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 assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis B e antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-alpha treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.
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PMID:Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study. 887 70

Drug-induced hypersensitivity syndrome is an uncommon but potentially life-threatening idiosyncratic drug reaction. In the literature, about five cases have been reported concerning hypersensitivity syndrome with lamotrigine. Most cases concern aromatic anticonvulsants but we report a case induced by lamotrigine which is a non aromatic anticonvulsant. A 73-year-old man was treated with lamotrigine for epilepsy due to a cerebrovascular stroke for 5 weeks. After 2 weeks with a single oral dose of 50 mg lamotrigine, the patient received 100 mg. Quickly thereafter fever, erythema and edema involving the periorbital area appeared. He was then admitted to hospital and lamotrigine was immediately discontinued. He developed acute hepatic and renal failure. During his hospital stay, he was treated with systemic and topical corticosteroids. After slow improvement, he was discharged 4 weeks later. Concerning this typical case, we review the characteristics of hypersensitivity syndrome and the different etiopathogenesis. The hypersensitivity syndrome typically develops two to six weeks after a drug is first administered, later than most other serious skin reactions. This syndrome manifests as rash, fever, tender lymphadenopathy, hepatitis and eosinophilia. The mechanism of hypersensitivity syndrome is unknown. Several theories have been proposed. The reaction is secondary to circulating antibodies or concerns toxic metabolities. On the other hand, association of human herpes virus 6 infection may play a role in the development of hypersensitivity syndrome. Hypersensitivity reactions to the aromatic antiepileptic drugs appear to have an immune etiology much like lamotrigine: bioactivation, detoxification, covalent adduct formation, processing and presentation of antigen to the immune system, and consequent formation of antibody and T-cell immune effectors. Another theory involves toxic metabolites; the aromatic antiepileptic agents are metabolised by cytochrome P-450 to an arene oxide metabolite. This is normally detoxified by epoxide hydrolase. This enzyme may be lacking or mutated in persons that develop the syndrome, and this is genetically determined. Lamotrigine is mainly metabolised by hepatic glucuronidation, but hypersensitivity may involve similar processes such aromatic antiepileptic drugs, except that the toxic metabolite has not yet been found. Because of slow evolution and clinical similarity to many infectious illnesses, the diagnosis of hypersensitivity syndrome may be delayed. Prompt recognition and withdrawal of the suspected drug is essential. The goal of research is to describe a "susceptibility profile" identifying individuals at risk for these forms of drug toxicity.
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PMID:[Characteristics of hypersensitivity syndrome to lamotrigine: review of one case reported in the Regional Center of Pharmacovigilance of Nantes]. 1242 44

We report a 26-month-old boy with Angelman syndrome associated with Lennox-Gastaut syndrome, who developed a rash and a persistent toxic hepatitis after lamotrigine was added to valproate therapy. The patient had typical findings of both Angelman and Lennox-Gastaut syndromes. Chromosome analysis performing by FISH analysis showed a deletion in chromosome 15 (q11.2 q11.2). Although some cases of Angelman syndrome associated with Lennox-Gastaut syndrome were reported in the literature, valproate and/or lamotrigine induced toxic hepatitis in Angelman syndrome has hitherto never been described. We conclude that VPA and LTG combination should be given with great caution or avoided in patients with Angelman syndrome.
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PMID:Toxic hepatitis in a case of Angelman syndrome associated with Lennox-Gastaut syndrome. 1551 29

Anticonvulsant hypersensitivity syndrome (AHS) is a potentially life-threatening adverse drug reaction presenting with fever, skin eruptions, and internal organ involvement. We describe a case of AHS with fulminant hepatitis that occurred two weeks after introduction of lamotrigine in a 40-year-old female patient with a recently diagnosed bipolar disorder, no pre-existent systemic organ involvement, and no other medication. Lamotrigine was introduced at a dosage of 25 mg daily and increased to 50 mg daily 12 days later. The patient had favorable evolution with cessation of lamotrigine and supportive treatment. This report suggests that AHS with fulminant hepatitis may occur idiosyncratically, independent of dosage, titration and comedication with other potentially hepatotoxic drugs.
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PMID:Fulminant hepatitis induced by lamotrigine. 1907 52

Lamotrigine is a non-aromatic antiepileptic drug. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe idiosyncratic reaction to drugs, especially anti-epileptic drugs. Associated clinical features include cutaneous eruption, fever, multiple peripheral lymphadenopathies, and potentially life-threatening damage of one or more organs. We report a case of DRESS syndrome induced by lamotrigine presenting with a hypersensitivity syndrome and fulminant hepatic failure requiring liver transplant. A 21-year old female patient presented an episode of seizure with loss of conscience. CT and EEG studies performed were normal. Treatment with lamotrigine was prescribed. In the course of 30 days, the patient developed skin lesions, pruritus, cholestatic hepatitis, and systemic symptoms -fever, lymphadenopathies, extensive exfoliative erythematous maculopapular rash, and jaundice. Serologic and laboratory tests showed no other causes responsible for the clinical spectrum. Hematologic tests revealed peripheral eosinophilia. Fulminant hepatic failure was diagnosed and an orthotopic liver transplant was performed. Histologic sections of the explanted liver demonstrated submassive hepatic necrosis, with the remnant portal spaces and lobules showing a mixed inflammatory infiltrate with lymphocytes and eosinophils. Lamotrigine treatment has been associated with multiorgan failure, DRESS syndrome, acute hepatic failure, and disseminated intravascular coagulation. In conclusion, we suggest that these potentially fatal side effects should be considered in any patient with clinical deterioration following administration of this drug.
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PMID:Dress syndrome and fulminant hepatic failure induced by lamotrigine. 1922 40

A number of newly developed antiepileptic drugs are currently in use, among them Lamotrigine (LTG) is more common. Despite the extensive use of this drug, it has not been possible to predict the side effects especially the hepatotoxic reactions after long-term treatment. The present study was designed to find out alterations in the activities of liver enzymes after chronic exposure of rats to different dose of LTG. Adults male (Wistar) rats were treated orally with LTG [5 mg/kg body weight or 25 mg/kg body wt.] for 60 days. After the experimental period, auto analyzer carried out liver function tests. The liver histopathology was obtained after scarifying the rats. There was a significant increase in the level of ALP, AST, ALT and bilirubin at therapeutic dose of LTG. The increase level of these enzymes and bilirubin at toxic dose were much higher and significant. However, the total protein and albumin significantly decreased at toxic dose of LTG. Elevation of liver enzymes and bilirubin after chronic exposure of rats to high dose of LTG reflects hepatocellular damage that may lead to hepatitis. It is concluded that regular liver function and drug monitoring should follow the treatment with LTG.
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PMID:Choronic effects of Lamotrigine on liver function in adult male rats. 2310 90

Drug induced hypersensitivity syndrome (DIHS) is often manifested as severe systemic drug trans-reactions characterized by acute and extensive skin lesions (mostly measles-like rash), fever, enlargement of lymph nodes, multiple organ involvement (hepatitis, nephritis, and pneumonia), eosinophilia and mononucleosis,within 2-6 weeks of the application of sensitizing drugs. In the early stage of the lesion, macular papules or erythema multiforme were common, and in severe cases, exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis were also common. Most of them developed after taking allergic drugs for 2-6 weeks (average: 3 weeks). Symptoms persisted after discontinuation of allergic drugs. It takes more than one month to alleviate, which may endanger life in severe cases. Documents report that the most common drugs causing DIHS are phenytoin sodium, carbamazepine and phenobarbital aromatic drugs. However, it was reported that phenobarbital sodium was the most common anticonvulsant among allergenic drugs in children, followed by antipyretics, analgesics and antibiotics, which may be related to the spectrum of childhood diseases and the particularity of the drug. Lamotrigine has been reported to cause DIHS in adults in China, but less in children. In order to improve the understanding of clinical diagnosis and treatment of DIHS in children, reduce misdiagnosis, missed diagnosis, and untimely treatment, and prevent the aggravation of the disease, we studied the case of a 4-year-old 7-month-old girl who presented with systemic erythematous papules, fever, hepatosplenomegaly, marked increase of white blood cells, marked decrease of anemia and platelets, abnormal liver function and coagulation routine after taking lamotrigine for one month due to epilepsy seizures. Now, according to the DIHS diagnostic criteria established by Registration of Severe Cutaneous Adverse Reactions Drug Review Group in 2007, plasma exchange was immediately given to replace the toxic metabolites in hemorrhagic plasma, and methylprednisolone was given intravenously for three days. At the same time, after symptomatic supportive treatments, such as loratadine and albumin, the condition gradually improved without recurrence. Through a case report of Drug reaction with eosinophilia and systemic symptoms in a child caused by lamotrigine, we can strengthen our understanding and improve the level of diagnosis and treatment of drug hypersensitivity syndrome in children. Lamotrigine can cause DIHS in children, which is very dangerous. Early diagnosis and early withdrawal of allergenic drugs, plasma exchange and glucocorticoid therapy are the key to treatment.
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PMID:[Lamotrigine induced hypersensitivity syndrome in children: a case report]. 3099 82