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)

The only antimalarial drug approved by the Food and Drug Administration for the treatment of lupus erythematosus is hydroxychloroquine (Plaquenil) sulfate. The dosage recommended officially for this disease is vague. Retinopathy has been caused by hydroxychloroquine but not in less than six months, nor when a total dosage of less than 72 gm or a daily dose of 200 mg or less is used. The ocular risk depends on the dose/weight ratio and is almost negligible at a dosage of less than 6 mg/kg/day. At a dosage of 400 mg or more daily, the risk/benefit ratio is acceptable for a person of average weight, provided that ophthalmologic monitoring is adequate. Risk of retinal toxicity is then proportional to duration of therapy and consequent cumulative dose. Ophthalmoscopic examinations at six-month intervals should be sufficient to detect occasional adverse reactions. Such tests could be conducted by the attending physician directly, as long as no pre-existing ocular abnormality exists.
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PMID:Hydroxychloroquine. 826 10

Chilblain lupus or lupus pernio is a particular clinical type of cutaneous chronic lupus erythematosus, more frequently met in adults and difficult do diagnose without specific lesions at the level of the face and/or the scalp. The patient B.A., female, aged 16 is hospitalized in the Dermatological Clinic Iasi for some red-to-violaceous plaques, infiltrated, slightly scaling located around the nails and on the hands and legs finger sides. The lesions come up at the age of 13 become even more serious and painful in cold weather, getting better in the warm season when they become slightly pruriginous and are accompanied by a discrete facial erythema in "vespertilio", completely neglected by the patient. The general status was very good during this time, without general manifestations or visceral touches. The clinical diagnosis that was initially suggested, pernio, was afterwards denied by a detailed anamnesis, by laboratory testes (positive antinuclear antibodies, positive anti-double-stranded DNA antibodies) and by the histopathological examination of the biopsy from cutaneous lesions. The introduction of the antimalarial drugs (Plaquenil 200 mg/ day) associated with photoprotective creams, led to cure of cutaneous lesions.
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PMID:[Chilblain lupus in an adolescent]. 2020 Dec 46

Derivates of chloroquine (Plaquenil, Delagil), used for long-term treatment of rheumatic diseases, may cause clinically proven irreversible maculopathy, which may progress even after the discontinuation of their application. The optimal early diagnosis of ocular toxicity of chloroquine or hydroxychloroquine drug remains controversial up to now. The aim of this review paper was to evaluate how appropriate is the indication of the electroretinographic (ERG) examination due to the early diagnosis of cumulative drug-related maculopathy. Photopic, pattern, and multifocal ERG (Retiscan, according to the ISCEV methodology) were examined in 10 patients (20 eyes) treated by means of antimalarics, 9 due to the rheumatoid arthritis (RA) and 1 due to the systemic lupus erythremathodes (SLE). The average age of the patients was 60 +/- 15 years, the treatment period was 10 +/- 11 years; the median of the treatment period was 5 years. The control group consisted of 12 healthy, age matched patients (20 eyes) without any obvious ocular pathology. In all of them, the complete ophthalmologic examination was performed: the best corrected visual acuity (BCVA) for far using the Snellen charts, intraocular pressure (IOP) measured by means of the non contact tonometer NIDEK NT-2000, the Amsler grid test, examination of the anterior segment and the posterior segment with the slit lamp. The entry criteria in both groups were BCVA 5/7,5 (0.67) and better, the IOP in the normal range, negative Amsler grid test, anterior segment without significant decrease of the transparency, and physiological posterior segment or with subtle granular pigment dysgrupancies in the macula only. The significant difference between the group treated with chloroquine or hydrochloroquine and the control group at the 1% level of significance was found in following parameters: in the photopic ERG the value of the b wave latency [ms], in pattern ERG, the values of the waves N35 - P50 [microV] and P50 - N95 [microV] amplitudes, and at the 5 % level of significance in photopic ERG, the wave a amplitude value [microV] and in multifocal ERG, the value of the P1 [ms] a N1 [ms] parts latency in the pericentral ring. It follows from the results, that the ERG examination is suitable for the early diagnosis drug cumulative maculopathy caused by chloroquine derivates. Optimal is the individual comparison of the ERG values of the patient before and in certain time intervals after the beginning of the chloroquine derivates treatment.
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PMID:[The ERG contribution in early diagnosis of chloroquine and hydroxychloroquine maculopathy]. 2092 39

The discovery that circulating nucleic acid-containing complexes in the serum of autoimmune lupus patients can stimulate B cells and plasmacytoid dendritic cells via Toll-like receptors 7 and 9 suggested that agents that block these receptors might be useful therapeutics. We identified two compounds, AT791 {3-[4-(6-(3-(dimethylamino)propoxy)benzo[d]oxazol-2-yl)phenoxy]-N,N-dimethylpropan-1-amine} and E6446 {6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole}, that inhibit Toll-like receptor (TLR)7 and 9 signaling in a variety of human and mouse cell types and inhibit DNA-TLR9 interaction in vitro. When administered to mice, these compounds suppress responses to challenge doses of cytidine-phosphate-guanidine (CpG)-containing DNA, which stimulates TLR9. When given chronically in spontaneous mouse lupus models, E6446 slowed development of circulating antinuclear antibodies and had a modest effect on anti-double-stranded DNA titers but showed no observable impact on proteinuria or mortality. We discovered that the ability of AT791 and E6446 to inhibit TLR7 and 9 signaling depends on two properties: weak interaction with nucleic acids and high accumulation in the intracellular acidic compartments where TLR7 and 9 reside. Binding of the compounds to DNA prevents DNA-TLR9 interaction in vitro and modulates signaling in vivo. Our data also confirm an earlier report that this same mechanism may explain inhibition of TLR7 and 9 signaling by hydroxychloroquine (Plaquenil; Sanofi-Aventis, Bridgewater, NJ), a drug commonly prescribed to treat lupus. Thus, very different structural classes of molecules can inhibit endosomal TLRs by essentially identical mechanisms of action, suggesting a general mechanism for targeting this group of TLRs.
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PMID:Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo. 2434 72