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)

Whether it is better to treat renal transplant patients with cyclosporine alone, combined with steroids, or combined with steroids and azathioprine is still unclear. After initial therapy with cyclosporine and steroids, 354 cadaver renal transplant recipients were randomly assigned at the post-transplant day 5 to cyclosporine alone (monotherapy), cyclosporine plus steroids (double therapy), or cyclosporine plus steroids plus azathioprine (triple therapy). Monotherapy patients, after a second acute rejection, were switched to either of the two alternative therapies. According to intention-to-treat (ITT) analysis, the 4-year patient survival was 97% in monotherapy, 91% in double therapy, and 96% in triple therapy; the graft survival including death was 84%, 77%, and 88%, respectively; and the pure graft survival was 87%, 85% and 91%, respectively (P = not significant). Acute rejections were diagnosed in 79 patients in monotherapy, 58 in double therapy, and 59 in triple therapy (P < 0.01). Of the patients on monotherapy, 52% were switched to double or triple therapy. In these patients, the 4-year graft survival including death was 68%, and the pure graft survival was 72%, in comparison with 93% and 94%, respectively, for patients who continued on cyclosporine alone. Patients with renal polycystic disease as a cause of renal failure and with low plasma creatinine at the time of randomization (5 days after transplant) had a higher probability of remaining on monotherapy, wherease those with glomerulonephritis or systemic lupus erythematosus (SLE) and with high plasma creatinine levels at randomization had a higher probability of being switched to double or triple therapy. According to ITT analysis, there were fewer ocular (P < 0.0001), osteomuscular (P < 0.002) and cardiovascular complications (P = 0.05) and fewer patients with hypercholesterolemia (P < 0.0028) in the monotherapy group, with no difference between double and triple therapy. Creatinine clearance at 3 years was lower in monotherapy, but no attrition of renal function was seen over the years in any of the groups. Cyclosporine, however used, provided good results in cadaveric renal transplantation. Triple therapy and monotherapy offered a nonsignificantly better patient and graft survival than double therapy. Patients on monotherapy had a higher risk of acute rejection but had fewer adverse events than those on double or triple therapy. Patients maintained on cyclosporine alone had the best graft survival, whereas those who were assigned to monotherapy and had to add steroids because of multiple rejections had the worst outcome. Therefore, it seems reasonable to limit the choice of monotherapy to patients without immune-mediated renal diseases and with good graft function in the early post-transplant period.
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PMID:A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation. Italian Multicentre Study Group for Renal Transplantation (SIMTRe). 1049 94

SLE is a multifaceted disease; over the past 20 years, as survival has improved dramatically, new challenges have emerged. It is now clear from the results of studies at several centers that SLE is associated with at least a fivefold increased risk of CAD, which is accelerated at its onset and seems to abolish a female premenopausal protection against CAD. Several groups have also found by various techniques that subclinical disease occurs at a frequency of about 35% to 40%. The pathogenesis of atherosclerosis in this context seems to be a complex interaction of factors associated with the disease, its therapy, and traditional risk factors. Indeed, experimental models suggest a synergy of these different dimensions in plaque formation. Hypercholesterolemia has been identified as predictive of both future CAD events and sub-clinical disease. This is mainly the case in those patients in whom hypercholesterolemia is a sustained phenomenon. In addition, SLE itself seems to be a strong risk factor for CAD over and above the effects of the known traditional CAD risk factors. There is a lot that is still unknown about the pathogenesis of CAD in SLE. Current knowledge is sufficient to justify the belief that an aggressive approach to management of traditional CAD risk factors in patients with SLE is likely to have a major impact on morbidity and mortality in this population. For this to happen, patients must be educated about this issue and be encouraged to play an active role in lifestyle modifications. In addition, clinicians who care for patients with SLE need to assume a primary role in screening and coordinating the management of CAD risk factors in these high-risk patients.
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PMID:Premature atherosclerosis in systemic lupus erythematosus. 1076 12

Observational cohort studies in SLE have led to the description of accelerated atherosclerosis as an important cause of mortality and morbidity in this disease. The clinical observation of coronary artery disease occurring in premenopausal females with SLE gave rise to the concept of the bimodal mortality pattern. This pattern was confirmed in autopsy and epidemiological studies. These studies identified hypercholesterolemia and particularly its persistence in the first three years of disease, hypertension, and lupus itself as important risk factors for the development of accelerated atherosclerosis in these patients. It also became evident that corticosteroid therapy plays an important role in the elevation of plasma lipids while antimalarials resulted in a reduction of plasma cholesterol, LDL, and VLDL, especially in steroid-induced hyperlipidemia. Studies of clinical outcomes for atherosclerotic disease (angina, myocardial infarction) have shown a prevalence of 6-12% in a number of SLE cohorts. However, more sensitive investigations including myocardial perfusion imaging and carotid ultrasound have demonstrated a prevalence of atherosclerotic disease in 40% of patients studied. Further studies of SLE disease process, including immunological factors, may more clearly define the pathogenesis of accelerated atherosclerosis in patients with SLE, and may help elucidate mechanisms of atherosclerosis in the general population.
Lupus 2000
PMID:Accelerated atheroma in lupus--background. 1080 81

Our purpose was to examine prospectively the relationship between systemic hypertension and vascular events in patients with SLE. SLE patients followed in the University of Toronto Lupus Clinic presenting between 1980 and 1988 and within one year of their diagnosis of SLE were identified. Standard definitions were used for hypertension and for all vascular events (MI, angina, CVA, PVD). The presence of traditional CAD risk factors, along with disease- and therapy-related risk factors for the development of vascular disease, were compared in the hypertensive and normotensive group. A multivariate logistic regression was performed to determine the best predictor of a vascular event. One hundred and fifty patients were identified in our inception cohort [75 hypertensive (50%) and 75 (50%) normotensive]. Seventeen hypertensive patients (22.7%) had at least one vascular event as compared to six (8.0%) normotensive patients (p = 0.022). The vascular events included 7 with CAD, 5 with CVA, and 5 with PVD in the hypertensive group while in the normotensive group 3 patients developed CAD, 2 CVA and 1 PVD. Fifteen deaths were recorded in the hypertensive group as compared to eight deaths in the non-hypertensive groups (P = 0.09). The groups were comparable with respect to associated risk factors, except for higher frequency of hypercholesterolemia (P = 0.003), azotemia (P = 0.001) and corticosteroid use (P = 0.038) in the hypertension group. In a multivariate analysis the best predictor of a vascular event was hypercholesterolemia (OR 6.9, 95% CI 2.4-24.8, P < 0.001). We conclude that systemic hypertension is associated with an increased frequency of vascular events in SLE. This is best explained by its association with hypercholesterolemia.
Lupus 2000
PMID:Vascular events in hypertensive patients with systemic lupus erythematosus. 1143 83

This review focuses on treatment and preventive issues relevant to cardiac problems associated with systemic lupus erythematosus, acute rheumatic fever, and Kawasaki disease in adolescence. Cardiac abnormalities occur as a result of the immune dysfunction and as side effects of therapy. With increased survival, more cardiac complications are being detected. Screening for cardiac risk factors, such as cigarette smoking, hypertension, obesity, and hypercholesterolemia, should begin in adolescence.
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PMID:Cardiac involvement in inflammatory disease: systemic lupus erythematosus, rheumatic fever, and Kawasaki disease. 1122 23

During the last decade, statins have been widely prescribed as lipid-lowering drugs. Their overall safety profile is good. The main musculoskeletal side effects have consisted of muscle pain and weakness, peripheral neuropathy, and a few cases of drug-induced lupus. We report the first four cases of tendinopathy in patients receiving statin therapy. There were three men and one woman. The diagnoses were extensortenosynovitis at the hands (case 1), tenosynovitis of the tibialis anterior tendon (case 2), and Achilles tendinopathy (cases 3 and 4). Two patients were on simvastatin and two on atorvastatin. The tendinopathy developed 1 to 2 months after treatment initiation. The outcome was consistently favorable within 1 to 2 months after discontinuation of the drug. Similar cases have been reported to French pharmacovigilance centers. This report of four cases of tendinopathy draws attention to a possible and heretofore unrecognized side effect of a drug class that is becoming increasingly popular. Statins are effective in lowering high cholesterol levels in patients with type IIa or IIb hypercholesterolemia. They have been widely used for the last decade, particularly in the secondary and primary prevention of major coronary events. Statins act by inhibiting the enzyme hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Although most patients tolerate statins extremely well, a few experience side effects requiring treatment discontinuation. Reported musculoskeletal side effects include myalgia and a few cases of rhabdomyolysis and polymyositis. Induced lupus and peripheral neuropathy are exceedingly rare.
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PMID:Four cases of tendinopathy in patients on statin therapy. 1170 10

Collagen vascular diseases commonly affect the heart; cardiovascular events are the major cause of mortality in people with these diseases. A striking feature of the cardiac involvement in individuals with systemic lupus erythematosus (SLE) and rheumatoid arthritis is aggressive and accelerated atherosclerosis; women with SLE in the 35- to 44-year-old age group are more than 50 times more likely to suffer myocardial infarction than are matched controls. Traditional risk factors contribute to the accelerated atherosclerosis, but cannot explain the extent of risk. It is possible that the inflammatory process, which is similar to the inflammatory process in atherosclerosis, pays a critical pathophysiologic role. It is critically important to identify the presence of traditional cardiovascular risk factors (eg, tobacco usage, hypertension, hypercholesterolemia, diabetes, homocysteinemia), and to modify these to secondary prevention targets. Cardiac valvular disease is common in individuals with SLE and rheumatoid arthritis; its presence should be anticipated and subacute bacterial endocarditis prophylaxis precautions initiated. Cardiac autonomic neuropathy and conduction disturbances are common in people with heart disease related to systemic sclerosis and human leukocyte antigen B27; these patients should be monitored carefully for evidence of dysrhythmias.
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PMID:Cardiovascular Complications of Collagen Vascular Disease. 1185 77

Atorvastatin and other members of the statin family are widely used for the treatment of hypercholesterolaemia in order to reduce the risk of atherosclerosis and cardiovascular disease. Atorvastatin-induced adverse events are mostly mild and only a few cases of lupus-like syndrome or severe acute hepatitis have been documented. In this case report we describe a patient who developed an atorvastatin-induced severe autoimmune hepatitis. In addition, this patient presented with a concomitant systemic lupus-like syndrome which has been already described for statins but not in association with severe liver disease. Although the drug was immediately withdrawn the disease persisted and even deteriorated to a fulminant disease with evidence of acute hepatic failure. The patient failed to respond to conventional immunosuppression with corticosteroids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery of the patient. Interestingly, the patient was HLA DR3- and HLA DR4-positive, which are well-known genetic factors associated with autoimmune diseases. This case is the first report of a drug-induced lupus-likesyndrome concomitant with a severe autoimmune hepatitis in a genetically predisposed patient.
Lupus 2003
PMID:Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. 1276 6

The Committee reviewed cardiac involvement in the antiphospholipid antibody syndrome. The Committee's recommendations are: Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review). Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulation for those who have suffered thrombosis in the absence of atherosclerosis, but recognizes that developing data may support the use of antiplatelet agents instead. Intracardiac thrombi: the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction: the Committee has no recommendations on this aspect of cardiac disease. Pulmonary hypertension: the Committee recommends intensive anticoagulation with warfarin and clinical trials of bosentan, epoprostenol and other new agents.
Lupus 2003
PMID:Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report. 1289 91

Abstract-Apheresis. using columns of cellulose microparticles with immobilized dextran sulfate, Riposorber, has been applied to treatment of patients with various diseases, such as hypercholesterolemia and systemic lupus erythematosus. Unfortunately, it has been reported that the apheresis activates the complement system. It might exert unpleasant side effects on patients during lifelong treatment. In this study, the interaction of the serum complement system with cellulose microparticles with immobilized dextran sulfate and its components, nontreated cellulose microparticles and dextran sulfate, were examined in vitro to get some ideas for development of an extracorporeal apparatus which does not give any serious damage to patient blood. The cellulose microparticles with immobilized dextran sulfate reduces both the CH50 and the ACH50. Decrease in CH50 is not due to the classical pathway activation, but to adsorption of C2 or Cl components including Clq. The alternative pathway was not activated by the addition of the dextran sulfate alone to serum, but the addition of non-treated cellulose microparticles to serum activated complement. Form these, decrease in ACH50 is not caused by dextran sulfate on the microparticles, but by the hydroxyl groups of the cellulose microparticles that is the core of the column. For prevention of complement activation, hydroxyl groups remaining after dextran sulfate immobilization should be blocked by further treatment with a reagent that reacts with them, or else dextran sulfate might be immobilized on particles without nucleophiles such as hydroxyl or amino groups.
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PMID:Effect of adsorbent of Riposorber, a cellulose microparticle with immobilized dextran sulfate, on the serum complement system. 1476 12


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