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)

Minocycline belongs to the second generation class of cyclines. It was synthesized in 1967 and marketed in 1972. Minocycline has an antiinfectious activity with a spectrum similar to that of other cyclines, notably against Chlamydias, Treonema and Proprionibacterium acenes. The antiinflammatory activity is associated with this antiinfectious action is greater than that of first generation cyclines with specifically a modulator effect on epidermal cytokines. The pharmokinetics of minocycline is characterized by an excellent absorption, a long half-life and an important lipophilic property inducing good tissue distribution. Clinical trials of minocycline have mainly been performed in sexually transmissible diseases and in acne, a field where randomized studies are the most frequent. These trials show that the effect of minocycline is not stronger than first generation cyclines or doxycycline, but that the action is quicker than that of tetracycline at the dose of 500 mg a day. Minocycline is also efficient in nocardiasis, mycobacteriosis, leprosy, Lyme disease, pyoderma gangrenosum, autoimmune bullous dermatitis, Carteaud disease, and prurigo. However, the effect of minocycline in these different conditions has always been evaluated in open trials with a small number of patients. The usual side effects of cyclines, i.e. digestive problems, fungal infections, are less frequent than with first generation cyclines. No photosensitivity has been demonstrated although pigmentations have been described. Dizziness is a specific side effect of minocycline. Furthermore, rare but severe side effects have been reported, including hypersensitivity syndrome, autoimmune hepatitis, and lupus. Regular indications for minocycline in dermatology are acne and three sexually transmissible diseases (mycoplasm, chlamydia, treponema). Proposed dosage is 100 mg per day in sexually transmissible disease with a reduction to 50 mg per day after 15 days in acne.
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PMID:[Minocycline]. 1142 98

Minocycline hydrochloride, a synthetic tetracycline, is a systemic antibiotic that has received much attention over the past several years. Currently, minocycline is considered the most widely prescribed oral antibiotic in the management of acne. Minocycline has been associated with autoimmune events, hepatitis, lupus-like syndromes, serum sickness, vasculitis, Sweet's syndrome, and hyperpigmentation. We report a case of a patient who developed drug-induced immune thrombocytopenic purpura (DITP) after taking minocycline. The initial clinical presentation of nonpalpable, discrete nonblanching petechiae and cayenne pepper-like macules on his lower legs was diagnosed as pigmented purpuric dermatosis (Schamberg's disease). We report the first case of DITP with the clinical picture of Schamberg's disease associated with minocycline therapy.
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PMID:Minocycline-induced immune thrombocytopenia presenting as Schamberg's disease. 1284 17

1. Minocycline has anti-inflammatory and antiapoptotic effects on cartilage, neurons and periodontal tissues, and both properties are central to the pharmaceutical treatment of liver diseases. We investigated the effects of minocycline on fulminant hepatitis in C57BL/6J mice induced by lethal challenge of the activating anti-Fas antibody, Jo2. 2. Intraperitoneal injection of Jo2 (0.6 microg g(-1)) to mice resulted in fulminant hepatitis, as evidenced by increase of serum alanine/aspartate transaminase activities and histopathological alterations in liver sections, as well as animal death. Nevertheless, mice pretreated with three doses of minocycline (5 mg kg(-1)) resisted this lethal effect significantly. Minocycline treatment improved the survival kinetics, although to a lesser extent, when mice were challenged simultaneously with Jo2 or even treated 30 min after the lethal challenge. 3. Jo2-induced activation of caspase-3 or -9 in liver tissues was inhibited by minocycline pretreatment, and yet the direct addition of minocycline to liver extracts from Jo2-challenged mice failed to block caspase activation in vitro. Moreover, minocycline efficiently suppressed the release of cytochrome c from mitochondria of the liver tissues from Jo2-challenged mice. In contrast, caspase-8 activation and Bid truncation triggered by Jo2 were not diminished by minocycline pretreatment in mouse livers. 4. Our results suggest that easing of Fas-triggered fulminant hepatitis by minocycline may involve a mitochondrial apoptotic pathway, probably through preventing cytochrome c release and thereby blocking downstream caspase activation.
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PMID:Effects of minocycline on Fas-mediated fulminant hepatitis in mice. 1566 64

Regional differences in the manifestations of autoimmune hepatitis underscore the importance of genetic and/or environmental factors in its expression. The -308 polymorphism of TNF-A increases susceptibility to type 1 autoimmune hepatitis; HLA DRB1*13 is an important risk factor in South America; and DRB1*07 characterizes type 2 autoimmune hepatitis. Minocycline and mesalazine can trigger the disease, and interferon therapy can accentuate autoimmune manifestations. Autoimmune cholangitis in Japan is similar to primary biliary cirrhosis, and assays for carbonic anhydrase II lack diagnostic specificity. Perinuclear antineutrophil cytoplasmic antibodies are reactive to diverse nuclear antigens, but high mobility nonhistone chromosomal proteins may be important targets in autoimmune hepatitis. T cells can cross-react with viral and host peptides, and the candidacy of glutathione S-transferases as target autoantigens has been weakened. A murine model of PBC will be useful in studying mechanisms of autoreactivity, and cyclosporine has shown promise in the treatment of children with autoimmune hepatitis. Recurrence after liver transplantation is common, and it may require retransplantation. The human transplantation model will be valuable in understanding the host-and organ-specific contributions to disease expression.
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PMID:Autoimmune liver disease. 1702 84

Minocycline is an effective antibiotic widely used in the treatment of acne vulgaris. We report a previously well 20-year-old woman who developed liver dysfunction with jaundice and malaise following a 1 year course of minocycline for acne vulgaris. Serum antinuclear antibody was strongly positive (1 : 2560) and liver transaminases were grossly deranged. All other causes of liver disease were excluded. Both the clinical symptoms and laboratory abnormalities resolved spontaneously on stopping the drug. We review the three different types of hepatotoxicity associated with minocycline and draw evidence to support the diagnosis of minocycline-induced autoimmune hepatitis. This case supports the call to monitor patients on minocycline therapy for autoimmune disease of the liver and highlights the need for a multicentre prospective trial of the risks and benefits of long-term minocycline therapy.
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PMID:Minocycline hepatitis. 1861 86

Over the years, a variety of abnormal immune reactions to minocycline have been reported including arthritis, systemic lupus erythematosus, and hepatitis. The current report describes the detailed clinical and pathologic features of 3 patients who presented with chronic/autoimmune hepatitis alone while on minocycline at our hospital over a 2-year period. Minocycline use in these patients was temporally related to onset of severe hepatitis. Adolescents with such a reaction to minocycline have been included in previous reports but have not been well described as a distinct entity. We have compared our cases with similar cases previously reported with a review of the literature and a discussion of the implications for prescribing physicians.
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PMID:Long-term minocycline use for acne in healthy adolescents can cause severe autoimmune hepatitis. 1926 6

Minocycline is a semi-synthetic, second-generation tetracycline. It was introduced in 1972 and has both antibacterial and anti-inflammatory properties. Minocycline is used for a variety of infectious diseases and in acne. Even today, new indications beyond the antibacterial indications are being investigated such as its use in neurologic diseases. Formerly, minocycline was thought to have a superior efficacy in the treatment of inflammatory acne, especially with respect to antibacterial-resistant Propionibacterium acnes. A thorough review of the literature, however, shows that minocycline is not more effective in acne than other tetracyclines. Compared with first-generation tetracyclines, minocycline has a better pharmacokinetic profile, and compared with doxycycline it is not phototoxic. However, minocycline has an increased risk of severe adverse effects compared with other tetracyclines. It may induce hypersensitivity reactions affecting the liver, lung, kidneys, or multiple organs (Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS] syndrome) in the first weeks of treatment and, with long-term treatment, may cause autoimmune reactions (systemic lupus erythematosus, autoimmune hepatitis). In addition, CNS symptoms, such as dizziness, are more frequent compared with other tetracyclines. Long-term treatment may induce hyperpigmentation of the skin or other organs. Resistance of P. acnes to minocycline also occurs, dependent on the prescribing behavior. Considering the aspects of efficacy, its adverse effect profile, resistance, price, and alternatives, minocycline is no longer considered the first-line antibacterial in the treatment of acne.
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PMID:Minocycline in acne vulgaris: benefits and risks. 2064 95

The clinical phenotype of classical autoimmune hepatitis can be mimicked by idiosyncratic drug-induced liver injury, and differentiation can be difficult. The goals of this review are to enumerate the major agents of drug-induced autoimmune-like hepatitis, describe the clinical findings and risk factors associated with it, detail the clinical tools by which to assess causality, discuss putative pathogenic mechanisms, and describe treatment and outcome. The frequency of drug-induced autoimmune-like hepatitis among patients with classical features of autoimmune hepatitis is 9%. Minocycline and nitrofurantoin are implicated in 90% of cases. Female predominance, acute onset, and absence of cirrhosis at presentation are important clinical manifestations. Genetic factors affecting phase I and phase II transformations of the drug, polymorphisms that protect against cellular oxidative stress, and human leukocyte antigens that modulate the immune response may be important pathogenic components. Clinical judgment is the mainstay of diagnosis as structured diagnostic methods for drug-induced liver injury are imperfect. The covalent binding of a reactive drug metabolite to a hepatocyte surface protein (commonly a phase I or phase II enzyme), formation of a neoantigen, activation of CD8 T lymphocytes with nonselective antigen receptors, and deficient immune regulatory mechanisms are the main bases for a transient loss of self-tolerance. Discontinuation of the offending drug is the essential treatment. Spontaneous improvement usually ensues within 1 month. Corticosteroid therapy is warranted for symptomatic severe disease, and it is almost invariably effective. Relapse after corticosteroid withdrawal probably does not occur, and its absence distinguishes drug-induced disease from classical autoimmune hepatitis.
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PMID:Drug-induced autoimmune-like hepatitis. 2169 69

Minocycline is a synthetic tetracycline-derived antibiotic with significant anti-inflammatory properties that may benefit patients with rheumatoid arthritis. Surprisingly, chronic exposure to minocycline can also cause a breach in immunologic tolerance resulting in a variety of autoimmune syndromes such as drug-induced lupus or autoimmune hepatitis. Vasculitis, most commonly resembling cutaneous polyarteritis nodosa, has also been seen in patients taking this drug. Herein, we present a case of biopsy-proven systemic vasculitis presenting as an ANA (+) ANCA (+) polyarteritis nodosa-like syndrome in a male patient who was taking minocycline for his acne for approximately 2 years. Patient initially presented with constitutional symptoms such as profound weight loss and fatigue, along with myalgias, oligoarticular arthritis, and livedo reticularis. About 2 months later, he developed a severe left testicular pain. Biopsy showed vasculitis complicated with the infarction of the left testis. Angiography revealed microaneurysms in the renal and splenic circulation. Stopping the offending drug, along with the short course of prednisone and hydroxychloroquine, resulted in prompt resolution of his symptoms. We additionally present a comprehensive review of biopsy-proven cases of vasculitis associated with chronic minocycline treatment focusing on its pathogenesis and clinical manifestations.
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PMID:ANA (+) ANCA (+) systemic vasculitis associated with the use of minocycline: case-based review. 2360 93

Drug-induced autoimmune hepatitis (DIAIH) is an increasingly recognized form of drug-induced liver injury that leads to a condition similar to idiopathic autoimmune hepatitis. A number of drugs have been associated with DIAIH, minocycline is one of the most well characterized. Minocycline is a semisynthetic tetracycline antibiotic used in the treatment of acne vulgaris. Minocycline-induced autoimmune hepatitis presents with serologic and histologic features similar to idiopathic autoimmune hepatitis. However, the natural history and outcomes of these two conditions differ significantly. The majority of patients with minocycline-induced autoimmune hepatitis experience complete resolution of symptoms after withdrawal of the medication. Some patients may require a short course of steroids and rarely use of an immunomodulator to achieve resolution of disease. Recurrence of symptoms is rare and typically only occurs with reintroduction of minocycline. It is important for primary care providers to consider minocycline-induced autoimmune hepatitis when liver injury develops during minocycline therapy.
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PMID:Minocycline-Induced Autoimmune Hepatitis: A Rare But Important Cause of Drug-Induced Autoimmune Hepatitis. 3034 50


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