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)

A 43-year-old male with eunuchoid body proportions and a history of deep venous thromboses in the right leg presented with recurrent ulcers in the right perimalleolar region for 6 years. Karyotyping revealed a 47 XXY Klinefelter's syndrome, while serologic testing showed protein S deficiency, hyperhomocysteinemia and positive lupus anticoagulant. He also had mixed connective tissue disease (Sharp's syndrome) with acrosclerosis, proximal finger edema, Raynaud's phenomenon, and high titers of ANA and U1-RNP-antibodies, as well as osteoporosis. There is evidence that patients with Klinefelter's syndrome are prone to develop connective tissue diseases and thrombophilia as a result of low androgen levels. Substitution of testosterone in Klinefelter's syndrome can have a favorable therapeutic effect on the associated connective tissue disease, thrombophilia and osteoporosis.
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PMID:[Klinefelter's syndrome associated with mixed connective tissue disease (Sharp's syndrome) and thrombophilia with postthrombotic syndrome]. 1603 81

Arterial thrombosis results from endovascular injury and, to a lesser extent, alterations in hemostatic equilibrium. Although multiple hereditary and acquired hemostatic risk factors have been described in the pathophysiology of venous thrombosis, the degree and type of abnormalities that contribute to arterial thrombosis are less well understood. Endothelial cell injury with the elaboration of proinflammatory mediators stimulates the process of arterial thrombosis. Although this is most often the result of endovascular injury attributable to atherosclerotic disease, other disease states can elicit a similar response as well. Similarly, once thrombosis has been initiated, variations in the activity of coagulation proteins and endogenous anticoagulants, as well as the kinetics of platelet aggregation, may alter the effectiveness of thrombus formation. Epidemiological studies have identified several acquired or inherited states that may result in endothelial damage or altered hemostatic equilibrium, thereby predisposing patients to arterial thrombosis. These include hyperhomocysteinemia, elevated C-reactive protein, antiphospholipid antibodies, elevated fibrinogen, Factor VII, plasminogen activator inhibitor-1 (PAI-1), hereditary thrombophilias, and platelet hyper-reactivity. This review explores our present understanding of these risk factors in the development of arterial thrombotic events. At present, the literature supports a role for hyperhomocysteinemia, elevated C-reactive protein, and elevated fibrinogen as risk factors for arterial thrombosis. Similarly, the literature suggests that lupus anticoagulants and, to a lesser extent, elevated titers of cardiolipin IgG antibodies predispose to arterial vascular events. In certain subsets of patients, including those with concomitant cardiac risk factors, <55 years of age, and women, hereditary thrombophilias such as carriership of the factor V Leiden and the prothrombin G20210A mutations may confer a higher risk of arterial thrombosis. However, the data on Factor VII, PAI-1, and platelet receptor polymorphisms are contradictory or lacking.
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PMID:Assessment of hemostatic risk factors in predicting arterial thrombotic events. 1642 55

The role of thrombophilia in the pathogenesis of preeclampsia is controversial. The aim of this case-controlled study was to determine whether thrombophilia increases the risk of preeclampsia or interferes with its clinical course. A total of 808 white patients who developed preeclampsia (cases) and 808 women with previous uneventful pregnancies (controls) matched for age and parity were evaluated for inherited and acquired thrombophilia (factor V Leiden; factor II G20210A; methylenetetrahydrofolate reductase C677T; protein S, protein C, and antithrombin III deficiency; anticardiolipin antibodies; lupus anticoagulant; and hyperhomocysteinemia). Odds ratios (ORs) with 95% confidence intervals (CIs) for risk of being carriers of thrombophilia in cases compared with controls and for risk of maternal life-threatening complications and adverse perinatal outcomes in preeclamptic patients with or without thrombophilia were calculated. Women with severe preeclampsia (406 cases) had a higher risk (OR, 4.9; 95% CI, 3.5 to 6.9) of being carriers of either an inherited or acquired thrombophilic factor, except for protein S, protein C, and antithrombin deficiency. In women with mild preeclampsia (402 cases), only prothrombin and homozygous methylenetetrahydrofolate reductase gene mutations were significantly more prevalent than in the controls. Thrombophilic patients with severe preeclampsia are at increased risk of acute renal failure (OR, 1.8; 95% CI, 1.5 to 2.2), disseminated intravascular coagulation (OR, 2.7; 95% CI, 1.1 to 6.4), abruptio placentae (OR, 2.6; 95% CI, 1.2 to 6.0) and perinatal mortality (OR, 1.7; 95% CI, 1.5 to 2.2) compared with nonthrombophilic preeclamptic patients. Our study demonstrates a significant association between maternal thrombophilia and severe preeclampsia in white women. Thrombophilia also augments the risk of life-threatening maternal complications and adverse perinatal outcomes in preeclamptic patients.
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PMID:Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study. 1628 82

Systemic lupus erythematosus (SLE) is associated with premature atherothrombotic complications. Hyperhomocysteinemia is considered a cardiovascular risk factor. Increased vascular stiffness may increase cardiovascular mortality. Pulse wave velocity (PWV) is a noninvasive method of analyzing vascular stiffness in the assessment of atherosclerosis. The objective of this study was to identify the relationship between plasma homocysteine levels and brachial-ankle pulse wave velocity (baPWV) measurement in SLE. Plasma homocysteine, baPWV, ankle-brachial index, blood pressure, C3, C4, anticardiolipin antibody (aCL), and anti-double-stranded DNA antibodies were determined in a total of 58 female patients with SLE. The control group comprised 32 age-matched healthy females. In addition, all patients were further classified into subgroups according to the presence of aCL (SLE/aCL+, n=27 vs SLE/aCL-, n=31) to determine the effect of aCL on the tested variables. The mean values for plasma homocysteine and baPWV were 13.19 mumol/l and 1,482 cm/s, respectively. Plasma homocysteine levels were significantly elevated in SLE patients when compared with the healthy controls. SLE patients with aCL had a significantly higher plasma homocysteine level than those without aCL. A significant positive correlation between plasma homocysteine and baPWV was found in patients with SLE (r=0.335, P=0.028, n=58). Plasma homocysteine also significantly correlated with right baPWV in all SLE patients (r=0.371, P=0.014, n=58) and in the SLE/aCL+ group (r=0.523, P=0.031, n=27). These findings indicate a possible link between plasma homocysteine and baPWV in SLE. In conclusion, SLE patients had an increased level of plasma homocysteine, and this phenomenon appeared to be related to vascular stiffness.
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PMID:A positive correlation between homocysteine and brachial-ankle pulse wave velocity in patients with systemic lupus erythematosus. 1642 35

Maternal thrombophilias increases the risk of an adverse pregnancy outcome. An extensive literature review highlights the role of inherited and acquired thrombophilic disorders in spontaneous abortion, both early and late, recurrent or isolate, in intrauterine growth retardation, in placenta abruption, in pre-eclampsia and in venous thromboembolism. We have particularly focused attention on the following factors: antithrombin III (ATIII), proteins C (PC) and S (PS) deficiencies, genetic mutations particularly factor V Leiden (FVL), prothrombin gene G20210A (PTM) and the thermolabile variant of the methylene tetrahydrofolate reductase C677T (MTHFR) gene, lupus anticoagulant (LAC) and anticardiolipin antibodies, VIIIc factor, hyperhomocysteinemia and acquired activated protein C resistance. Appropriate treatment can improve pregnancy outcome without teratogenic effects.
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PMID:Inherited and acquired thrombophilia: pregnancy outcome and treatment. 1679 17

Hyperhomocysteinemia (HHcy), lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) are independent risk factors for thrombosis. Even though risks are cumulative, the clinical impact of the association is unknown. Preliminary data suggested that HHcy might be associated with transient LA and ACA, disappearing after lowering HHcy. We prospectively evaluated the association of HHcy and LA/ACA, the effect of lowering HHcy with folic acid in LA behavior, and the correlation of the initial dRVVT with LA behavior after folic acid in 210 patients with thrombosis and adverse pregnancy outcomes. Prevalence of HHcy among patients with LA/ACA was 40%. Thirty-one patients exhibited only HHcy (15%; Group 1), 106 (50%; Group 2) had only LA/ACA, while 73 (35%; Group 3) had both. After therapy, 63% and 64% of LA/ACA remained positive in Group 3 and 2, respectively. We observed a trend towards a more positive dRVVT in persistent LA after lowering HHcy. No differences in clinical presentation or in outcomes after two years of followup were observed among the groups. Even though the association of HHcy and LA/ACA is common in patients with thrombosis, it might have no prognostic implications if Hcy levels are lowered. Currently, no laboratory findings correlate with LA behavior, which is independent of homocysteine levels and vitamin treatment.
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PMID:Antiphospholipid antibodies and hyperhomocysteinaemia in patients with vascular occlusive disease. 1680 46

Dermatologists are in the unique position to be able to diagnose serious systemic diseases through skin findings; in addition, cutaneous manifestations can be associated with internal symptoms and clarify the pathogenesis and treatment of challenging new syndromes. Calciphylaxix, now renamed Calcific Uremic Arteriolopathy, primarily affects patients with end-stage renal disease with concomitant hyperphosphatemia, increased calcium-phosphate product and hyperparathyroidism, skin biopsy and wound care are crucial parts of the diagnosis and treatment. Hyperhomocysteinemia may play a very important role in many cutaneous and systemic diseases including, chronic cutaneous wounds, systemic lupus erythematosus, Behcet's disease and psoriasis. Through a skin biopsy and biochemical analysis of the proteoglycans accumulation it may be possible to diagnose a new systemic mucinosis and prevent sudden death in patients with severe mitral valve prolapse. Nephrogenic Fibrosing Dermopathy is a newly described fibrosing disorder occurring in patients with end stage renal disease, the etiology and pathogenesis are still unknown, and the ultimate course of this disease has not been defined.
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PMID:New clinical syndromes in dermatology. 1690 97

Homocysteine (Hcy), a sulfur-containing amino acid, is eliminated through B vitamins-dependent pathways. Hyperhomocysteinemia has been found to be an independent risk factor for atherosclerotic cardiovascular, cerebrovascular, and peripheral vascular diseases. Recently, psoriasis, lupus, and rheumatoid arthritis were reported to be associated with hyperhomocysteinemia. This study was aimed to evaluate the changes of plasma Hcy level before and after sulfasalazine and MTX therapy in patients with ankylosing spondylitis (AS). One hundred and two patients with AS and ten normal controls were enrolled in the cross-sectional case-control study. Fasting plasma Hcy levels were determined by ELISA kits (IMX, Abbott). Hcy levels were compared to their Bath AS disease activity index (BASDAI) and the usage of sulfasalazine and/or MTX. Active disease was defined by BASDAI as more than 3 in a 10-cm scale with ESR >20 mm/h. For those patients with plasma Hcy >or=15 micromol/l, a perspective trial of daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg for 2 weeks were also tested for the efficacy. Plasma Hcy level increased significantly in AS patients under sulfasalazine (10.4+/-3.8 micromol/l, p<0.05), MTX (11.9+/-4.7, p<0.05) and sulfasalazine/MTX combination treatment (11.2+/-2.6, p<0.05) compared with normal controls (8.6+/-1.2 micromol/l) and AS patients without DMARD(9.4+/- 2.6 micromol/l). No correlation between disease activity and plasma Hcy level was found. Daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg can lower Hcy level in 2 weeks (32.3+/-24.0 vs 15.6+/-11.1 micromol/l, p=0.007). Plasma homocysteine level did significantly increase in AS patients under sulfasalazine or MTX treatment. B-vitamins should be considered as a routine supplementation for patients who underwent sulfasalazine and/or MTX treatment. Further longitudinal studies are required to confirm the conclusions.
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PMID:Plasma homocysteine status in patients with ankylosing spondylitis. 1702 18

The primary hypercoagulable states are inherited thrombotic disorders, resulting from mutations in genes encoding a plasma protein component of one of the coagulation mechanisms. The anticoagulant pathways most frequently involved include antithrombin III, protein C, and protein S deficiencies and activated protein C (APC) resistance. Around 80 % of all individuals with APC resistance carry a mutation of the factor V gene. Abnormalities in procoagulant pathways mostly concern elevated levels and/or function of procoagulant factors. Elevation in plasma prothrombin (FII) levels is associated with a FII gene mutation. Hyperhomocysteinemia as a risk factor for thrombosis is determined by genetic or dietary factors. The acquired or secondary hypercoagulable states consist of a heterogeneous group of disorders with an increased risk for developing thrombosis. Many underlying conditions (e.g., malignancies) may induce changes in the coagulation system. The risk of thrombosis is increased in individuals with antiphospholipid antibodies. They are found in about one-half of patients with systemic lupus erythematosus, but also in the course of infections, neoplastic diseases, and sometimes in apparently normal subjects. A definite molecular abnormality of hypercoagulable states can be identified in the special coagulation laboratory, using two types of molecular risk factors for thrombosis (genetic factors and abnormal laboratory phenotypes). Its recognition is useful for a prevention and/or therapy of thrombosis (Tab. 4, Ref. 10).
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PMID:Diagnostic approach to hypercoagulable states. 1712 64

Folic acid is a vitamin B essential for the integrity and function of DNA. Relative deficiency of folic acid may occur in conditions such as pregnancy and hyperproliferative or chronic inflammatory disorders. Folic acid supplementation has been proven to be beneficial in the prevention of neural tube defects and in limiting methotrexate side effects, and may reduce the risk of colorectal cancer. Folate is a critical vitamin in determining plasma homocysteine levels, which in turn is a major risk factor for cardiovascular diseases. The results of large clinical trials with dietary supplementation of folic acid, vitamin B12 and vitamin B6 have shown that this homocysteine-lowering therapy is effective in the secondary prevention of non-fatal strokes, but had no effect in the prevention of fatal cardiovascular diseases. Hyperhomocysteinemia has also been reported in age-related neurological conditions with cognitive impairment (e.g. dementia), and psychiatric disorders such as depression. Elevated homocysteine levels are frequent in patients with chronic immune-mediated disorders including rheumatoid arthritis, systemic lupus erythematosus, chronic plaque psoriasis and psoriatic arthritis, which have in common a tendency to an accelerated atherosclerosis leading to increased deaths from cardiovascular events. Folic acid supplementation appears as a reasonable therapeutic option in patients affected by chronic inflammatory skin diseases, such as moderate to severe psoriasis; in particular, those with concomitant hyperhomocysteinemia, low plasma folate and additional cardiovascular risk factors.
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PMID:Folic acid in general medicine and dermatology. 1753 1


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