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)

We report four cases of the side effects of minocycline seen during the last two years in our department. There was one case of drug-related lupus and three cases of hypersensitivity reactions, including one eosinophilic pneumopathy with pericarditis, one nephropathy and one severe, pseudo-infectious episode of high fever, rash, lympadenopathy, hepatitis and eosinophilia. Minocycline is a tetracycline agent widely used for acne therapy in France and all over the world. During the last few years, there has been an increasing number of reports concerning systemic adverse reactions to minocycline, with on the one hand auto-immune disorders (lupus, autoimmune hepatitis, vascularitis with ANCA), occurring after a prolonged course of therapy and reported recently in the last few years, and on the other hand, hypersensitivity reactions (eosinophilic pneumopathies, hepatitis, nephropathies, myocarditis, serum sickness or pseudo-infectious reactions), occurring precociously in the course of therapy, and potentially severe. Although these side effects are uncommon in the context of the high number of patients who have been prescribed the drug, the first-line antibiotic therapy in acne must probably be reconsidered.
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PMID:[Systemic reaction induced my minocycline treatment: a report of four patients and a review of the literature]. 1057 23

Minocycline is an oral antibiotic widely used for the long-term treatment of acne vulgaris. Unusual side effects of this medication include two overlapping autoimmune syndromes: drug-induced lupus and autoimmune hepatitis. In addition, in a few patients livedo reticularis or subcutaneous nodules have developed in association with arthritis and serum perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) during long-term minocycline therapy. We report the cases of two young women receiving long-term minocycline therapy (>3 years) in whom P-ANCA-positive cutaneous polyarteritis nodosa developed. Both patients presented with a violaceous reticulated pattern on the lower extremities. Histologic examination of biopsy specimens from a reticulated area and a subcutaneous nodule showed necrotizing vasculitis of medium-sized arteries in the deep dermis, consistent with the diagnosis of polyarteritis nodosa. The cutaneous lesions rapidly resolved on discontinuation of minocycline and initiation of prednisone therapy. A high index of suspicion and testing for antineutrophil cytoplasmic antibody in addition to the standard antinuclear antibody panel can facilitate diagnosis of minocycline-related autoimmune disorders.
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PMID:Perinuclear antineutrophilic cytoplasmic antibody-positive cutaneous polyarteritis nodosa associated with minocycline therapy for acne vulgaris. 1160 37

Several observations suggest that bacteria induce autoimmunity in primary biliary cirrhosis (PBC). Since no PBC-specific bacterial species could be identified, it can be speculated that the triggers are non-species-specific bacterial proteins. This hypothesis would imply that several or even all bacterial species can trigger PBC. Therefore, we investigated whether PBC exhibits immune reactions to non-species-specific bacterial antigens. Yersinia enterocolitica O3 was screened for the presence of proteins that were labeled by immunoblotting using PBC sera. We focused our investigations on a 160-kDa protein, which was further enriched and characterized by partial N-terminal amino acid sequencing. The prevalence of antibodies to this protein was determined by immunoblotting in a variety of diseases. The 160-kDa protein was identified as the beta-subunit of bacterial RNA-polymerase, a highly conserved bacterial protein with a very high degree of sequence identity among all bacterial species. Antibodies to the beta-subunit of bacterial RNA polymerase were specific for this protein. Until now no mammalian protein could be found that cross-reacts with these antibodies. The prevalence of antibodies to the beta-subunit of bacterial RNA polymerase (ARPA) using the protein from Yersinia enterocolitica O3 (serum dilution 1:1000) was: healthy controls (HC, N = 101) 7.9%, primary biliary cirrhosis (PBC, N = 61) 32.8%, autoimmune hepatitis type 1 (AIH, N = 46) 26.1%, alcoholic liver cirrhosis (ALC, N = 44) 9.1%, Crohn's disease (CD, N = 38) 7.9%, ulcerative colitis (UC, N = 24) 8.3%, primary sclerosing cholangitis + UC (PSC/UC, N = 11) 0%, acute yersiniosis (Yers, N = 36) 19.4%, acute infection with Campylobacter jejuni (Camp, N = 10) 0%, acute Q-fever (QF, N = 16) 6.25%, chronic hepatitis C (HCV, N = 39) 7.7%, c-ANCA-positive vasculitis (Vasc, N = 40) 15%, systemic lupus erythematosus (SLE, N = 28) 10.7%, and malaria tropica (MT, N = 24) 16.7%. There was no significant difference between PBC and AIH. The group of autoimmune liver diseases (PBC + AIH, N = 107, 29.9%) differed highly significantly from HC, chronic inflammatory bowel diseases (CD + UC + PSC/UC, N = 73, 6.8%), ALC, and HCV and also differed significantly (P = 0.01) from the group with bacterial and parasitic diseases (Yers + Camp + QF + MT, N = 86,13.95%) and from the group with Vasc + SLE (N = 68,13.2%). Testing of ARPA using the protein from E. coli yielded nearly identical results. In conclusion, an increased prevalence of antibodies to the beta-subunit of bacterial RNA polymerase, a highly conserved non-species-specific bacterial protein, can be found in primary biliary cirrhosis, but also in autoimmune hepatitis type I. These findings do not add an argument for a bacterial trigger of PBC. Rather, they suggest that ARPA belong to the pool of natural antibodies that are up-regulated in autoimmune liver diseases.
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PMID:Identification of beta-subunit of bacterial RNA-polymerase--a non-species-specific bacterial protein--as target of antibodies in primary biliary cirrhosis. 1275 71

Antibodies to the baker's yeast Saccharomyces cerevisiae (ASCA), recently proposed as a serological marker of Crohn's disease, have also been detected in other autoimmune disorders. The aim of this study was to determine prevalence and clinical significance of ASCA in autoimmune liver disease. The presence of IgG and IgA ASCA was evaluated using a commercially available immunoassay in 215 patients with autoimmune liver disease (primary biliary cirrhosis, PBC, 123 cases; autoimmune hepatitis, AIH, 67 cases; primary sclerosing cholangitis, PSC, 25 cases), 48 with inflammatory bowel disease and 19 healthy blood donors. Anti neutrophil cytoplasmic antibodies with the perinuclear pattern (p-ANCA) were assessed by indirect immunofluorescence in PSC patients. The main clinical and biochemical parameters between ASCA-positive and negative patients were analysed and compared. ASCA are predominant in Crohn's disease (70%); among liver patients, PSC and AMA-negative PBC show the highest ASCA prevalence (53% and 44%). In PBC ASCA correlate with higher levels of circulating IgA (P < 0.05). In PSC the detection of either ASCA or p-ANCA is neither associated with any clinical or biochemical feature, nor with an underlying inflammatory bowel disease. ASCA can not be considered an additional serological marker of autoimmune liver disease, but the possibility of detecting such a reactivity in autoimmune liver disorders should be considered; their correlation with elevated IgA in PBC suggests that ASCA may be an indirect sign of enhanced mucosal immunity; in PSC patients neither ASCA nor p-ANCA predict the occurrence of a concomitant inflammatory bowel disease.
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PMID:Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases. 1278 Jun 95

A 17-year-old woman was admitted because of proteinuria, microhematuria and liver dysfunction with increased antinuclear antibody and anti-myeloperoxidase antibody (MPO-ANCA). Fourteen months' previously, urinalysis and liver function showed normal range. At that time she suffered from tachycardia and weight reduction, diagnosed as Graves' disease, she was given propylthiouracil for treatment of her Graves' disease. The histological finding of renal biopsy was compatible with minor glomerular abnormalities. Liver biopsy finding was compatible with autoimmune hepatitis. After we had administered prednisolone, liver function returned to normal range and urine protein became negative. Then we performed subtotal thyroidectomy, and she was not given propylthiouracil. MPO-ANCA decreased gradually.
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PMID:Graves' disease accompanied by anti-myeloperoxidase antibody-related nephropathy and autoimmune hepatitis. 1528 91

Primary biliary cirrhosis (PBC), autoimmune cholangitis (AIC = AMA-negative PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholestatic liver diseases. Overlap syndromes combine characteristics of cholestatic liver diseases and autoimmune hepatitis. In PBC, alkaline phosphatase and gamma-glutamyl transferase are elevated, to a lesser degree aminotransferases. Histology shows bile duct lesions. Anti-mitochondrial antibodies are typical. Ursodeoxycholic acid (UDC) is established therapy that slows or even stops the disease progression, at least in early stages of the disease. In non-responders immunosuppression is recommended. PSC is mostly associated with chronic inflammatory bowel diseases. P-ANCA are frequent. Bile duct lesions revealed by retrograde cholangiography are characteristic. UDC is given as therapy. Bile duct strictures or bacterial cholangitis may be late sequelae and should be treated by antibiotics or bile-duct dilatation. Cirrhosis may ultimately develop in PBC and PCS. In progressed PBC or PSC liver transplantation is indicated.
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PMID:[Cholestatic liver diseases]. 1545 69

Autoimmune hepatitis (AIH) is a disease of unknown etiology, characterized by liver-related autoantibodies. Autoimmune hepatitis is subdivided into two major types: AIH type 1 is characterized by the detection of ANA, SMA, ANCA, anti-ASGP-R, and anti-SLA/LP. Autoimmune hepatitis type 2 is characterized to be mainly related with drug-metabolizing enzymes as autoantigens, such as anti-LKM (liver-kidney microsomal antigen)-1 against CYP2D6, anti-LKM-2 against CYP2C9-tienilic acid, anti-LKM-3 against UGT1A, and anti-LC1 (liver cytosol antigen)-1 and anti-APS (autoimmune polyglandular syndrome type-1) against CYP1A2, CYP2A6, and others. Anti-LKM-1 sera inhibited CYP2D6 activity in vitro but did not inhibit cellular drug metabolism in vivo. CYP2D6 is the major target autoantigen of LKM-1 and expressed on plasma membrane (PM) of hepatocytes, suggesting a pathogenic role for anti-LKM-1 in liver injury as a trigger. Anti-CYP1A2 was observed in dihydralazine-induced hepatitis, and radiolabeled CYP1A2 disappeared from the PM with a half-life of less than 30 min, whereas microsomal CYP1A2 was stably radiolabeled for several hours. Main antigenic epitopes on CYP2D6 are aa 193-212, aa 257-269, and aa 321-351; and D263 is essential. The third epitope is located on the surface of the protein CYP2D6 and displays a hydrophobic patch that is situated between an aromatic residue (W316) and histidine (H326). Some drugs such as anticonvulsants (phenobarbital, phenytoin, and carbamazepine) and halothane are suggested to induce hepatitis with anti-CYP3A and anti-CYP2E1, respectively. Autoantibodies against CYP11A1, CYP17, and/or CYP21 involved in the synthesis of steroid hormones are also detected in patients with adrenal failure, gonadal failure, and/or Addison disease.
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PMID:Autoantibodies against CYP2D6 and other drug-metabolizing enzymes in autoimmune hepatitis type 2. 1574 2

Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.
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PMID:Autoimmune liver disease 2007. 1806 56

Nephrogenic systemic fibrosis (NSF) is a rare disorder in patients with chronic kidney disease characterized by an increased tissue deposition of collagen. Its pathogenesis remains unclear. Prior studies indirectly suggested a possible impact of chronic inflammation and accelerated atherosclerosis--a common feature in kidney diseased patients--whereas recent data focused almost exclusively on gadolinium (Gd)-based MR contrast agents. Usually NSF develops a maximum of 2-3 months after Gd. Longer intervals have not yet been described. Therefore, we present the first case with an extraordinary long time course in terms of chronic inflammation. A 52-year-old Caucasian woman with end-stage renal disease was admitted to our hospital with progressive muscle weakness and skin induration resulting in growing immobility. Her past medical history revealed a secondary HPT, multiple vascular complications, a seronegative rheumatoid arthritis, and a pituitary gland adenoma. The latter conditions led to multiple MR examinations with Gd-based contrast agents, the last one more than 4 years ago. Numerous laboratory tests were performed including ESR, CRP, intact parathyroid hormone (iPTH), serum ferritin, cyclic-citrullinated peptide antibodies (CCP), ANA, ANCA, immunoelectrophoresis, and serology for hepatitis as well as human immunodeficiency virus. Eventually a skin biopsy of her left thigh was obtained. The laboratory investigation showed persistently elevated levels of CRP, ESR, serum ferritin, and iPTH, whereas all other parameters were inconspicuous. The hisology displayed typical signs of nephrogenic systemic fibrosis. NSF can occur at any time after Gd exposure in the long term. Gd is a necessary, but not the sole cause of NSF. Certain other cofactors such as chronic inflammation and accelerated atherosclerosis seem to be involved.
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PMID:Chronic inflammation and accelerated atherosclerosis as important cofactors in nephrogenic systemic fibrosis following intravenous gadolinium exposure. 1855 Dec 45

Celiac disease is associated with a number of extra-gastrointestinal features such as hepatitis, arthralgia, and recurrent foetal loss. However respiratory involvement is an extremely rare disorder. We report a case of celiac disease revealed by bronchiectasia in a 39-year-old man. The patient reported a history of recurrent pulmonary infections and intermittent intestinal symptoms in childhood. Wegner granulomatosis was initially suspected because of rhinopulmonary involvement. Serum's patient was tested for ANCA and anti-tissue antibodies. The latest test was performed on histological sections from rat and revealed the presence of anti-reticulin antibodies. Further testing, for anti-tissue transglutaminase and anti-endomysium antibodies, revealed positive results. Celiac disease was confirmed by histological examination of intestinal biopsy. Pulmonary symptoms were improved on a gluten free diet suggesting a causal relationship between celiac disease and respiratory symptoms.
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PMID:[Recurrent rhinitis and pulmonary infections revealing celiac disease: case report]. 1860 76


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