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)

A profound defect in granulocyte chemotaxis was documented in an otherwise healthy 21-yr-old man who failed to localize granulocytes to an area of cellulitis during an allergic reaction to cephalothin. During the period of drug allergy, characterized by urticaria, eosinophilia, and profound hypocomplementemia, in vitro migration of the patient's granulocytes in the Boyden chamber was markedly impaired. Although devoid of hemolytic complement activity, the patient's serum possessed supranormal chemotactic activity, even following heat inactivation, suggesting the presence of chemotactically active complement split products. Chemotactic function improved concomitantly with steroid therapy and normalization of serum complement levels, and was entirely normal following clinical recovery and cessation of steroid therapy. The chemotactic abnormality noted in the patient's cells was reproduced in normal granulocytes by preincubation either with patient serum or with cobra venom-activated fresh (but not heated) normal serum, suggesting that in vivo exposure of granulocytes to activated complement was responsible for the patient's abnormal chemotactic response. This mechanism may contribute to the increased infection propensity noted in other conditions characterized by in vivo complement activation, such as rheumatoid arthritis and systemic lupus erythematosis.
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PMID:Acquired granulocyte abnormality during drug allergic reactions: possible role of complement activation. 83 Mar 75

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

Hypersensitivity drug reactions are a major source of serious adverse drug reactions, yet very little is known about their mechanism. Several drugs are oxidized by activated neutrophils and mononuclear cells to reactive metabolites. Jack Uetrecht explains that the pattern of hypersensitivity reactions associated with these drugs - drug-induced lupus, agranulocytosis, and generalized hypersensitivity reactions - fits a mechanism in which leukocyte-generated reactive metabolites initiate the hypersensitivity reaction. Because activation of the leukocyte is necessary for reactive metabolite formation, one risk factor for a drug hypersensitivity reaction may be an infection or other inflammatory condition.
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PMID:Mechanism of hypersensitivity reactions: proposed involvement of reactive metabolites generated by activated leukocytes. 269 59

Cats receiving propylthiouracil (PTU) develop antinuclear antibodies (ANA) and an immune-mediated disease syndrome characterized by anorexia, lymphadenopathy, weight loss, and Coombs-positive hemolytic anemia. Investigation of the ANA specificity indicated that the predominant ANA activity consistent of anti-native DNA (nDNA) antibodies. The formation of anti-nDNA antibodies and immune-mediated disease syndrome appeared to be dose-dependent, even in cats in which a response had been induced on 4 prior occasions. These results supply further evidence that PTU-induced autoimmunity is not the result of a simple drug allergy. Rather, it appears that PTU induces a lupus-like syndrome, including the hallmark sign of systemic lupus erythematosus, anti-nDNA antibodies.
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PMID:Dose-dependent induction of anti-native DNA antibodies in cats by propylthiouracil. 325 86

A concept of the pathogenesis of tubular interstitial nephritis (TIN) is presented, based on histologic, immunohistologic and electromicroscopic investigations on 61 patients with glomerulonephritis, lupus erythematodes and rheumatoid arthritis. The pathogenic model is a hypersensitivity reaction which leads to alterations in the tubular basement membrane (TBM) and results in changes in the TBM and secondary damage to stroma, vessels and tubular cells. The findings change depending on the stage, reflecting the transition from an acute to a chronic process. In acute TIN which is generally a drug allergy, the dominant characteristic of the inflammatory process allows the reaction to be categorized in edematous (72%), cellular (23%) and tubular necrotic (5%) types. The cellular types show 4 subdivisions: plasma cellular, eosinophil-granulocytic, lymphohistiocytic and granulomatous. Chronic TIN is in particular characterized through the destruction of the TBM, dystrophy and atrophy of the tubules as well as their degeneration, lymphohistiocytic infiltrates and sclerotic stroma reactions. A distinction is made between cellular destructive and atrophic-sclerotic types. At view of the etiology and pathogenesis a distinction should be made between an infectious and non-infectious TIN and further by the character of the immunoreaction, into a primary and secondary form. If there glomerular changes are present and there is evidence of an immune phenomenon in the glomeruli and TBM we recommend the use of the term glomerulo-tubulo-interstitial nephritis.
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PMID:[Tubulointerstitial nephritis]. 356 28

Diphenylhydantoin (DFH) treatment for epileptic patients has shown adverse effects such as malignant lymphadenopathy, systemic lupus erithematosus, periarteritis nodosa and recently immunological alterations such as a decreased lymphocytic response to fitohemaglutinin and serum IgA concentration, therefore we thought DFH effect on secretory IgA would be an important finding. This phenomenon might imply a defect in resistance local mechanisms for infection. Two groups of patients were studied: a) 25 children with an established diagnosis of epilepsy, "grand mal" type, that received anticonvulsive treatment with DFH for six months and b) 25 children with a diagnosis of infectious meningoencephalitis that required DFH to control convulsive crisis. Patients with a history of recurrent infections, lymphadenopathies, hepatosplenomegaly, drug allergy, collagenopathies and immunodeficiency were ruled out from this study. In all patients T and B lymphocytes, serum IgA, saliva and duodenal fluid and IgA determinations were made. Results show IgA concentration decrease in saliva and duodenal fluid of epileptic and meningoencephalitic patients (p less than 0.05), as well as lymphocyte T depression in epileptic and non epileptic patients treated with DFH (p less than 0.001).
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PMID:Effect of diphenylhydantoin in serum and secretory IgA concentrations. 677 21

A 52-year-old woman was admitted to our hospital because of a skin rash, high fever and myalgia. She had been diagnosed ten years ago by a dermatologist as having MCTD (mixed connective tissue disease). At the time of admission a diagnosis of active SLE was made by fulfilling four of the 1982 ARA criteria together with increasing levels of anti-DNA antibody and low levels of complements. Prednisolone (PSL) given orally in an initial dosage of 60 mg/day was effective during the first 6 weeks. Then a high fever, skin rash and pancytopenia appeared without active findings of SLE. Infection caused by bacteria, fungus or virus was suspected, but no infectious agent was present in cultures derived from blood or other sources. Antimicrobic drugs used were not effective at all. The clinical picture was suggestive of a drug allergy, but no causative drug was found. A diagnosis of hemophagocytic syndrome (HPS) was made because of the increased number of unusual hemophagocytic cells in the bone marrow. High levels of serum ferritin and neopterin, which are known to reflect macrophage activation, supported the diagnosis of HPS. HPS is characterized by activated phagocytosis presumably induced by hypersecretion of cytokines. Malignant lymphoma and infection are the two representative diseases which may cause HPS. Recently, an acute lupus HPS was reported in patients with active SLE. Here we reported a case of reactive HPS observed in a patient with SLE who had been receiving high dose PSL. Symptoms and findings of the patient gradually disappeared in several weeks after rapid reduction of the PSL dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hemophagocytic syndrome observed in a patient with systemic lupus erythematosus]. 797 30

Allergic disorders commonly occur in patients with systemic lupus erythematosus (SLE) and allergies to some drugs may occasionally be related to disease flares. We evaluated the prevalence of several types of allergy in 132 patients with SLE and their families and compared the SLE patients with a control group of 66 patients with non-lupus disorders. Total IgE levels were tested in 117 SLE patients and 61 controls. Eighty-three of the 132 SLE patients (63%) had a history of at least one type of allergic disorder. This prevalence was significantly higher (P < 0.0001) than that of the control group (20 of 66 controls). The prevalence of drug allergy (38% vs. 17%; P < 0.005), skin allergy (36% vs. 17%; P < 0.01) and insect allergy (14% vs. 2%; P < 0.02) were significantly higher in SLE patients when compared with controls. Family members of SLE patients had an increased prevalence of at least one type of allergy (55% vs. 24%; P < 0.0001), allergic rhinitis (30% vs. 14%; P < 0.02), asthma (25% vs. 9% P < 0.02), and both rhinitis or asthma (44% vs. 20%; P < or = 0.002). The presence of allergy both in the patient and in the family was more frequent in SLE patients than controls (42% vs. 15%; P < 0.001). We found no differences in total IgE levels between the two groups. Drug, skin and insect allergies were particularly frequent in SLE patients. We also found a high prevalence of rhinitis and asthma in their families.
Lupus 1993 Jun
PMID:Allergic disorders in systemic lupus erythematosus. 836 10

Carbamazepine is an anticonvulsant which is associated with a significant incidence of hypersensitivity reactions including agranulocytosis. We have postulated that many drug hypersensitivity reactions, especially agranulocytosis and lupus, are due to reactive metabolites generated by the myeloperoxidase (MPO) (EC 1.11.1.7) system of neutrophils and monocytes. This led to a study of the metabolism and covalent binding of carbamazepine with MPO/H2O2/Cl- and neutrophils. Metabolism and covalent binding were observed in both systems and the same pathway appeared to be involved; however, the metabolism observed with the MPO system was approximately 500-fold greater than that observed with neutrophils. The metabolites identified were an intermediate aldehyde, 9-acridine carboxaldehyde, acridine, acridone, choloroacridone, and dichloroacridone. We postulate that the first intermediate in the metabolism of carbamazepine is a carbonium ion formed by reaction of hypochlorous acid (HOCl) with the 10,11 double bond. Although we have no direct proof for the proposed carbonium ion, it provides the most likely mechanism for the observed ring contraction. Iminostilbene, a known metabolite of carbamazepine, was also metabolized by a similar pathway leading to ring contraction; however, the rate was much faster and the first step may involve N-chlorination and a nitrenium ion intermediate. These data confirm that carbamazepine is metabolized to reactive intermediates by activated leukocytes. Such metabolites could be responsible for some of the adverse reactions associated with carbamazepine, especially reactions such as agranulocytosis and lupus which involve leukocytes.
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PMID:Carbamazepine metabolism to a reactive intermediate by the myeloperoxidase system of activated neutrophils. 838 60

Systemic rheumatic symptoms occur with widely different frequencies as a side effect of long-term therapy with some 39 medications currently in use. Because symptoms are nonspecific, subjective, and protean, diagnosis of drug-induced lupus (DIL) requires awareness of this risk of chronic medication. However, laboratory features and the characteristic of full recovery after discontinuing treatment are helpful in differentiating drug-induced from spontaneous lupus or other syndromes. Drug-induced lupus is probably mediated by reactive drug metabolites, not the ingested medications, and susceptibility to neutrophil-mediated oxidative transformation is a property of ten lupus-inducing drugs reported so far. Mechanisms for DIL modeled after drug hypersensitivity reactions are unsupported experimentally and inconsistent with the features of DIL. However, several new lines of investigation using mouse models have opened up promising leads into the origin of autoreactive T cells and disease development in DIL.
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PMID:Etiology and mechanisms of drug-induced lupus. 1050 55


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