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)

Active rheumatic disease may necessitate the treatment of pregnant and lactating patients with disease modifying (DMARD) or immunosuppressive drugs. This review summarizes data from the literature, and attempts to give some recommendations. Possible teratogenic effects of gold, penicillamine, and chloroquine are still disputed. As long as the issue is not settled, it seems prudent to stop using these agents as soon as pregnancy is diagnosed. Hydroxychloroquine has been used by some rheumatologists for treating pregnant patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) without malformations detected in the neonates. Sulphasalazine does not increase the rate of congenital abnormalities. Selected case reports have not shown any teratogenicity of cyclosporine A so far. However, the drug may cause fetal retardation. The use of standard doses of azathioprine does not increase the risk of congenital anomalies. By contrast, the antitumor agents cyclophosphamide, chlorambucil, and methotrexate are possibly teratogenic when given during early pregnancy, but may be less harmful in late pregnancy. Data on the excretion of DMARD and the cytostatic drugs are sparse. Because of insufficient data, breast feeding is not recommended in patients on antimalarials, penicillamine, cyclosporine A, and cytostatic drugs. Intramuscular gold and sulphasalazine seem to impose no major risk on the nursing infant.
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PMID:Treatment with immunosuppressive and disease modifying drugs during pregnancy and lactation. 128 66

The prognosis of systemic lupus erythematosus has improved over the past four decades. Articles published in the past year continue to demonstrate this improved survival, both overall and in patients with renal disease. Several factors may be associated with improved survival, including earlier diagnosis, better treatment for systemic lupus erythematosus, and improved medical therapy in general. Hydroxychloroquine has now clearly been shown to prevent flares, and ancrod has been shown to improve renal disease in patients with glomerular thrombosis. Treatment with dialysis and transplantation resulted not only in improved survival but also in improved renal status, and reduction in overall disease activity. Specific organ damage continues to be an issue, primarily with regard to kidney disease and neurocognitive impairment. The inclusion of health status assessment in the evaluation of patients with lupus, and as an outcome measure, is discussed.
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PMID:Prognosis of systemic lupus erythematosus and the factors that affect it. 175 11

Active rheumatic disease during pregnancy may require drug treatment to ensure the mother's health is maintained and that there is a good outcome for the fetus. However, knowledge on the use of antirheumatic drugs during pregnancy is limited, rendering decision making difficult both for the patient and the physician. The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis has been investigated in depth for aspirin (acetylsalicylic acid) and indomethacin only. Information about the use of ibuprofen, sulindac, ketoprofen and diclofenac during pregnancy is scanty and there is no such information for newer agents such as the fenemates and oxicams. There is no evidence for teratogenicity of any NSAID in humans. However, due to the shared property of inhibition of prostaglandin synthesis, adverse effects such as constriction of the ductus arteriosus in utero, persistent pulmonary hypertension in the neonate and prolongation of pregnancy and labour are possible. When administered to pregnant patients, NSAIDs should be given in the lowest effective dose, and should be withdrawn within the 8 weeks prior to expected delivery. Transplacental passage varies for different corticosteroids. Because of the inability of the fetal liver to convert prednisone to its active metabolite and the ability of the placenta to convert prednisolone to the inactive prednisone, both prednisolone and prednisone are drugs of choice in pregnant patients requiring corticosteroid treatment. Corticosteroids do not increase the risk of congenital malformations. Possible adverse effects are perinatal infection and adrenal insufficiency in the newborn. Both events are only rarely reported in the literature, which comprises information on more than 1000 pregnancies. The clinical experience on the effect of slow-acting antirheumatic drugs (SAARDs) on pregnancy is insufficient to draw substantial conclusions. Available data from the literature give no clear evidence of an increased risk of teratogenicity for any of these drugs. Rheumatologists differ in their view on the advisability of using SAARDs during pregnancy. Hydroxychloroquine, which is regarded as less toxic than chloroquine, is recommended by some rheumatologists for the treatment of pregnant patients with active systemic lupus erythematosus (SLE) or rheumatoid arthritis. Sulfasalazine can be continued during pregnancy. Data on gold compounds and penicillamine are sparse and inconclusive. A reasonable approach is to stop these agents as soon as pregnancy is confirmed. The limited experience with cyclosporin has been obtained when the drug was used to prevent allograft rejection. Further data regarding the use of this drug in pregnant patients with rheumatic diseases are needed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Optimisation of antirheumatic drug treatment in pregnancy. 788 37

Hydroxychloroquine has several less well-known actions that may have clinical relevance in treating systemic lupus erythematosus (SLE). (1) Hydroxychloroquine has a possible anti-thrombotic action. It is a platelet inhibitor and appears to decrease the risk of thromboembolism in patients with anticardiolipin antibodies. (2) Hydroxychloroquine is associated with lower serum cholesterol and low-density lipoprotein levels compared to those present in patients who are taking corticosteroids but not antimalarials for SLE. (3) It may also decrease abnormal levels of cytokines. Interleukin-6 (IL-6), soluble CD8 and soluble IL-2 receptors (sIL-2R) are lower in patients taking antimalarials compared to those on corticosteroids alone or on neither medication. Serum levels of CD8 and sIL-2R decrease after 6 weeks of hydroxychloroquine treatment. These findings may help explain the favorable response of SLE patients treated with antimalarials.
Lupus 1993 Feb
PMID:The relevance of antimalarial therapy with regard to thrombosis, hypercholesterolemia and cytokines in SLE. 848 65

The ophthalmologic safety of antimalarial drugs is well established, but absolute safety cannot be assured. Three types of side effects may develop. Corneal deposits and neuromuscular-associated blurred vision are always reversible and therefore benign. Visual loss has occurred in patients with retinopathy. Retinopathy may be divided into true retinopathy and premaculopathy. It is true retinopathy that may be associated with visual loss, while premaculopathy consists of subtle visual field and funduscopic abnormalities. These premaculopathic changes are generally completely reversible with drug discontinuation and have not been shown to progress. Hydroxychloroquine appears safer than chloroquine when currently accepted equivalent doses are used. Fewer than 20 patients with true retinopathy caused by hydroxychloroquine have been reported; more patients have developed true retinopathy when taking chloroquine. The safety profile is most dependent on low daily dose and regular ophthalmologic monitoring. The optimal strategy of ophthalmologic testing has not yet been determined, but visual acuity, funduscopic examination and visual field examination should be monitored. Self-administered ophthalmologic testing with Amsler grids may contribute additional safety but is not a replacement for physician testing.
Lupus 1993 Feb
PMID:Ophthalmologic safety profile of antimalarial drugs. 848 66

Transverse myelitis has been cited as a rare and unusual complication of systemic lupus erythematosus (SLE). A review of the literature reveals only 10 cases of transverse myelitis as the initial presentation of SLE, and only one with reported benefits from antimalarial therapy. The case of a 30-year-old woman is reviewed. She presented to the emergency room with complaints of hypogastric and low back pain. The ensuing course was one of frank urinary retention and rapidly progressing quadriparesis. Magnetic resonance imaging of the spine revealed marked edema of the cervical and thoracic spine. A diagnosis of SLE was based on positive antinuclear antibodies and leukopenia. The patient was treated with high dose methylprednisolone, plasmapheresis and pulse cyclophosphamide for 3 months. Subsequently, treatment was begun with hydroxychloroquine, and significant improvement in her neurologic and functional status was achieved after 1 month of therapy. Ten months after her onset of symptoms, the patient suffered an acute exacerbation of paraparesis and urinary retention. Again, she improved clinically after high dose methylprednisolone and pulse cyclophosphamide for 1 month. Hydroxychloroquine was continued throughout the duration of therapy.
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PMID:Transverse myelitis complicating systemic lupus erythematosus: treatment including hydroxychloroquine. Case report. 851 79

We report the case of a previously healthy 54-year-old woman, without any family history, who developed an angioneurotic edema with acquired C1 inhibitor deficiency and systemic lupus erythematosus. The search for a lymphoproliferative disorder was negative. Hydroxychloroquine therapy induced simultaneous resolution of lupus and angioedema. The pathophysiology of this association is discussed.
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PMID:Acquired C1 inhibitor deficiency revealing systemic lupus erythematosus. 851 91

Vascular damage in systemic lupus erythematosus (SLE) occurs through vasculitis, premature atherosclerosis, and hypercoagulability (predominantly due to the antiphospholipid antibody syndrome). In the Hopkins Lupus Cohort, a prospective cohort study, the incidence of thrombosis is 2 per 100 person-years of follow-up. Markers of immune-complex mediated injury (high anti-dsDNA and low C3), atherosclerosis (hypertension, hyperlipidemia, homocysteine) and antiphospholipid antibodies (lupus anticoagulant or anticardiolipin) are independent predictors of thrombosis. Hydroxychloroquine use is protective against future thrombosis.
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PMID:Thrombosis and systemic lupus erythematosus: the Hopkins Lupus Cohort perspective. 879 94

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well absorbed (0.7-0.8 bioavailability) when given orally. Severe malnutrition (such as kwashiorkor) effects absorption but diahrrea does not. Both HCQ and CQ have prolonged half-lives, between 40 and 50 days, and low blood clearance (e.g. hydroxychloroquine's blood clearance is 96 ml/min). There is great variability of blood concentrations with an eleven-fold range of drug concentrations found after similar doses in RA patients. Protein binding ranges between 30 and 40% with binding to both albumin and alpha, glycoprotein. There is differential binding and metabolism of the (R) and (S) stereoisomers. Both drugs bind strongly to pigmented tissues but also bind to mononuclear cells, muscles, etc. There is stereo-selective excretion of both drugs and 40-50% of the drug is excreted renally. Between 21 and 47% is excreted unchanged. There is a suggestion of concentration response and concentration toxicity relationships with decreased morning stiffness as HCQ concentrations increase and increased EKG abnormalities as CQ concentrations become higher, but further testing is required. Pharmacokinetic interaction studies are limited. Potentially important kinetic interactions have been documented for d-penicillamine and cimetidine but have not been found for aspirin, ranitidine or imipramine.
Lupus 1996 Jun
PMID:Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases. 880 4

Hydroxychloroquine is used by 35% of SLE patients enrolled in the Baltimore Lupus Cohort. Eighty per cent of patients who took hydroxychloroquine at cohort entry remain on it six years later. In addition to its role for disease manifestations of lupus, hydroxychloroquine may be indicated for the prevention of disease or treatment-induced complications, including hyperlipidemia, diabetes mellitus, liver function test elevation and thrombosis.
Lupus 1996 Jun
PMID:Hydroxychloroquine use in the Baltimore Lupus Cohort: effects on lipids, glucose and thrombosis. 880 5


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