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ID PMID Title PublicationDate abstract
14571456 Positive salivary gland biopsy, Sjögren syndrome, and neuropathy: clinical implications. 2003 Nov The relationship between neuropathy and Sjögren syndrome has been predicated largely on sicca symptoms or serological abnormalities rather than salivary gland pathology. We reviewed consecutive neuropathy patients who had had a lip biopsy to identify features of the neuropathy that were associated with a positive lip biopsy suggesting Sjögren syndrome. Twenty of 54 neuropathy patients were biopsy positive; 13 had a painful or nonspecific sensory neuropathy and only 4 were ataxic. Sicca symptoms were not associated with a positive biopsy (P = 0.14). Serological abnormalities were found more often in the biopsy-positive group (P = 0.008), but anti-Sjögren syndrome A or B (anti-SSA or SSB) antibodies were detected in only 30%. There were no other clinical or electromyographic (EMG) features associated with a positive biopsy. From this experience, we conclude that: (1). most patients with neuropathy and a positive lip biopsy for Sjögren syndrome have a painful, distal, sensory axonal neuropathy; (2). there are no clinical or EMG features that are predictive of a positive lip biopsy; (3). ataxic neuropathy is uncommon; and (4). the lack of sicca symptoms or anti-SSA or SSB antibodies in patients with neuropathy does not exclude Sjögren syndrome based upon salivary gland pathology.
12215905 Immunoglobulin kappa light chain gene alleles are not associated with primary Sjögren's s 2002 Oct The immunoglobulin kappa (Km) light chain gene is polymorphic and is believed to play a role in the pathology of infectious and autoimmune diseases. Polymorphisms within the constant region of the Km gene encode three alleles designated Km1, Km1,2 and Km3. Previous studies using serological detection of Km allotypes reported associations between specific Km allotypes, systemic lupus erythematosus and the presence of anti-La antibodies, yet these findings were not confirmed in other studies. In order to more precisely define any associations between Km alleles and anti-Ro/La antibodies we used the polymerase chain reaction and restriction fragment length polymorphisms for Km genotyping in a large cohort of patients with primary Sjögren's syndrome (SS). No associations were observed between specific Km alleles and primary SS when compared with a control population, nor within serologically defined subsets of SS patients. We conclude that Km alleles are not associated with primary SS or the Ro/La autoantibody response.
12760805 [Clinical characteristics of patients with dry eye syndrome]. 2003 Jan OBJECTIVE: To learn the clinical characteristics of patients with dry eye syndrome. METHODS: The following items were recorded in 115 patients (229 eyes) with dry eye, including symptoms, causation, systematic diseases, slit-lamp examination, tear break-up time, basal and reflex Schirmer's test, vital staining (fluorescent and rose bangle) and meibomian gland dysfunction examination. Rheumatoid factor and auto-antibody detection were performed in Sjögren's syndrome suspected patients. RESULTS: Aqueous tear deficiency (ATD, 48.7%) ranked the most common type, followed by over-evaporation dry eye (34.8%), mixed type (13.9%) and conjunctivochalasis (3.5%). In all the causes of the dry eye, about 11.3% had Sjögren syndrome (SS). Females suffering from dry eye were more than males, especially SS. Dryness was the most common symptom (84.0%), especially in ATD patients, then followed by ocular fatigue (72.0%), foreign body sensation (64.0%) and impairment of vision (56.0%). The ocular irritation was more severe in meibomain gland dysfunction (MGD) patients than in ATD patients. Among the results of tear break-up time (BUT), rose bangle (Rb) staining and fluorescent (Fl) staining in all types of dry eye, significant relationship was found among them, especially between Rb and Fl score (r = 0.612, P = 0.000). SS patients had much more severe abnormality in all the four signs than non-SS aqueous tear deficiency (NSTD) and MGD patients. However, in the comparisons of BUT, Rb and Fl between NSTD and MGD patients, there were no significant differences. CONCLUSION: Symptoms combined with examinations of BUT, Schirmer's test, Fl and Rb staining and meibomian gland function are the necessary means to diagnose most of the dry eye patients.
12427434 CT and MR findings of bilateral lacrimal gland enlargement in Sjögren syndrome. 2002 Nov Two women with primary Sjögren syndrome underwent computed tomography (CT) and magnetic resonance (MR) imaging because of bilateral lacrimal gland enlargement. Histopathologic confirmation was obtained in both patients. Of the four lacrimal glands, one had lymphoepithelial disease, two had pseudolymphoma and one had mucosa-associated lymphoid tissue (MALT) lymphoma, respectively. From the imaging findings, however, it was not possible to differentiate benign lymphoproliferative disorders and malignant lymphoma.
12126064 Involvement of Fas/Fas ligand in the induction of apoptosis in chronic sialadenitis of min 2002 Mar The role of apoptosis and contribution of Fas/FasL systems in the pathogenesis of Sjogren's syndrome (SS) are still controversial. With serial sections, we explored apoptosis assessed by the dUTP nick end labeling (TUNEL) method and expression of Fas and FasL by immunohistochemistry, and compared their distribution in minor salivary gland (MSG) of SS and sialolithiasis (SIL) patient tissues. Fas and FasL were co-localized in ductular and acinar cells of SS and SIL TUNEL+ cells co-distributed with the Fas and FasL expressing cells in ductular and acinar cells of SS in the vicinity of lymphocytic infiltration, while not in those of SIL Moreover, to morphologically confirm apoptosis, we identified TUNEL-positive(+) cells in the MSGs of SS at the ultra structural level by applying an inversion method to paraffin-embedded sections stained by TUNEL method. Surprisingly, these cells did not show characteristic apoptotic figures although TUNEL products were deposited on the hyperchromatin of acinar and ductular cells. On the other hand, acinar and ductular cells of SIL included clusters of TUNEL+ apoptotic bodies as did those cells by phagocytosis or having fallen into the ductular lumen. These findings suggest that Fas and FasL expressed in ducts and acini of chronic sialadenitis in SS patients induce apoptosis, possibily in an autocrine and/or paracrine manner.
11892716 Co-occurrence of spondyloarthropathy and connective tissue disease: development of Sjögre 2002 Jan Spondylarthropathies (SpA) and connective tissue diseases (CTD) are clinically distinct entities which, at first glance, seem to have little in common. However, a link between SpA and CTD has recently been suggested by a study in which a higher prevalence of Sjögren's syndrome (SS) and sicca symptoms was reported in patients with ankylosing spondylitis (AS) and undifferentiated SpA (1). Another link between SpA and CTD is a possible side effect of a DMARD widely used to treat SpA: sulfasalazine (SAS). SAS was reported to induce antinuclear antibodies (ANA) and systemic lupus erythematosus (SLE)-like syndromes such as drug-induced lupus. This report describes a 54-year-old white male, HLA B27-positive AS patient with some syndesmophytes who, after 15 years of disease, developed SS with salivary gland involvement, Raynaud's syndrome and anti-Ro antibodies. Then, 20 years after the onset of AS, he became acutely ill, suffering severe myositis and myocarditis along with swollen hands and highly elevated autoantibody titers recognizing UIRNP; his condition was interpreted as mixed connective tissue disease (MCTD). The patient had been treated with SAS and azathioprine (AZA) alone several times during the last years because he had not tolerated other DMARDs. A combination of both drugs had been prescribed 3 weeks before a severe flair because of progredient high disease activity with painful peripheral arthritis of the MCP and PIP joints which, however, had not shown radiographic erosions. We describe the rare development of MCTD in an AS patient and report, for the first time, the onset of MCTD potentially triggered by sulfasalazine.
15084915 The additive role of innate and adaptive immunity in the development of arthritis. 2004 Apr The development of rheumatoid arthritis (RA) occurs as a result of interactions between genes and environment. The most well established association with both susceptibility and severity of disease is variations in the major histocompatibility complex (MHC) class II genes. This fact constitutes evidence in favor of a contribution from specific MHC class II restricted adaptive immunity to the pathogenesis of RA. However, considerable difficulties have been encountered in identifying reactivities within the adaptive immune system that are responsible for the development of chronic arthritis in humans. In this article, the authors suggest a hypothesis for arthritis development based on their, as well as others', research. In patients with certain genetic contexts, RA can be initiated by activation of the innate immune system alone. In other patients, the adaptive immune system may be needed for the induction of disease. Additionally, the authors believe that a perpetuation to a severe chronic arthritis occurs only when both the adaptive and the innate immune systems have been recruited.
12403342 Adhesion molecules in inflammatory diseases: insights from knockout mice. 2002 Leukocyte/endothelial cell adhesion molecules are essential mediators of both immune and inflammatory responses. However, their specific roles in the initiation and progression of inflammatory diseases remain largely undefined. The focus of our laboratory is the identification of the adhesion molecule interactions that mediate leukocyte recruitment and tissue damage during the development of rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. For these studies, we use a basic genetic approach in mice, analyzing different gene-targeted adhesion molecule mutants, or "knockouts," in murine disease models. Our findings suggest that loss of intercellular adhesion molecule-1 significantly inhibits the development of arthritis and glomerulonephritis, while selectin deficiency results in accelerated development of joint and kidney inflammation. Our results also indicate that the beta2 integrins may play a key role in regulating the initiation of psoriasiform skin diseases.
14527177 Complete Freund's adjuvant promotes the increases of IFN-gamma and nitric oxide in suppres 2003 Aug The aim of this study was to determine therapeutic effects of complete Freund's adjuvant (CFA) on the progression and relapsing of pristine-induced arthritis (PIA) and investigate the mechanism involved. Chronic relapsing arthritis was induced by pristine in LEW rats. After onset of arthritis, rats were intradermally injected CFA and rats in control group were injected the same volume of PBS. Arthritis was monitored visually, and joint pathology was examined histologically. Cytokine mRNA expression in inguinal lymph nodes was assessed by RT-PCR. The levels of nitric oxide (NO) in serum were measured by colorimetric assay. The results showed that CFA significantly suppressed the progression and relapsing of PIA. Relapsing rate of PIA in CFA-treated group was 12.5% and it was 85.7% in PBS-control group (P < 0.005). CFA markedly inhibited the infiltration of inflammatory cells and cartilage damage in the joints of CFA-treated rats and promoted the increases of IFN-y mRNA and NO levels. The present study provided an implication that adjuvant therapy may be a new strategy for the treatments of rheumatoid arthritis (RA) and other chronic inflammatory diseases.
12841301 Musculoskeletal involvement in scleroderma. 2003 May Scleroderma can be accompanied by arthralgias, inflammatory arthritis, flexion contractures, nerve entrapment, myositis, or myopathy. Antibodies in scleroderma can occur in other connective tissue diseases; overlap syndromes between scleroderma and Sjogren's syndrome, lupus, and rheumatoid arthritis are reported. Many of the musculoskeletal symptoms in scleroderma are treated symptomatically; most treatments are not proven in randomized controlled trials in these patients. Musculoskeletal manifestations are a major cause of morbidity and disability in scleroderma.
12585981 Comparing celecoxib with traditional nonsteroidal anti-inflammatory drugs. 2003 Feb Celecoxib is as effective as other nonsteroidal anti-inflammatory drugs (NSAIDs) for treating the symptoms of osteoarthritis or rheumatoid arthritis. However, patients taking celecoxib are less likely to discontinue the medication because of gastrointestinal upset than patients taking traditional NSAIDs. Nevertheless, celecoxib does not decrease the incidence of serious gastrointestinal adverse events with long-term therapy.
13130489 Suppression of arthritic bone destruction by adenovirus-mediated dominant-negative Ras gen 2003 Sep OBJECTIVE: To determine the role of Ras-mediated signaling pathways in synovial cell activation and bone destruction in arthritic joints. METHODS: The E11 rheumatoid synovial cell line and primary synovial fibroblast-like cells (SFCs) from patients with rheumatoid arthritis (RA) were gene-transferred by replication-deficient adenovirus vector carrying the dominant-negative mutant of the ras gene (AxRasDN). The effects of RasDN overexpression on cellular proliferation, interleukin-1 (IL-1)-induced activation of mitogen-activated protein kinases (extracellular signal-regulated kinase [ERK], p38, c-Jun N-terminal kinase [JNK]), and IL-6 production by synovial cells were analyzed. The in vivo effects of Ras inhibition on synovial cell activation and arthritic bone destruction were analyzed by injection of AxRasDN into ankle joints of rats with adjuvant arthritis. RESULTS: AxRasDN markedly reduced the proliferation of RA SFCs. IL-1, a proinflammatory cytokine involved in RA pathology, induced activation of ERK, p38, and JNK in the cells. Adenovirus vector-mediated RasDN overexpression suppressed ERK activation, but not p38 or JNK activation, in SFCs. IL-6 is also an important proinflammatory cytokine, and RasDN inhibited IL-1-induced production of IL-6 by RA SFCs at both the transcriptional and protein levels. Injection of AxRasDN into ankle joints of rats with adjuvant arthritis ameliorated inflammation and suppressed bone destruction in the affected joints. CONCLUSION: Ras-mediated signaling pathways are involved in the activation of RA SFCs and the destruction of bone in arthritic joints, suggesting that inhibition of Ras signaling can be a novel approach for RA treatment that targets both synovial cell activation and bone destruction in the RA joint.
24383830 Nuclear factor-κB regulates RANTES chemokine expression in response to tumor necrosis fac 2002 Mar Abstract We investigated the role of nuclear factor (NF)-κB on tumor necrosis factor (TNF)-α-induced regulated upon activation, normal T-cell expressed and secreted (RANTES) expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA). Using cultured human fibroblast-like synoviocytes from patients with RA, semiquantitative reverse transcriptase-polymerase chain reaction, electrophoretic mobility shift assay, and Western blot were performed for RANTES expression, NF-κB activation, and degradation of IκB, respectively. In addition, the transcriptional effect of TNF-α on RANTES gene expression was analyzed by reporter gene assay. We found that TNF-α clearly induced RANTES protein production and expression of RANTES mRNA in a time-dependent manner. Furthermore, TNF-α persistently induced NF-κB activation caused by IκBα and IκBβ1 degradation. Supershift analysis revealed that TNF-α-induced DNA-binding complexes were composed principally of the p65 and p50 Rel family members. Moreover, transcriptional activation of the RANTES promoter by TNF-α was dependent on specific NF-κB response elements that were regulated by NF-κB. Results herein indicate that NF-κB activation caused by degradation of IκBα and IκBβ1 by TNF-α increased RANTES gene expression in fibroblast-like synoviocytes, suggesting that NF-κB plays an important role in the migration of inflammatory cells by RANTES to the synovium in patients with rheumatoid arthritis.
17041986 The development of a user-led clinical service for newly diagnosed rheumatoid arthritis pa 2004 OBJECTIVE: To identify the clinical services required to meet the perceived needs of patients within the first 6-12 months following a diagnosis of rheumatoid arthritis in an orthopaedic NHS trust. METHODS: An action research methodology was utilized. Twenty three newly diagnosed patients were asked to complete a questionnaire focusing on their needs at the time of diagnosis. The content included reactions to diagnosis, physical and psychological implications and clinical services that were required. A sub-sample of patients (n = 6) participated in an interview to explore these issues in more depth. A questionnaire was also distributed to 14 members of the multidisciplinary team (MDT) to ascertain their views on the purpose, content, and provision of a clinical service for newly diagnosed patients. RESULTS: Eighteen patients agreed to take part (M:F, 9:9, age range 23-74 years, mean age 52.3 years, mean disease duration from diagnosis 16 weeks). Data from the questionnaires and interviews led to the following themes being identified: pre-diagnosis anxiety and fear, the impact of the diagnosis, physical and psychological implications of the diagnosis, and issues related to control perceptions. There was concordance between the MDT and the patients regarding impact of the disease and the need for information. Areas of the service that were identified independently by patients related to the importance of the period of time pre-diagnosis while awaiting the hospital appointment, and employment issues. CONCLUSIONS: This study has identified the impact of RA in the early stages of pre- and post- diagnosis on physical, psychological and social functioning and has consequently informed service development.
17041965 Being a parent or grandparent with back pain, ankylosing spondylitis or rheumatoid arthrit 2004 Research that explores being a parent or grandparent with musculoskeletal problems has been fairly limited to date. The aim of this study was to describe the experience of parenting in the context of back pain (BP), ankylosing spondylitis (AS) and rheumatoid arthritis (RA), with a particular focus on the extent and nature of childcare experiences and to compare these experiences across the three groups. In addition, the possible reasons for these reported experiences, the availability of advice and support and the development of strategies for coping were explored using a cross-sectional descriptive survey. A total of 448 participants was recruited from relevant charitable organizations and the National Health Service (280 with BP, 106 with AS and 62 with RA). A combination of opportunistic and random sampling was used. Quantitative data were analysed with appropriate descriptive and inferential statistics using Statistical Package for the Social Sciences (SPSS version 10). Qualitative data were analysed using content analysis. Results indicate that a high proportion of all groups experienced a wide range of difficulties with parenting (81% BP, 77% AS, 97% RA). The most prevalent problems were similar for all three groups: lifting baby/child from the floor or cot, encouraging children/grandchildren to help with domestic chores and keeping up (in terms of energy) with children/grandchildren. However, the RA group reported having greater difficulties than the other two groups. Very little advice was offered to participants with parenting difficulties which may indicate a gap in service provision. However, a wide range of strategies for coping were described by respondents. The study highlighted a need for healthcare professionals to develop a greater awareness of parenting issues and to provide opportunities for these issues to be addressed.
12571866 Mapping and functional characterization of rat chromosome 4 regions that regulate arthriti 2003 Feb OBJECTIVE: DA rats are highly susceptible to experimental models of rheumatoid arthritis (RA). Linkage analyses in different models have identified several quantitative trait loci (QTLs) within a 70-cM region of DA rat chromosome 4 (C4). We produced congenic strains for these QTLs in order to map and characterize their impact on arthritis development. METHODS: Selective breeding was used to transfer C4 intervals from arthritis-resistant PVG.1AV1 rats onto DA rats. These congenic strains were evaluated for susceptibility to arthritis induced by intradermal injection of rat type II collagen, pristane (a well-defined synthetic adjuvant oil), mycobacteria, or squalene (an endogenous adjuvant oil used in human vaccine). RESULTS: Rats congenic for PVG.1AV1 genes in the 70-cM region were less susceptible than DA rats to collagen-induced arthritis (CIA), pristane-induced arthritis, adjuvant-induced arthritis, and squalene-induced arthritis (SIA). Experiments in subcongenic strains indicated a gene regulating arthritis in males located in a 20-cM interval overlapping the QTL Pia5. A second gene, located in a 10-cM interval harboring the QTL Oia2, attenuated SIA and CIA. The latter caused a change in anticollagen antibody isotype levels toward a pattern similar to that seen in PVG.1AV1 rats. CONCLUSION: The QTL Oia2 regulates arthritis induced both by the nonimmunogenic immunostimulant squalene and by cartilage collagen. In CIA, it also skews anticollagen isotype profiles, suggesting qualitative regulation of autoimmunity. Interestingly, the homologous human chromosome region 12p12-p13 has also been linked to RA, suggesting that genetic and functional dissection of this locus will provide clues to disease pathways that lead to joint inflammation.
14677010 Joint symptoms and diseases associated with moisture damage in a health center. 2003 Dec Rheumatic diseases do not usually cluster in time and space. It has been proposed that environmental exposures may initiate autoimmune responses. We describe a cluster of rheumatic diseases among a group of health center employees who began to complain of symptoms typically related to moldy houses, including mucocutaneous symptoms, nausea and fatigue, within a year of moving into a new building. Dampness was found in the insulation space of the concrete floor below ground level. Microbes indicating mold damage and actinobacteria were found in the flooring material and in the outer wall insulation. The case histories of the personnel involved were examined. All 34 subjects working at the health center had at least some rheumatic complaints. Two fell ill with a typical rheumatoid factor (RF)-positive rheumatoid arthritis (RA), and 10 had arthritis that did not conform to any definite arthritic syndrome (three met the classification criteria for RA). Prior to moving into the problem building one subject had suffered reactive arthritis, which had then recurred. Another employee had undiagnosed ankylosing spondylitis and later developed psoriatic arthritis, and another developed undifferentiated vasculitis. A total of 16 subjects developed joint pains, 11 of these after beginning work at the health center. Three subjects developed Raynaud's symptom. Fourteen cases had elevated levels of circulating immune complexes in 1998, 17 in 1999, but there were only three cases in 2001, when the health center had been closed for 18 months. The high incidence of joint problems among these employees suggests a common triggering factor for most of the cases. As some of the symptoms had tended to subside while the health center was closed, the underlying causes are probably related to the building itself and possibly to the abnormal microbial growth in its structures.
15495286 Rheumatic patients in primary and secondary care: differences in structure of diagnoses an 2004 Oct AIM: To compare conditions handled by family doctors and rheumatologists and analyze changes in the distribution of work between primary and secondary care. METHODS: The study population consisted of patients listed with five family doctors. The number and structure of patients with rheumatic diseases and dynamics of visits were examined on the basis of yearly reports dating from 1999 to 2003. Statistics for 1999-2003 were analyzed to provide a background for data concerning outpatient rheumatic care at the University Hospital. A 2-month survey of all consecutive patients referred to rheumatology outpatient center was performed. RESULTS: The number of visits per patient to a family doctor has decreased to 3.0 in 2003 while the number of visits of rheumatic patients to family doctors has increased to 5.9. In 2003 rheumatic patients made up 16.9% of all family doctors' patients, while their number of visits constituted 33.5% of the total visits to a family doctor. The share of visits to a family doctor by rheumatoid arthritis patients has decreased, whereas the share of patients with osteoarthritis has increased. Waiting time for a specialist appointment in 2004 does not exceed three weeks. Out of all the patients referred to rheumatologists, 31.2% were patients with rheumatoid arthritis and 10.4% with osteoarthritis. Patients assessed the availability of rheumatologists as excellent in 47% of cases. CONCLUSION: Since a new model of primary health care was implemented, the division of work between primary and secondary care has been rearranged and currently corresponds to the patient structure and available resources in outpatient care.
14766392 Cytokines in osteoarthritis-current status on the pharmacological intervention. 2004 Jan 1 Cytokines and their broad spectrum of effects have been investigated since the 1980s. The already existing preliminary scientific results have been highly suggestive of the idea that cytokines play an essential role in the pathogenesis of OA. Nevertheless, the extent to which cytokines participate in the origin of OA, or are taken as a consequence of the OA process, remain unanswered questions. Unlike the case with rheumatoid arthritis, studies on the application of anti-cytokine medications with OA remain in their infancy. At the present time no clinical studies relating to OA have confirmed that anti-cytokine medications are antiphlogistically effective and/or prevent the origin of morphologically recognizable cartilage defects or at least decelerate the increasing destruction of joint cartilage. As with every other therapeutic approach the risk-benefit scenario is decisive for deciding on the current application of anti cytokine medications for rheumatoid arthritis as well as their potential future use against OA. Considering the long-term consequences of an anti-cytokine based therapy, our poor state of knowledge should be seen in a very critical light, since the discussed approach represents an immunesuppressive therapy that entails consequences with regard to defence against infections and tumour suppression. Also, little is currently known about the interplay between pro- and anti-inflammatory cytokines and growth factors in OA; the resulting specific and fundamental therapeutic possibilities for performing a structure-modifying basic therapy in OA are worthy of further study on the part of academic and industrial institutions.
12722608 [Anti-cytokines in the treatment of inflammation]. 2003 Mar 1 Tumour necrosis factor (TNF) alpha and interleukine 1 (IL-1) have a pro-inflammatory effect in all targets of the body. However, every inflammatory disease is characterized by a peculiar profile of secretion of cytokines. TNF alpha blocking agents are a major advance in the treatment of of rheumatoid arthritis, spondylarthropathies and Crohn disease. To date, the most common adverse events are reactions to infusions and reactivation of active tuberculosis with infliximab. Association of another immunosuppressive drug, such as methotrexate, decreases the first of these adverse events. IL1-RA is an inhibitor of IL-1 effects which have demonstrated its efficiency in rheumatoid arthritis. These anticytokines represent a dramatic progress in the treatment of inflammatory diseases but we have to stay very careful concerning the possible increased risk of infection or cancer.