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ID PMID Title PublicationDate abstract
1496169 Treatment of the patient with Sjögren's syndrome. 1992 Aug SS is a systemic autoimmune disease characterized by lymphocytic infiltrations of lacrimal and salivary glands. Extraglandular organs including skin, nerve, lung, and kidney may be involved. At the present time, there remains a great deal of confusion regarding the precise definition of SS. As a result, both patients and clinicians frequently have a difficult time in making a specific diagnosis and instituting a specific plan of therapy. Regardless of the diagnostic label, all patients with significant eye and mouth dryness should receive conservative therapy of tear replacement and intensive oral hygiene. Based on the presence or absence of clinical or laboratory features of systemic autoimmunity, additional therapies may prove beneficial in controlling the symptoms and progression of SS.
1605152 Chronic inflammatory arthritis after treatment with high-dose interleukin-2 for malignancy 1992 Jun Interleukin-2 (IL-2) immunotherapy resulted in the development of inflammatory arthritis in three male patients with metastatic cancer. Two patients developed a clinical picture consistent with rheumatoid arthritis. A third patient with a remote history of Reiter's syndrome developed a recrudescence of an inflammatory arthritis after treatment with IL-2. The clinical, laboratory, and histologic data on the patients and the potential pathophysiologic mechanisms are discussed.
1617910 Oxaprozin: a once-daily nonsteroidal anti-inflammatory drug. 1992 Jul The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of oxaprozin are reviewed. Oxaprozin, a nonsteroidal anti-inflammatory drug (NSAID) under consideration for approval by the Food and Drug Administration, is characterized as a propionic acid. By inhibiting cyclo-oxygenase, oxaprozin decreases the formation of prostaglandin (PG) precursors from arachidonic acid, resulting in decreased PG biosynthesis and reduced pain and inflammatory responses. Oxaprozin is well absorbed after oral administration, and peak plasma concentration is reached in three to six hours. Oxaprozin is primarily eliminated by urinary excretion of the unchanged drug. It has a long elimination half-life and persists in synovial fluid. In clinical studies, oxaprozin was equally or more effective than aspirin and as effective as naproxen in the treatment of rheumatoid arthritis. For treatment of osteoarthritis, oxaprozin was as effective as naproxen and more effective than aspirin or piroxicam. Studies have also shown oxaprozin to be effective therapy for juvenile rheumatoid arthritis and ankylosing spondylitis. Oxaprozin, like other NSAIDs, can cause gastrointestinal adverse effects. Other possible adverse effects include allergic reactions, analgesic nephropathy, hepatotoxicity, and increased bleeding times. For adults, the anticipated daily dosage is 600-1200 mg given as a single dose for rheumatoid arthritis, osteoarthritis, and analgesia. In children, oxaprozin 10-20 mg/kg/day has been used to treat juvenile rheumatoid arthritis. Oxaprozin is as effective as other NSAIDs and offers once-daily dosing; however, it does not offer any therapeutic advantage over other currently available NSAIDs.
8151484 Naproxen-induced pseudoporphyria in patients with juvenile rheumatoid arthritis. 1994 Apr Pseudoporphyria, a cutaneous disorder characterized by skin fragility, vesiculation, and scarring, has been reported as a side effect of naproxen therapy in children with juvenile rheumatoid arthritis (JRA). We report the results of a 6-month prospective study to determine the prevalence of pseudoporphyria in our JRA population. All the patients with pseudoporphyria had received naproxen for > or = 4 weeks at the time of the study. Of the patients treated with naproxen, 12% (9/74) developed this complication. No patient had significant elevation of free erythrocyte protoporphyrin, excluding the diagnosis of true erythropoietic protoporphyria. We conclude that pseudoporphyria is a common side effect of naproxen therapy in children with JRA, even in geographic areas without high sun exposure. Because of the risk of facial scarring with pseudoporphyria, physicians and parents of children with JRA should be aware of this complication.
8484096 Does sport negatively influence joint scores in patients with juvenile rheumatoid arthriti 1993 The influence of sporting activities performed using joint protective measures on deterioration in hand and lower extremity function was evaluated over 8 years in 62 patients with juvenile rheumatoid arthritis (JRA). Sporting activities usually recommended to patients with JRA, such as cycling and swimming, did not negatively influence hand or lower extremity function as compared to a control group of patients not taking part in sporting activities. Besides cycling and swimming, other sporting activities were only performed by a minority of patients (less than 10%). Decreases in total joint scores of both the hands and lower extremities, showed significant correlations with disease duration in patients taking part and in patients not taking part in sporting activities. Polyarticular onset of disease was associated with higher total joint scores of the hands as compared to pauciarticular onset of disease. In lower extremity function, no difference was found between patients with polyarticular onset and patients with pauciarticular onset. Disease duration of longer than 10 years, accompanied by severe functional deterioration, was followed by low participation in sporting activities. Therefore, we suggest that appropriate sporting activities, such as cycling and swimming, can be advised to patients with JRA regardless of disease duration, since no negative effects were observed in our study over a period of 8 years.
1404133 The economic impacts of juvenile rheumatoid arthritis. 1992 Jun Our study documents the direct costs, family costs and community (extra school) costs. One hundred and twenty families with children who had juvenile rheumatoid arthritis (JRA) diagnosed by established criteria and who lived in New England were asked to participate. All data except inpatient charged were collected via questionnaire. The questionnaire return rate was 59% (N = 70). The mean annualized direct cost/child was 7,905 (inpatient, $1,717; outpatient, $5,700; and nonmedical, $488). Family costs averaged $1,524/year (out of pocket medical and nonmedical, $1,196; lost salary, $328), which represented 5% of mean family income. The mean extra school cost was $1,449/9 months. The economic impacts of JRA appear to be substantial.
1280861 [The use of interferon in the combined therapy of juvenile rheumatoid arthritis]. 1992 The efficacy of recombinant gene engineering alpha 2-interferon (reaferon) was studied and compared in 60 patients suffering from verified juvenile rheumatoid arthritis (JRA). Reaferon was shown to possess good tolerance and to produce an adequate therapeutic effect. The combined use of reaferon and methotrexate permits potentiating the therapeutic effect of interferon and avoiding side effects seen with methotrexate used alone. Besides, it makes it possible to reduce the incidence of respiratory infections which are often associated with exacerbation of the underlying disease when treated by conventional methods.
8006893 Experimental induction of arthritis in rats immunized with Escherichia coli 0:14 lipopolys 1994 Mar OBJECTIVE: Escherichia coli 0:14 (E. coli 0:14) induces arthritis in rabbits, mice and rats. This study was designed to investigate the effects of lipopolysaccharide (LPS) on the rat arthritis model induced by systemic injections of E. coli 0:14. METHODS: The induction of arthritis in the ankles of rats immunized by subcutaneous injections with heat-killed E. coli 0:14 and its LPS was studied. The appearance and levels of serum IgM rheumatoid factor-like substance (RFLS) was also investigated. The localization of interleukin 1 (IL-1) and LPS in the ankle joints were investigated immunohistochemically. RESULTS: The induction rate of arthritis in rats immunized with LPS was the same as that in rats immunized with E. coli. LPS and IL-1 were detected in synovial cells, infiltrating cells and some cells on pannus in arthritic joints. Anti-LPS IgM levels in rats immunized with E. coli were as high as those in rats immunized with LPS. RFLS levels in rats immunized with LPS increased more gradually than those in rats immunized with E. coli. CONCLUSION: Our findings suggest that LPS induces arthritis resembling rheumatoid arthritis in rats. The detection of IL-1 in synovial cells in conjunction with LPS suggests that local stimulation of IL-1 production may play an important role in the induction of this experimental arthritis.
8284388 Juvenile rheumatoid arthritis of the knee: evaluation with US. 1994 Feb PURPOSE: To evaluate the value of ultrasound (US) in assessing joint inflammation in patients with juvenile rheumatoid arthritis (JRA) of the knee. MATERIALS AND METHODS: US scans obtained in 36 children (mean age, 8 years) with JRA of the knee were compared with those obtained in 30 healthy children. RESULTS: Changes in synovial membrane (synovial thickness), presence of fluid in the suprapatellar bursa, and alterations in the contour (blurring) of the articular cartilage showed statistically significant differences between JRA patients and control subjects. US was more sensitive than physical examination for detecting a minimal amount of intra-articular fluid in 21% of JRA-affected knees with no clinical evidence of active disease. CONCLUSION: US is a simple, rapid, inexpensive, and accurate method for assessing joint inflammation in patients with JRA of the knee.
8295080 Psychological factors affecting reported pain in juvenile rheumatoid arthritis. 1993 Oct Examined the extent to which psychological variables are correlated with pain reported by children with juvenile rheumatoid arthritis (JRA). In a hierarchical multiple regression analysis with pain as the dependent variable, four psychological measures of child and family functioning resulted in a significant increase in R2 = .31, p < .0001, after the effects of disease characteristics were considered. Greater emotional distress in the child, greater emotional distress of the mother, and greater family harmony were related to higher reported pain. Findings suggest that more attention should be given to nonpharmacological aspects of pain and pain management in children with JRA.
1456851 How useful is the rheumatoid factor? An analysis of sensitivity, specificity, and predicti 1992 Dec BACKGROUND: The rheumatoid factor (RF) is frequently ordered in an effort to detect disease, yet its diagnostic utility has not been thoroughly examined. To determine the test's sensitivity, specificity, positive predictive value, and negative predictive value, we analyzed tests ordered in our institution. METHODS: We performed a retrospective analysis of all 86 patients with a positive RF over a 6-month period identified consecutively soon after the test was ordered. A similar analysis was applied to 86 seronegative patients selected at random from a total seronegative population of 477 during the same period. The patients represented the primary care and subspecialty practices and inpatient wards of a 504-bed university teaching hospital. RESULTS: A positive RF result was strongly associated with rheumatoid arthritis or another rheumatic disease. For rheumatoid arthritis, sensitivity = 0.28 and specificity = 0.87, while for any rheumatic disease, sensitivity = 0.29 and specificity = 0.88. The positive predictive values for rheumatoid arthritis and any rheumatic disease were 0.24 and 0.34, respectively, and the negative predictive values were 0.89 and 0.85, respectively. Seropositive patients were slightly older (55 vs 49 years old), but the incidence of false-positive RFs among the elderly (69%) was not significantly higher than among younger patients (65%). The cost per true-positive RF result was $563. CONCLUSIONS: In this study, most positive RF results were not helpful since the majority represented false-positive results. The low positive predictive value of the RF casts doubt on the utility of the RF in the diagnostic evaluation of patients. Contrary to traditional clinical expectations, the diagnostic utility of the RF may be greatest when it is negative. However, the subset of patients with seronegative rheumatic disease reduces the test's power to exclude such disorders even when the RF is negative. Given the test's limitations, clinicians should reconsider their expectations when ordering an RF. The utility of the RF may improve if it is ordered more selectively.
8600183 Development and histologic characterizations of an animal model of antigen-induced arthrit 1995 Dec Children with juvenile rheumatoid arthritis or juvenile chronic arthritis often exhibit temporomandibular joint (TMJ) involvement accompanied by pain, dysfunction, and growth abnormalities. Despite the severe functional and developmental consequences of this disease, its pathogenesis remains poorly understood, but important insights may be provided by a suitable animal model of this disease. The purpose of this study was to develop and histologically characterize a juvenile animal model of antigen-induced arthritis of the TMJ. Arthritis was induced with an intra-articular administration of ovalbumin in previously sensitized 10-week-old male New Zealand white rabbits. Sham-treated and untreated rabbits were used as controls. The TMJs were retrieved en bloc at 5, 10, 15, 35, and 55 days post-challenge for histology and matrix histochemistry. Antigen-treated joints demonstrated severe arthritis, including mononuclear cell infiltration, synovial lining and villous hyperplasia, and pannus formation, as early as 5 days after challenge; the arthritis was maintained up to 55 days post-challenge. A decrease in the area of the TMJ disc that stained positively for glycosaminoglycans was observed throughout the experimental period. Loss of collagen staining was primarily localized to sites at the junction of the synovium with bone and fibrocartilage. The histopathologic features of this model of antigen-induced arthritis of the juvenile rabbit TMJ are similar to those observed previously in adult animal models of experimental arthritis and in human rheumatoid arthritis. This animal model will be useful for understanding the pathogenesis of juvenile rheumatoid arthritis of the TMJ, and for exploring the mechanisms for aberrant craniofacial growth.
1574684 Assessing and understanding patient risk. 1992 Nonsteroidal anti-inflammatory drug (NSAID) gastropathy is the most frequent and one of the most severe drug side effects in the United States. NSAID-associated gastropathy has been estimated to account for at least 7600 deaths and 76000 hospitalizations each year in the United States alone. Hospitalizations in rheumatoid arthritis patients occurred in 1.6% of patients; for patients with osteoarthritis the incidence appears to be substantially lower. This is based on a consecutive series of 3000 patients with rheumatoid arthritis who were followed prospectively for an average of five years by ARAMIS, the Arthritis, Rheumatism and Aging Medical Information System. Multivariate analyses assessing risk factors for serious gastrointestinal (GI) events were performed on 1694 rheumatoid arthritis patients taking NSAIDs. The most important risk factors of higher age, use of prednisone, previous NSAID GI side effects, prior GI hospitalization, functional disability (based on the American Rheumatism Association classification), and NSAID dose are variables in an algorithm which estimates the risk of a serious GI event occurring in the next 12 months. Knowledge of risk factors and their interrelationships provides a tool for identifying patients at high risk and guides therapeutic decisions.
7621587 Large granular lymphocyte expansions in patients with Felty's syndrome: analysis using ant 1995 Jul Felty's syndrome (FS), the association of rheumatoid arthritis (RA) and idiopathic neutropenia, remains an unexplained phenomenon. HLA-DR4 is found in over 90% of cases. Patients with FS may have a T cell lymphocytosis of CD3+CD8+CD57+ large granular lymphocytes (LGL syndrome). In this study of 47 patients with FS, 19% had clear evidence for LGL expansions, while in total 42% had variable evidence for the LGL syndrome using currently available techniques. Of these T cell expansions, 76% were clonal, as demonstrated by Southern blotting and analysis with T cell receptor (TCR) beta chain constant region probes. This technique may fail to detect clonal populations in some patients. Cytofluorographic analysis using antibodies specific for TCR V beta chains identified patients with clonal LGL expansions with results comparable to those obtained with Southern blotting. No evidence for shared V beta usage among expansions from different patients was seen. The role of LGL in RA and FS is currently unclear, but this technique offers a practical and accessible means of identifying patients with LGL expansions, as a starting point for further investigation.
8474073 Mechanisms of cartilage degradation in inflammatory arthritis: interaction between chondro 1993 Feb A possible role for immune complexes in the degradation of cartilage (rheumatoid arthritis and antigen induced arthritis) has been modelled in vitro by studying interactions between cultured bovine chondrocytes and monomeric (M) or heat aggregated (HA) IgG. Concentrations of IgG used were within the range of values reported in the synovial fluids of rheumatoid joints. ELISA and rosetting assays revealed Fc receptor mediated binding of MIgG and HAIgG to chondrocytes that had been cultured, but not to freshly isolated cells. Both forms of IgG stimulated the production of metalloprotease, but only HAIgG boosted generation of superoxide anion and reduced proteoglycan synthesis. HAIgG also stimulated cells to produce immunoreactive interleukin 1 although no biological activity was apparent. It is concluded that the equivalent behavior of chondrocytes in vivo, triggered by immune complexes, could contribute or lead directly to matrix degradation.
1361203 DNA analysis of HLA-DR, DQ, and DP alleles in children with polyarticular juvenile rheumat 1992 Oct HLA-DR, DQ and DP alleles were determined by restriction fragment length polymorphism analysis and oligonucleotide probe hybridization of polymerase chain reaction amplified genomic DNA in 94 Caucasian children with polyarticular juvenile rheumatoid arthritis (JRA) [13 rheumatoid factor (RF)+ and 81 RF-] and 100 healthy controls. HLA-DRw8, DQw4, DQA1*0401, DQB1*0402 were increased in frequency in those patients with RF seronegative disease, with highest frequencies seen in patients with young age at onset (< 5 years of age). These findings were similar to what we observed in children with pauciarticular JRA, especially those with young age at onset. DPB1*0301 was also found in increased frequency in the RF- group, and in particular those seronegative for antinuclear antibody. In contrast to what is observed in patients with pauciarticular JRA, the frequency of DPB1*0201 was not increased in any polyarticular JRA patient group. These data suggest that polyarticular JRA shares many genetic features with pauciarticular JRA.
1623918 Anti-arthritic effects demonstrated by an interleukin-2 receptor-targeted cytotoxin (DAB48 1992 Jul DAB486IL-2 is an interleukin-2 receptor-specific cytotoxin which selectively targets and kills cells which bear the high-affinity form of the IL-2 receptor. Since elimination of activated T lymphocytes may be useful in the treatment of rheumatoid arthritis, the effect of DAB486IL-2 treatment in an animal model of arthritis was investigated. We demonstrated that rats treated with DAB486IL-2 during the induction phase of disease have delayed onset of symptoms and significantly reduced severity of inflammation as well as a depressed proliferative response to mycobacterial stimulation in vitro. In addition, the presence of preexisting antibodies to the molecule had no impact on the anti-arthritic effects observed in this model. These data suggest that DAB486IL-2 may have therapeutic potential in the treatment of rheumatoid arthritis.
8201932 [Seropositive polyarthritis as a presentation form of angioimmunoblastic lymphadenopathy]. 1993 We present a 59-year-old male who was admitted due to fever and generalized lymphadenopathy. The patient had polyclonal hypergammaglobulinemia, Coombs-positive anemia, positive rheumatoid factor (latex 1:1280-SCAT 1:128), hypocomplementemia, negative LE cells and FAN negative. He had a 2 months history of a rheumatoid arthritis-like polyarthritis with poor response to non-steroid antiinflammatory drugs. On physical examination a mild symmetrical polyarthritis of small and large joints was seen. A lymph node biopsy showed architectural effacement, absence of germinal centers, arborization of postcapillary venules and a polymorphonuclear infiltrate that included immunoblasts. Thus, this patient fulfills the morphologic criteria of angioimmunoblastic lymphadenopathy (AILD) (Fig. 1 and 2). Our purpose was to describe the association of seropositive polyarthritis with AILD as a presentation sign. Whether this represents a case of a rheumatoid arthritis with AILD or the polyarthritis which has been described as part of the clinical picture or AILD is difficult to say due to the short time evolution of the disease.
1606732 Genetic, hormonal and behavioural influence on spontaneously developing arthritis in norma 1992 Jun DBA/1 male mice develop arthritis spontaneously at the age of 4 months. The affected joints show cell-rich pannus formation without T cell infiltration and only limited MHC class II expression. Specific pathogen-free DBA/1 mice from different sources developed the same disease. Analyses of inbred mouse strains with various genetic backgrounds and F1 hybrids revealed that the disease is genetically dependent of DBA/1 recessive genes. However, F1 hybrids between DBA/1 and BXSB spontaneously developed arthritis with earlier onset than DBA/1 mice, suggesting that the BXSB autoimmune gene background had both permissive and contributing effects on the development of arthritis. The complete male preponderance for disease susceptibility was investigated by castration and testosterone treatment of DBA/1 males. No arthritis developed after castration and disease susceptibility was restored by testosterone treatment. Arthritis developed only where more than two males were kept in cages, suggesting an influence by aggressive behaviour. Thus, the spontaneous development of arthritis is dependent on hormonal and behavioural mediated effects and differs from experimental models for rheumatoid arthritis such as type II collagen-induced arthritis and pristane-induced arthritis. We conclude that the spontaneously developing arthritis in the normal DBA/1 strain may be more useful as a disease model for osteoarthritis than for rheumatoid arthritis.
8778211 Immunopathogenesis of juvenile rheumatoid arthritis: role of T cells and MHC. 1995 Juvenile rheumatoid arthritis (JRA) is defined as chronic arthritis of unknown etiology appearing in patients less than 16 years of age. The disease is heterogeneous and is classified as pauciarticular, polyarticular, or systemic-onset disease. A few lines of evidence suggest that T cells are involved in the pathogenesis of the disease. T cells infiltrating the synovial membrane bear markers of activation and produce cytokines. The association of particular subtypes of JRA with certain HLA class II alleles provides strong evidence in favor of T cell involvement through an HLA-peptide-T cell receptor complex. Limited data from a few patients with JRA on T cell receptor transcripts from synovial membrane or synovial fluid cells point towards oligoclonality. This further supports the concept that T cells infiltrating the synovial membrane or extravasating into synovial fluid in patients with JRA reflect antigen-driven T cell proliferation.