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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antiphospholipid syndrome has received considerable attention from the medical community because of its association with a number of serious clinical disorders, including arterial and venous thromboembolism, acute ischemic encephalopathy, recurrent pregnancy loss, thrombocytopenia, and livido reticularis. It can occur within the context of several diseases, mainly autoimmune disorders, and is then called secondary antiphospholipid syndrome. However, it may be also be present without any recognizable disease, or so-called primary antiphospholipid syndrome. There is no defined racial predominance for primary antiphospholipid syndrome, although a higher prevalence of systemic lupus erythematosus (SLE) occurs in African Americans and the Hispanic population. Multiple terms exist for this syndrome, some of which can be confusing. Lupus anticoagulant syndrome, for example, is a misleading term, because patients may not necessarily have SLE, and it is associated with thrombotic rather than hemorrhagic complications. To avoid further confusion, antiphospholipid syndrome is currently the preferred term for this clinical syndrome. Antiphospholipid antibodies are found in 1% to 5% of young healthy control subjects; however, the incidence increases with age and coexistent chronic disease. The syndrome occurs most commonly in young to middle-aged adults; however, it also can occur in children and the elderly. Among patients with SLE, the prevalence of antiphospholipid antibodies is high, ranging from 12% to 30% for anticardiolipin antibodies, and 15% to 34% for lupus anticoagulant antibodies. In general, anticardiolipin antibodies occur approximately five times more often then lupus anticoagulant in patients with antiphospholipid syndrome. This syndrome is the most common cause of acquired thrombophilia, associated with either venous or arterial thrombosis or both. It is characterized by the presence of antiphospholipid antibodies, recurrent arterial and venous thrombosis, and spontaneous abortion. Rarely, patients with antiphospholipid syndrome may have fulminate multiple organ failure, or catastrophic antiphospholipid syndrome. This is caused by widespread microthrombi in multiple vascular beds, and can be devastating. Patients with catastrophic antiphospholipid syndrome may have massive venous thromboembolism, along with respiratory failure, stroke, abnormal liver enzyme concentrations, renal impairment, adrenal insufficiency, and areas of cutaneous infarction. According to the international consensus statement, at least one clinical criterion (vascular thrombosis, pregnancy complications) and one laboratory criterion (lupus anticoagulant, antipcardiolipin antibodies) should be present for a diagnosis of antiphospholipid syndrome. The hallmark result from laboratory tests that defines antiphospholipid syndrome is the presence of antibodies or abnormalities in phospholipid-dependent tests of coagulation, such as dilute Russell viper venom time. There is no consensus for treatment among physicians. Overall, there is general agreement that patients with recurrent thrombotic episodes require life-long anticoagulation therapy and that those with recurrent spontaneous abortion require anticoagulation therapy and low- dose aspirin therapy during most of gestation. Prophylactic anticoagulation therapy is not justified in patients with high titer anticardiolipin antibodies with no history of thrombosis. However, if a history of recurrent deep vein thrombosis or pulmonary embolism is established, long-term anticoagulant therapy with international normalized ratio (INR) of approximately 3 is needed.
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PMID:Antiphospholipid syndrome. 1467 58

In the last years it has been recognized that patients with systemic lupus erythematosus (SLE) are at high risk of osteoporosis (OP) and fractures, both occurring through disease-specific (chronic arthritis, reduced physical activity, induction of cytokines promoting bone resorption, renal impairment, endocrine factors) and nondisease-specific mechanisms (sunshine avoidance with consequent vitamin D deficiency, glucocorticoids, immunosuppressants and chronic anticoagulants). Regarding anticoagulants, subcutaneous heparin is crucial against the risk of recurrent thromboembolism or pregnancy loss, specifically in patients with SLE and anti-phospholipid syndrome (APS). Thus heparin-induced OP represents one of the hazards of this treatment, first because heparin must be used long-term and secondly because pregnancy and lactation themselves may predispose to OP and fractures. Current data suggest the use of prophylaxis with calcium and vitamin D in all patients treated with heparin during pregnancy. Nevertheless glucocorticoid-induced OP (GIOP) is considered the most serious risk factor for OP and fractures in SLE patients. All guidelines recommend general measures and supplementation with calcium and vitamin D in all patients. However when considering premenopausal patients, there is no generally recommended treatment. Bisphosphonates, which are considered the first choice therapy for the prevention and treatment of GIOP, should be used 'cautiously' in these patients. Therefore the potential risks and lack of efficacy data on fracture risk reduction in premenopausal patients must be weighed against their proven efficacy in postmenopausal patients.
Lupus 2004
PMID:Risk factors for osteoporosis in female patients with systemic lupus erythematosus. 1548 12

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects women more frequently than men. In the (NZB times NZW)F1 mouse, a murine SLE model, the presence or absence of estrogen markedly influences the rate of progression of disease. Three organochlorine pesticides with estrogenic effects were administered chronically to ovariectomized female (NZB times NZW)F1 mice, and we measured the time to development of renal disease, the principal clinical manifestation of lupus in this model. Treatment with chlordecone, methoxychlor, or o,p -dichlorodiphenyltrichloroethane (o,p -DDT) significantly decreased the time to onset of renal impairment, as did treatment with 17ss-estradiol used as a positive control. In an expanded study of chlordecone, we found a dose-related early appearance of elevated anti-double-strand DNA autoantibody titers that corresponded with subsequent development of glomerulonephritis. Immunohistofluorescence confirmed early deposition of immune complexes in kidneys of mice treated with chlordecone. These observations are consistent with an effect of these organochlorine pesticides to accelerate the natural course of SLE in the (NZB times NZW)F1 mouse. Although we originally hypothesized that the effect on progression of autoimmunity was due to estrogenic properties of the pesticides, autoimmune effects and estrogenicity, assessed through measurement of uterine hypertrophy, were not well correlated. This may indicate that uterine hypertrophy is a poor indicator of comparative estrogenic effects of organochlorine pesticides on the immune system, or that the pesticides are influencing autoimmunity through a mode of action unrelated to their estrogenicity.
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PMID:Acceleration of autoimmunity by organochlorine pesticides in (NZB x NZW)F1 mice. 1574 22

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a strong female predilection. Cardiovascular morbidity and mortality is a frequent complication, particularly in females aged 35-44 years, in whom the risk of myocardial infarction is raised 50-fold. The mechanisms underlying this increased risk are not fully understood. Certain traditional risk factors, such as hypertension and diabetes mellitus, are more common in SLE patients than in the general population. These factors do not, however, completely account for the increased cardiovascular risk; factors such as renal impairment, increased homocysteine levels and early menopause probably have a role. In addition, several factors more specifically related to lupus are proposed to be of importance, including chronic inflammation, antiphospholipid antibodies and therapy, especially corticosteroid use. Thus, we need to be proactive in our approach to risk-factor management in SLE patients. Here, we propose that, like diabetes mellitus, SLE should be considered a coronary heart disease equivalent condition for baseline risk and that assessment of cardiovascular risk should be done routinely. In addition to lifestyle modifications, blood pressure and cholesterol levels should be stringently controlled, and administration of aspirin should be considered in selected patients. The increased use of certain interventions, such as statins, also needs to be more widely investigated in this population.
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PMID:Therapy insight: systemic lupus erythematosus as a risk factor for cardiovascular disease. 1611 5

Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene which encodes the receptor for nerve growth factor (NGF). We report the clinical course in three sibs with CIPA and proven NTRK1 gene mutations with a follow-up over a 25-year period in one of them. They had the characteristic clinical features of an abnormally high pain threshold, and mental retardation; in addition their clinical course was marked by the occurrence of early onset renal disease with recurrent microhematuria and proteinuria and frequent observations of increased serum creatinine and blood urea levels. Light microscopy study of a renal biopsy performed in one of them at age of 20 months showed focal glomerulosclerosis, interstitial fibrosis and tubular atrophy. This patient and his younger brother died because of renal failure at the age of 25 years and 14 years, respectively. The sister still alive showed renal impairment and deep venous thrombosis associated with lupus anticoagulant activity, decrease of circulating autoreactive CD5 (+) B lymphocytes and increased urinary levels of IgG and kappa and lambda light chains, suggesting a possible defect in regulation of B-lymphocyte function. In the light of the NGF-related molecular defect, the extraneurological tissue involvement in CIPA might in part reflect dysregulation of immune mechanisms which possibly brings about a chronic inflammatory response. This, in turn, could result in renal disease which should be mentioned among the life-threatening complications associated with this disorder.
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PMID:Congenital insensitivity to pain with Anhidrosis (NTRK1 mutation) and early onset renal disease: clinical report on three sibs with a 25-year follow-up in one of them. 1613 53

Premature coronary heart disease (CHD) has emerged as a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Overall SLE patients have a 5-6-fold increased risk of CHD and this excess risk is especially pronounced in younger women where the excess risk may be >50-fold. Studies from our group and others have also demonstrated that SLE patients have a higher prevalence of subclinical atherosclerosis compared with controls, with approximately 30% having evidence of subclinical involvement. It is important to consider what factors may underlie this excess risk. We have found that certain 'classic' risk factors, i.e. hypertension and diabetes mellitus, are more prevalent in SLE and that persistent hypercholesterolaemia independently predicts patients who will develop CHD. These risk factors alone do not completely explain the excess risk observed, and after adjusting for classic risk factors SLE remains independently associated with both clinical and subclinical outcomes. Certain other metabolic changes also occur more frequently in SLE, namely premature menopause, renal impairment, high triglycerides and higher plasma homocysteine. In addition, insulin resistance is more pronounced in patients with SLE, and approximately 18% have the metabolic syndrome. It is also increasingly accepted that atherosclerosis is a chronic inflammatory condition, and in SLE systemic complement activation as well as immune complex formation can result in changes that promote the development of atheroma. Similarly, autoantibody production, especially antibodies directed against lipoprotein subtypes and those in the antiphospholipid (APLA) family, are gaining increasing attention. The role of the latter are particularly controversial as different subtypes have been shown to both promote and protect against atherogenesis. In a study looking at carotid plaque in SLE, we found that APLA was independently associated with the presence of plaque; this study also found that patients with plaque had higher white cell counts, suggesting ongoing chronic inflammation. We have also noted a negative correlation between activation of transforming growth factor beta-1 and carotid intima-medial thickness. This cytokine, which is known to be a potent anti-inflammatory molecule, has also been shown to be protective against atherogenesis. With regard to therapy, steroids may be a true double-edged sword, with low doses exerting a beneficial anti-inflammatory role whereas higher doses may be detrimental through exacerbation of metabolic risk factors. In contrast, we have found that antimalarials have a beneficial effect on lipids especially when co-prescribed with steroids, and this, along with anti-inflammatory and proposed antiplatelet effects, may confer protection against CHD in lupus. The risk of premature CHD in SLE is therefore mediated by a number of factors that involve not only classic risk factors but also a range of factors associated with SLE itself. Preventative strategies will therefore need to address all potential risk factors of relevance. A more through understanding of the interplay between autoimmunity and atherogenesis should be possible by the study of SLE, and this may not only benefit lupus patients but also may have implications for our understanding of atherosclerosis in general.
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PMID:'Not only...but also': factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus. 1623 77

It has been shown previously that chronic treatment with relatively low doses of chlordecone accelerates the development of systemic lupus erythematosus (SLE) in ovariectomized female (NZBxNZW) F(1) mice. In this study, the effect of chronic chlordecone treatment on SLE was evaluated in ovary-intact female (NZBxNZW) F(1) mice, as well as in female mice from a strain that is not lupus-prone, BALB/c. Chlordecone was administered chronically via implanted sustained-release pellets, and mice were monitored over time for the appearance of elevated autoantibodies (anti-dsDNA and anti-chromatin) and for the development of renal impairment, both indicators of SLE. Chlordecone treatment in (NZBxNZW) F(1) mice shortened significantly the time to onset of elevated autoantibody titers and renal disease in a dose-related manner. The doses required to produce this effect were similar to those observed previously to accelerate SLE development in ovariectomized females. Treatment of female BALB/c mice with chlordecone for up to one year did not produce elevated autoantibody titers or renal disease, suggesting an inability of chlordecone to cause a break in tolerance in this strain. These observations confirm the ability of chronic chlordecone to influence SLE, but demonstrate the importance of genetic background for this effect.
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PMID:Comparison of chlordecone effects on autoimmunity in (NZBxNZW) F(1) and BALB/c mice. 1630 13

Management of pregnant women with renal disease involves awareness of, and allowance for, physiological changes including decreased serum creatinine and increased proteinuria. For women with systemic lupus erythematosus (SLE), pregnancy increases likelihood of flare. These can occur at any stage, and are more difficult to diagnose, as symptoms overlap those of normal pregnancy. Renal involvement is no more common in pregnancy. Worsening proteinuria may be lupus flare but differential includes pre-eclampsia. In women with chronic renal disease, pregnancy may accelerate decline in renal function and worsen hypertension and proteinuria, with increased risk of maternal (eg, pre-eclampsia) and fetal (eg, IUGR, IUD) complications, strongly correlating with degree of renal impairment peri-conception. Pregnancy success rate varies from 20% to 95% depending on base-line creatinine. Best outcome is obtained if disease was quiescent for >6 months pre-conception. Women on dialysis or with renal transplants can achieve successful pregnancy but have higher maternal and fetal complication rates. Acute on chronic renal failure can develop secondary to complications such as HELLP and AFLP. Management needs to be by a multidisciplinary team involving physicians and obstetricians, ideally beginning with pre-pregnancy counselling. Treatment of flares includes corticosteroids, hydroxychloroquine, azothioprine, NSAIDs and MME Blood pressure is controlled with methyldopa, nifedipine or hydralazine.
Lupus 2006
PMID:Lupus nephritis and renal disease in pregnancy. 1663 68

The objective of this study was to compare the limit of agreement of creatinine clearance (CrCl) estimated by different equations with the CrCl measured by 24-hour urine collection in Hong Kong Chinese patients with systemic lupus erythematosus (SLE). Forty-three SLE patients with mild to moderate renal impairment (serum creatinine concentration >80 micromol/L to <300 micromol/L for females; and >106 micromol/L to <300 micromol/L for males) and not requiring renal replacement therapy were assessed. The estimated clearances were calculated by the Cockcroft-Gault (CG) equation, the Modification of Diet in Renal Disease (MDRD) study equation and the abbreviated MDRD (aMDRD) study equation. The estimated clearances were compared against the measured CrCl by 24-hour urine collection for their limit of agreement. Forty-three patients with mean (+/-SD) age of 41.6 (+/-8.4) years were assessed. As compared to the measured CrCl in patients with SLE, the clearances by CG equation, MDRD and aMDRD equations predicted a mean difference of -0.8% (95% confidence interval, -43.9-42.3%); -8.6% (95% CI, -24.3-7.2%) and -4.7% (95% CI, -21.4-12%), respectively. There is a tendency for the MDRD and aMDRD study equations to underestimate CrCl. The MDRD and aMDRD study equations have better predictive value than the CG equation.
Lupus 2006
PMID:Estimation of glomerular filtration rate in patients with systemic lupus erythematosus. 1676 1

In an Afro-Caribbean population, 111 new cases of systemic lupus erythematosus were diagnosed in the 10-year period from January 1995. Fifty-three cases (48%) presented with or subsequently developed lupus nephritis (SLEN). We recorded clinical characteristics and treatment outcomes of SLEN. We retrospectively categorized patients into four groups based on presence or absence of proteinuria with or without renal impairment. Group 1 (n = 15, 28%) had normal renal function (creatinine clearance (CrCl) > 70 mL/minute) with urinary protein excretion (UPE) of 0.5-3.0 g/24 hour, group 2 (n = 7, 13%) had normal renal function with UPE > 3.0 g/24 hour, group 3 (n = 9, 17%) had renal impairment (CrCl < 70 mL/minute) with UPE of 0.5-3.0 g/24 hour and group 4 (n = 22, 42%) had renal impairment with UPE > 3.0 g/24 hour. Renal biopsies were performed in 15 patients (28%). The number of treated patients in-remission decreased across the groups, from 100% in group 1 and 71% in group 2, to 33% in group 3 and 32% in group 4 (Pr < 0.001). There were 12 deaths from renal causes: none in groups 1 and 2, two (22%) from group 3 and 10 (45%) from group 4 (Pr = 0.003). In resource-poor clinical settings with limited access to histopathological services, CrCl and UPE may be useful predictors of therapeutic response and clinical outcomes in SLEN.
Lupus 2006
PMID:Lupus nephritis in an Afro-Caribbean population: renal indices and clinical outcomes. 1712 May 98


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