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)

Conflicting data exist with respect to the existence and clinical manifestations of a hyperlipidemic arthropathy. Reasonable evidence supports the existence of a migratory polyarthritis similar to rheumatic fever in patients homozygous for type II hyperlipidemia. Although similar complaints have been described in patients heterozygous for this condition, findings have been inconsistent among various reports. It is possible that high lipid levels are required to induce rheumatic complaints, and these are found predominantly in homozygous patients. Even so, rheumatic syndromes appear to be more attributable to periarthritis because evidence of inflammatory arthritis is largely lacking. In contrast, Achilles tendinitis appears to be associated with heterozygous type II hyperlipidemia and presumably is based on lipid deposits within the tendon. Gout is an accepted association of type IV hyperlipidemia. In addition, oligoarticular symptoms have been described with type IV hyperlipidemia. However, no consistent clinical entity has emerged. Drugs used in the treatment of hyperlipidemia are associated with a variety of rheumatic problems, including proximal myopathy and lupus-like syndromes. The most commonly implicated drugs are the hydroxymethylglutaryl-coenzyme A reductase inhibitors and the fibric acid derivatives.
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PMID:Rheumatic manifestations of hyperlipidemia and antihyperlipidemia drug therapy. 826 12

Fifteen patients with cerebral venous thrombosis were ascertained retrospectively. Their case notes were reviewed, and stored or new blood was assayed for factor V Leiden (FVL) mutation, prothrombin gene mutation 20201A, and 5,10 methylene tetrahydrofolate reductase (MTHFR) C677T mutation. A clinical risk factor was identified in 13 patients--the oral contraceptive pill (5), puerperium (1), HRT (1), mastoiditis (1), dehydration (1), lumbar puncture and myelography (1), carcinoma (1), lupus anticoagulant (2). In addition, two patients had the FVL mutation and five (one of whom also had the FVL mutation) were homozygous for the MTHFR mutation. The latter showed a higher than expected frequency compared to 300 healthy controls from South Wales (OR 3.15.95% Cl 1.01-9.83). No patient had the prothrombin 20201A mutation. Two patients died and three had a monocular visual deficit following anticoagulation (13) or thrombolytic (2) treatment, but there was no association between the presence of a primary prothrombotic risk factor and outcome. These results confirm the importance of investigating patients for both clinical predisposing factors and primary prothrombotic states.
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PMID:Inherited prothrombotic risk factors and cerebral venous thrombosis. 1002 25

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are widely used as cholesterol lowering agents that have an acceptable safety profile. As a group, this class of drugs has been associated with few immunologic reactions. Simvastatin (Zocor) has been linked to three cases of drug-induced lupus-like syndrome. We report the case of an additional patient who developed pleurisy and arthralgia after he started taking this low-density lipoprotein and cholesterol-lowering agent.
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PMID:Simvastatin-induced lupus-like syndrome. 1062 62

Thrombophilia can result from either inherited or acquired conditions. We describe a teenager who developed extensive thrombosis requiring aggressive and prolonged anticoagulation. Laboratory evaluation revealed an acquired lupus anticoagulant, consistent with the antiphospholipid antibody syndrome (APS). DNA analysis revealed inherited thrombophilic mutations in the factor V and methylene tetrahydrofolate reductase genes. We believe that the combination of inherited and acquired hypercoagulable conditions affected her therapeutic response to anticoagulant therapy. Inherited thrombophilic DNA mutations may contribute to the hypercoagulability observed in patients with acquired thrombophilic conditions such as APS and systemic lupus erythematosus.
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PMID:Effects of inherited thrombophilic mutations in an adolescent with antiphospholipid syndrome and systemic lupus erythematosus. 1124 80

A subgroup of children with arterial ischemic stroke in the pre- or perinatal period present with delayed diagnosis. We identified 22 children who met the following criteria: (1) normal neonatal neurological history, (2) hemiparesis and/or seizures first recognized after two months of age, and (3) computed tomography or magnetic resonance imaging showing remote cerebral infarct. Laboratory evaluations included protein C, protein S, antithrombin, activated protein C resistance screen (APCR), Factor V Leiden (FVL), prothrombin gene defect, methylene tetrahydrofolate reductase variant (MTHFR), anticardiolipin antibody (ACLA), and lupus anticoagulant. Not all children received all tests. Age at last visit ranged from 8 months to 16.5 years (median 4 years). Twelve were boys. Fourteen had left hemisphere infarcts. Median age at presentation was 6 months. Eighteen had gestational complications. Fourteen children had at least transient coagulation abnormalities (ACLA = 11, ACLA + APCR = 1, APCR = 2 with FVL + MTHFR = 1); six of these children had family histories suggestive of thrombosis. Cardiac echocardiogram was unremarkable in the 15 tested. Outcomes included persistent hemiparesis in 22; speech, behavior, or learning problems in 12; and persistent seizures in five, with no evidence of further stroke in any patient. The persistence and importance of coagulation abnormalities in this group need further study.
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PMID:Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes. 1150 98

During the last decade, statins have been widely prescribed as lipid-lowering drugs. Their overall safety profile is good. The main musculoskeletal side effects have consisted of muscle pain and weakness, peripheral neuropathy, and a few cases of drug-induced lupus. We report the first four cases of tendinopathy in patients receiving statin therapy. There were three men and one woman. The diagnoses were extensortenosynovitis at the hands (case 1), tenosynovitis of the tibialis anterior tendon (case 2), and Achilles tendinopathy (cases 3 and 4). Two patients were on simvastatin and two on atorvastatin. The tendinopathy developed 1 to 2 months after treatment initiation. The outcome was consistently favorable within 1 to 2 months after discontinuation of the drug. Similar cases have been reported to French pharmacovigilance centers. This report of four cases of tendinopathy draws attention to a possible and heretofore unrecognized side effect of a drug class that is becoming increasingly popular. Statins are effective in lowering high cholesterol levels in patients with type IIa or IIb hypercholesterolemia. They have been widely used for the last decade, particularly in the secondary and primary prevention of major coronary events. Statins act by inhibiting the enzyme hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Although most patients tolerate statins extremely well, a few experience side effects requiring treatment discontinuation. Reported musculoskeletal side effects include myalgia and a few cases of rhabdomyolysis and polymyositis. Induced lupus and peripheral neuropathy are exceedingly rare.
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PMID:Four cases of tendinopathy in patients on statin therapy. 1170 10

Paediatric patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL), specifically lupus anticoagulants (LAC) are at high risk of developing thromboembolic events (TE). Our objectives were to determine the prevalence of TE in paediatric SLE patients with LAC and to determine if anticoagulation was effective to decrease morbidity, and prevent recurrent TE. We reviewed data on 149 paediatric SLE patients treated over 10 years. In all, 24 patients (16%) were LAC positive, and 21 TE occurred in 13 of these LAC positive patients (54% incidence of TE in LAC positive patients). The events were cerebral venous thrombosis (9), arterial stroke (3), deep venous thrombosis (4), pulmonary embolism (2), other venous event (1) and other arterial events (2). The median duration between SLE diagnosis and first TE was 15.2 months (range 0-62), and the median age at first TE was 15.1 years (range 11.4-18.4). Long-term anticoagulation was prescribed, and eight patients (62%) were transferred to adult care on lifelong oral warfarin; four (31%) remain under our care on lifelong warfarin, and one patient died of causes unrelated to her TE. No patient has been identified with deficiencies of protein C, protein S or antithrombin III. One patient is heterozygous for Factor V Leiden, and one is heterozygous for both the Prothrombin 20210A mutation and the MTHFR (methylene tetrahydrofolate reductase) mutation. Four patients had recurrent TE (31%), and three were not anticoagulated at the time of their second event. One patient had two recurrences on therapeutic anticoagulation. Thromboembolic events are prevalent in the LAC positive paediatric SLE population, and consideration for lifelong anticoagulation must occur after an initial TE.
Lupus 2003
PMID:Thromboembolism in paediatric lupus patients. 1459 22

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), atorvastatin, cerivastatin, fluvastatin, pravastatin, lovastatin and simvastatin, reduce atherogenesis and cardiovascular morbidity. Besides, there is growing evidence that statins have immunomodulatory activities. Statins downregulate the expression of adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MAC-1) and lymphocyte function-associated antigen-1 (LFA-1), on leucocytes and endothelial cells and, through binding to LFA-1, interfere with ICAM-1-LFA-1 interaction, which is crucial for activation of lymphocytes by antigen-presenting cells, ingress of leucocytes into the inflammation sites and immunologic cytotoxicity. Statins inhibit the inducible expression of major histocompatibility complex class II in several cell types including macrophages and downregulate the expression of T-helper-1 (Th1) chemokine receptors on T cells, leading further to inhibition of activation of lymphocytes and their infiltration into the inflammation sites. Statins block the induction of inducible nitric oxide synthase and the expression of several proinflammatory cytokines such as tumour necrosis factor-alpha and interferon-gamma in macrophages and possess antioxidant effects. These agents inhibit the proliferation of immunocytes and the activation of natural killer cells. Regarding the above facts and in view of their safety and inexpensiveness, statins may prove invaluable in the treatment of a multiplicity of dermatologic disorders, especially those characterized by ingress of activated leucocytes into the skin, such as alopecia areata, vitiligo, lichen planus, subacute cutaneous lupus erythematosus, erythema multiforme, psoriasis, bullous pemphigoid, systemic sclerosis, mycosis fungoides, toxic epidermal necrolysis and Behcet's disease.
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PMID:Statins: novel additions to the dermatologic arsenal? 1518 18

Inhibitors of 3-hydroxy-3-methylgluttaryl coenzyme A (HMG-CoA) reductase, or statins, are used extensively to reduced elevated lipid levels and reduce cardiovascular risk. However, accumulated evidence suggests that stains not only act by lowering cholesterol levels, but also exert pleiotropic effects on many essential cellular functions including cell proliferation, differentiation, and survival and participate in the regulation of cell shape and motility. Thus cardiovascular benefit is provided by lowering raised cholesterol levels and by modulation of the inflammatory component of this disease. Such an anti-inflammatory effect may also benefit patients with autoimmune rheumatic disease. This overview assesses the evidence for using statins in patients with rheumatoid arthritis and systemic lupus erythematosus (SLE).
Lupus 2005
PMID:Statins: immunomodulators for autoimmune rheumatic disease? 1580 95

The 3-Hydroxy-3-methyl-glutaryl coenzyme A (HGM-CoA) reductase inhibitors, or statins, are competitive inhibitors of the rate-limiting enzyme in cholesterol synthesis. Generally, statins have an excellent safety profile. Elevations of liver transaminases and creatine phosphokinase with myalgia have been associated with the use of HGM-Co A reductase inhibitors, case reports of rhabdomyolysis are rare, most occurring with concomitant use with other drugs such as cyclosporin, fusidic acid and gemfibrozil. We describe here the clinical case of a patient who developed interstitial lung disease as probably a result of the use of statins which particularly increased with long-term atorvastatin treatment. The present review details some case-reports of interstitial lung disease reported under statins in the literature. Few systemic adverse effects such as lupus-like-syndromes and polymyositis have been reported. Recent experimentations have demonstrated that cholesterol is not the only intracellular target of statins but that they also have a potential role in atherosclerosis and in organ transplantation as immunosuppressor agents.
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PMID:[A case of interstitial lung disease with atorvastatin (Tahor) and a review of the literature about these effects observed under statins]. 1679 55


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