Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7488278 | Double-blind, placebo-controlled multicenter trial using chimeric monoclonal anti-CD4 anti | 1995 Nov | OBJECTIVE: To evaluate the clinical response to and safety of single and repeat doses of a chimeric anti-CD4 monoclonal antibody, cM-T412, in patients with rheumatoid arthritis (RA) concomitantly treated with a stable regimen of low-dose methotrexate. METHODS: Sixty-four patients with refractory RA, who were already receiving stable doses of methotrexate, were randomized into a multicenter, double-blind, placebo-controlled trial to receive 3 monthly treatments with either a placebo, or 5, 10, or 50 mg cM-T412, given intravenously. RESULTS: Using > or = 50% improvement in swollen joint counts as a criterion for clinical response, 13%, 13%, 18%, and 13% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response at 3 months of therapy. Using > or = 50% improvement in tender joint counts as a measure of clinical efficacy at 3 months, 19%, 13%, 12%, and 6% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response. "Flu-like" symptoms (fever, chills, rigor) within 24 hours of the infusion occurred more frequently in the groups receiving 50-mg (29%) and 10-mg (31%) doses of cM-T412 than those receiving 5 mg cM-T412 (12%) or the placebo (13%). Significant CD4+ T cell depletion occurred in the 50-mg group (mean of 353 CD4+ T cells/mm3 at 6 months versus 856 CD4+ T cells/mm3 at baseline). All patients were followed up for 12 months after the final treatment; no opportunistic infectious complications occurred. CONCLUSION: Treatment with cM-T412 in this cohort of RA patients who were also taking methotrexate was not associated with clinical efficacy or enhanced toxicity from infectious complications, despite significant peripheral CD4+ T cell depletion. | |
| 7914739 | Disease-modifying antirheumatic drugs, including methotrexate, sulfasalazine, gold, antima | 1994 May | Recently, there has been an interest in rethinking the classification of antirheumatic drugs. Emphasis continues to be on aggressive control of inflammation in the early phase of rheumatoid arthritis. The mistake of extrapolating short-term clinical trial results to long-term outcomes has been appreciated, pointing to the need for long-term studies. Interest in the role of cytokines and their receptors in the inflammatory process continues, as well as in the cellular mechanisms of action of the various disease-modifying antirheumatic drugs (DMARDs). Troublesome toxicity profiles continue to be reported, and a consideration of efficacy-toxicity trade-offs are important. Methotrexate still shows long-term efficacy, and low-dose folinic acid has been shown to reduce toxicity but not efficacy. New information on other DMARDs is presented, ie, sulfasalazine inhibition of signal transduction, the effects of hydroxychloroquine on cytokines and lipid metabolism, and the immunosuppressive effects of bucillamine, a penicillamine-related compound. | |
| 1613698 | Life table analysis of 879 treatment episodes with slow acting antirheumatic drugs in comm | 1992 May | In 596 patients with RA managed over a decade in a community practice setting, 879 slow acting antirheumatic drug (SAARD) treatment episodes were analyzed using 5-year life tables. The probability of continuation of therapy was 50% by 9-24 months for all drugs except for methotrexate (MTX), which was 62% by 5 years [corrected]. MTX treatments were of significantly longer duration than those of all other SAARD (p less than 0.001); terminations for both inefficacy (p less than 0.001) and toxicity (NS) were less likely. These findings concur with recent evidence suggesting that MTX is a superior SAARD in this setting. | |
| 8656264 | Spontaneous regression of lymphoproliferative disorders in patients treated with methotrex | 1996 Jun | PURPOSE: To determine the clinicopathologic features of lymphoproliferative disorders (LPD) that occur in the setting of methotrexate (MTX) therapy for rheumatic diseases (RD) and to define the relationship between the presence of Epstein-Barr virus (EBV) in tumor cells and the response of LPD to MTX withdrawal. PATIENTS AND METHODS: In addition to nine new cases, we analyzed 28 cases previously reported in the literature of LPD in patients receiving MTX for RD. In addition to MTX, immunosuppressive therapy included corticosteroids in 19 patients, azathioprine in three, and cyclosporine in one. Extranodal disease was identified in 16 patients, but none had CNS involvement. Pathologic findings included five cases of Hodgkin's disease and seven low-grade lymphomas. The remaining patients had intermediate or aggressive lymphomas. In situ hybridization studies (ISHS) for EBV-RNA transcripts were positive in 12 of 27 patients (44%). RESULTS: Among 37 patients, 16 were initially observed after MTX withdrawal without additional antitumor therapy. Six achieved a spontaneous complete remission (CR), three had a partial response (PR), one had a minimal response, and six had no response to MTX withdrawal. Of 10 responding patients, EBV was detected by ISHS (n = 6) or polymerase chain reaction (PCR) (n = 2); one patient had a CR despite the absence of EBV by PCR and one had a CR but did not have viral assays performed. Only one of six patients with negative EBV by ISHS or PCR responded to MTX withdrawal. CONCLUSION: MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Responses were consistently observed, but not limited to patients in whom EBV was detected by ISHS or PCR. Further studies are required to confirm these findings and to evaluate the role for EBV in LPD that occur in patients receiving MTX. | |
| 7962779 | Monitoring patients taking methotrexate for hepatotoxicity. Does the standard of care matc | 1994 Dec | BACKGROUND: Controversy persists regarding the validity of published guidelines for the monitoring of methotrexate-induced hepatotoxicity. OBJECTIVE: The purpose of our study was to assess the standard of care by gastroenterologists in the monitoring of methotrexate-induced hepatotoxicity and to compare this standard of care with guidelines in the medical literature. METHODS: Gastroenterologists in Connecticut and Massachusetts were surveyed by a mail-in questionnaire that inquired about their protocol for the monitoring of hepatotoxicity in patients taking methotrexate. RESULTS: Gastroenterologists in Connecticut and Massachusetts generally follow the guidelines in the medical literature. Variation in recommendations from the rheumatologic and the dermatologic literature is reflected in the practice habits of gastroenterologists whose patients are restricted to one particular population. CONCLUSION: Long-term follow-up studies should be continued to obtain further data from which to make future recommendations, especially with regard to the effects of large cumulative doses of methotrexate. | |
| 7818568 | Rheumatoid arthritis treated with tenidap and piroxicam. Clinical associations with cytoki | 1995 Jan | OBJECTIVE: To compare the effects of tenidap and piroxicam on acute-phase protein and cytokine levels in the blood of rheumatoid arthritis (RA) patients and to explore their associations with clinical disease activity. METHODS: A double-blind, randomized, crossover trial in 49 patients with active RA compared 6 weeks of treatment with tenidap (120 mg/day) versus 6 weeks of treatment with piroxicam (20 mg/day). RESULTS: Median values for C-reactive protein (CRP), Westergren erythrocyte sedimentation rate (ESR), serum amyloid A (SAA) protein, and interleukin-6 (IL-6) were significantly lower after tenidap treatment compared with piroxicam treatment, even in the presence of stable background treatment with prednisone, methotrexate, or prednisone plus methotrexate. The median within-patient treatment differences (after tenidap minus after piroxicam) in the CRP, ESR, SAA, and IL-6 values were -1.7 mg/dl, -10.0 mm/hour, -22.0 micrograms/ml, and -3.7 pg/ml, respectively, and represent -60.4%, -17.7%, -35.5%, and -26.1% of the respective baseline levels. IL-6 levels were positively correlated with CRP and SAA. Plasma IL-1 beta was generally below the level of detection. Tumor necrosis factor alpha levels were similar after tenidap and after piroxicam. Treatment differences for 4 of 7 clinical parameters favored tenidap, but did not reach statistical significance. IL-6, CRP, and ESR were significantly correlated with clinical treatment differences. Tenidap and piroxicam toleration were similar, although tenidap-treated patients exhibited a reversible increase in urinary protein excretion. CONCLUSION: Tenidap was differentiated from piroxicam by lower levels of acute-phase proteins, ESR, and IL-6 after tenidap treatment. These treatment differences were significantly correlated with clinical parameters. | |
| 1494743 | [Effects of methotrexate on leukotriene and derivated lipoxygenase synthesis in polynuclea | 1992 Oct | Methotrexate (MTX) has been proved to be effective in rheumatoid arthritis (RA). The mechanism of action of MTX in this disease remains unelucidated but may involve inhibition of the enzyme 5-lipoxygenase. Arachidonic acid metabolites were studied in eight patients with active RA immediately prior to and 24 hours after the first intramuscular injection of 10 mg MTX. None of the patients were taking corticosteroids. Nonsteroidal antiinflammatory drugs were withdrawn four days before the study. Reverse phase high-performance liquid chromatography was used to quantitate metabolites produced by 5-lipoxygenase (5-LO) and 12-LO in plasma (full spectrum of blood cells) and purified neutrophils (PN) after stimulation with calcium ionophore A 21387 (50 microM for 30 minutes and 5 microM for 5 minutes, respectively). LTB4 production by PNs was significantly decreased (-32%, p < 0.01) 24 hours after MTX administration. A moderate (-17%), nonsignificant (NS) fall in LTB4 omega-oxidation products (wP) was seen. Production of 5-HETE was also slightly decreased (-15%, NS). Findings in plasma were comparable, with a significant decrease in total LTB4 (-29.8%, p < 0.01) and moderate falls in wP (-18.8%, NS) and in 5-HETE production (-17%, NS). Production of 12-HETE was unchanged. These findings suggest that MTX in a single dose is responsible for a decrease in the synthesis of LTB4 and 5-LO products in neutrophils and other blood cells in RA patients but does not affect 12-LO activity. | |
| 8452574 | The relative toxicity of disease-modifying antirheumatic drugs. | 1993 Mar | OBJECTIVE: To compare the toxicities of commonly employed disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA). METHODS: Toxicity Index scores, computed from symptoms, laboratory abnormalities, and hospitalizations attributable to DMARD therapy, were assessed in 2,747 patients with RA receiving 3,053 courses of 6 DMARDs and 1,309 courses of prednisone over 7,278 patient-years. Results were adjusted for severity of illness and other covariates. RESULTS: Least toxic was hydroxychloroquine (mean +/- SEM score 1.38 +/- 0.15), followed by intramuscular gold (2.27 +/- 0.17) and the closely grouped D-penicillamine (3.38 +/- 0.36), methotrexate (3.82 +/- 0.35), and azathioprine (3.92 +/- 0.39). Auranofin (5.25 +/- 0.32) was most toxic, but this toxicity resulted from a high frequency of minor complications. Hospitalizations because of auranofin or hydroxychloroquine therapy were not noted. Prednisone (3.83 +/- 0.39) was of comparable toxicity, although it is likely that not all events of prednisone toxicity were captured. For reference, the toxicity of methotrexate and azathioprine was similar to that of the most toxic nonsteroidal antiinflammatory drugs (NSAIDs) (indomethacin 3.99, tolmetin sodium 3.96, and meclofenamate 3.86). Hydroxychloroquine showed less toxicity than the most commonly used prescription NSAIDs. CONCLUSION: There are substantial differences in toxicity among DMARDs and less important differences in toxicity between specific DMARDs and specific NSAIDs. | |
| 8635373 | Pulmonary function in patients receiving long-term low-dose methotrexate. | 1996 Apr | STUDY OBJECTIVE: Acute interstitial pneumonitis is the main pulmonary side effect during methotrexate (MTX) treatment for rheumatoid arthritis. The aim of the study was to determine the following: (1) the incidence of MTX-induced pneumonitis during low-dose long-term MTX treatment for chronic arthritis; (2) whether periodic pulmonary function tests were useful for detecting MTX pneumonitis before clinical symptoms; and (3) whether any subclinical abnormality of pulmonary function was present in asymptomatic patients receiving MTX treatment. DESIGN: Pulmonary function tests, including diffusing capacity for carbon monoxide (DCO) measurements, were performed in 124 patients receiving low-dose MTX for rheumatologic diseases at the time of initiating treatment, and then at 3 months, 6 months, and at 6-month intervals thereafter. Mean duration of treatment was 23 months. RESULTS: MTX treatment was interrupted in six patients for acute onset of clinical symptoms; criteria for diagnosis of MTX pneumonitis were fullfilled in four cases (incidence: 3.2%); no risk factor could be identified. No significant decrease in pulmonary function parameters could be observed before the onset of clinical symptoms of MTX pneumonitis, and this adverse effect could not be predicted by periodic function tests. A statistically significant decrease was found in FVC (-2.2%, p=0.04), FEV1 (-5.0%, p<0.001), and diffusing capacity per alveolar volume, DCO/VA (-4.8%, p=0.03), but not DCO (-1.3%, p>0.05), in the 118 other asymptomatic patients during MTX treatment. CONCLUSION: We found minor subclinical alterations in pulmonary function in asymptomatic patients receiving low-dose long-term MTX treatment, but periodic pulmonary function tests did not allow us to detect MTX-induced pneumonitis before clinical symptoms. Therefore, we recommend that these tests should not be systematically performed while patients are receiving treatment. | |
| 7553058 | [A case of Felty's syndrome with marked thrombocytopenia and severe hypocomplementemia]. | 1995 Apr | Felty's syndrome is diagnosed when a patient shows both splenomegaly and leukocytopenia of various degree during the course of rheumatoid arthritis (RA). The accompanying immunologic abnormalities (e.g., antinuclear antibody, antiplatelet antibody, and hypocomplementemia) also characterize Felty's syndrome, but some authors may regard these abnormalities as a transitional form into overlap syndrome [RA + systemic lupus erythematosus (SLE)]. Here we reported a female case of Felty's syndrome who showed marked thrombocytopenia and severe hypocomplementemia. Thrombocytopenia had been refractory against several forms of therapies including high-dose methylprednisolone. Simultaneously, she had various autoantibodies (i.e., antiplatelet antibody, positive Coombs' test, antithyroglobulin antibody, antimicrosome antibody and anti-RNP antibody). Although she did not fulfill the ARA diagnostic criteria for SLE, the degree of thrombocytopenia as well as that of hypocomplementemia argued in favor of the overlap of SLE in this patient. Low-dose cyclosporin A (CsA) combined with small dose of prednisolone could increase both platelet count and level of complement. Notably, the titers of several autoantibodies dropped after CsA was started. These findings might suggest that CsA could normalize the underlying immunologic abnormalities in this patient. However, the disease activity of RA could not be decreased without a help of low-dose methotrexate. | |
| 8803912 | The use of antimalarials in combination with other disease modifying agents in RA--the Bri | 1996 Jun | Antimalarial drugs are effective disease modifying agents in RA with a low incidence of serious toxic effects. Recently, combinations of second-line agents have been used in RA in attempts to treat patients with no response to a number of single agents, or suboptimal response to a single agent. Combinations of drugs have been selected for maximum efficacy and minimum toxicity, but clinical trials are difficult to design and interpret. In particular, ensuring adequate power to detect small differences in response poses a major problem. Antimalarials are an attractive choice for combination therapy due to their efficacy, mechanisms of action and toxicity profile. In this review, the evidence for the use of antimalarials in combination in RA is examined. No advantage has been shown in combining antimalarials with gold, penicillamine or sulphasalazine compared with monotherapeutic regimens. There is some evidence to suggest a beneficial combination of antimalarials with methotrexate, but this is as yet inconclusive. Open non-randomised uncontrolled studies have shown that antimalarials combined with cytotoxic agents are effective but highly toxic. The authors conclude that there is little good evidence to support the introduction of combination second-line drug therapy for RA into widespread therapeutic use. | |
| 1358240 | The effect of second-line antirheumatic drugs on interleukin-8 mRNA synthesis and protein | 1992 Sep | Interactions between interleukin 8 (IL-8) and endothelial cells play an important role in the emigration of mononuclear cells from the blood into areas of inflammation. We examined the ability of specific second-line antirheumatic drugs to regulate (IL-8) gene expression and protein secretion in interleukin 1 (IL-1) stimulated human umbilical vein endothelial cells and peripheral blood mononuclear cells. The drugs sodium aurothiomalate, D-penicillamine and sulphasalazine were all able to modulate IL-8 mRNA synthesis in and protein secretion from endothelial cells. A bimodal effect was observed: at low concentrations IL-8 was suppressed, whereas higher concentrations resulted in an increased IL-8 production. In endothelial cells, treatment with hydrocortisone led to a linear suppression of IL-8 production in concentrations ranging from 0.5 micrograms/ml up to 500 micrograms/ml. Sulphapyridine, auranofin, hydroxychloroquine and methotrexate, had no effect on IL-8 secretion in endothelial cells. By contrast, 5-aminosalicylic acid induced a threefold increase in the IL-8 release. In peripheral blood mononuclear cells it was only possible to suppress the IL-8 production by hydrocortisone treatment. These results indicate that suppression of IL-8 production in endothelial cells could be an important factor in the mode of action for a number of second-line antirheumatic drugs. | |
| 7572311 | Effects of methotrexate on human osteoblasts in vitro: modulation by 1,25-dihydroxyvitamin | 1995 Jun | This study was designed to investigate whether methotrexate (MTX), used in the treatment of rheumatoid arthritis (RA), affects proliferation and differentiation of human osteoblasts in culture. The effects of MTX were assessed by analyzing markers of proliferation and differentiation of human trabecular bone-derived osteoblast-like cells cultured in the presence or absence of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Treatment of the osteoblastic cells with MTX resulted in a strong dose-dependent inhibition of cell proliferation with half maximal response at a dose of 30 nM. MTX did not interfere with cellular alkaline phosphatase (AP) activity, the number of cells expressing cytochemical AP, or basal osteocalcin production. Addition of 1,25(OH)2D3 to the cultures caused an enhanced AP expression and osteocalcin production coinciding with a decreased osteoblast proliferation. Coincubation of 1,25(OH)2D3 with MTX in doses > or = 100 nM further inhibited osteoblast growth and induced a significant stimulation of AP expression and activity, and production of osteocalcin above the values reached in the 1,25(OH)2D3 cultures. In conclusion, MTX proved to be a potent inhibitor of osteoblast proliferation but did not affect basal osteoblastic phenotypic expression. In the presence of the osteoblast differentiation-promoter, 1,25(OH)2D3, MTX further inhibited cell growth which was associated with enhanced AP activity and osteocalcin production. Thus, MTX may have profound effects on bone metabolism and remodeling by interfering with bone cell turnover. | |
| 8371202 | Pancytopenia associated with low dose methotrexate therapy. A regional survey. | 1993 Jul | OBJECTIVE: To determine which risk factors are associated with serious pancytopenia associated with low dose methotrexate (MTX) therapy. METHODS: All Ottawa area rheumatologists, hematologists and dermatologists were surveyed to obtain cases of pancytopenia associated with low dose MTX therapy between 1981 and 1991. Pancytopenia was defined as white blood cells < 3.5 x 10(9)/l and platelets < 140 x 10(9)/l and hemoglobin < 100 g/l. A case control method was used to evaluate risk factors. RESULTS: Fifteen cases of pancytopenia were identified from returned questionnaires (93% response rate) and from reviewing the medical records of 2 major teaching hospitals. All patients were hospitalized, had MTX therapy discontinued and were treated: 12 patients received transfusions, 8 leucovorin therapy, and 4 folic acid. Two patients died, only 1 directly due to MTX therapy. Identified risk factors were (1) elevated BUN or creatinine levels, (2) increasing mean corpuscular volume values, (3) increased age and (4) concomitant trimethoprim-sulfamethoxazole therapy. CONCLUSIONS: Pancytopenia associated with low dose MTX therapy is a life threatening adverse effect often associated with known risk factors. A change in monitoring guidelines and patient education are suggested as means of risk reduction. | |
| 8870112 | Distinctive features of idiopathic inflammatory myopathies in French Canadians. | 1996 Aug | This is the first report on idiopathic inflammatory myopathies (IIM) in French Canadians. We reviewed retrospectively 30 French Canadian adults (20 women and 10 men) with IIM seen consecutively over 12 years. The median age at diagnosis was 45 years. The IIM were 8 (27%) primary polymyositis (PM), 9 (30%) primary dermatomyositis (DM), 5 (17%) IIM with neoplasia (lymphoma, breast, esophageal, colonic, and skin cancer) and 8 (27%) IIM with a connective tissue disease (4 with systemic sclerosis, 2 with mixed connective tissue disease, and 2 with rheumatoid arthritis). The most common presenting symptom was proximal muscle weakness (n = 10,33%). Of the remaining 20 patients, 6 (20%) had the onset of their weakness within 1 month of the presenting symptom. Only 3 (10%) patients did not have proximal muscle weakness. Twenty-six (87%) patients had weakness in the pelvic girdle, 25 (83%) in the shoulder girdle, and 7 (23%) in the neck muscles. Other common symptoms included dyspnea on exertion and dysphagia, each present in 13 (43%) patients. Gottron's papules and the heliotrope rash were the most common skin lesions documented in 11 (37%) and 10 (33%) patients, respectively. The serum creatine kinase (CK) level was between 171 and 1,000 U/L in 13 (43%) patients and between 1,001 and 6,000 U/L in 13 (43%) patients. Antinuclear antibodies (ANA) on HEp-2 cells were positive in 16 (53%) patients, of which 2 (13%) expressed autoantibodies to nuclear pore complexes. Autoantibody specificities were anti-La (n = 4, 13%), anti-U1RNP (n = 3, 10%), and anti-Ro (n = 2, 7%). None of the patients expressed anti-Jo-1, anti-topoisomerase I, or anticentromere antibodies. Twenty-eight (93%) patients received corticosteroid therapy, and 8 (27%) patients responded to prednisone alone. Thirteen (43%) patients were treated with methotrexate, and 9 (69%) responded. The mean follow-up was 62 months: 23 (77%) had their disease controlled, 3 (10%) patients were lost to follow-up, and 4 (13%) died (no death occurred because of IIM or its treatment). Therapy was discontinued because of remission in 5 (17%) patients. Cumulative survival rates at 2, 5, and 10 years were 89%, 89%, and 85%, respectively. The presence of autoantibodies to nuclear pore complexes and anti-La autoantibodies, the rare occurrence of anti-Jo-1 autoantibodies, the response to conventional therapies, and a high survival rate may distinguish IIM in French Canadians from that of other reported series. | |
| 19078031 | Pneumococcal vaccine in rheumatoid arthritis. | 1996 Apr | To determine the ability of patients with rheumatoid arthritis to respond to pneumococcal vaccination and whether age or methotrexate affects this response, we studied 40 patients with rheumatoid arthritis who received pneumococcal vaccination. Patients were equally divided into four groups according to age and whether or not they were taking methotrexate. Pneumococcal antibody levels were drawn prevaccination and 6 weeks post-vaccination.Eighty percent of rheumatoid arthritis patients vaccinated achieved protective levels of antibodies. The age of the patient did not affect this response, but methotrexate-treated patients responded less well than those not taking methotrexate (p = 0.03).In general, patients with rheumatoid arthritis respond well to the pneumococcal vaccine. Pneumococcal vaccination of rheumatoid arthritis patients before initiating methotrexate therapy is strongly recommended. | |
| 1538301 | Morbidity associated with long-term methotrexate therapy in juvenile rheumatoid arthritis. | 1992 Mar | To evaluate the adverse effects associated with long-term methotrexate (MTX) therapy in children with juvenile rheumatoid arthritis, we conducted a retrospective review of 62 patients with polyarticular juvenile rheumatoid arthritis, treated from 84 to 296 weeks with MTX weekly. Pulmonary function testing was performed before MTX therapy on 46 patients older than 6 years of age; 26 patients had serial pulmonary function testing, and no abnormalities were detected. In all 62 patients, liver function (alanine aminotransferase and aspartate aminotransferase activity) was monitored every 3 months. Transient liver function abnormalities developed in nine patients during treatment. Twelve patients underwent percutaneous liver biopsies after receiving 815 to 2980 mg of MTX; none had fibrosis or cirrhosis. Macrocytic anemia developed in one child receiving simultaneous long-term trimethoprim-sulfamethoxazole therapy and resolved after the trimethoprim-sulfamethoxazole was discontinued. No stomatitis or rashes were observed. Six patients were able to discontinue MTX therapy when their disease remitted; 56 continue MTX therapy. No child permanently discontinued MTX therapy because of an adverse effect. These data suggest that MTX may be better tolerated in children with juvenile rheumatoid arthritis than in adults with rheumatoid arthritis. | |
| 8519616 | Juvenile rheumatoid arthritis and spondyloarthropathies. | 1995 Sep | Further insight into the etiology and pathogenesis of juvenile rheumatoid arthritis (JRA) is presented in recent immunogenetic studies, particularly the allele associations of the pauciarticular pattern of disease. Evidence suggests that bacterial heat-shock proteins may be significant in the chronic inflammatory response in children with arthritis. Data on the role of complement activation and cytokines and their receptors also are presented. Coagulopathy in JRA may have more than one etiologic factor, including a viral agent, as may the disease itself. In the treatment of growth abnormalities in JRA, the neuroendocrine system, recombinant growth hormone, intravenous iron therapy, and nutritional supplementation are all areas of recent investigation. In outcome studies, ocular involvement and the presence of circulating IgM rheumatoid factor appear to be risk factors for disability. However, disease of less than 2 years' duration and absence of radiographic lesions likely predict good response to methotrexate therapy. | |
| 7691140 | Treatment of juvenile rheumatoid arthritis. | 1993 Sep | New information on the treatment of juvenile rheumatoid arthritis emphasizes more aggressive control of arthritis, particularly the use of methotrexate, both in low- and higher-dose regimens. Information concerning drug toxicity, including that of the nonsteroidal anti-inflammatory drugs, second-line agents, and methotrexate, suggests that these drugs are well tolerated in children. A new corticosteroid, deflazacort, minimizes bone demineralization and growth retardation. Adjunctive measures, including erythropoietin, pain management techniques, conditioning programs, and nutrition, have demonstrated advantages in some children with juvenile rheumatoid arthritis. | |
| 8451058 | Methotrexate use in juvenile rheumatoid arthritis. | 1993 Jan | Juvenile Rheumatoid Arthritis (JRA) is a chronic, inflammatory, autoimmune disease of childhood. Methotrexate is an emerging antirheumatic drug in the pediatric population for disease refractory to conventional medications. While observations are encouraging, the toxic side effects can be potentially serious. Toxicity includes gastrointestinal intolerance, ulcerative stomatitis, chemical hepatitis, minor liver fibrosis, infection, hematologic suppression, acute pneumonitis, reversible oligospermia, and cirrhosis. The liver toxicities are of the greatest concern. If proper dosage and monitoring are followed, serious toxic effects can be prevented from occurring. |