Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a retrospective study of 17 patients with systemic lupus erythematosus who were treated with oral methotrexate given as a mean weekly dose of 8.47 +/- 1.72 mg. Methotrexate treatment resulted in symptomatic improvement in 57% of patients and allowed the reduction of the mean daily dose of prednisone from 16.66 mg initially to 8.99 mg at one year follow-up. Twelve of 17 patients (70.6%) experienced at least one episode of toxicity. Factors which might be associated with toxicity are analyzed. Because of its potential as a corticosteroid-sparing agent, controlled studies of methotrexate for the treatment of systemic lupus erythematosus are indicated.
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PMID:Methotrexate for systemic lupus erythematosus: a retrospective analysis of 17 unselected cases. 176 40

The objective of this study was to determine the effects of Methotrexate (MTX) on the development and the course of experimental murine SLE, as well as on the cytokine profile involved in the disease. SLE was induced in naive BALB/c female mice by injection of the human anti-DNA MoAb bearing a common idiotype (16/6 Id). Six weeks following immunization, when high levels of autoantibodies were demonstrated, the mice were treated with MTX (2 mg/kg once a week) for a period of 10 months. MTX treatment had no effect on 16/6 Id-induced autoantibody production. However, MTX treatment had beneficial effects on the clinical manifestations of the experimental disease (i.e. leucocyte counts, levels of protein in the urine and immune complex deposits in the kidneys). Thus, only 20% of 16/6 Id-immunized BALB/c mice that were treated with MTX had immune complex deposits in their kidneys compared with 100% of SLE-afflicted BALB/c mice that were not treated. We have observed a significant elevation in IL-1, tumour necrosis factor (TNF) and IL-10 secretion in BALB/c mice afflicted with experimental SLE. IL-2, IL-4, IL-6 and interferon-gamma (INF-gamma) levels were decreased in these mice compared with the levels detected in healthy controls. Treatment with MTX reversed the levels of all the above cytokines to normal levels observed in control mice. These studies demonstrate therapeutic effects of MTX on murine experimental SLE. The normal cytokine profile observed following treatment with MTX is suggested to play a role in the amelioration of the clinical manifestations of experimental SLE.
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PMID:Methotrexate treatment in murine experimental systemic lupus erythematosus (SLE); clinical benefits associated with cytokine manipulation. 762 94

The authors report an open prospective study in a group of 16 patients who presented systemic lupus erythematosus with cutaneous and articular symptoms, and who required treatment with a minimum dose of 15 mg per day of prednisone. Methotrexate was given at a dose of 7.5 mg IM per week. Efficacy was demonstrated at the third month with a statistical analysis of four evolution parameters. Improvement was observed in 13 patients out of 16 and permitted the reduction of the amount of prednisone required. Secondary relapse occurred in four cases in spite of an increase in the dose of methotrexate (10 mg per week). Minor side effects were observed in four cases, and methotrexate was discontinued in only two cases. This study suggests that treatment by low doses of methotrexate is beneficial to patients with articular and cutaneous manifestations of corticodependent systemic lupus erythematosus and this therapy could be corticosteroid-sparing.
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PMID:[Treatment of corticodependent systemic lupus erythematosus with low-dose methotrexate]. 857 Sep 50

Women with rheumatic diseases frequently need treatment throughout pregnancy and lactation. Physicians must confront the dual challenge of monitoring the possible effects of the underlying maternal disease and the medications on both mother and child. It is essential that the maternal disease be well controlled before, during, and after pregnancy to ensure the best possible outcome for the mother and child. Corticosteroids have been used extensively and safely in pregnant patients with systemic lupus erythematosus and rheumatoid arthritis; there have been no reports of congenital malformations in the exposed infants. There is considerable experience using azathioprine during pregnancy if the maternal condition requires use of a cytotoxic drug; there has been no increased risk of congenital malformations in the exposed infants. There is limited information on the safety of other medications, including 6-mercaptopurine, cyclophosphamide, and cyclosporine. Methotrexate is contraindicated during pregnancy, and chlorambucil should be avoided because there are other effective immunosuppressive agents available for use. Corticosteroids (prednisone and methylprednisolone) can be used safely during lactation. All other immunosuppressive medications, azathioprine and 6-mercaptopurine, chlorambucil, cyclophosphamide, cyclosporine, and methotrexate, are contraindicated during lactation.
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PMID:Immunosuppressive drug use during pregnancy. 903 80

Current recommendations for the treatment of pediatric SLE are from uncontrolled trials, case reports, retrospective descriptive data or extrapolation from studies in adults. Glucocorticoids are the mainstay of therapy and the doses depend on the disease severity. Diffuse proliferative glomerulonephritis (DPGN) requires high-dose prednisone for prolonged periods of time. We suggest the addition of azathioprine for DPGN at the time of diagnosis of DPGN and reserve cyclophosphamide for refractory cases. While we do not recommend the routine use of cyclophosphamide in this or other forms of lupus nephritis, others advocate the aggressive use of intravenous cyclophosphamide and prednisone. Severe central nervous system disease should be treated with high dose prednisone and immunosuppressive agents are reserved for life-threatening disease or steroid failure or dependency. We suggest the routine use of hydroxychloroquine in all cases of SLE at a dose of 5 mg/kg/day (maximum of 400 mg/day). Methotrexate has been recently used with some success in both children and adults, the safety profile appears to be very good and therefore further studies of this drug are warranted. Collaboration in the development of a limited number of defined treatment protocols and large scale collection of data on a multicenter and multinational basis is needed if we hope to improve the outcome of patients with severe disease.
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PMID:An overview of the treatment of childhood SLE. 931 Jan 1

The goal of treatment for juvenile rheumatoid arthritis (JRA) and other pediatric rheumatic disorders is to minimize joint destruction, pain, and deformity and to maximize all aspects of growth and development. Oral and injectable methotrexate are now often given early in the treatment of JRA, childhood dermatomyositis, difficult-to-control arthritis in the pediatric spondyloarthropathies, SLE, sarcoidosis, several of the vasculopathies, and idiopathic iritis. Weekly low-dose MTX has become a mainstay of long-term improved control of these disorders, and is associated with strikingly few documented long-term side effects. Dosages, pharmacology, side effects, efficacy, and treatment strategies are discussed. Although formal studies are lacking, MTX for the pediatric rheumatic disorders seems to be associated with less frequent physician visits, lower total costs, improved function, and fewer late reconstructive surgeries.
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PMID:Methotrexate in the treatment of juvenile rheumatoid arthritis and other pediatric rheumatoid and nonrheumatic disorders. 936 Nov 57

Methotrexate has proven to be a safe, effective, long-term therapy for rheumatoid arthritis. Its property as a corticosteroid-sparing drug in rheumatoid arthritis has been recognized and its potential has been explored in other inflammatory and autoimmune diseases. This article describes and analyzes the use of methotrexate for a wide variety of diseases, some of which are not the usual province of rheumatologists, to provide some guidance concerning its role for treatment. Methotrexate therapy seems promising for systemic lupus erythematosus, inflammatory myopathy, inflammatory eye disease, inflammatory bowel disease, and some manifestations of sarcoidosis. Its role in other diseases is not as well defined.
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PMID:Methotrexate use in miscellaneous inflammatory diseases. 936 Nov 59

Current therapies for systemic lupus erythematosus (SLE) are targeted at immunosuppression and at reducing inflammation. The current therapies are broad-spectrum and include steroids and cytotoxic agents that are counterbalanced by toxicity and side effects of the medications. Methotrexate can be utilized to reduce steroid requirements in mild to moderate SLE. Manipulation of the hormonal axis includes DHEA and bromocriptine. Mycophenolate mofetil is an immunosuppressive agent that is being investigated for SLE renal disease. Autologous stem cell transplantation or high-dose cyclophosphamide may be an option for severe refractory SLE. The aim of the future is to target therapies by altering specific known mechanisms of inflammation and autoimmunity. Although the inciting antigen is still unknown in SLE, it may be possible to alter the regulation of the immune response by targeted molecular therapy. Methods to do so would include manipulation of idiotypes, manipulation of second signal stimulation of the immune response, manipulation of cytokines, and the induction of tolerance by administration of blocking peptides. IVIg is an immunomodulator that has been successful in the treatment of SLE. Targeted molecular therapy is undergoing phase I trials with monoclonal anti-CD40L, a signaling inhibitor. Anti-CTLA4Ig, another signaling blocker, is presently being investigated for psoriasis, but may be a potential therapy for SLE. Finally, therapies may include the administration of peptides to induce tolerance.
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PMID:Novel approaches to therapy for systemic lupus erythematosus. 1085 17

Systemic lupus erythematosus (SLE) is a disease of relatively low prevalence with a wide range of clinical manifestations. Due in part to these two facts, there is little new evidence on the treatment of lupus. In fact, randomised controlled studies and prospective series are few and usually involve a small number of patients. Despite this, some therapies have shown to be beneficial within the last five years, while others emerge as possibilities in the near future. Among the former, antimalarials appear to be the treatment of choice for maintaining mild to moderate disease in remission. Methotrexate may be an alternative to other corticosteroid-sparing drugs, especially in patients with active arthritis and skin disease. Cyclosporin can be of use in proteinuric nephritis, although the incidence of hypertension with this drug is high. Thalidomide is useful for refractory skin lesions, but the efficacy of lower, less toxic doses is still to be studied. Immunoglobulins should probably be limited to selected patients with manifestations such as thrombocytopoenia. Experience is more limited with cladribine, fludarabine, tacrolimus, danazol and pentoxifylline. New therapies for severe SLE include mycophenolate mofetil, a potent immunosuppressive drug with a reasonable safety profile and immunoablative therapy with or without stem cell transplantation, in highly resistant cases or those with a poor prognosis. Other recently developed molecules, including anti-CD40L monoclonal antibodies (mAbs), are still under investigation.
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PMID:Therapy of systemic lupus erythematosus: new agents and new evidence. 1106 Jul 62

RA is an autoimmune rheumatic disorder resulting from the combination of several predisposing factors, including the relation between epitopes of possible triggering agents and histocompatibility epitopes, the status of the stress response system, and the sex hormone status. Estrogens are implicated as enhancers of humoral immunity, and androgens and progesterone are natural immune suppressors. Sex hormone concentrations have been evaluated in RA patients before glucocorticoid therapy and have frequently been found to be altered, especially in premenopausal women and male patients. In particular, low levels of gonadal and adrenal androgens (testosterone and DHT, DHEA and DHEAS) and a reduced androgen:estrogen ratio have been detected in body fluids (i.e., blood, synovial fluid, smears, saliva) of male and female RA patients. These observations support a possible pathogenic role for the decreased levels of the immune-suppressive androgens. Exposure to environmental estrogens (estrogenic xenobiotics), genetic polymorphisms of genes coding for hormone metabolic enzymes or receptors, and gonadal disturbances related to stress system activation (hypothalamic-pituitary-adrenocortical axis) and physiologic hormonal perturbations such as during aging, the menstrual cycle, pregnancy, the postpartum period, and menopause may interfere with the androgen:estrogen ratio. Sex hormones might exert their immune-modulating effects, at least in RA synovitis, because synovial macrophages, monocytes, and lymphocytes possess functional androgen and estrogen receptors and may metabolize gonadal hormones. The molecular basis for sex hormone adjuvant therapy in RA is thus experimentally substantiated. By considering the well-demonstrated immune-suppressive activities exerted by androgens, male hormones and their derivatives seem to be the most promising therapeutic approach. Recent studies have shown positive effects of androgen replacement therapy at least in male RA patients, particularly as adjuvant treatment. Interestingly, the increase in serum androgen metabolism induced by RA treatment with CSA should be regarded as a possible marker of androgen-mediated immune-suppressive activities exerted by CSA, at least in RA and at the level of sensitive target cells and tissues (i.e., synovial macrophages). The absence of altered serum levels of estrogens in RA patients and the reported immune-enhancing properties exerted by female hormones have represented a poor stimulus to test estrogen replacement therapy in RA. The different results obtained with OC use seem to depend on dose-related effects and the different type of response to estrogens in relation to the cytokine balance between Th1 cells (cellular immunity, i.e., RA) and Th2 cells (humoral immunity, i.e., SLE). The androgen replacement obtained directly (i.e., testosterone, DHT, DHEAS) or indirectly (i.e., antiestrogens) may represent a valuable concomitant or adjuvant treatment to be associated with other disease-modifying antirheumatic drugs (i.e., MTX, CSA) in the management of RA.
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PMID:Sex hormone adjuvant therapy in rheumatoid arthritis. 1108 49


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