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-induced hypersensitivity syndrome is a multiorgan-system reaction characterized by fever, pleomorphic eruption, lymphadenopathy, eosinophilia, lymphocytosis and hepatitis. We report a drug hypersensitivity syndrome in a 6-year-old Tunisian child treated for epileptic absences with sodium valproate and ethosuximide. Imputability of these 2 drugs is probable because of the chronological and clinical features. Positive rechallenge with ethosuximide confirmed the toxicity of this drug. Sodium valproate was also responsible because patch testing was positive and followed by a generalized eruption. Human herpesvirus 6 (HHV6) antibody titers increased significantly within 15 days. There was a favourable outcome after discontinuation of the drugs and corticosteroid therapy. Our case is interesting because this drug hypersensitivity syndrome occurred with non-aromatic anticonvulsant drugs. It is the 1st case with ethosuximide and the 2nd with sodium valproate. We also observed a reactivation of HHV6 infection that may contribute to the development of this hypersensitivity syndrome.
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PMID:Hypersensitivity syndrome due to 2 anticonvulsant drugs. 1047 12

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

Drug-induced hypersensitivity syndrome (DIHS), also called drug rash with eosinophilia and systemic symptoms (DRESS), is a severe reaction usually characterized by fever, rash, and multiorgan failure, occurring 1-8 weeks after drug introduction. It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release, although no consensus has been reached as to its etiology. The skin, hematopoietic system, and liver are frequently involved. DIHS can mimic severe sepsis, viral infection, adult-onset Still disease (AOSD), or lymphoproliferation.We describe 24 consecutive patients with DIHS who were hospitalized between September 2004 and March 2008. Criteria for inclusion in this observational study were suspected drug reaction, eosinophilia >or=500/microL and/or atypical lymphocytes, involvement of at least 2 organs (skin being 1 of them), with suggestive chronology and exclusion of other diagnoses. Our cohort of 12 women and 12 men had a median age of 49 years (range, 22-82 yr), and 11 had skin phototype V or VI. Patients with mild or no rash were immunocompromised (7/24)- defined as treatment with prednisone (>or=10 mg/d) and another immunosuppressant drug, or human immunodeficiency virus infection. All patients were febrile (>38 degrees C), 14 had localized or generalized edema, 7 had pharyngitis, 8 had lymphadenopathy, 22 had hepatitis, 4 had nephritis, 2 had noninfectious and nonlithiasic angiocholitis or cholecystitis. Ten patients were hypotensive, 5 of whom had associated laboratory signs and/or imaging findings suggestive of acute myocardial dysfunction. Half of the patients had hemogram abnormalities, including eosinophilia. Nine DIHS patients fulfilled the Fautrel criteria for AOSD diagnosis, including glycosylated ferritin <20% in 4/11, with or without laboratory characteristics of hemophagocytosis. Twenty DIHS episodes occurred during the less sunny months of October to March.We determined 25-hydroxyvitamin D3 (25[OH]D3) levels in 18 patients and found that 9 patients had vitamin D deficiency (<25 nmol/L or <10 microg/L) and 5 had vitamin D insufficiency (25-50 nmol/L). Moreover, 25(OH)D3 levels were inversely correlated with ferritin values. After culprit-drug withdrawal, outcomes were favorable for all patients, including those with cardiac abnormalities under slow tapering of glucocorticoids.We recommend looking for the frequent but underdiagnosed hypersensitivity myocarditis with noninvasive diagnostic tools, such as N-terminal probrain natriuretic peptide, and promptly withdrawing the culprit drug and starting glucocorticoids. Vitamin D deficiency might be a DIHS risk or severity factor, especially for patients with high skin phototype and during the winter. Because DIHS clinical and laboratory patterns share similarities with AOSD and hemophagocytosis, DIHS should be included in their differential diagnoses.
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PMID:Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients. 1944 Jan 16

Drug-induced hypersensitivity syndrome (DIHS) is a rare and potentially fatal reaction characterized by fever, rash, and internal organ involvement that typically occurs between 3 and 6 weeks after commencing the drug. We describe such a case in a 26-year-old woman, who developed fever, exfoliative erythroderma, facial edema, cervical lymphadenopathy, hepatitis, and leukocytosis 6 weeks after commencing carbamazepine for lower back pain. Her serum angiotensin-converting enzyme level was also raised to 144 U/L (8-52 U/L). Skin biopsies demonstrated an unusual superficial dermal perivascular inflammatory infiltrate, which included conspicuous granulomas mixed with moderate numbers of lymphocytes. Eosinophils were not a feature. Her carbamazepine was withdrawn, and oral prednisone was commenced initially at a dose of 1 mg.kg.d and slowly weaned over a 6-week period. Her fever, rash, facial edema, and hepatitis gradually resolved within this period, and her serum angiotensin-converting enzyme level returned to within the normal range. Although the patient's clinical course was consistent with a DIHS, it was accompanied by a previously unreported finding of a superficial granulomatous dermatitis. Granuloma formation as a sequel to medication use is a feature of interstitial granulomatous drug reaction. However, interstitial granulomatous drug reaction consists of localized violaceous plaques with a predilection for skin fold areas and liver function abnormalities have not been described. Granulomatous inflammation in other organ systems, including the liver and kidney, has also been described after the use of carbamazepine, but these reactions are not associated with the systemic manifestations observed in DIHS.
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PMID:Drug-induced hypersensitivity syndrome with superficial granulomatous dermatitis--a novel finding. 2204 62

Drug-induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash, and internal organ involvement. The culprit drugs of DIHS are limited to several drugs such as carbamazepine, phenytoin, phenobarbital, zonisamide, allopurinol, salazosulfapyridine, diaphenylsulphone, and mexiletine. The association of HHV-6 reactivation with DIHS has been known. Flaring of symptoms such as fever and hepatitis is closely related to HHV-6 reactivation. A combination of immunologic reaction to a drug and HHV-6 reactivation results in the severe course of DIHS.
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PMID:[Drug-induced hypersensitivity syndrome and HHV-6 reactivation]. 1992 85

Drug-induced hypersensitivity syndrome (DIHS) is characterized by fever, rash and internal organ involvement, mostly in form of hepatitis, myocarditis, nephritis or pneumonitis, which may occur 1-8 weeks after medicine exposure. Fever is an early feature, usually preceding a widespread erythematous skin eruption, but the severity of the skin-related changes does not correlate with the extent of internal organ involvement. It is considered that anticonvulsants (particularly carbamazepine), antibiotics, allopurinol are the most frequent causative agents of DIHS. The underlying mechanisms causing DIHS are poorly understood--defective detoxification of the reactive drug's metabolites or genetic predisposition have been implicated. Diagnosis of DIHS is based on clinical presentation connected with drug intake, supported by a finding of eosinophilia, increased concentration of inflammation markers and abnormal biochemical parameters, mainly liver function tests. Treatment consists of immediate withdrawal of all suspected medicines, followed by supportive systemic corticosteroids. We describe a case of a 72-years-old female who developed symptoms of drug-induced hypersensitivity syndrome after approximately 4 weeks of taking anticonvulsant (Amizepin) due to sensual axonal polyneuropathy. Withdrawal of drug and treatment with systemic corticosteroids caused clinical improvement rapidly.
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PMID:[Drug-induced hypersensitivity syndrome--a literature review and the case report]. 2119 Jan 54

Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia with systemic symptoms, is a life-threatening multiorgan system reaction caused by a limited number of drugs such as anticonvulsants. This syndrome is characterized by fever, rash, lymphadenopathy, hepatitis, and leukocytosis with eosinophilia. DIHS has several unique features that include the delayed onset, paradoxical deterioration of clinical symptoms after withdrawal of the causative drug and unexplained cross-reactivity to multiple drugs with different structures. Because of these features and a lack of awareness of this syndrome, DIHS is undoubtedly underdiagnosed in many countries despite its worldwide distribution. The clinical variability in the presentation and course of clinical symptoms of DIHS could now be interpreted as an indication that several herpesviruses reactivate in a sequential manner independently in the different organs. Dramatic expansions of functional regulatory T (Treg) cells observed in the acute stage would serve to induce such sequential reactivations of herpesviruses while a gradual loss of Treg function occurring after resolution of DIHS could increase the risk of subsequently developing autoimmune disease. Although systemic corticosteroids are the mainstay of treatment, it remains to be determined whether this treatment is beneficial from a viewpoint of disease outcome and sequelae.
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PMID:Drug-induced hypersensitivity syndrome: recent advances in the diagnosis, pathogenesis and management. 2261 58

Drug-induced hypersensitivity syndrome (DIHS; also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) is a life-threatening condition first described by Chaiken et al. in 1950. It is characterized by extensive mucocutaneous rash; fever; lymphadenopathy; hepatitis; hematological abnormalities; damage to several organs such as kidney, heart, lungs, and pancreas; and possible reactivation of human herpesvirus-6 (HHV-6) or other herpes virus. Rare and severe cases may present hepatic necrosis, and about 15% of them result in death or liver transplantation. A hallmark of this syndrome is the late onset of symptoms after the drug exposure. The most common culprit drugs are the aromatic anticonvulsants (in almost 30% of the cases) and the antibiotics (which in some series represent 20% of the cases). The authors report a case of a 41-year-old female who presented to the emergency department with erythroderma, acute hepatitis, acute pancreatitis and acute renal failure, and was then treated with corticosteroid after the diagnosis of DIHS/DRESS. A specific culprit drug could not confidently be determined due to the presence of multiple drugs used by the patient. The clinical and laboratory outcome was apparently satisfactory, but unexpectedly, on the sixth day of hospitalization, the patient complained of nonspecific malaise, drowsiness, which progressed in a few hours with signs and symptoms of hepatic failure, refractory shock, and death. The autopsy findings showed submassive hepatic necrosis, and the immediate cause of death was attributed to hepatic failure.
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PMID:Hepatic necrosis associated with drug-induced hypersensitivity syndrome. 3152 83