Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug allergy must be in relation with a phenomenon of immunopathology which induces: Anaphylactic shock; Toxidermia; Cytopenia; Allergic Hepatitis. Diagnosis is based on the cutaneous testing and "in vitro" tests. The evidence of drug responsibility will be supplied by challenge test, practised in hospital according to special conditions. Treatment is preventive with cortisone, epinephrine, antihistamine. Treatment is also curative with those same drugs in respect to the clinical pathology.
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PMID:[Diagnosis of drug-induced allergy]. 333 Oct 97

Previous studies have demonstrated that antibodies in sera from patients with halothane hepatitis recognize halothane-induced liver microsomal polypeptide neoantigens, and have suggested that these antibodies may play a role in the pathogenesis of the hepatitis. In the present study, the mechanism of neoantigen generation was investigated. Liver microsomes from rats treated in vivo with halothane or deuterated halothane were tested by immunoblotting for reactivity with patients' sera and with an antiserum specific for the covalently bound trifluoroacetyl (TFA) halide metabolite of halothane. Rat liver microsomes incubated aerobically or anaerobically with halothane or deuterated halothane in vitro, +/- NADPH and/or NADH, were also analyzed. The results obtained demonstrate that neoantigen expression involves oxidative halothane metabolism by cytochromes P-450 to TFA halide and covalent binding of the TFA group to the proteins. Incubation of microsomes from halothane-treated rats with 1 M piperidine cleaved the TFA groups from the proteins and abolished antigenicity, confirming this conclusion. Recognition of the neoantigens by the patients' antibodies was inhibited only partially using the hapten derivative N-E-TFA-L-lysine. It appears that the patients' antibodies recognize epitopes consisting of the TFA group plus associated structural features of the protein carriers (100 kDa, 76 kDa, 59 kDa, 57 kDa and 54 kDa), not the TFA hapten alone. To our knowledge, this constitutes the first characterization of drug metabolite-tissue protein neoantigens implicated in a drug hypersensitivity. The approach described may be of general utility for characterization of drug-induced neoantigens associated with other drug hypersensitivities.
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PMID:Metabolic basis for a drug hypersensitivity: antibodies in sera from patients with halothane hepatitis recognize liver neoantigens that contain the trifluoroacetyl group derived from halothane. 338 39

A study of the clinical associations of a recently defined tissue autoantibody, the liver/kidney microsomal (L.K.M.) antibody, showed that out of 33 patients 26 had clinical liver disease. Fifteen of the patients had active chronic hepatitis and there were seven cases of acute hepatitis, precipitated by presumed virus A infection in three instances and by drug hypersensitivity in the other four. The remaining cases with liver disease included two with subclinical hepatitis and two with hepatocellular carcinoma. Evidence is presented that the patients with active chronic hepatitis may represent a distinct subgroup of the disease with a young mean age, an even male to female ratio, and a striking lack of other nonorgan-specific autoantibodies-that is, antinuclear and smooth muscle-which are usually present in the other autoimmune variant of the disease.
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PMID:Hepatic disorders associated with liver-kidney microsomal antibodies. 459 2

The general features of allergic drug reactions in man have recently been reviewed by Parker (85). By definition allergic drug reactions are produced by specific immunologic processes. Allergic drug reactions must be distinguished from adverse reactions due to overdosage, normal pharmacologic action, toxic metabolite formation, idiosyncrasy, nonspecific release of pharmacologic effector molecules, or drug interactions. The clinical manifestations of drug allergy are quite protean. In addition to classical manifestations of allergy such as serum sickness, anaphylaxis, contact dermatitis or urticaria, drug allergy may produce hemolytic anemia, thrombocytopenia, granulocytopenia, hepatitis, nephritis, pneumonitis, vasculitis, or neuritis where a single organ or cell type is affected. While many drugs produce reactions with suggestive of allergy, definitive experimental evidence either for or against mechanism is usually not available. Some of these reactions may involve allergic mediators released or produced nonimmunologically through pharmacologic, osmotic, or toxic effects on cells involved in immune inflammation (mast cells, basophils, phagocytes, and lymphocytes) or through nonspecific activation of effector molecules in extracellular fluid such as the complement proteins. Drugs may also induce the formation of autoantibodies through mechanisms that are largely obscure, but may in some instances involve the direct participation of the drug as a hapten and in other instances occur indirectly through a pharmacologic or toxic action on the cells responsible for immune homeostasis.
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PMID:Allergic reactions in man. 704 Nov 44

Liver disease in 193 patients (17 male and 176 female) with systemic lupus erythematosus (SLE) at Kawasaki Municipal Hospital were analyzed. Abnormal transaminase levels were found in 78 case (40.4%). Among them, there were 35 patients whose liver disease were identified. There were 12 patients whom no cause could be found other than SLE. Other liver disease were as follows: fatty liver in 9 cases, virus infection in 5 cases, gall stone and/or cholecystitis in 3 cases, drug allergy in 2 cases, autoimmune hepatitis 2 cases, primary biliary cirrhoses in 1 case. Liver disease with systemic lupus erythematosus was frequent, but there was no severe case.
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PMID:[Liver disease in systemic lupus erythematosus]. 755 39

Amodiaquine, a 4-aminoquinoline antimalarial, has been associated with hepatitis and agranulocytosis in humans. Drug hypersensitivity reactions, especially agranulocytosis, have been attributed to reactive intermediates generated by the oxidants discharged from stimulated polymorphonuclear leucocytes (PMN). The metabolism of amodiaquine to both stable and chemically reactive metabolites by human PMN has been investigated in vitro. Incubation of [14C]-amodiaquine with PMN resulted in irreversible binding of radiolabel to protein and depletion of intracellular reduced glutathione, which were enhanced by phorbol myristate acetate (PMA), a PMN activator. Two metabolites were identified: the C-5' glutathione adduct of amodiaquine, derived from both endogenous and exogenous glutathione, and 4-amino-7-chloroquinoline, which was presumed to be formed by hydrolysis of amodiaquine quinoneimine. Desethylamodiaquine, the major plasma metabolite of amodiaquine in humans, also underwent bioactivation to a chemically reactive species in the presence of PMA-stimulated PMN. Substitution of the 4'-hydroxyl group in amodiaquine with fluorine significantly reduced irreversible binding to protein and abolished depletion of intracellular glutathione in the presence of PMA. These findings indicate that the bioactivation of amodiaquine by PMN is associated with the formation of a quinoneimine intermediate. Such a reactive metabolite, if produced in PMN or bone marrow in vivo, may be responsible for the drug's myelotoxicity.
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PMID:The bioactivation of amodiaquine by human polymorphonuclear leucocytes in vitro: chemical mechanisms and the effects of fluorine substitution. 757 70

To investigate how T cells are involved in hypersensitivity reactions to drugs that become immunogenic after metabolization, e.g., sulfonamides and antiepileptics, we analyzed in vitro the drug-induced activation of CD4+ and CD8+ T cell subsets, cytokine secretion, TCR V beta distribution, and proliferation of T cells from four drug-allergic individuals. In addition, the activation parameters CD25 and HLA-DR were analyzed in vivo on CD4+ and CD8+ T cells from five patients with acute drug allergies, some of them with anticonvulsant hypersensitivity syndrome with hepatitis. Our results show that, in vitro, drug-induced proliferation of PBMC from patients with allergy to sulfamethoxazole, phenytoin, or carbamazepine was specific and dose dependent. CD4+ as well as CD8+ T cells expressed elevated levels of CD25 and HLA-DR molecules after drug stimulation. Drug-activated lymphocytes secreted high amounts of IL-5 and normal or low levels of IL-2, IFN-gamma, IL-4, and TNF-alpha. An enhanced expansion of TCR V beta 17+ T cells 9 days after in vitro stimulation with sulfamethoxazole was observed in one patient with sulfamethoxazole allergy. The drug specificity of the in vitro-activated T cells was confirmed by generation of different sulfamethoxazole specific T cell lines and CD4+ and CD8+ T cell clones. T cell analysis of patients with acute drug allergy to carbamazepine, phenytoin, allopurinol, or paracetamol confirms the in vitro data, because all patients had activated CD4+ or CD8+ T cells in the circulation. Our data clearly show the involvement of drug-specific T cells in drug allergies.
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PMID:Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine. 760 18

The finding of epithelioid cell granulomas within liver biopsies is a not uncommon occurrence. We undertook this study to investigate the underlying conditions responsible for a diagnosis of granulomatous hepatitis in Northern Ireland during the thirteen year period 1980-1992. One hundred and sixty-three patients with hepatic granulomas were identified, accounting for 4% of all liver biopsies undertaken during the period of the study. In 145 cases (89%) a definite clinical diagnosis was established. The most common clinical diagnoses were primary biliary cirrhosis which accounted for 90 cases (55%) and sarcoidosis which accounted for 30 cases (18%). Other less common conditions associated with hepatic granulomas included tuberculosis (3 cases), Crohn's disease (3 cases), chronic active hepatitis (2 cases), drug hypersensitivity (2 cases) and extra-hepatic biliary obstruction (2 cases). Six patients were identified with a clinical diagnosis of psoriasis. Other miscellaneous conditions accounting for single examples of granulomatous inflammation were schistosomiasis, gout, Hodgkin's disease, secondary adenocarcinoma, collapse and necrosis of tumour following radiotherapy and chemotherapy, granulomatous inflammation within the wall of an abscess cavity and idiopathic cirrhosis. Only eighteen cases (11%) remained idiopathic with no definite diagnosis established after detailed investigation. The findings confirm the wide range of clinical conditions which can result in hepatic epithelioid cell granulomas. This has been emphasised in several previous major studies which are reviewed in this paper.
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PMID:Hepatic granulomas in Northern Ireland: a thirteen year review. 782 89

The lymphocyte stimulation test (LST) is useful for diagnosing drug-induced allergy and identifying the causative drug. In this study, we examined the usefulness of 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as a marker for LST in diagnosing drug allergy. In a basic study using normal peripheral blood mononuclear cells, the normal range of stimulation index (SI) was 0.92-1.38, and the mean SI for all drugs tested was 1.134 +/- 0.111 (mean +/- S.D.). The cut-off value of SI for diagnosis of drug allergy was thus set at over mean + 2S.D. for possibly positive, and at over mean + 3S.D. as a definitely positive reaction. Forty-six cases of suspected drug-induced allergic hepatitis involving 85 drugs were diagnosed by this assay, and the possibly positive and definitely positive rates were 54.3% (SI > or = 1.4) and 41.3% (SI > or = 1.5), respectively. A clinical study was made of 113 patients with diagnosed drug-induced allergic hepatitis. Forty-nine (43%) of the patients were male and 64 (57%) were female. In 85% of cases the allergic reaction occurred within one month of taking medication, but there were a number of cases in whom onset occurred after long-term incubation. The main clinical symptoms were jaundice, itching, eruption, fever, and general malaise. In about 75% of cases glutamic oxaloacetic transaminase (GOT) or glutamic pyruvic transaminase (GPT) returned to normal range within one month after medication was halted.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lymphocyte stimulation test with tetrazolium-based colorimetric assay for diagnosis of drug-induced allergic hepatitis. 800 Mar 78

A prospective study was conducted to determine the etiologies of isolated pruritus among out-patients attending a hospital dermatology clinic in Lome. Two hundred and twenty patients (120 men and 100 women) suffering from isolated pruritus were included in the study. The most frequent etiologies were; digestive parasitosis (n = 50), onchocercosis (n = 45), drug allergy (n = 26), food allergy (n = 10), psychological pruritus (n = 25) and hepatitis (n = 13). The etiology was not determined for 29 cases. This study shows the large contribution of parasites to the pathogenesis of pruritus in tropical Africa.
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PMID:[Etiology of isolated pruritus in dermatology consultations at Lome (Togo)]. 861 9


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