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)

The antimalarials, mainly chloroquine and hydroxychloroquine, derive from the quinoleine core of quinine. Their initial therapeutic indication was the treatment of malaria attacks but, because of anti-inflammatory and immuno-modulatory activities, they have been since used to treat many other pathologies, in particular dermatological ones. For some of these pathologies, lupus or porphyria cutanea tarda for example, the use of these molecules is based on obvious scientific evidence. For other pathologies (cutaneous sarcoidosis, polymyositis, polymorphous light eruption...), the data on the medical literature corroborating the daily clinical practice are extremely poor. Their toxicity is limited. Their most common toxic effects are gastrointestinal (mild nausea or diarrhea) or mucocutaneous (reversible skin or mucosal pigmentation). Their most serious and dreaded side effect, retinopathy, can be largely prevented by using amounts of APS adapted to the weight of the patients. The recommended "safe" daily dose for hydroxychloroquine is 6.5 mg per kilogramme of body weight and for chloroquine 4 mg per kilogramme of body weight. However, at 6- to 12 months intervals, follow-up eye examinations should be performed.
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PMID:[Synthetic antimalarials]. 1623 Sep 16

We have analysed in vitro the complement-fixing activity of anticardiolipin antibodies (C-fix aCL) from patients with persistent and moderate/high titres IgG aCL antibodies: 21 with thrombosis and 11 without thrombosis. Titre and C-fix ability of aCL were measured by ELISA. APS and non-APS patients were similar with regard to mean levels of IgG aCL (46 +/- 24 versus 51 +/- 30 GPL, P = 0.7), frequency of IgM aCL (P = 0.7) and a comparable predominance of IgG2 aCL reactivity on ELISA (95% versus 100%, respectively, P = 1.0). Remarkably, a high frequency of C-fix aCL (71% versus 92%, P = 0.35) was observed in both groups. Similarly, no difference was observed in the mean level of C-fix aCL in APS and non-APS patients (7 +/- 6 versus 9 +/- 8 SDunits, P = 0.3). Analysis of 10 primary and 11 secondary APS also revealed a comparable IgG aCL mean titre (57 +/- 29 versus 37 +/- 11, P = 0.06), frequency of IgM aCL (P = 0.6) and of C-fix aCL (70% versus 73%, P = 0.99). Among APS patients six had exclusive arterial events and seven exclusive venous events. The IgG aCL mean titre (36 +/- 10 versus 36 +/- 11 GPL, P = 0.9) and the frequency of IgM aCL antibodies (P = 0.56) in these subgroups of patients were comparable. There was a trend of higher frequency of C-fix aCL in patients with exclusive venous events (100%) compared to 50% of those with exclusive arterial events (p = 0.07). Importantly, C-fix aCL titre was higher in the former group compared to the later one (8 +/- 5 SDunits versus 2 +/- 2 SDunits, P = 0.016). Our data support the notion of a high frequency of C-fix aCL in APS. Although it does not discriminate those patients without thrombotic events with persistent moderate/high levels of aCL, this property seems to be more relevant in venous events and may provide the basis for further understanding the distinct pathogenic mechanisms underlying arterial and venous occlusive disorders of APS.
Lupus 2005
PMID:Complement-fixing activity of anticardiolipin antibodies in patients with and without thrombosis. 1642 75

Antiphospholipid syndrome is characterized by arterial or venous thrombosis, and the presence of antiphospholipid antibodies (aPL). APL are considered to be a cause of an acquired hypercoagulable state leading to stroke and transient ischemic attack (TIA). We examined the causes in 50 young patients with ischemic stroke. The most prevalent cause was atherosclerosis and the incidence of APS was 12.5%. APL comprise a heterogeneous group of autoantibodies, such as beta2-glycoprotein I dependent anticardiolipin antibody (beta2-GPIaCL), lupus anticoagulant (LA), and other antiphospholid-protein antibodies. We examined the incidence and the pathogenic role of antiphospholipid protein antibodies. The subjects comprised 250 patients (155 male, 95 females) with ischemic stroke, aged 26 to 92 years (mean 72 years). We measured beta2-GPI aCL, IgG aCL, LA, phosphatidyserine dependent antiprothrtombin antibody (PS-PT), antiphosphatidyl-serine antibody (PS), antiphosphatidyl-inositol antibody (PI) in each patient. The incidence of beta2-GPI aCL, IgG aCL, LA, phosphatidyserine, PS-PT, PS, and PI was 2.8%, 12%, 9.2%, 7.2%, 9.6%, and 8.8%, respectively. The incidence of young stroke patients under 50 years was 5.2%. Among 13 young stroke patients, 5 had SLE. Among 23 patients with LA., 18 (78%) patients had PS-PT. Anti-PS-PT antibody is closely related to LA. Antinuclear antibody was detected in 79% of the patients with aPS and/or aPI. We compared the carotid ultrasonographic findings in positive aPI or aPS patients with those in negative ones. Increased IMT, plaque score and carotid stenosis were more common in aPI and aPS-positive patients than in negative ones Three of 5 patients who showed positive beta2-GPI, aCL and LA, simulataneously, had sysyemic lupus erythematosus as an immulological background. Two of 3 patients with PI and/or PS and beta2-GPI and/or LA were patients with SLE. Antiphospholipid antibody was considered to be a risk factor of stroke, especially in SLE and/or young female patients. The incidence of lupus anticoagulant is more common than beta2-GPI aCL in ischemic stroke. In SLE patients with stroke, multi-antiphospholipid-protein antibodies was inclined to be present. LA is closely related to ant-PS-PT and aPI and aPS are associated with anti-nuclear antibody and precipitation of atherosclerosis.
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PMID:[Antiphospholipid syndrome and stroke]. 1644 44

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). In addition to systemic inflammation, additional mechanisms have been put forward that are more specific for the pathophysiology of the individual chronic inflammatory disorders.
Lupus 2006
PMID:Atherogenesis in rheumatology. 1663 62

Antiphospholipid (aPL) antibodies bind to beta2glycoprotein I (beta2GPI) and cause endothelial cell (EC) activation and thrombosis in mice. beta2GPI binds to EC through its Vth domain and induces their activation. TIFI is a 20 amino acid synthetic peptide that shares similarity with the Vth domain of beta2GPI. Our objectives were to examine the ability of TIFI to affect aPL-mediated thrombosis in mice and the interactions of TIFI, beta2GPI with phospholipid surfaces and target cells. CD1 mice were injected with IgG from a patient with antiphospholipid syndrome (IgG-APS) or with control IgG-NHS and with either TIFI or with control peptide (VITT). Size of induced thrombi was determined. Inhibition and competition studies were done using aPL antibodies, cardiolipin (CL) liposomes in the presence of varying amounts of TIFI and beta2GPI. Binding of fluorescinated beta2GPI to human ECs and to murine macrophages in the presence or absence of TIFI, was also examined. TIFI significantly decreased thrombus size in mice injected with IgG-APS. TIFI reverted the beta2GPI-dependent binding of aPL antibodies to CL liposomes in a dose-dependent fashion. This effect was abrogated by addition of beta2GPI, suggesting that TIFI displaces the binding of beta2GPI to phospholipids. TIFI inhibited the binding of fluorescinated beta2GPI to human EC and to murine macrophages. The data indicate that TIFI abrogates thrombogenic properties of aPL in mice by competing with beta2GPI and preventing its binding to target cells. This may be important in designing new modalities for the treatment of thrombosis in APS.
Lupus 2006
PMID:A peptide that mimics the Vth region of beta-2-glycoprotein I reverses antiphospholipid-mediated thrombosis in mice. 1683 Aug 82

The importance of cerebral disease in patients with the Hughes syndrome is now becoming more widely recognized. The range of neuropsychiatric manifestations of APS is comprehensive, and includes focal symptoms attributable to lesions in a specific area of the brain as well as diffuse or global dysfunction. Patients with APS frequently present with strokes and TIA, but a wide spectrum of other neurologic features-also including non thrombotic neurologic syndromes-has been described in association with the presence of aPL. The recognition of APS has had a profound impact on the understanding and management of the treatment of CNS manifestations associated with connective tissue diseases, in particular, SLE. Many patients with focal neurologic manifestations and aPL, who a few years ago would have received high-dose corticosteroids or immunosuppression, are often successfully treated with anticoagulation. In our opinion, testing for aPL may have a major diagnostic and therapeutic impact not only in patients with autoimmune diseases and neuropsychiatric manifestations, but also in young individuals who develop cerebral ischemia, in those with atypical multiple sclerosis, transverse myelitis, and atypical seizures. We would also recommend testing for aPL for young individuals found with multiple hyperintensity lesions on brain MRI in the absence of other possible causes,especially when under the age of 40 years. It is our practice to anticoagulate patients with aPL suffering from cerebral ischemia with a target INR of 3.0 to prevent recurrences. Low-dose aspirin alone (with occasional exceptions)does not seem helpful to prevent recurrent thrombosis in these patients. Our recommendation, once the patient has had a proven thrombosis associated with aPL, is long-term (possibly life-long) warfarin therapy. Oral anti coagulation carries a risk of hemorrhage, but in our experience the risk of serious bleeding in patients with APS and previous thrombosis treated with oral anticoagulation to a target INR of 3.5 was similar to that in groups of patients treated with lower target ratios. Although a double-blind crossover trial comparing low molecular weight heparin with placebo in patients with aPL and chronic headaches did not show a significant difference in the beneficial effect of low molecular weight heparin versus placebo, in our experience selected patients with aPL and neuropsychiatric manifestations such as seizures, severe cognitive dys-function, and intractable headaches unresponsive to conventional treatment may respond to anticoagulant treatment. The neurologic ramifications of Hughes syndrome are extensive, and it behoves clinicians in all specialties to be aware of this syndrome because treatment with anticoagulation may profoundly change the outlook for these patients.
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PMID:Cerebral manifestations in the antiphospholipid (Hughes) syndrome. 1688 79

In conclusion, arthralgias represent a rather common osteoarticular manifestation of primary and secondary APS, while arthritis is mainly described in SLE-related APS. Osteonecrosis is frequently described in association with aPL in patients with and without autoimmune disorders. The presence of osteonecrosis in primary APS patients in the absence of corticosteroid use suggests an association between osteonecrosis and APS. Clinicians should be aware of this possible clinical manifestation of APS, because early diagnosis may lead to early management. A systematic screening for aPL in all cases with diagnosed osteonecrosis in the absence of precipitating factors should be considered.
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PMID:Osteoarticular manifestations of antiphospholipid syndrome. 1688 82

The antiphospholipid antibody syndrome (or the anticardiolipin antibody syndrome) is characterized by the presence of autoantibodies. Its major association is with systemic lupus erythematosus. 'Catastrophic' antiphospholipid syndrome (CAPS) is defined as an accelerated form of APS usually resulting in multiorgan failure and can be precipitated by surgery. We present the case of a 12-year-old male child who presented for enucleation of his left eye for fungal endopthalmitis. This patient had a history of CAPS 2 months before surgery with myocardial, gastrointestinal, renal and laryngeal involvement that improved on aggressive treatment and was subsequently managed on an outpatient basis for 2 months before presenting for enucleation. To the best of our knowledge, this is the first case of CAPS in a child reported in the anesthetic literature. Further aspects of this puzzling condition and its anesthesia implications are discussed.
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PMID:Anesthetic implications of the catastrophic antiphospholipid syndrome. 1697 44

Pulmonary involvement in the primary antiphospholipid syndrome (PAPS) has generally been on the basis of thromboembolism. We describe a patient with hemorrhagic alveolitis, a life-threatening complication that must also be considered. The patient was a 63-year-old Caucasian man who had a past history of recurrent deep vein thromboses as well as an arterial occlusion of the left popliteal artery and who developed hemorrhagic alveolitis and capillaritis at age 57 years, which was treated with long-term cyclophosphamide, steroids, and anticoagulation. Four years later, he had a recurrence of the same condition, and a positive lupus anticoagulant test was found. Severe thrombocytopenia, diagnosed as idiopathic thrombocytopenic purpura, was treated with platelet transfusions and increasing steroid dosage. Hemorrhagic adrenal infarction supervened at this time, and a septicemic illness was treated with intravenous antibiotics. Diffuse alveolar pulmonary hemorrhage is an unusual complication of the APS that is being increasingly reported, and recognition of its possible fatal course is of great importance for the treating physician. Severe thrombocytopenia that could contribute to hemorrhage may also accompany the APS, but this is unusual.
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PMID:Recurrent alveolar hemorrhage and pulmonary capillaritis in the "primary" antiphospholipid syndrome. 1703 85

Gallbladder disease is no more common in patients with systemic lupus erythematosus (SLE) than in the general population. We describe a 17-year-old patient with SLE, who developed nephritis that was well controlled with medications. Initial treatment consisted of azathioprine, aspirin and prednisone with stable control of her symptoms. Two years later she developed a right quadrant abdominal pain, and an abdominal ultrasound revealed microlithiasic cholecystitis. Open cholecystectomy was performed and the histopathological findings revealed vasculitis with thrombotic microangiopathy in the gallbladder. This case presentation illustrates that calculous or acalculous cholecystitis should be considered as a manifestation of active SLE and APS.
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PMID:Thrombotic microangiopathy involving the gallbladder as an unusual manifestation of systemic lupus erythematosus and antiphospholipid syndrome: Case report and review of the literature. 1713 89


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