Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a previously healthy 28-year-old woman who presented with the clinical picture of large vessel occlusions (stroke with left hemiparesis, myocardial infarction) and developed multi-organ failure (i.e. kidneys, heart, brain, liver, blood, skin) over a very short period of time. Peripheral blood smear was consistent with thrombotic thrombocytopenic purpura. Transesophageal echocardiogram was supportive of the diagnosis of catastrophic antiphospholipid syndrome (CAPS), revealing Libman-Sacks endocarditis. Blood cultures were negative, anticardiolipin antibodies were highly increased and lupus anticoagulant was positive. Cerebral and coronary angiograms were negative, suggesting possible microthrombotic occlusive disease in the setting of CAPS.
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PMID:A role for transoesophageal echocardiography in the early diagnosis of catastrophic antiphospholipid syndrome. 1115 45

AVANT Immunotherapeutics is developing TP-10, a recombinant soluble complement receptor type 1 (sCR1), for the potential treatment of reperfusion injury (following surgery, ischemic disease and organ transplantation), organ rejection, acute inflammatory injury to the lungs and autoimmune diseases [348669]. TP-10 has been awarded Orphan Drug status from the FDA for the prevention and reduction of adult respiratory distress syndrome (ARDS) and as a treatment for infants undergoing cardiac surgery [180849], [359588]. A placebo-controlled phase II trial, conducted at approximately 30 sites in the US and involving approximately 600 adult patients undergoing cardiac surgery utilizing cardiopulmonary bypass, was initiated in November 2000. This safety and efficacy study was designed to assess the ability of TP-10 to mitigate the injury to the heart, brain and other organs that occurs when patients are placed on cardiopulmonary bypass circuits, thus potentially improving postoperative outcomes [391437]. In September 2000, the company was planning a double-blind, placebo controlled phase IIb trial in infants undergoing cardiac surgery; AVANT expected to initiated in 30 infants in January 2001 [395086]. The data from this trial will enable the company to further define its clinical endpoints before inititating a pivotal phase III trial in 2001 [382529]. A phase I/II trial of TP-10 involving 15 infants, under 12 months of age, undergoing cardiac surgery for congenital heart defects was initiated by the company in September 1999. The trial will evaluate the ability of TP-10 to mitigate the injury to the heart and other organs when patients are placed on cardiopulmonary bypass circuits [340602]. Enrollment was complete by January 2000 [352458]. Phase I safety trials of TP-10, including studies in adult patients at risk for adult respiratory distress syndrome (ARDS), adult patients with first-time myocardial infarction (heart attack), and pediatric patients undergoing cardiac surgery demonstrated that TP-10 is well tolerated. However, after completion, in December 1997, of a phase IIa trial in nine patients with ARDS, AVANT decided to cease development for this indication. TP-10 was licensed to Novartis AG for use in xeno- and allotransplantation in July 1999. Extensive animal studies have shown TP-10 to have potential in a wide variety of complement-mediated conditions, including organ transplantation, multiple sclerosis, rheumatoid arthritis and lupus [238093]. Early work demonstrated favorable results in animal models of reperfusion injury [180849] and hyperacute xenograft rejection in guinea pig to rat and pig to primate organ transplants [191552]. AVANT has received Notices of Allowance (July 1998) from the USPTO for three separate patent applications covering pharmaceutical compositions of TP-10, methods of purification and methods of certain TP-10 glycoforms for treating diseases or disorders resulting from inappropriate complement activation [291776]. In January 1999, the company was awarded US-05856297 which covers pharmaceutical compositions of TP-10. US-05856300 was also awarded covering compositions and methods of producing the drug [312267].
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PMID:TP-10 (AVANT Immunotherapeutics). 1157 6

Primary antiphospholipid syndrome is associated with an increased risk of vascular thrombosis. The authors describe a young patient without any risk factor for coronary artery disease who was admitted to the hospital because of a transient cerebral ischemic attack. Standard EKG showed signs of a previous silent inferior wall myocardial infarction, confirmed by echocardiography, technetium-99 scintigraphy, and left ventricular angiography. Coronary arteries appeared normal at angiography. Blood tests showed the presence of antiphospholipid antibodies and lupus anticoagulant. Since there is evidence that these antibodies are associated with an increased risk of microvascular thrombosis, the authors conclude that this silent myocardial infarction could be caused by a cardiac microvascular disease accompanying the antiphospholipid syndrome.
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PMID:Myocardial infarction with normal coronary arteries in a patient with primary antiphospholipid syndrome--case report and literature review. 1171 32

Antiphospholipid antibodies are a heterogeneous family of immunoglobulins that includes lupus anticoagulant and anticardiolipin antibodies. They are strongly associated with a clinical syndrome characterized by venous and arterial thrombosis and spontaneous fetal losses. This syndrome may be primary or else secondary to autoimmune or neoplastic diseases. The cardiovascular system is frequently involved with mitral or aortic insufficiency, juvenile myocardial infarction, and primitive pulmonary hypertension. However, the occurrence of intracardiac thrombi is rare. We describe a case of an intracardiac right atrial thrombus in a 19-year-old asymptomatic woman who was admitted in December 1998 to the Thrombosis Center owing to the finding, during routine work-up, of a prolonged activated partial thromboplastin time (71 s) and thrombocytopenia (71 x 1000/mm3), a positive antinuclear antibody test (1/320), positivity for lupus anticoagulant, and increased IgG (92 GPL-U/ml) and IgM (27 MPL-U/ml) anticardiolipin antibodies. Six months later, the patient presented with headache, edema and cyanosis of the face and jugular swelling. Transthoracic and transesophageal echocardiography revealed a right atrial mass which was clearly distinguishable from the tricuspid valve and extended to the superior vena cava. The patient was successfully submitted to surgical excision of the thrombus. Histology revealed that the mass was adherent to an abnormal septum consisting of mesenchymal tissue. Although the American Rheumatology Association criteria for the diagnosis of systemic lupus erythematosus were not fulfilled, the positivity of antinuclear antibody test is in favor of a lupus-like syndrome. The decision to opt for surgical excision of the thrombus was determined by the unclear nature of the atrial mass. It may be necessary that such patients be submitted to anticoagulant therapy for the rest of their lives or temporarily (6-12 months). This underscores the importance of the anatomical abnormality as a promoting factor. Transthoracic echocardiography (as well as transesophageal echocardiography in selected cases) must be considered as an essential component of the initial diagnostic work-up in patients presenting with antiphospholipid antibodies.
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PMID:[Left atrial thrombosis in patients with antiphospholipid antibody syndrome and mesenchymal abnormal septum]. 1172 15

The objective of this study was to study cardiac valve morphology and function and ventricular function in systemic lupus erythematosus (SLE) patients with and without co-existing cardiovascular disease (CVD) and in population controls. Twenty-six women (52 +/- 8.2 years) with SLE (SLE cases) and a history of CVD (angina pectoris, myocardial infarction, cerebral infarction or intermittent claudication) were compared with 26age-matched women with SLE but without manifest CVD (SLE controls) and 26 age-matched control women (population controls). Echocardiographywas performed to assess valvular abnormalities and manifestations of ischaemic heart disease. Thirteen of the 26 SLE cases but only one of the SLE controls and one of the population controls had cardiac valvular abnormalities. Three of the SLE cases had already undergone valve replacement and another had significant aortic insufficiency; the other nine had thickening of mainly mitral leaflets without hemodynamic significance. Among SLE cases, patients with valvular abnormalities had higher homocysteine (P < 0.001) and triglyceride (P = 0.02) concentrations than patients without valvular disease. In contrast atherosclerosis as determined by IMT, oxidized LDL as measured by the monoclonal antibody E06, autoantibodies against epitopes of OxLDL (aOxLDL) or phospholipids (aPL), disease duration or activity, or acute phase reactants did not differ between SLE cases with or without valvular abnormalities. Valvular abnormalities were not more common in SLE cases with stroke as compared to those with myocardial infarction, angina or claudication. In conclusion, valvular abnormalities are strongly associated with CVD in SLE. Raised levels of homocysteine and triglycerides characterize patients with cardiac valve abnormalities.
Lupus 2002
PMID:Cardiac valvular abnormalities are frequent in systemic lupus erythematosus patients with manifest arterial disease. 1247 5

The classical clinical picture of the antiphospholipid syndrome (APS) is characterized by venous and arterial thromboses, fetal losses and thrombocytopenia, in the presence of antiphospholipid antibodies (aPL), namely lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or antibodies to the protein "cofactor" b2 glycoprotein I. Single vessel involvement or multiple vascular occlusions may give rise to a wide variety of presentations. Any combination of vascular occlusive events may occur in the same individual and the time interval between them also varies considerably from weeks to months or even years. Deep vein thrombosis, sometimes accompanied by pulmonary embolism, is the most frequently reported manifestation in this syndrome. Cerebrovascular accidents-either stroke or transient ischemic attacks-are the most common arterial thrombotic manifestations. Early and late fetal losses, premature births and pre-eclampsia are the most frequent fetal and obstetric manifestations. Additionally, several other clinical features are relatively common in these patients, i.e., thrombocytopenia, livedo reticularis, heart valve lesions, hemolytic anemia, epilepsy, myocardial infarction, leg ulcers, and amaurosis fugax. However, a large variety of other clinical manifestations have been less frequently described in patients with the APS, with prevalences lower than 5%. These include, among others, large peripheral or aortic artery occlusions, Sneddon's syndrome, chorea, transverse myelopathy, intracardiac thrombus, adult respiratory distress syndrome, renal thrombotic microangiopathy, Addison's syndrome, Budd-Chiari syndrome, nodular regenerative hyperplasia of the liver, avascular necrosis of the bone, cutaneous necrosis or subungual splinter hemorrhages. In this article, some of these "unusual" manifestations are reviewed.
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PMID:Unusual manifestations of the antiphospholipid syndrome. 1279 62

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Treatment of the disease has contributed dramatically in the long-term survival of the patients and now SLE has become a chronic inflammatory disorder. Present data suggest 5, 10 and 20-year survival rates of 93%, 85% and 68% respectively. Accelerated atherosclerosis and early coronary artery disease have become important causes of death and hospitalisation in SLE patients. Many cardiovascular risk factors can be considered: disease activity (particularly kidney involvement), sedentary life (in nearly 70% of the patients), hyperlipidemia, antiphospholipid antibodies, serum homocysteine and many others. Although traditional risk factors are operative in patients with SLE, the risk for myocardial infarction was increased 8.3 folds after controlling these factors in a study, suggesting that SLE itself was the strongest risk factor for cardiovascular disease. Lipid abnormalities may play a major role in increasing cardiovascular risk in SLE patients who are characterized by elevated triglycerides, very low-density lipoprotein cholesterol (VLDL-C), reduced levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A-1. Anticardioli-pin antibodies may influence lipid levels in SLE; in particular SLE patients with IgG anticardiolipin antibodies had significantly lower HDL-C compared with patients with no anticardiolipin antibodies. Elevation of serum homocysteine is observed in 15% of SLE patients and is significantly associated with the development of stroke and arterial thrombotic events. The antiphospholipid syndrome (APS) is an acquired thrombotic disorder characterised by recurrent venous or arterial thrombosis or recurrent miscarriages, or both, associated with the presence in the serum of IgG or IgM anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC). APS may occur as a primary disorder (PAPS) or associated with connective tissue diseases, mainly systemic lupus erythematosus (secondary APS). Primary and secondary APS are both associated with a significant increase of cardiovascular risk.
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PMID:[Cardiovascular risk factors in systemic lupus erythematosus and in antiphospholipid syndrome]. 1285 54

The objective of this paper is to investigate the long-term outcome of primary antiphospholipid syndrome (APS) in the paediatric age. The features of unselected patients with primary APS who had disease onset before the age of 16 years were retrospectively analysed in three Italian referralcentres. Clinical and laboratory manifestations were assessed to establish whether, at the end of follow-up, the final diagnosis was still primary APS or whether they had developed definite SLE or lupus-like syndrome. Fourteen patients, nine boys and five girls, who had the presenting clinical manifestation of APS between three and 13 years of age (median nine years) and were followed for two to 16 years (median six years). Six patients presented with deep vein thrombosis, five with cerebral stroke, two with peripheral artery occlusion and onewith myocardial infarction. During follow-up, four patients had one or more recurrences of vascular thrombosis. At last observation, 10 patients could still be classified as having primary APS, two had developed SLE, one lupus-like syndrome and one Hodgkin's lymphoma. In conclusion; our analysis suggests that some children who present with the features of primary APS may progress to develop SLE or lupus-like syndrome.
Lupus 2003
PMID:Outcome of primary antiphospholipid syndrome in childhood. 1287 46

We report the diagnosis and management of a 32-year-old Hungarian male, whose only known risk factor for coronary artery disease was smoking, who presented with an acute thrombotic anterolateral wall myocardial infarction requiring percutaneous transluminal coronary angioplasty (PTCA) stenting of his proximal left anterior descending coronary artery. He arrived to the emergency room with an abnormally prolonged partial thromboplastin time (PTT) that subsequently did not correct by mixing with normal plasma. This was suggestive of an underlying coagulopathy. An extensive coagulopathy work up found him to have the antiphospholipid antibody syndrome with antibodies positive for anticardiolipin, lupus anticoagulant and false-positive VDRL. Genetic typing found him to be homozygous for a mutation in the methylenetetrahydrofolate reductase (MTHFR A1298C) gene, which, in the presence of additional thrombophilic factors, may have increased his risk of myocardial infarction. He was discharged on high dose coumadin.
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PMID:Case report: Acute myocardial infarction in a 32-year-old white male found to have antiphospholipid antibody syndrome and MTHFR mutation homozygosity. 1289 Nov 67

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


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