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)

Effective induction therapy is of pivotal importance in minimizing renal parenchymal damage by the active immune-mediated inflammatory processes in severe proliferative lupus nephritis. Preservation of nephron mass is prerequisite to long-term renal survival. Data from US-based studies have shown improved efficacy with induction treatment comprising corticosteroid and cyclophosphamide, compared with corticosteroid treatment alone. Data from European studies have shown similar efficacy with a modified treatment regimen, in which smaller doses of cyclophosphamide were given at weekly or fortnightly intervals over a shortened treatment duration, and the treatment related adverse effects appeared less frequent with the reduced-dose regimen. We have also reported that sequential immunosuppression with prednisolone and oral cyclophosphamide as induction followed by azathioprine maintenance was associated with a high incidence of remission and relatively favourable long-term renal outcome in Chinese patients. However, cyclophosphamide treatment is associated with considerable adverse effects, which could be potentially fatal. Mycophenolate mofetil selectively inhibits lymphocyte proliferation, and thus targets an instrumental step in the pathogenesis of systemic lupus erythematosus. There is accumulating evidence that the combined use of mycophenolate mofetil and corticosteroid presents an effective treatment for severe proliferative lupus nephritis in different ethnic groups, and is associated with much fewer adverse effects compared with cyclophosphamide-based regimens. Recent data from our group also demonstrate the long-term efficacy of mycophenolate mofetil in preserving renal survival, when used continuously as both induction and maintenance therapy.
Lupus 2005
PMID:Lupus nephritis: induction therapy. 1580 28

Mycophenolate mofetil (MMF) initially found widespread use in the immunoprophylaxis of rejection in organ transplantation. It has subsequently been used in lupus glomerulonephritis, where early studies have shown it to be effective in induction and maintenance therapy. The randomized studies have mostly studied small groups of patients and their conclusions do need to be confirmed in larger studies. MMF has also been used in small numbers of patients in a variety of nonlupus glomerulopathies, which have different underlying immunopathology as well as clinical course, including IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, hepatitis-C-associated glomerulonephritis and even Goodpasture's syndrome. In this article, we discuss its use in such nonlupus glomerular diseases.
Lupus 2005
PMID:Mycophenolate mofetil in nonlupus glomerulonephropathy. 1580 30

Myasthenia gravis (MG) represents the prototypic autoimmune disorder with well characterized immunopathology. Advances in the diagnosis and treatment of this neuromuscular transmission disorder have significantly improved the management of myasthenic patients. Unfortunately the currently available immunomodulating treatments have significant side effects and some patients do not tolerate them or adequately respond to them. Therefore the possibility of a new immunosuppressant agent that is safe, effective and has steroid-sparing effect is very appealing. Mycophenolate mofetil (MMF) has shown promising effects in MG patients in preliminary studies and is currently being studied in two prospective, randomized, double-blind, placebo controlled, multicenter trials to better establish its role in the treatment of MG.
Lupus 2005
PMID:Mycophenolate mofetil and myasthenia gravis. 1580 32

The systemic vasculitides are a group of potentially life-threatening multi-system autoimmune connective tissue diseases characterized by vascular inflammation. The gold standard therapies include corticosteroids and cyclophosphamide as induction therapy and other agents such as azathioprine and methotrexate to maintain remission. Mycophenolate mofetil (MMF) is increasingly being used in autoimmune disorders and this article reviews the use of this agent in the systemic vasculitides.
Lupus 2005
PMID:Mycophenolate mofetil in systemic vasculitis. 1580 34

Mycophenolate mofetil (MMF) is an immunosuppressive drug the efficiency of which has been established in renal transplantation. Recent studies suggest that it may also be effective in the treatment of variant skin diseases especially if the skin lesions are triggered by lymphocytes. Studies have shown efficacy in autoimmune bullous dermatoses, atopic dermatitis and psoriasis. However, there are no placebo-controlled trials that support the use of MMF as first line therapy in these skin diseases.
Lupus 2005
PMID:Mycophenolate mofetil and skin diseases. 1580 35

The optimal treatment of severe lupus nephritis remains unclear. Regimens consisting of steroid and cyclophosphamide (CYC) appear to be most effective. Infection and gonadal toxicity is a major concern of CYC use in patients of reproductive age. In addition, failure to respond or refractory to CYC treatment may lead to the development of end-stage renal disease. Mycophenolate mofetil (MMF) is a new immunosuppressive agent that selectively inhibits activated lymphocytes and renal mesangial cells. Data from experimental lupus nephritis and controlled studies, albeit small and lacking statistical power, have revealed that MMF is as effective in lupus patients as CYC in the induction of renal remission or as maintenance therapy to reduce renal flare in the short term. The significantly less ovarian toxicity and infection when compared to CYC are particularly attractive for the consideration of MMF in lupus nephritis. The potential of other new therapeutic agents is discussed together with the need for patient recruitment in future trials of lupus nephritis to address the importance of ethnicity as well as histological grading.
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PMID:Treatment for lupus nephritis: a revisit. 1587 79

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5'-monophosphate dehydrogenase, has several immunosuppressant actions. MPA depletes guanosine and deoxyguanosine nucleotides preferentially in T and B lymphocytes, inhibiting proliferation and suppressing cell-mediated immune responses and antibody formation, major factors in acute and chronic rejection. MPA also can induce T-lymphocyte apoptosis. MPA suppresses dendritic cell maturation and can induce human monocyte-macrophage cell line differentiation, decreasing the expression of interleukin (IL)-1 and enhancing expression of the IL-1 receptor antagonist. In addition, MPA inhibits adhesion molecule glycosylation and expression and lymphocyte and monocyte recruitment. Activated macrophages produce nitric oxide (NO) and superoxide, which combine to generate tissue-damaging peroxynitrite. MPA depletes tetrahydrobiopterin and decreases NO production by inducible NO synthase without affecting constitutive NO synthase activity. By these mechanisms, MMF exerts anti-inflammatory activity, which could attenuate both acute and chronic rejection. Unlike calcineurin inhibitors, MMF is nonnephrotoxic and does not induce transforming growth factor-beta production, which is fibrogenic. MMF inhibits arterial smooth muscle cell proliferation, a contributor to graft proliferative arteriopathy, and does not increase blood pressure, cholesterol, or triglyceride levels. By decreasing high-density lipoprotein oxidation and macrophage recruitment, MMF also may delay onset/progression of graft atherosclerosis. Thus, MMF may prevent chronic rejection by several mechanisms. MMF activity is synergistic with that of other agents such as valganciclovir for treating cytomegalovirus infection. MMF also has synergistic activity with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists in the treatment of some nephropathies in experimental animals. This combination may prevent progression toward end-stage renal disease in humans with chronic allograft, lupus, and diabetic nephropathies.
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PMID:Mechanisms of action of mycophenolate mofetil in preventing acute and chronic allograft rejection. 1625 60

Progress in understanding the pathogenesis and treatment of rheumatologic and glomerular diseases such as systemic lupus erythematosus and particularly lupus nephritis has been closely linked with the development of newer immunosuppressive agents. With improved patient survival following the institution of cyclophosphamide and corticosteroid therapy, longer-term management issues came to the forefront, especially how to decrease adverse effects of the immunosuppressive regimen. Many of the immunosuppressive regimens used in lupus patients were first established as efficacious and safe through their use in solid organ transplantation. Mycophenolate mofetil (MMF) is now widely used in the field of transplantation. Following anecdotal reports describing benefits of MMF in lupus and lupus nephritis patients, small studies and finally large randomized, controlled trials have established the use of MMF in these patients, particularly those with lupus nephritis. MMF use in other rheumatologic and renal diseases has been evaluated in only smaller studies and very few randomized controlled trials. Nevertheless, many studies currently are ongoing with this immunosuppressive agent. This article will review the published data and the experience of two major New York medical centers with the use of MMF in autoimmune and renal diseases.
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PMID:Use of mycophenolate mofetil in autoimmune and renal diseases. 1625 60

Mycophenolate mofetil (MMF) has been increasingly used in patients with systemic lupus erythematosus (SLE). While most information concentrates on lupus nephritis, its efficacy in nonrenal manifestations of SLE has not been systematically studied. We describe the successful use of MMF in a patient with SLE-related hemolytic anemia that was refractory to cyclophosphamide, pulse methylprednisolone, intravenous immunoglobulin and cyclosporine. The mechanisms of action of MMF are briefly reviewed.
Lupus 2005
PMID:Mycophenolate mofetil for refractory haemolytic anemia in systemic lupus erythematosus. 1630 83

Acute pancreatitis (AP) rarely complicates the clinical course of systemic lupus erythematosus (SLE). AP as the initial manifestation of SLE is exceptional, but its outcome is often fatal. Corticosteroids have been suspected to play a role in the development of AP, but the therapeutic benefit seems to be far above the risk of exacerbation of pancreatic lesions. We report a 13-y-old girl presenting with arthralgia and malaise, followed by abdominal pain, generalized oedema and haemodynamic instability. Increased CRP (325 ng/ml), serum amylase (14,000 IU/l) and lipase (2500 IU/l) levels suggested AP. Acute anuric renal failure required haemodialysis. Multiorgan involvement suggested SLE, which was confirmed 3 d later by increased anti-ds-DNA levels. Three methylprednisolone pulses were administered promptly, followed by oral prednisone (1.5 mg/kg/d) and six pulses of cyclophosphamide (500 mg/1.73 m2/2 wk). Mycophenolate mofetil was introduced for long-term disease control. Amylase and lipase levels decreased over 4 wk. Renal function was normal after 3 wk and proteinuria negative after 6 wk. This case suggests that steroid pulse therapy should be promptly administered if clinical and biochemical investigations suggest SLE to be responsible for AP. Aggressive treatment may be life saving.
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PMID:Acute pancreatitis in paediatric systemic lupus erythematosus. 1637 10


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