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)

Improvement in the prognosis of SLE prognosis has led to considering infertility therapy. The earliest reports displayed complications such as SLE revealed by ovulation induction or thrombophlebitis. Fertility is known to be normal in women with SLE, excepting amenorrhea accompanying severe flare-ups, renal insufficiency-related hypofertility and ovarian failure secondary to cyclophosphamide therapy. Anti-phospholipid antibodies are suspected to cause defective nidation and placental ischemia. An exponential rise of serum estradiol is observed irrespective of the ovulation induction protocol used, leading to SLE flare-up and thrombosis. We have experience with 114 cycles in 21 women with SLE and/or APS. A complication (fetal loss, SLE flare-up, thrombophlebitis) revealed the underlying disease in 8 women. Eighteen pregnancies led to 9 live-births, 4 fetal deaths and 5 embryonic losses. Pregnancy rate was higher after ovulation induction using gonadotropins (25% per cycle), than clomiphene (4%). Pregnancy rate was similar after IVFETE, whether the protocol was planned or not. However, three-quarters of the pregnancies after unplanned IVFETE led to abortions. On the contrary, 6 out of 7 pregnancies after planned IVFETE led to live-births. Two women developed thrombophlebitis after gonadotropins therapy. A SLE flare-up appeared after 13 out of 62 cycles, with a flare-up rate higher after gonadotropins (27% per cycle) than clomiphene therapy (6%), and after an unplanned (30%) than a planned procedure (10%). In conclusion, ovulation induction therapy can reveal SLE or APS. Clomiphene complications are uncommon. When gonadotropin therapy is considered, a preventive anti-inflammatory therapy should be discussed in SLE patients, in conjunction with heparin and/or anti-aggregate therapy for those with asymptomatic anti-phospholipid antibodies or prior thrombotic events.
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PMID:[Ovulation induction therapy and systemic lupus erythematosus]. 1274 58

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

Although it is clear that the specific antigenic reactivity of antiphospholipid (aPL) antibodies is critical to their effect, the pathogenic mechanisms that result in injury in vivo are incompletely understood. We hyphothesized that aPL antibodies targeted to the placenta activate complement locally, generating split products that mediate placental injury and lead to foetal loss and growth retardation. To test this hypothesis, we used a murine model of APS in which pregnant mice are injected with human IgG containing aPL antibodies. Mice treated with inhibitors of complement activation and mice deficient in complement components were protected from aPL antibody-induced foetal damage. Although the cause of tissue injury in this disease is probably multifactoral, we have shown that complement activation is an absolute requirement for foetal loss and growth restriction and, therefore, thatthis pathway acts upstream of other important effector mechanisms. Identification of complement activation as a mechanism that is necessary for aPL-induced tissue damage and definition ofthe complement components necessary to trigger such injury is likely to lead to a better understanding of the pathogenesis of vascular and tissue injury in SLE and to new and improved treatments.
Lupus 2003
PMID:Activation of complement mediates antiphospholipid antibody-induced pregnancy loss. 1289 94

Although Addison disease and hypoadrenalism are rare in patients with systemic lupus erythematosus (SLE), early reports of the association suggested the presence of antiphospholipid antibodies (aPL) in these patients. Data from literature reveal that adrenal failure was present in between 10 and 26% of patients with catastrophic APS and that one-third of patients presented with adrenal involvement during the course of catastrophic APS. Adrenal involvement may be the first clinical manifestation of this syndrome, whereas a few patients may have a history of Addison's disease in the past. The pathological mechanisms involved in the production of adrenal insufficiency in APS are still not clearly understood, but the hypercoagulable state in these patients supports the concept that adrenal haemorrhagic infarction may possibly be related to adrenal vein thrombosis. In the present article,we review the pathogenic mechanisms and main clinical, laboratory and treatment features of patients suffering adrenal involvement with aPL to support the idea that APS leads to the development of adrenal insufficiency.
Lupus 2003
PMID:Adrenal involvement in the antiphospholipid syndrome. 1289 1

The objective of this study was to compare the clinical findings, laboratory data, functional outcome and chronic damage in male patients with primary antiphospholipid syndrome (PAPS) and systemic lupus erythematosus (SLE). We studied 29 male patients with PAPS and 44 with SLE. Clinical findings, laboratory data, lupus damage index (SLICC/ACR DI), and functional outcome in PAPS, were analysed in each group. The mean age at diagnosis was 29.8 +/- 10.4 years in patients with PAPS and 26 +/- 10.1 years in SLE patients. The duration of disease was 4.5 +/- 2.6 versus 5.2 +/- 3.8 years in patients with PAPS and SLE, respectively (P = NS). In patients with PAPS the most frequent clinical manifestations were venous thrombosis, thrombocytopenia, and pulmonary thromboembolism. Patients with SLE had joint, skin and renal involvement more frequently than those with PAPS (P = 0.0001). All PAPS patients had anticardiolipin antibodies (aCL), and 14 patients (48%) had lupus anticoagulant (LA). All SLE patients had antinuclear antibodies (ANAs). Anti-dsDNA antibodies were positive in 39% of SLE patients. Five patients died: one with 'catastrophic' APS and four with SLE. SLICC/ACR-DI score in SLE patients was 1.9 (SD = 1). In PAPS patients poor functional outcome was due to myocardial infarction, pulmonary thromboembolism, stroke and mesenteric thrombosis. Lupus nephritis was the principal organ damage in SLE. In conclusion, in male patients with PAPS and SLE, the clinical manifestations were significantly different. Arterial thrombosis was the major cause of functional impairment and permanent organ damage in PAPS. Renal involvement was the major cause of chronic damage in SLE.
Lupus 2004
PMID:Clinical spectrum of males with primary antiphospholipid syndrome and systemic lupus erythematosus: a comparative study of 73 patients. 1487 Sep 12

Immunization of mice with beta2 glycoprotein I (beta2GPI) and also with GDKV, a synthetic peptide representing the phospholipid (PL)-binding site of beta2GPI, induced pathogenic aPL antibodies that bind and activate endothelial cells, enhanced thrombus formation and caused fetal death in pregnant mice. TIFI is a PL-binding peptide spanning the Thr101-Thr120 of ulb0-hcmva from human cytomegalovirus (CMV), which shares structural similarity with the PL-binding site of beta2GPI. Immunization with this peptide induced pathogenic aPL and anti-beta2GPI antibodies in mice. These antibodies activated endothelial cells and enhanced thrombus formation in vivo, but whether these antibodies cause fetal death in mice is not known. The objective of this study was to examine the effects of these antibodies on pregnancy outcome in mice. Two groups of pregnant BALB/c mice were injected with either hybridoma supernatant containing D3/AC10, a CMV-peptide-induced monoclonal aPL, at days four, eight and 12 of the pregnancy, 100 microg per mouse (study group) or with culture media alone (control group). The litter size was significantly smaller in the study group (4.80 +/- 1.15 versus 7.28 +/- 0.18, t = - 2.526, P < 0.03). In conclusion, aPL induced by CMV peptides may have pathogenic properties similar to human autoimmune aPL. These findings further support the hypothesis that at least in some patients with APS, pathogenic aPL antibodies may be generated by immunization with CMV products during incidental exposure to the virus via a molecular mimicry mechanism.
Lupus 2004
PMID:Intrauterine fetal death in mice caused by cytomegalovirus-derived peptide induced aPL antibodies. 1487 Sep 13

Morphology of gastric mucosa is characterized in the presence of Helicobacter pylori (HP) and Herpes viruses (HSV-1 and CMV). A total of 85 patients were examined (20 patients with primary APS and 65 with SLE). Chronic active gastritis was revealed in 85% patients with APS and 96% with SLE. 60% patients with APS and 45% with SLE had mucosal erosions. HP was detected in 70-87% of cases. Mixed infection of the gastric mucosa was observed in all the groups which was significantly associated with increased fibroblast and plasma cell number in the tunica propria. Tissue eosinophilia of the antral part of the stomach was observed in 39% of SLE patients. Glucocorticoid therapy was not associated with erosions and was combined with vascular thrombosis of gastric mucosa.
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PMID:[Morphologic features of the gastric mucosa in systemic lupus erythematosus and antiphospholipid syndrome]. 1505 1

We report on a 32-year old female patient with primary antiphospholipid syndrome (PAPS) and several thromboembolic events despite stable doses of oral anticoagulation, good patient compliance and maintained INR values of >3. Over the preceding 3 years the patient had presented a wide spectrum of manifestations of APS, including recurrent venous and arterial thromboses, cardiac, gynecological (HELLP syndrome), neurological involvements, livedo reticularis, a mild thrombocytopenia and the most feared manifestation of the catastrophic antiphospholipid syndrome (CAPS). Life-threatening bilateral subdural bleeding occurred while she was anticoagulated. The clinical features appeared to be refractory to oral anticoagulation with phenprocoumon. They were life threatening on each occasion and she developed repetitive episodes of organ damage with cardiac insufficiency (NYHA III), pulmonary hypertension and other residual defects. Even during heparinization recurrent thromboembolism supervened as well as livedo reticularis of the extremities. Lupus anticoagulants (LAC), anticardiolipin (aCL) antibodies and anti-beta(2)-glycoprotein-1 (beta(2)GPI) titers were all markedly elevated. This case report shows that recurrent episodes of thrombosis can occur despite seemingly adequate anticoagulation in patients with CAPS.
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PMID:Recurrent life-threatening thromboembolism and catastrophic antiphospholipid syndrome in a patient despite sufficient oral anticoagulation. 1516 58

The diagnostic and clinical relevance of Ab to pure and phosphatidylserine-complexed prothrombin for primary and secondary APS was investigated in a total of 357 patients with (n = 169) and without (n = 188) connective tissue diseases. The overall frequency of anti-prothrombin Ab in sAPS, pAPS and patients without APS-related symptoms were found to be 50.0, 37.5 and 22.0%, respectively. From a total of 72 anti-prothrombin-positive samples, 12.5% were specific for pure prothrombin, 31.9% for phosphatidylserine/prothrombin-complexes and 55.6% recognized both antigenic forms. The simultaneous occurrence of other anti-phospholipid Ab was observed in 84% of all sera. Both types of anti-prothrombin Ab are significantly associated with lupus anticoagulant activity, but only Ab to pure prothrombin display such a relationship to clinical manifestations of APS. Based on these results, it cannot be recommended at present to include anti-prothrombin assays in the routine procedure for the serodiagnosis of APS. However, patients negative for lupus anticoagulant and typical APS-related anti-phospholipid Ab should be tested for anti-prothrombin reactivity, favoring, mainly due to its higher specificity, the ELISA containing pure prothrombin as antigen.
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PMID:Autoantibodies to prothrombin and phosphatidylserine/prothrombin-complexes: do they contribute to the serodiagnosis of primary and secondary anti-phospholipid syndrome? 1520 38

Background: Splenectomy has been performed to treat refractory autoimmune thrombocytopenia. However, some reports have suggested that an increased risk of thrombosis could be present in splenectomized patients. This study aims to evaluate the possibility of an increased risk of thrombosis after splenectomy in patients with systemic lupus and antiphospholipid syndrome. Methods: Thrombotic-related events in patients with systemic lupus erythematosus (SLE) and/or primary antiphospholipid syndrome (PAPS), before and after splenectomy for severe thrombocytopenia, were compared. Clinical data, laboratory investigations, and anticoagulation or antiaggregation treatment data were collected from the notes of outpatients attending three European centers. Results: Twenty patients who had had a splenectomy were identified: eight with SLE, five with PAPS, and seven with SLE and APS. The mean time between diagnosis and splenectomy was 3.1 years and mean follow-up was 6.5 years. There were no differences in anticardiolipin antibody titers, lupus anticoagulant, anti-DNA or anti-nuclear antibodies before and after surgery. The incidence of venous events before and after splenectomy was not significantly different. There was a trend towards an increase in the total number of arterial events post-splenectomy. In aCL-positive patients, and in the pre-splenectomy period, the total number of miscarriages was higher (p=0.017), as was the number of patients who had had a miscarriage (p=0.025). Conclusions: The total risk of thrombosis in patients with PAPS and SLE was not increased after splenectomy, but there was a trend towards an increase in the number of arterial events. Splenectomy induced long-term remission of thrombocytopenia (partial or complete) in all patients.
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PMID:Thrombotic risk in patients submitted to splenectomy for systemic lupus erythematosus and antiphospholipid antibody syndrome-related thrombocytopenia. 1524 18


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