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 used the transplantation of purified autologous peripheral blood CD34+ stem cells to treat a 16-year-old female patient with systemic lupus erythematosus (SLE), who had received unsuccessful treatment with steroids and immunosuppressants, and has achieved satisfactory therapeutic effect. The diagnosis of SLE was established one year ago, and the patient had SLE Disease Activity Index (SLEDAI) of 21 on admission. After ineffective treatment with dexamethasone and cyclophosphamid (CTX) for 3 months, purified autologous peripheral blood CD34+ stem cell transplantation was adopted. Autologous peripheral hematopoietic stem cells were mobilized by intravenous injection of 2.0 g/d cyclophosphamid (CTX) for 3 d and subcutaneous injection of granulocyte colony-stimulating factor (G-CSF, 300 microgram/d). A CS-3000 plus blood cell separator was used to collect peripheral blood stem cells, and cell count of mononuclear cells and CD34+ stem cells and epitope analysis of T and B lymphocytes were performed by FACscan flow cytometry. After purification with CliniMACS, the number of CD34+ stem cells reached 15.13x106/kg, while that of CD3+ cells were only 1.35x105/kg. Pretreatment of the patient consisted of intravenous injection of (50 mg/kg each day)for 4 consecutive days and antithymocyte globulin (ATG, 2.5 mg/kg each day) for 3 consecutive days with methylprednisolone (MP) at the dose of 1.0 g on the first day and 0.5 g on the following 2 days. The granulocytes were recovered by G-CSF stimulation. The purified CD34+ stem cells (60 ml) were reinfused within 24 h after pretreatment, following which changes in clinical manifestations and immunologic markers were compared with those before the transplantation. Clinical and immunologic remissions were achieved after transplantation, with all the autoantibodies reversed to the negative, suggesting the short-term effectiveness of this therapy. Based on this observation, we conclude that this therapy is possible to effect an eventual cure of SLE in this case, but the long-term effect needs to be further observed in the follow-up study.
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PMID:[Transplantation of purified CD34+ stem cells from autologous peripheral blood for treatment of systemic lupus erythematosus]. 1243 52

This article first reviews the current treatment of lupus nephritis, with a focus on the most serious forms, that is, the proliferative subtypes. Current standards for treatment have been developed empirically. Corticosteroids form the basis of all regimens. Cyclophosphamide given intravenously for prolonged periods is the current gold standard. Azathioprine can be regarded as an effective drug for maintenance treatment of lupus nephritis. Studies on its efficacy in schedules for remission induction are in progress. It has been learned from studies on 'conventional' immunosuppression that randomised, clinical trials should comprise large numbers of patients and a follow-up of many years to elucidate differences between effective strategies. These requirements are not met by any of the 'new' treatments we discuss in this review. There is only limited experience in patients with lupus nephritis with drugs that are currently used for immunosuppression in other autoimmune diseases, such as methotrexate, cyclosporin and high-dose intravenous gammaglobulins, nor with new immunosuppressive drugs that have been developed for immunosuppression in organ transplantation (mycophenolate mofetil, tacrolimus, fludarabine and cladribine). Hormonal therapy with the weak androgen prasterone (dehydroepiandrosterone; DHEA) has no role in treatment of active lupus nephritis. There are interesting experiences with agents that have evolved from progress in immunobiology and in our understanding of immunological processes. These modalities enable more specific immunosuppression and include monoclonal antibodies directed at immune cells, cytokines and components of the complement system, constructs developed to induce tolerance in pathogenic B cells, and gene therapy. Finally, we review data on autologous bone marrow transplantation in patients with systemic lupus erythematosus. We conclude that some strategies (like mycophenolate mofetil) are good candidates for further investigation in large-scale, prospective, randomised trials with prolonged follow-up (which are almost by definition hard to perform). Most new biological agents still are in a pre-clinical phase.
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PMID:Newer drugs for the treatment of lupus nephritis. 1251 64

Immunological manipulations are the basis for modern treatments of autoimmune diseases (AID). Targeted immune suppression with lymphopenic based chemotherapy, and monoclonal anti B or T lymphocytic antibodies, are integral part of the conditioning for stem cell transplantation (SCT). Immune manipulation by Cyclophosphamide (Cy), ATG, Campath and recently rituximab (RI), with or without stem cell support are the basis for emerging therapeutic modalities aiming to eradicate the autoreactive clone in various autoimmune disorders. Couple of hundreds of SCTs have been recently performed in various autoimmune disorders, mainly multiple sclerosis (MS), progressive systemic sclerosis (PSS), systemic lupus erythematosis (SLE) and rheumatoid arthritis (RA). Preliminary results are encouraging. Better selection of patients and earlier treatment, before irreversible organ failure develops will probably improve results. Current ongoing multicenter studies are evaluating the role of SCT in MS, RA, SLE, and PSS.
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PMID:Treatment of refractory autoimmune diseases with ablative immunotherapy using monoclonal antibodies and/or high dose chemotherapy with hematopoietic stem cell support. 1257 Aug 32

Cyclophosphamide (CY) is an alkylating agent used to treat a variety of autoimmune disorders. Water intoxication is a well-known complication of high-dose intravenous (i.v.) CY, but is rare in patients treated with low dose i.v. CY. We describe two patients with lupus nephritis and water intoxication following low dose i.v. CY. The first patient was treated with oral prednisolone and azathioprine for eight weeks with inadequate response and persistent renal inflammatory activity. Eight hours after the first i.v. CY pulse she had a grand mal seizure. The second patient had WHO class III lupus nephritis, and after a single i.v. CY pulse developed vomiting, diarrhoea and grand mal seizures. They were both fluid-restricted and their serum sodium levels returned to normal. In conclusion, even at low doses i.v. CY may induce hyponatremia related to inappropriate antidiuretic hormone secretion. This potentially life-threatening complication of i.v. CY could be minimized by avoidance of overhydration following pulse i.v. CY.
Lupus 2003
PMID:Water intoxication induced by low-dose cyclophosphamide in two patients with systemic lupus erythematosus. 1294 25

Immunosuppressive drugs have become the gold standard for the treatment of major organ involvement in systemic lupus erythematosus. The use of immunosuppressive therapy in systemic lupus erythematosus carries significant risks for infection. This article reviews infectious complications in systemic lupus erythematosus, focusing on effects of immunosuppressive therapy. Patients with systemic lupus erythematosus appear to carry an intrinsically increased risk for infection. Recent studies support this notion further by showing increased risk for serious infections in patients with systemic lupus erythematosus who had mannose-binding lectin deficiency associated with homozygous mannose-binding lectin variant alleles. Patients with systemic lupus erythematosus who were homozygous for mannose-binding lectin variant alleles had a fourfold increase in the incidence of infections, requiring hospitalization. In terms of extrinsic risk factors for infection, use of steroids and cyclophosphamide are the strongest risk factors. The effect of these drugs on infection is also dose dependent. The incidence of infectious complications in patients treated with mycophenolate mofetil, a newly used immunosuppressive drug in systemic lupus erythematosus, appears less frequent compared with cyclophosphamide. Herpes zoster is still the most common viral infection in patients with systemic lupus erythematosus treated with cyclophosphamide and mycophenolate mofetil. Overall data indicate that patients with systemic lupus erythematosus may have intrinsically increased risks for infection that are augmented by immunosuppressive therapies. Cyclophosphamide, in particular in combination with high-dose glucocorticoids, has the strongest effect in suppressing the immune responses against microorganisms. Careful monitoring of infectious complications is warranted in patients with systemic lupus erythematosus receiving immunosuppressive therapies, in particular those on high-dose glucocorticoids and cytotoxic drugs.
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PMID:Infectious complications in SLE after immunosuppressive therapies. 1296 Apr 76

Cyclophosphamide remains the 'gold standard' treatment for severe organ threatening systemic lupus erythematosus (SLE), especially renal and central nervous system lupus. Intravenous and oral cyclophosphamide have been compared, retrospectively, with similar two year remission rates of 73% and 90%. In a meta-analysis, intravenous cyclophosphamide with oral prednisone is more effective than oral prednisone alone. The efficacy of cyclophosphamide in lupus nephritis has been proven in multiple clinical trials, but efficacy has to be balanced with toxicity, including infection, gonadal failure, and malignancy. Although the continued use ofcyclophosphamide for renal lupus has been challenged by a recent trial of mycophenolate mofetil, and may be challenged in the future by planned trials of biologics, it continues to be widely used. This review will touch on the traditional intravenous 'pulse' cyclophosphamide regimen, consider its toxicity, and contrast it with newer approaches to cyclophosphamide.
Lupus 2004
PMID:Cyclophosphamide: new approaches for systemic lupus erythematosus. 1523 Feb 94

Proliferative lupus glomerulonephritis World Health Organization Class III and IV patients should benefit from an induction and maintenance therapy with a combined immunosuppressive treatment. Cyclophosphamide is the main recommended drug in induction therapy for a 3- to 6-month treatment period. Refractory lupus nephritis may be considered for immunoablative cyclophosphamide treatment with or without haematopoietic CD34(+) stem-cell transplantation or rituximab. Maintenance therapy should contain either quarterly cyclophosphamide pulses, azathioprine or mycophenolate mofetil for a total treatment duration of at least 2 years. Recent studies suggested a similar efficacy of mycophenolate mofetil and cyclophosphamide in induction and maintenance therapy. This result has to be confirmed in long-term studies.
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PMID:Lupus nephritis: a review of the current pharmacological treatments. 1550 Mar 73

A 31-year-old woman was admitted to the hospital for investigation of left lower limb thrombophlebitis. History, physical examination, and laboratory investigations led to the diagnosis of systemic lupus erythematosus (SLE), complicated by secondary antiphospholipid syndrome (APS). Treatment included steroids, azathioprine, aspirin, and low molecular weight heparin. Sixty-three days later, she was admitted to the hospital again because of high fever, macroscopic hematuria, and dyspnea. Laboratory testing showed anemia and impaired renal function. High-resolution chest computed tomography (CT) revealed bilateral multiple peribronchial infiltrates with hemorrhage. Magnetic resonance imaging (MRI) angiography of the kidneys revealed left renal vein thrombosis combined with ischemia of the left kidney. Cyclophosphamide and methylprednisolone pulse treatment as well as intravenous immunoglobulins were started immediately. Despite intensive immunosuppressive and supportive treatment, she suffered three relapses of alveolar hemorrhage and died on day 40, due to severe intracerebral bleeding. The final diagnosis was catastrophic APS with diffuse alveolar hemorrhage and kidney involvement. The unusual combination of recurrent alveolar hemorrhage and death from intracerebral hemorrhage rather than thrombosis in a CAPS patient is discussed.
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PMID:Intracerebral hemorrhage in a patient with SLE and catastrophic antiphospholipid syndrome (CAPS): report of a case. 1591 67

Systemic lupus erythematosus, which predominantly affects young women, is frequently complicated by renal involvement. The presence of acute glomerulonephritis significantly adds to morbidity and mortality. Cyclophosphamide has become the mainstay of treatment in patients with proliferative forms of lupus nephritis. However, adverse events such as severe infections and infertility have spurred the search for novel treatment regimens and agents. Sequential therapy has significantly reduced adverse events. In several pilot studies, mycophenolate mofetil (MMF) has emerged as a promising therapeutic approach for both the induction and maintenance phase in patients with lupus nephritis, delivering equal efficacy and a better adverse effect profile; however, these studies had a limited power, and a large, multicentre and probably multinational clinical trial will be needed to discern the optimal therapeutic approach. On the basis of the currently available literature, sequential therapy with cyclophosphamide induction followed by azathioprine or MMF maintenance can be recommended for most patients. In selected populations, induction with MMF is a reasonable option to reduce adverse events.
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PMID:Defining the role of mycophenolate mofetil in the treatment of proliferative lupus nephritis. 1629 69

We report a rare case of systemic lupus erythematosus (SLE) complicated by alveolar hemorrhage and cytomegalovirus (CMV) colitis. Despite the successful treatment of lupus nephritis by steroid pulse therapy, the patient developed an acute alveolar hemorrhage 2 months later. Cyclophosphamide pulse therapy ameliorated the hemorrhage. One month later, she suddenly developed melena secondary to CMV colitis. Antiviral therapy was successful. We emphasize the importance of timely and precise differential diagnosis for successful management of complicated SLE.
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PMID:A case of systemic lupus erythematosus complicated by alveolar hemorrhage and cytomegalovirus colitis. 1636 89


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