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 retina is relatively protected from systemic drug administration because of the blood-retinal barrier, a highly selective mechanism adapted to providing a regulated homeostatic environment for this highly specialised tissue. However, a number of drugs have been associated with retinal toxicity. Vigabatrin, as an adjunctive therapy for the management of partial epilepsy, is associated with visual field defects in approximately 40% of patients. Hydroxychloroquine, used in the treatment of rheumatoid arthritis and systemic lupus erythematosus, is also associated with a retinopathy. In view of this, ophthalmological screening and monitoring is recommended during prescription of both of these drugs. In these cases, the retina is the site for an adverse drug reaction and the dose of therapy may be important in determining the likelihood of retinal toxicity. However, in the case of cytomegalovirus retinitis, the retina is the intended site for pharmacological action. The treatment of this condition with the antiviral agents ganciclovir, valganciclovir, foscarnet and cidofovir, can also be associated with significant systemic toxicity.
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PMID:Drugs and the retina. 1515 52

Hydroxychloroquine (HCQ) is widely used in the treatment of systemic lupus erythematosus (SLE). Even if it is generally agreed that pregnancy per se increases disease activity in patients with SLE and that withdrawal of HCQ at the onset of pregnancy may result in exacerbation of SLE, use of HCQ during pregnancy has remained controversial for a long time. Parke was the first to propose continuation of HCQ throughout gestation. Currently, more than 250 pregnancies resulting in live births have been reported and no increase in the rate of birth defects have been demonstrated. When studied, no retinal toxicity and ototoxicity have been found. Data concerning lactation and HCQ treatment are rare. However, the amount of HCQ received by children through lactation seems very low. In conclusion, HCQ should probably be maintained throughout pregnancy in patients with SLE and it does not seem necessary to advise against breastfeeding.
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PMID:Safety of hydroxychloroquine in pregnant patients with connective tissue diseases. Review of the literature. 1572 58

Hydroxychloroquine (HCQ) is an antimalarial agent with immunomodulatory effects. It is widely used in rheumatologic diseases, and has a very high efficacy/toxicity ratio. It is particularly important in the treatment of systemic lupus erythematosus (SLE) since it reduces new organ involvement and disease flares, and relieves skin and joint symptoms. Some patients develop hypersensitivity rash in response to HCQ. In such patients the drug is withdrawn and replaced by another medication. All the alternative medications for rheumatological patients are significantly more toxic than HCQ. We describe our initial experience of HCQ slow oral desensitization. All 4 patients who were recruited completed the procedure successfully without significant difficulty. Our results suggest that HCQ slow oral desensitization is safe, effective, and easy to perform.
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PMID:Desensitization to hydroxychloroquine--experience of 4 patients. 2196 96

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which is autoimmune in origin and is characterized by the presence of autoantibodies directed against nuclear antigens. It is a multi-system disease, and patients can present in vastly different ways. Prevalence varies with ethnicity, but is estimated to be about 1 per 1000 overall with a female to male ratio of 10:1. The clinical heterogeneity of this disease mirrors its complex aetiopathogenesis, which highlights the importance of genetic factors and individual susceptibility to environmental factors. SLE can affect every organ in the body. The most common manifestations include rash, arthritis and fatigue. At the more severe end of the spectrum, SLE can cause nephritis, neurological problems, anaemia and thrombocytopaenia. Over 90% of patients with SLE have positive anti-nuclear antibodies (ANA). Significant titres are accepted to be of 1:80 or greater. SLE is a relapsing and remitting disease, and treatment aims are threefold: managing acute periods of potentially life-threatening ill health, minimizing the risk of flares during periods of relative stability, and controlling the less life-threatening, but often incapacitating day to day symptoms. Hydroxychloroquine and non-steroidal anti-inflammatory drugs are used for milder disease; corticosteroids and immunosuppressive therapies are generally reserved for major organ involvement; anti-CD20 monoclonal antibody is now used in patients with severe disease who has not responded to conventional treatments. Despite enormous improvements in prognosis since the introduction of corticosteroids and immunosuppressive drugs, SLE continues to have a significant impact on the mortality and morbidity of those affected.
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PMID:Systemic lupus erythematosus. 1672 94

After many barren years, conceptual advances and the introduction of new biotherapies are yielding improvements in the management of systemic lupus erythematosus (SLE). The result is a radical change in the management strategy. The main therapeutic advances rest on new discoveries (or rediscoveries), some of which are original. They can be summarized under 12 headlines. Smoking is inadvisable, as it promotes not only atheroma but also lupus flares. Hydroxychloroquine and conventional drugs (cyclophosphamide) are helpful provided they are used appropriately. Combined oral contraception and hormone replacement therapy may be less hazardous than previously thought, although caution remains in order. Drugs used in transplant recipients, such as mycophenolic acid, are generating optimism as treatments for SLE. Rituximab and new anti-B-cell drugs hold promise for the treatment of severe SLE. Efforts to develop an "etiologic" treatment for SLE based on type 1 (alpha/beta) interferon blockade still face a number of obstacles. Peptide vaccines, whose main effect is stimulation of regulator T cells, hold promise-but confirmation is needed. Whether TNF antagonists can be used in lupus with skin and joint manifestations or in SLE is generating debate. Complement blockade for treating SLE and antiphospholipid syndrome is an attractive avenue of research. Numerous new immunotherapy modalities based on modulating intracellular signaling are being evaluated. In the most severe forms of SLE, autologous peripheral stem cell transplantation deserves consideration. A key component of the treatment of SLE is control of atheroma, which is among the most severe complications. This rich harvest of new treatment possibilities can be expected to radically modify the prognosis of SLE, whose more aggressive forms remain severe.
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PMID:Treatment of systemic lupus erythematosus in 2006. 1711 Jan 51

Ocular manifestations of lupus are fairly common, may be the presenting feature of the disease and can be sight-threatening. Almost any part of the eye and visual pathway can be affected by inflammatory or thrombotic processes. Ocular pain and visual impairment require urgent assessment by an ophthalmologist. Infection should be excluded. Optic neuritis and ischaemic optic neuropathy may be difficult to distinguish. Scleritis and severe retinopathy require systemic immunosuppression but episcleritis, anterior uveitis and dry eyes can usually be managed with local eye drops. Vaso-occlusive disease, particularly in the presence of antiphospholipid antibodies, requires treatment with anticoagulation and proliferative retinopathy is treated with laser therapy. Hydroxychloroquine rarely causes ocular toxicity at doses under 6.5 mg/kg/day. When this has occurred, it has been associated with more than 5 years of drug exposure.
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PMID:Ocular manifestations of systemic lupus erythematosus. 1768 81

Systemic lupus erythematosus (SLE) is an independent risk factor for atherosclerosis, placing children and adolescents with SLE at great risk for developing cardiovascular sequelae, including myocardial infarction, in adulthood. Dyslipidemia and other traditional cardiac risk factors occur frequently in pediatric SLE and are often under-recognized and under-treated. Two dyslipidemia patterns are evident in pediatric SLE. Active disease is characterized by elevated triglycerides (TG) and low high density lipoprotein (HDL). With SLE treatment HDL and TG often normalize, while total cholesterol and low density lipoprotein (LDL) rise. The complex pathophysiology of dyslipidemia in SLE involves cytokines, autoantibodies, disease activity, medications, diet, and physical activity level, as well as other factors. Routine screening for dyslipidemia with fasting lipid profiles is indicated for children and adolescents with SLE. If lipoprotein levels are abnormal, first line therapy involves diet and exercise interventions for a minimum of six months. For persistent dyslipidemia, several pharmacologic therapies are available. Hydroxychloroquine, a common treatment for SLE, can improve lipid profiles and should be considered for all patients with SLE. Statins and bile acid sequestrants are typically added first for dyslipidemia, while niacin and fibrates are reserved for refractory disease and optimally prescribed in a multidisciplinary lipid clinic. Future research is needed to further illuminate the mechanisms of dyslipidemia in pediatric SLE with well designed clinical trials to determine the safest and most effective interventions to correct lipid profiles and prevent atherosclerosis.
Lupus 2007
PMID:Management of dyslipidemia in children and adolescents with systemic lupus erythematosus. 1771 98

Chloroquine (CHQ), an antimalarial, is also used as an anti-inflammatory drug for systemic lupus erythematosus and rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) reduces the frequency of organ involvement and disease flares, and relieves skin and joint symptoms. CHQ reduces the immunologically-mediated inflammation of the joints. HCQ and combination therapies have a significant benefit on synovitis, pain and physical disability on RA. We advocate the investment of resistance Plasmodium prevalence determinations in countries beset by malaria, and to match thereafter the quantity of persons administered CHQ. Follow-up investigations are essential to diagnose and prevent visual damage.
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PMID:Chloroquine has not disappeared. 1805 74

Hydroxychloroquine- or chloroquine -induced cardiomyopathy is a rare but potentially fatal condition. Hydroxychloroquine and chloroquine are often used for long-term treatment of rheumatic diseases and for malaria prophylaxis. Hydroxychloroquine- and chloroquine-induced cardiomyopathy have well-described microscopic features, with the classic electron microscopic findings of myelin figures (myeloid bodies). We report on 2 new cases with novel findings. The first case, in a patient with systemic lupus erythematosus, was found to have megamitochondria in addition to myelin figures seen by electron microscopy. The second report describes the first case of hydroxychloroquine cardiomyopathy described in a patient with scleroderma. These novel findings will add to the present knowledge of hydroxychloroquine-induced cardiomyopathy in its pathology and its implication for treatment of rheumatic diseases.
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PMID:New clinical and ultrastructural findings in hydroxychloroquine-induced cardiomyopathy--a report of 2 cases. 1806 91

Lupus treatment has evolved considerably with spectacular advances that can be summarized in 10 points. Hydroxychloroquine and cyclophosphamide are still standard drugs, provided their use is optimized. Contraception and postmenopausal hormone replacement therapy have finally been tested in randomized studies with fairly reassuring results, although prudence remains essential in patients with severe lupus and above all in those with thrombotic complications (antiphospholipid syndrome). Mycophenolic acid has been shown to be useful in the treatment of lupus nephropathies, but its specific place in the therapeutic strategy remains to be defined. Other drugs (sirolimus, abatacept) are currently being evaluated. Anti-lymphocyte B therapies are growing in popularity. Rituximab and other drugs (anti-BAFF, TACI-Fc) are also being evaluated and their results appear very interesting. Interferon alpha (type I) inhibition is an attractive therapeutic approach in lupus but its use in humans is still premature. Peptide vaccination with fragments of autoantibodies or autoantigens is an elegant strategy, and preliminary results justify further studies. Anti-TNF molecules may be beneficial in lupus. Complement inhibition can be useful in lupus and antiphospholipid syndrome but drugs usable in humans (anti-C5) must be developed. Atheromatosis in lupus is the principal cause of morbidity and mortality and must be managed. Smoking cessation is essential, but other approaches (statins) should also be discussed. Many futuristic types of immune manipulation may be envisioned (proteasome inhibition, modulation of Fc gammaRIIB, and modulation of cell signaling (PI3kgamma)). Hence the perspectives are numerous. We will soon be able to optimize the treatment of our patients. Nevertheless, rigorous evaluation of the risk/benefit ratio of new drugs and of their most appropriate place in the therapeutic strategy against systemic lupus is indispensable.
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PMID:[Systemic lupus erythematosus: news and therapeutic perspectives]. 1824 45


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