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 existence of iatrogenic lupus is now well-established and seems to be on the increase. A number of drugs must take the blame for these outbreaks: Hydrazine derivatives (Hydralazine, I.N.H.), anticonvulsants, Procainamide, psychotropics, antibiotics, antalgics, contraceptives. Clinically, these drugs can: --either mimic L.E. without showing any visceral or biological signs; --or aggravate a chronic L.E., or a systemic L.E. during a remission with biological symptoms appearing; --or trigger a true L.E.: all the various clinical symptoms of idiopathic L.E. may be encountered, certain articular, cutaneous symptoms predominating, renal symptoms rarely appearing. The discovery of HARGRAVES cells is the only certain biological sign to confirm systemic lupus, the existence of antinuclear antibodies or antinuclear factors merely serving as a guide to the collecting of a whole gamut of clinical and biological symptoms.
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PMID:[Iatrogenic lupus-like syndromes]. 13 11

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease affecting a variety of tissues and organs. The diagnosis of SLE can be made only after several related illnesses are considered and ruled out. The etiology of SLE is unclear, but hormonal factors, environmental toxins, infectious viruses, genetic predisposition, and certain medications have all been considered risk factors. Idiopathic SLE is seen predominantly in young women, with a female:male ratio of approximately 10:1. Each patient is unique and may suffer from a variety of signs and symptoms. The disease is highly unpredictable, and most patients experience flare-ups or fluctuations. The epidemiologic characteristics of medication-induced SLE (MI-SLE) are different from those of idiopathic SLE. Musculoskeletal symptoms predominate the clinical presentation of MI-SLE, while renal and central nervous system involvement is rare or absent. Moreover, a greater percentage of caucasian patients with no female predominance is evidenced in MI-SLE. Several medications can produce positive results on an antinuclear antibody test with or without evidence of clinical lupus. Hydralazine and procainamide are the most commonly recognized medications for inducing SLE. The onset of procainamide- and hydralazine-induced SLE occurs after 50 years of age, which is directly related to the age of the population using these medications. Estrogen-containing oral contraceptives and ibuprofen can exacerbate the symptoms of idiopathic SLE. Clinical judgment dictates the importance of careful patient monitoring and selection of therapy.
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PMID:Medication-induced systemic lupus erythematosus. 135 74

Hydralazine is associated with a lupus-like syndrome. There is evidence that many drug hypersensitivity reactions are due to reactive metabolites. Incubation of hydralazine with activated neutrophils or monocytes led to the production of phthalazinone, phthalazine and 3 unidentified metabolites. Formation of the metabolites, with the exception of phthalazine, required activation of the leukocytes. Using radiolabelled hydralazine, covalent binding to activated neutrophils was observed. Oxidation of hydralazine catalyzed by myeloperoxidase (MPO) produced the same metabolites and covalent binding to protein. We conclude that hydralazine is metabolized by activated leukocytes to a reactive metabolite which may be associated with hydralazine induced lupus.
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PMID:Metabolism of hydralazine by activated leukocytes: implications for hydralazine induced lupus. 166 57

Hydralazine caused site-specific DNA damage in the presence of Cu(II), Co(II), Fe(III), or peroxidase/H2O2. The order of inducing effect of metal ions on hydralazine-dependent DNA damage [Cu(II) greater than Co(II) greater than Fe(III)] was related to that of accelerating effect on the O2 consumption rate of hydralazine autoxidation. Catalase completely inhibited DNA damage by hydralazine plus Cu(II), but hydroxyl radical (.OH) scavengers and superoxide dismutase did not. On the other hand, DNA damage by hydralazine plus Fe(III) was inhibited by catalase and .OH scavengers. Hydralazine plus Cu(II) induced piperidine-labile sites predominantly at guanine and some adenine residues, whereas hydralazine plus Fe(III) caused cleavages at every nucleotide. Activation of hydralazine by peroxidase/H2O2 caused guanine-specific modification in DNA. ESR-spin trapping experiment showed that .OH and superoxide are generated during the Fe(III)- or Cu(II)-catalysed autoxidation of hydralazine, respectively, and that nitrogen-centered radical is generated during the Cu(II)- or peroxidase-catalysed oxidation. The generation of nitrogen-centered radical was also supported by HPLC-mass spectrometry. The results suggest that the guanine-specific modification by the enzymatic activation of hydralazine is due to the nitrogen-centered hydralazyl radical or derived active species, whereas .OH participates in DNA damage by hydralazine plus Fe(III). The mechanism of hydralazine plus Cu(II)-induced DNA damage is complex. The possible role of the DNA damage induced by hydralazine in the presence of Cu(II) or peroxidase/H2O2 is discussed in relation to hydralazine-induced lupus, mutation, and cancer.
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PMID:Free radical production and site-specific DNA damage induced by hydralazine in the presence of metal ions or peroxidase/hydrogen peroxide. 184 78

A range of drugs including hydralazine, isoniazid, procainamide and penicillamine cause toxic side effects which resemble systemic lupus erythematosus (SLE). Deficiencies of C1, C4 and C2 are associated with idiopathic SLE, and these defects may compromise the ability of the patient to deal with immune complexes. Immune complexes with protein as antigen, such as has been reported to be diagnostic of procainamide-induced SLE, interact more with the C4A isotype of C4 than the C4B isotype. It is shown that hydralazine, isoniazid and penicillamine inhibit the covalent binding of C4 to a complement-activating surface and that the drugs themselves become covalently bound to C4. For each of these drugs, C4A is inhibited more than C4B, and it is suggested that this is an important contributory factor in the development of the toxic side effects to these drugs involving immune-complex deposition. For procainamide, it is shown that the hydroxylamine metabolite rather than the drug itself inhibits the covalent binding reaction of C4. Hydralazine, isoniazid and procainamide are metabolised by the polymorphic N-acetyltransferase, and slow acetylators are at increased risk of drug-induced lupus. For procainamide, oxidation to the hydroxylamine form is an alternative metabolic route of increased importance in slow acetylators, and it is suggested that investigation of C4 type in susceptible patients could provide a means of identifying those at greatest risk of immunotoxicity.
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PMID:Drug-induced immune-complex disease. 252 48

Anti-hypertensive drugs, including diuretics and beta-blocking drugs, belong to a group of therapeutics used by about a fourth of the Danish population. As with cytostatics, antibiotics, and topical remedies, they rather frequently cause adverse drug reactions (ADR) in the skin. No exact statistical information is available concerning the extent of such side effects. The information obtained by Danish National Board of Health's Committee on Adverse Drug Reactions shows that 10-60% of ADR from diuretics, beta-blocking agents, and anti-hypertensive drugs are dermatological. The skin symptoms are not unique for any specific drug. But certain symptoms occur more frequently than others. Thiazides can give vasculitis, a phototoxic/-allergic eruption, erythema multiforme, or eczema. The combination of amiloride (5 mg) and hydrochlorothiazide (50 mg) carries the highest number of recorded ADR; 59% of these are in the skin. Half of the skin ADR are phototoxic eczema. Furosemide may give eczema, purpura, a bullous eruption, or Steven-Johnson's syndrome in rare cases. Methyldopa can induce eczematous eruptions on hands and feet, a lichenoid eruption, a lupus erythematosus-like eruption, or purpura. Hydralazine may give lupus erythematosus-like eruptions, eczema, or urticaria. Non-specific beta-blocking drugs can induce a morbilliform rash and may aggravate psoriasis. Captopril may induce pruritus in up to 15% of the patients and skin eruptions in 2%. The most serious dermatological side effect, exfoliative dermatitis, is very rarely seen following the use of anti-hypertensive drugs or diuretics.
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PMID:Adverse reactions in the skin from anti-hypertensive drugs. 289 92

The acetylation pathway of drug metabolism is the pathway by which aromatic amines and hydrazines are metabolized. Hydralazine and procainamide are aromatic amines or hydrazines that are metabolized by this pathway. Persons who are genetically slow acetylators are predisposed to development of lupus from these two drugs, suggesting that the free amine or hydrazine moiety is the inciting agent. When acetylprocainamide was given as an antiarrhythmic drug to patients with procainamide-induced lupus, the disease went into remission, indicating that the free amine group on procainamide had induced the disease. The genetic acetylator phenotypes of persons with idiopathic lupus were studied, and an excess of genetic slow acetylators was observed. This suggests amines or hydrazines induce some cases of this disease. One patient was identified with a lupus-like illness due to occupational exposure to hydrazine itself.
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PMID:Aromatic amines and the pathogenesis of lupus erythematosus. 619 68

The true incidence of the lupus syndrome induced by hydralazine was determined in a longitudinal study of 281 patients consecutively starting hydralazine for hypertension over a 51 month period. Data on the duration of treatment and the maximum dose achieved were examined using life table analysis. After three years' treatment with hydralazine the incidence of the lupus syndrome was 6.7% (95% confidence limits 3.2-10.2%). The incidence was dose dependent, with no cases recorded in patients taking 50 mg daily and incidences of 5.4% with 100 mg daily and of 10.4% with 200 mg daily. The incidence was higher in women (11.6%) than in men (2.8%). In women taking 200 mg daily the three year incidence was 19.4%. Hydralazine is an effective antihypertensive drug that has come to be used in restricted dosage (not more than 200 mg daily) because of its risk of inducing the lupus syndrome. This study shows that the true incidence of the syndrome is still unacceptably high even when the drug is prescribed according to current recommendations.
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PMID:The lupus syndrome induced by hydralazine: a common complication with low dose treatment. 643 20

Relapsing polychondritis is a rare disease of uncertain etiology, characterized by inflammation of cartilage. Cartilage of the respiratory tract is engaged in more than half of all cases. Hydralazine-induced systemic lupus erythematosis (SLE) is a well known disease. Females who are slow acetylators and are HLA-DR4 positive when treated with hydralazine are at serious risk of contracting SLE syndrome. We describe here a woman, treated for 10 years with hydralazine, who was a slow acetylator and was HLA-DR4 positive and who presented with a relapsing polychondritis and ultimately required a permanent tracheostoma. To our knowledge, this is the first published case of relapsing polychondritis induced by hydralazine.
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PMID:Hydralazine-induced relapsing polychondritis-like syndrome. Report of a case with severe chronic laryngeal complications. 660 52

Twenty-seven hypertensive patients (23 blacks, 4 whites) treated with hydralazine had frequent serologic evidence of autoimmunity. However, only 1 patient developed a lupus syndrome. Acetylator phenotype influenced the autoimmune response; slow acetylators had a higher incidence and titers of autoantibodies. The lupus patient not only had high titers of autoantibodies but they were predominantly IgG in contrast to the predominant IgM antibodies found in other slow acetylators. Hydralazine treatment did not alter cell-mediated immune responses and hydralazine antibodies were not detected. However, half the patients tested who received hydralazine had positive lymphoproliferative responses to the drug.
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PMID:Immunologic effects of hydralazine in hypertensive patients. 697 54


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