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)

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women in childbearing age. SLE tissue damage is mediated by autoantibodies, complement activation and immune complexes deposition. The disease is diagnosed on the basis of its clinical manifestations and the demonstration of characteristic immunological phenomena, especially antinuclear antibodies. Management of the disease includes regular monitoring of disease activity, avoidance of predisposing factors and therapy guided by the activity and severity of the leading organ manifestation. Treatment ranges from nonsteroidal antirheumatic drugs to intensive treatment with cytotoxic agents. Corticosteroids form the basis of all regimens. Antimalarials and azathioprine are important for treating mild and moderate SLE cases, especially for the long time. Cyclophosphamide given intravenously is the current gold standard for severe lupus nephritis. More recently new strategies for immunosuppression in SLE, that interfere with the syntesis of DNA and nucleotides have been developed (such as mycophenolate mofetil, fludarabine and cladribine). Other agents like cyclosporine and tacrolimus inhibit effect of the activation signals for T cells by inhibition of calcineurin. Some monoclonal antibodies against cytokines or components of the complement system interfere with the effector phase of the immune response. Abetimus (LJP-394) inhibits the production of anti-dsDNA antibodies and may prevent glomerulonephritis caused by anti-DNA containing immune complexes. Somatic gene therapy is also a novel approach in autoimmune disorders and my be a valuable method of SLE therapy in the future. The adrenal steroid prasterone (DHEA) has also shown benefitial effects in mild to moderate SLE. Finally, autologous stem cell transplantation can induce tolerance to self-antigens and cause significant improvement in SLE patients. However, new therapeutic strategies must be tested according to the established principles of clinical trial methods.
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PMID:[Progress and perspectives in the treatment of systemic lupus erythematosus]. 1654 25

A 32-year-old Japanese woman, who had a treatment history of systemic lupus erythematosus (SLE) with lupus nephritis World Health Organization class IV for 11 months, visited our hospital due to fever, facial erythema, and erosion of the oral cavity on November 10, 2003. Her mucosal erosion and facial skin erythema progressed over the following week, and Stevens-Johnson syndrome was diagnosed due to pathological findings of the skin. Among the administrated drugs, only mizoribine, started 6 months earlier, produced a positive reaction in the drug lymphocyte stimulation test. Increased prednisolone and high dose intravenous gamma-globulin were given successfully. Cyclosporine at 50 mg was administered to control the SLE, followed by an increase to 100 mg on January 7, 2004. She suffered from abdominal pain, blindness, and convulsion on January 9. The magnetic resonance image of her brain prompted a diagnosis of reversible posterior leukoencephalopathy syndrome. After withdrawal of cyclosporine and control of hypertension, symptoms disappeared rapidly. Cyclophosphamide pulse therapy was successfully administrated to control lupus nephritis. This is the first report describing the relationship between Stevens-Johnson syndrome and mizoribine. Although the use of mizoribine is thought to be safe, careful observation is necessary.
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PMID:Stevens-Johnson syndrome induced by mizoribine in a patient with systemic lupus erythematosus. 1663 33

The objective of this study was to determine the medical outcomes including the ovarian function childhood-onset SLE (cSLE). The medical records of all patients diagnosed with cSLE in the Greater Cincinnati area between 1981 and 2002 were reviewed. Patient interviews were performed to obtain additional information on current medication regimens, disease activity [SLE Disease Activity Index (SLEDAI-2k)], and damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)]. The occurence of premature ovarian failure (POF) and reduction of the ovarian reserve was assessed by timed gonadotropin levels. There were 77 patients (F : M = 70 : 7, 53% Caucasian, 45% African-American and 2% Asian) with a mean age at diagnosis of 14.6 years. Nine patients died (88.3% survival) during the mean follow-up of 7.1 years (standard deviation [SD] 5.6) and 88% of the patients continued to have active disease (SLEDAI-2k mean/SD: 6.6/6.7), with 42% of them having disease damage (SDI mean/SD: 1.62/2.1); Non-Caucasian patients had higher disease activity (mean SLEDAI-2k: 10 versus 3.4; P < 0.0001) and more disease damage (mean SDI : 2.1 versus 1.2; P < 0.02) than Caucasian patients. Cyclophosphamide was given to 47% of the patients during the course of their disease and associated with the presence of significantly reduced ovarian reserve (RR = 2.8; 95% CI: 1.7-4.8; P = 0.026). Patient mortality and disease damage with cSLE continue to be high. Although overt POF with cyclophosphamide exposure is rare, it is a risk factor for significantly decreased ovarian reserve cSLE.
Lupus 2006
PMID:Disease outcomes and ovarian function of childhood-onset systemic lupus erythematosus. 1668 58

There is accumulating evidence that mycophenolate mofetil (MMF), when combined with corticosteroid, is an effective induction treatment for severe proliferative lupus nephritis and is associated with fewer adverse effects compared to cyclophosphamide (CTX), but the quality of life (QOL) associated with these regimens as perceived by the patient has not been compared. This study included patients who had experienced both treatment regimens, for distinct episodes of diffuse proliferative lupus nephritis. QOL parameters during the first six months of each treatment were assessed through SF36 and WHOQOL questionnaires. Twelve patients and 24 episodes of severe lupus nephritis were studied. CTX-treated and MMF-treated episodes showed comparable baseline characteristics and response rate, with complete remission occurring in 83.3%. MMF treatment was associated with higher numerical scores for all domains across both QOL instruments than CTX. MMF treatment was associated with significantly less fatigue, less impediment of physical and social functioning, and better psychological well being compared to CTX. When each patient served as her/his own control, most patients ascribed higher QOL domain scores to the MMF-treated episode. Seventy-five percent of patients found MMF treatment more acceptable and preferred when compared with CTX, and the complications that most concerned them included Cushingoid features, alopecia, menstrual disturbance and infections. These data showed that MMF-based induction immunosuppression for severe lupus nephritis was associated with better QOL than CTX as perceived by patients, which was most likely attributed to the reduced side-effects during MMF treatment.
Lupus 2006
PMID:Quality of life comparison between corticosteroid- and-mycofenolate mofetil and corticosteroid- and-oral cyclophosphamide in the treatment of severe lupus nephritis. 1683 Aug 84

The presence of renal noninflammatory necrotizing vasculopathy (NNV) is often associated with a severe form of lupus nephritis (LN), which is unresponsive to standard therapy. We conducted a 6-month randomized, prospective, open-label trial comparing mycophenolate mofetil (MMF) (1.5-2.0 g/day) with monthly i.v. cyclophosphamide (CTX) (0.75-1.0 g/m2) as induction therapy for class IV LN with NNV. The primary and second end points were complete remission (CR) and partial remission (PR), respectively. Of 20 patients recruited, nine were randomly assigned to MMF and 11 to CTX. The baseline characteristics between groups were not significant. CR was achieved in four patients (44.4%) receiving MMF and in none of the patients receiving CTX (P = 0.026). PR was achieved in two patients (22.2%) in the MMF group and three patients (27.2%) in the CTX group. The total remission rate (CR + PR) in the MMF and CTX group was 66.6 and 27.2%, respectively (P = 0.17). MMF was more effective than i.v. CTX in reducing proteinuria and haematuria. Adverse events were significantly less frequent with MMF than with CTX (P = 0.028). MMF was superior to i.v. CTX in inducing CR of LN with NNV and had a more favourable safety profile.
Lupus 2007
PMID:Induction therapies for class IV lupus nephritis with non-inflammatory necrotizing vasculopathy: mycophenolate mofetil or intravenous cyclophosphamide. 1772 63

Systemic Lupus Erythrematosus (SLE) is an inflammatory autoimmune disorder that may affect multiple organ systems. The clinical course is marked by spontaneous remission and relapses. Severity may vary from mild episodic disorder to a rapidly fulminant life threatening illness. Clinical manifestations of Lupus Nephritis (LN) are varied according to the renal pathologic lesions. Treatment of LN remains controversial. As a chronic disease with periods of remission and relapses, it is unclear whether relapses should be treated as the initial presentation of the disease. This prospective study was designed to compare between three different modalities of therapy for treating LN patients. The study includes all systemic lupus patients seen in Alexandria University Hospital since January 2004 for 6 months. Forty-three patients with SLE were presented to us by SLE, only 31 had LN and 22 were included in the study. The patients were classified randomly into 3 arms. All patients received steroid therapy plus from the beginning either Cyclophosphamide (CYP) [Group I, n=7], or Cyclosporine (CsA) [Group II, n=7], or Azathioprine (AZA) [Group III, n=8], Full history and examination were done. Laboratory investigations included routine and immunological studies of ANA, Anti-DNA, C3 and C4. Renal biopsy was done in all patients. After 6 months of follow up; Serum creatinine was stationary in CYP group from 2.2 +/- 1.1 to 2.1 +/- 1.7; while significantly decreased in CsA from 2.8+1.7 to 1.0 +/- 0.5 mg/dl. Moreover; while proteinuria decreased in CYP from 2.7 +/- 0.7 to 1.8 +/- 2.2; there was more pronounced decreased from 6.9 +/- 10.0 to 2.4 +/- 1.2 g/24 hr in CsA group despite very huge increase in glomerular filtration rate (GFR). 2 out 7 cases of CsA group; while 2 of 6 of CYP group did not show improvement. Moreover; 3 of 6 of CYP group and 1 of 6 of AZA group needed to be shifted to CsA group because of side effects and/or no response to CYP and showed good response. These patients were either class V or IV. However; only one case in this study with signs of acute CsA toxicity was reversed by monitoring the dose. In conclusion, CsA in this study proved to be superior over CYP in LN at least in the short term follow up; provided to be given with appropriate doses even if it is used in class IV, which was thought to be very responsive to CYP.
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PMID:Comparative clinical prospective therapeutic study between cyclophosphamide, cyclosporine and azathioprine in the treatment of lupus nephritis. 1797 49

The patient was a 33 year female. In 2001, she was diagnosed with systemic lupus erythematosus (SLE) and treated with prednisolone and ciclosporin. In May 2006, she noticed slight muscle weakness in the bilateral lower limbs. In July of the same year, she experienced gait difficulty and was admitted to our hospital because of fatigue, appetite loss, fever and disorientation. Soon afterwards, she had a fit of general convulsion and suffered from urinary retention and fecal incontinence. A brain magnetic resonance image revealed atrophy of the thoracic cord in T2 weighted images, and cerebrospinal fluid examination showed high total protein and interleukin-6 concentration, indicating complication of lupus myelitis as well as cerebral involvement. Steroid pulse and oral prednisolone treatment resulted in ameriolation of cerebral complications such as disorientation and convulsion, but muscle weakness and paresthesia in the lower limbs and urinary retention persisted. Cyclophosphamide pulse therapy was started and resulted in a marked recovery from muscle weakness, paresthesia and urinary retention, and she could discharge. We conclude that steroid and cyclophosphamide pulse therapy for a SLE patient with CNS lupus and lupus myelitisis is effective for ameriolation of symptoms such as disorientation, convulsion, urinary retension, fecal incontinence, muscle weakness and paresthesia in the lower limbs as well as elevated level of serum anti-ribosomal P antibody.
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PMID:[Successful therapy with steroid and cyclophosphamide pulse for CNS lupus and lupus myelitis]. 1798 83

Lupus nephritis (LN) is one of the major complications of Systemic Lupus Erythematosus (SLE) and its treatment remains a challenge. Although the classical and widely used immunosuppressive agents have accounted for a significant improvement in the survival and decreased the progression to end-stage renal failure they lack selectivity for the underlying immune dysregulation. In addition the toxicity related to their use and the relapses after treatment are of major concern not least because of the adverse effect on the prognosis of the patients with SLE who have kidney involvement. The development of more specific pharmacological agents for patients with SLE is still a major research goal. Ideally these agents should provide a better long-term prognosis for SLE patients and be less toxic. In this review we summarise the mechanism of action and the results obtained with a variety of drugs that have recently been utilized in the treatment of patients with lupus especially those with nephritis. We discuss the clinical usefulness of B- -cell depletion principally anti-CD20 antibodies blockage of co-stimulatory pathways (anti-CD40 ligand antibody CTLA4Ig) the induction of immune tolerance (LJP 394 peptide specific vaccination) and therapy targeting cytokines (anti-IL10 antibody BLyS blockage) and the complement system (anti-C5 antibody). Immunoablative doses of Cyclophosphamide (CyC) with or without Haematopoietic Stem Cell Transplantation (HSCT) and the possibilities of gene therapy are also reviewed. The use of intravenous immunoglobulin (IVIg) and plasmapheresis are not discussed because these treatments have been used in clinical practice for several years.
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PMID:Novel therapies in lupus - focus on nephritis. 1860 81

To assess clinical characteristics, pathological findings, and therapeutic response in children with lupus nephritis (LN), we retrospectively studied 25 children under 16 years of age with LN at the Abozar children's hospital from 1995 to 2006. The study included 13(65%) girls and 7(35%) boys. The mean age at the time of diagnosis of SLE was 10.2 (+/- 4.8) years. Eighteen patients (90%) were more than 8 years old. Sixty percent of the patients presented as nephritic-nephrotic syndrome. All the patients underwent percutaneous renal biopsy and were followed up for at least 36 months. The clinical and serologic parameters at the time of renal biopsy were recorded. Twenty patients were treated with the following regimens: one (class I) with low dose prednisone, 7 (class II, III) with high-dose of prednisone, 12 (class IV) with high-dose prednisone plus 13 intermittent intravenous cyclophosphamide (CTX) pulses (monthly for 6 months and then every 3 months), followed by mycophenolate mofetil (MMF) as maintenance therapy. Remission was achieved in 17 (85%) cases; one required hemodialysis and 2 died due to renal failure and central nervous system involvement. Among 12 cases with class IV, 11 responded to prednisone and intravenous CTX pulses. We conclude that i.v. pulses of CTX induced clinical remission of renal disease in the majority of children with severe LN. MMF maintenance therapy was effective after induction of remission in refractory cases. However, this study was performed in a small number of subjects, further studies to confirm the long-term efficacy and safety of CTX pulse therapy on larger numbers of patients are warranted.
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PMID:A clinicopathological study of lupus nephritis in children. 1871 Dec 91

Systemic lupus erythematosus involves the kidney in up to 60% of patients, and if untreated, may result in complete loss of kidney function. In this article, we review meta-analyses and clinical trial data on the therapeutic options for proliferative lupus nephritis, and complete a meta-analysis of the use of mycophenolate mofetil (MMF) compared with cyclophosphamide-based regimens. Clinical trials have found that cyclophosphamide-based regimens result in a decreased risk of end-stage renal disease, but are associated with significant toxicity in lupus nephritis. Even though the survival advantage of the US National Institutes of Health and Euro-Lupus regimens based on intravenous and oral cyclophosphamide has not been established, these approaches are broadly adopted in proliferative lupus nephritis. Recent studies have confirmed the therapeutic equivalence and potential comparative superiority of MMF and cyclophosphamide in induction of remission in patients with lupus nephritis. Use of MMF resulted in a lower incidence of infection and loss of gonadal function compared with cyclophosphamide regimens. Cyclophosphamide plus corticosteroids could represent the induction agents of choice in patients with severe lupus nephritis, whereas MMF could be used as an induction agent in patients with mild disease, patients who wish to preserve fertility and those at high risk of infections. However, given the complexity of disease activity in patients with lupus nephritis, the initial treatment options need to be individualized and altered based on the subsequent treatment response. Ongoing clinical trials will provide further evidence.
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PMID:Treatment options for proliferative lupus nephritis: an update of clinical trial evidence. 1884 1


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