antigens (HLA-B13, 17, w16). In conclusion, our 23-year prospective follow-up study of patients with seronegative oligoarthritis confirms their favourable outcome. The reason is that the endpoint diagnoses seemed to be similar to those of mild spondylarthropathies.
12629931 Cyclooxygenase-2: from arthritis treatment to new indications for the prevention and treat 2003 Jan The discovery of the isoenzymes cyclooxygenase-(COX-) 1 and COX-2 led to the development of newer nonsteroidal anti-inflammatory drugs (NSAIDs) designed to block COX-2, such as rofecoxib, celecoxib, and valdecoxib. Because of the specificity of COX-2 expression, COX-2 inhibitors have the potential to reduce the risk of gastrointestinal bleeding experienced with the use of classic NSAIDs. With their crucial role in the control of inflammation, the COX-2 agents originally were marketed for the treatment of rheumatoid and osteoarthritis. However, promising new indications for COX-2 agents in the prevention and treatment of cancer are under investigation. The role of aberrant COX-2 expression in the development of cancer has been studied most widely in patients with colon cancer and adenomas. Recent studies suggest that COX-2-derived prostaglandins may play an important role in tumor viability, growth, and control of metastasis. Possible new indications for the use of COX-2 inhibitors to prevent and treat cancers may be monumental. However, therapy with these agents is not without risk. Oncology nurses must be aware of the potential problems inherent in the use of COX-2 as well as COX-2 agents for chemoprevention in certain cancers.
12102471 Treating rheumatoid arthritis early with disease modifying drugs reduces joint damage: a r 2002 May BACKGROUND: Current disease management in rheumatoid arthritis (RA) has moved towards "inverting the therapeutic pyramid" by introducing disease-modifying anti-rheumatic drugs (DMARDs) early. Despite the logic of early DMARD therapy, there is a dearth of supportive evidence for this approach. We report a randomised controlled trial comparing sulphasalazine monotherapy with diclofenac monotherapy in early RA. The primary aim was to provide unequivocal evidence that early DMARDs prevent erosive damage. The secondary aim was to evaluate if sulphasalazine used alone has comparable symptomatic benefits to NSAIDs. METHODS: 117 patients with RA for under 12 months of diagnosis (mean 2 months) were randomised (62 sulphasalazine; 55 diclofenac). Sulphasalazine patients comprised 76% women, and 58% were rheumatoidfactor positive. Diclofenac patients comprised 74% women, and 54% were seropositive. 36% completed 12 months of therapy (16 sulphasalazine; 26 diclofenac); sulphasalazine was given for a mean period of 21 weeks and diclofenac for a mean period of 33 weeks. Results were analysed on an intention to treat basis. RESULTS: After 12 months the mean number of new erosions in patients randomised to receive sulphasalazine was 2.0 (95%CI 0.9, 3.1) and in patients randomised to receive diclofenac was 7.5 (95%CI 4.1, 10.9; p = 0.002 by Student's unpaired t-test). An analysis of valid compliant completers showed the mean number of new erosions in patients who received 12 months therapy with sulphasalazine was 2.3 (95%CI 0.6, 4.0) and in patients who received 12 months diclofenac was 10.5 (95%CI 5.0, 15.9; p = 0.018 by Student's unpaired t-test). The Ritchie articular index, swollen joint counts and pain scores decreased with both sulphasalazine and diclofenac, with mean falls in both groups of 15-20% at 2 weeks and 30-40% at 4 and 8 weeks. There were no differences between treatments. Disease activity scores showed similar highly significant mean decreases within both treatment groups (P < 0.001 in all cases) of 0.5 at 2 weeks and 1.0 at 4 weeks; at 12 and 26 weeks they were significantly lower with sulphasalazine (p = 0.036 and 0.045). 75% of the patients given sulphasalazine and 65% of those given diclofenac had one or more adverse events with no major differences between treatments. CONCLUSIONS: These results show that an accelerated dosing schedule of sulphasalazine has identical effects to diclofenac in reducing symptoms, indicating it is a rapidly effective DMARD. They also provide unequivocal evidence, analysed on an intention to treat basis, that early treatment with sulphasalazine significantly reduces the extent of radiological progression in active RA.
11754305 Neurologic manifestations of connective tissue disease. 2002 Feb The clinical features, diagnosis, and treatment of systemic lupus erythematosus, scleroderma, rheumatoid arthritis, Sjögren's syndrome, mixed connective tissue disease, Behcet's disease, Cogan's syndrome, and relapsing polychondritis are reviewed from a neurological perspective with an emphasis on pathogenic mechanisms and their relationship to treatment.
12585576 Should the cement mantle around the femoral component be thick or thin? 2003 Jan We have compared the survival and radiological outcome at ten years after total hip replacement using two techniques for preparing the femoral canal. The same prosthesis was used throughout and all operations were performed by the same surgical team. In technique 1 the canal was over-reamed by 2 mm and in technique 2 it was reamed to the same size as the prosthesis. Technique 1 was performed on 92 patients and technique 2 on 97 patients. The survival at ten years was 97.2% (90.6 to 99.2) for technique 1 and 98.8% (92.9 to 99.8) for technique 2. Vertical migration was greater in technique 1 (1.8 mm versus 1.0 mm at five years; p = 0.36). There were significantly more lytic lesions and radiolucent lines at five years (p = 0.0061) with technique 1. We conclude that technique 2 is not worse and may produce better long-term results than current teaching suggests.
12913925 Differential expression of leukotriene B4 receptor subtypes (BLT1 and BLT2) in human synov 2003 Aug To evaluate the role of leukotriene B4 (LTB4) receptors in inflammatory arthritis, we investigated the expression of BLT1 and BLT2 mRNA in synovial tissues of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods. BLT1 and BLT2 mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization in synovial tissues from 40 patients with RA and 10 patients with OA. Results. BLT2 (the low-affinity receptor for LTB4) showed stronger expression than BLT1 (the high-affinity receptor) in actively inflamed synovial tissue from patients with RA. Synovial macrophages, fibroblast-like cells, and lymphocytes expressed BLT2 mRNA in RA synovial tissues showing active inflammation. BLT2 mRNA was strongly expressed in the synovial lining cells, which also expressed 5-lipoxygenase, an enzyme that synthesizes LTB4. BLT1 and BLT2 mRNA expression in synovial tissues was stronger in RA than in OA by real-time quantitative PCR. In contrast, leukocytes infiltrating synovial fluid predominantly expressed BLT1 mRNA in patients with RA. It was recently reported that these 2 receptors for LTB4 have quite different pharmacological effects and a different tissue distribution. Conclusion. BLT2 is the main receptor mediating the effects of LTB4 in the synovial tissues of patients with RA; this suggests the possibility of developing a new therapy to block LTB4 in inflammatory arthritis.
12073796 [Corneal ulcers associated with rheumatoid arthritis]. 2002 Apr Keratoconjonctivitis sicca, scleritis and keratitis remain the major ocular manifestation, associated with rheumatoid arthritis. Corneal ulcers are a rare complication but can lead to perforation. Unstable epithelial barrier and immune disorders play a key role in the pathophysiology of such corneal melting. Moreover the association with systemic vasculitis reveals the need for an appropriate immunosuppressive treatment. New surgical approaches and early immunotherapy allow to maintain ocular integrity even if the visual prognosis is poor.
12808231 The induction of apoptosis by methotrexate in activated lymphocytes as indicated by fluore 2003 Apr The objectives of this study were to test the in vitro response of healthy non-activated, activated, and rheumatoid arthritis (RA) lymphocytes to methotrexate (MTX), and design an in vitro model for predicting the efficiency of MTX treatment for RA patients. Considering the RA profile of clonal-expanded CD4(+) T cells, phytohemagglutinin-activated mononuclear cells taken from healthy donors were incubated with different concentrations of MTX. The MTX-immunosuppressive effect was tested by fluorescence intensity measurements, including PI assay and annexin V assay. For simple detection, we used the Individual Cell Scanner (IC-S), which enables the measurement of early events in individual cells. Healthy mononuclear cells (MNC), and MNC derived from RA patients, were tested by the IC-S while utilizing fluorescence polarization (FP) measurements of fluorescein diacetate (FDA) as an established marker of activation or suppression. In healthy activated MNC, we found that MTX, through its early incubation period, interferes with the activation signal obtained by PHA and exerts an apoptotic signal, which is noted by increases in the FP. Comparing our model to six long-standing RA patients and five newly-diagnosed patients revealed significant differences in the FP measurements, including fluorescence depolarization as an early established measurement of lymphocyte activation, and hyperpolarization as a measurement of an early immunosuppressive effect. We conclude that MTX, an effective therapy for RA patients, could easily be tested by fluorescence polarization measurements of FDA before (or during) clinical use in order to predict its efficiency on a specific RA patient. Moreover, the FP measurements can be used for the diagnosis, and making timing and dosage decisions.
12723975 CD44 in rheumatoid arthritis. 2003 CD44 is a multistructural cell-surface glycoprotein that can theoretically generate close to 800 isoforms by differential alternative splicing. At present, several dozen isoforms are known. The polymorphic nature of CD44 might explain its multifunctionality and its ability to interact with many cell-surface and extracellular ligands, the principal one being hyaluronic acid (HA). Of the many CD44 functions, our review focuses on its involvement in cell-cell and cell-matrix interactions, as well as on its implication in the support of cell migration and the presentation of growth factors to their cognate receptors. Cells involved in pathological activities such as cancer cells and destructive inflammatory cells, and also normal cells engaged in physiological functions, use cell-surface CD44 for their localization and expansion at extravascular sites. This article reviews the evidence that the joint synovium of patients with rheumatoid arthritis (RA) contains considerable amounts of various CD44 isoforms as well as the HA ligand. The review also shows that anti-CD44 monoclonal antibody (mAb) directed against constant epitopes, shared by all CD44 isoforms, can markedly reduce the inflammatory activity of arthritis induced by collagen or proteoglycans in mice. Anti-CD44 mAb also interferes with the migration of RA synovial-like fibroblasts in vitro and is able to disturb the destructive interaction between RA synovial-like fibroblasts and the cartilaginous matrix. However, the transition from the experimental model to the patient's bedside is dependent on the ability to target the CD44 of cells engaged in RA pathology, while skipping the CD44 of normal cells.
14579034 [Sauvé-Kapandji procedure in destructive monarthritis of the distal radioulnar joint]. 2003 Oct INTRODUCTION: Detructive monarthritis of the distal radioulnar joint (DRUJ) is rare. PATIENTS AND METHODS: Three patients with destructive monarthritis of the DRUJ were treated by arthrodesis in the technique described by L. Sauvé and M. Kapandji, modified by I. A. Kapandji. Prospective evaluation with a mean follow-up of 12 months was performed. RESULTS: After cast immobilization for 3 weeks and mobilization, bone healing was uneventful. All patients were completely free of pain. Even a painless "snap" at the end of the ulna was mentioned in all, if rotating the forearm with powerful grasp. Rotation of the forearm improved completely. Wrist motion also improved after arthrodesis of DRUJ but did not reach the range of motion of the unaffected hand. Irritation of the ramus dorsalis nervi ulnaris was found in one patient 9.5 months after arthrodesis and disappeared after removal of the screws. CONCLUSION: Arthrodesis of the DRUJ with distal segmental resection of the ulna seams to be an effective therapy for destructive monarthritis of the DRUJ after failed non-operative and joint-preserving operative treatment.
15529384 Lectin-like oxidized low-density lipoprotein receptor 1 mediates matrix metalloproteinase 2004 Nov OBJECTIVE: To investigate for the presence of oxidized low-density lipoprotein (ox-LDL) and lectin-like oxidized LDL receptor 1 (LOX-1) in cartilage specimens from rheumatoid arthritis (RA) joints and to determine whether the interaction of ox-LDL with LOX-1 can induce matrix metalloproteinase 3 (MMP-3) in articular cartilage explant culture. METHODS: Human articular cartilage specimens obtained from patients with RA, osteoarthritis (OA), and femoral neck fractures were examined for LOX-1 and ox-LDL by confocal fluorescence microscopy. The association between ox-LDL and LOX-1 was evaluated by immunofluorescence analysis. Articular cartilage specimens from patients with femoral neck fractures were incubated with ox-LDL, with or without preincubation with neutralizing anti-LOX-1 antibody. MMP-3 synthesis by chondrocytes in explant cartilage was evaluated by immunofluorescence, and protein secretion into conditioned medium was monitored by immunoblotting and enzyme-linked immunosorbent assay. RESULTS: The majority of the RA chondrocytes stained positively with both anti-LOX-1 and anti-ox-LDL antibodies; however, no positive cells were found in OA and normal cartilage specimens. Anti-LOX-1 antibody suppressed the binding of DiI-labeled ox-LDL to chondrocytes in explant culture, suggesting that the interaction was mediated by LOX-1. In contrast to native LDL, ox-LDL induced MMP-3 synthesis by articular chondrocytes in association with the induction of LOX-1, which resulted in enhanced secretion of MMP-3 into the culture medium. Anti-LOX-1 antibody reversed ox-LDL-stimulated MMP-3 synthesis to control levels. CONCLUSION: Ox-LDL, principally mediated by LOX-1, enhanced MMP-3 production in articular chondrocytes. Increased accumulation of ox-LDL with elevated expression of LOX-1 in RA cartilage indicates a specific role of the receptor-ligand interaction in cartilage pathology in RA.
12638086 [Coping and appraisal in rheumatoid arthritis and fibromyalgia patients]. 2003 OBJECTIVES AND METHODS: In a cognitive framework appraisal and coping are seen as major factors in the adaptation of chronic pain patients. This study evaluates the differences between rheumatoid arthritis (N = 70) and fibromyalgia (N = 74) outpatients in regard to coping and appraisal, and the relationship between appraisal, coping and adaptation in general. RESULTS: In rheumatoid arthritis patients acceptance of illness and cognitive-reappraising coping prevails. In fibromyalgia patients, however, passive, emotion-focused coping and the judgement of illness as a "threat" or "punishment" (Lipowsky) was pronounced. A connection between individual appraisal of the illness and means of coping was observed. There was also a strong relationship between coping and adaptation, with one third of the variance of the mood variables explained by appraisal and coping. The presence of a psychic disorders played only a minor role. CONCLUSIONS: A detailed understanding of the relationship between appraisal, coping, and adaptation may contribute to improved treatment concepts in pain patients. One aim of psychotherapy in chronic pain patients should be to reduce passive, emotion-focused coping and to change maladaptative concepts of illness.
12447670 Morphological and molecular pathology of the B cell response in synovitis of rheumatoid ar 2002 Nov The synovitis of rheumatoid arthritis (RA) was long regarded merely as an unspecific chronic inflammatory process of minor diagnostic value and therefore did not play a major role in the understanding of the pathogenesis of RA. It is only in recent years, along with the observation that T and B cells are expanded oligoclonally in synovial tissue and that B cells are able to undergo a local germinal center (GC) reaction, that the synovial tissue has come to be regarded as a site of specific immune processes. The analysis of the immunoglobulin (Ig) gene repertoire had great impact on the understanding of B cell response in lymphatic organs and was subsequently applied to B cells from RA patients. The analyses of the variable (V) regions of the Ig heavy (H) and light (lambda) chains suggested that an antigen specific activation and differentiation of B cells into plasma cells (Plc) takes place in the chronically inflamed synovial tissue of patients with RA. It seems that in a subset of RA patients the synovial tissue develops into an ectopic lymphoid tissue that supports a local GC reaction. Ectopic GC are characteristic of RA; however, they are in general absent from synovitis of osteoarthritis (OA). Here the accumulation of Plc follows a different mechanism. Highly mutated VH genes suggest that in OA memory B cells migrate into the synovial tissue with subsequent differentiation into Plc but without further V gene diversification. Therefore in synovitis two patterns of B cell activation can be differentiated: the maturative and the accumulative type. These two patterns are not definitely disease linked. The maturative type is only found in RA whereas the accumulative type occurs in both diseases. Clinically RA is defined via serum antibodies to the constant region of Ig, so-called rheumatoid factor. However, the spectrum of autoreactive B cells in RA patients is wide and is based on the study of antibody specificities in serum, in synovial fluid and B cell lines derived from peripheral blood, bone marrow, synovial fluid and synovial tissue. These analyses defined non-organ-specific and organ-specific antigens. One can reasonably assume that the disease is far too complex to be explained by only a single antigen. There is a whole combination of antigens acting in a multistep manner that is responsible for RA pathogenesis. It can be hypothesized that chronic synovitis, which is the underlying mechanism of joint destruction, follows a three-step process: (a) initiation, (b) destruction, and (c) perpetuation. The characterization of antigens driving the local synovial B cell maturation and accumulation could lead to an understanding of the process perpetuating the disease. Identification of arthritogenic antigens may yield new avenues for diagnostics and immunotherapy but also a new approach for prevention by vaccines with antigens probably defined by synovial B cell reactivity.
12069703 [Pseudoachalasia and secondary amyloidosis in a patient with rheumatoid arthritis]. 2002 Jun Rheumatic diseases cover a wide spectrum of clinical syndromes and frequently present with gastrointestinal alterations. Systemic amyloidosis is associated with infectious diseases or chronic inflammatory processes such as rheumatoid arthritis and it can also affect the gastrointestinal tract. Although esophageal involvement is difficult to quantify because its course is frequently asymptomatic, systemic amyloidosis is recognized as a cause of motor disorders of the esophagus. Typical manometric patterns, including achalasia, are usually absent. Esophageal involvement due to amyloid deposits usually corresponds to primary amyloidosis as only a few cases of secondary esophageal deposits (type AA) have been described. We describe a new case of this exceptional association that first presented as dysphagia in a patient with rheumatoid arthritis. The initial suspicion of pseudoachalasia led to the definitive diagnosis of secondary amyloidosis.
15071491 Allelic variants in genes associated with hereditary periodic fever syndromes as susceptib 2004 Jun We investigated the hypothesis that low-penetrance mutations in genes (TNFRSF1A, MEFV and NALP3/CIAS1) associated with hereditary periodic fever syndromes (HPFs) might be risk factors for AA amyloidosis among patients with chronic inflammatory disorders, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), Crohn's disease, undiagnosed recurrent fevers and HPFs themselves. Four of 67 patients with RA plus amyloidosis had MEFV variants compared with none of 34 RA patients without amyloid (P value=0.03). The E148Q variant of MEFV was present in two of the three patients with TNF receptor-associated periodic syndrome (TRAPS) complicated by amyloid in two separate multiplex TRAPS families containing 5 and 16 affected members respectively, and the single patient with Muckle-Wells syndrome who had amyloidosis was homozygous for this variant. The R92Q variant of TNFRSF1A was present in two of 61 JIA patients with amyloidosis, and none of 31 nonamyloidotic JIA patients. No HPF gene mutations were found in 130 healthy control subjects. Although allelic variants in HPFs genes are not major susceptibility factors for AA amyloidosis in chronic inflammatory disease, low-penetrance variants of MEFV and TNFRSF1A may have clinically significant proinflammatory effects.
15228189 Autoantibodies to glucose-6-phosphate isomerase are elevated in the synovial fluid of rheu 2004 OBJECTIVE: This study investigated whether anti-glucose-6-phosphate isomerase (GPI) antibody in the synovial fluid is specifically related to human rheumatoid arthritis (RA). METHODS: Synovial fluid was collected from patients with RA, osteoarthritis (OA), gout, Behcet's disease, or ankylosing spondylitis. GPI-binding activity was measured in the synovial fluid using a surface plasmon resonance (SPR) biosensor. RESULTS: The mean level of anti-GPI signal in the synovial fluid of RA patients was significantly elevated compared with that of OA patients (2.84 +/- 1.41 AU versus 1.19 +/- 0.42 AU, respectively; p < 0.0001). Anti-GPI signals in the synovial fluids of patients with non-rheumatoid arthritis, such as gout, Behcet's disease, or ankylosing spondylitis were significantly lower than in the synovial fluid of RA patients (p < 0.005), and were similar to those of OA patients. CONCLUSION: Our study indicates that anti-GPI antibody in the synovial fluid is specifically related to RA, and suggests that GPI and its autoantibody might be important in the pathogenesis of human RA.