Anticonvulsant hypersensitivity syndrome T88.7

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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anticonvulsant hypersensitivity syndrome; Carbamazepine Hypersensitivity Syndrome; Carbamazepine Phenytoin Hypersensitivity Syndrome; DiHS; drug-induced hypersensitivity

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Optional fatal drug reaction to carbamazepine, phenytoin, phenobarbital and other drugs ( DADPS, allopurinol, minocycline, terbinafine, calcium antagonists) with high fever, pronounced exanthema and organ involvement. There is a close connection with the reactivation of herpes virus infections (HHV-6, HHV-7) and cytomegalovirus infections.

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Incidence: 1/1.000 to 1/10.000 treated patients.

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Possibly genetically fixed defect of the cytochrome P450 system.

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Usually occurs within 3-6 weeks after the start of anticonvulsive therapy.

Clinical features
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Mostly severe clinical picture with considerable general symptoms such as fever, multiform exanthema (possibly erythrodermia), possibly pustular discharge, generalized lymphadenopathy, multi-organ disease with liver and/or kidney failure or blood picture changes (leukocytosis with neutrophilia, eosinophilia). The first symptoms appear 10 days to 8 weeks after the first intake of the drug.

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Leukocytosis, eosinophilia, increase in IL-5, IL-6, INF-gamma. Frequently hypogammaglobulinemia (possibly caused by anticonvulsant therapy is unknown).

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Epicutaneous test, lymphocyte transformation test.

Notice! Neither test is particularly conclusive. The diagnosis is made clinically!

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Reactivation of HHV-6, HHV-7 and CMV.

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  • Immediately discontinue the triggering drug and avoid all drugs that are broken down by cytochrome P450. Otherwise, avoid symptomatic therapy, liver- and kidney-damaging drugs. If necessary, intensive care measures are necessary.

Remember! Cross-reactivity between the different anticonvulsants: carbamazepine, phenytoin and phenobarbital! If the metabolic defect situation is not recognized, there is a risk that carbamazepine is converted to e.g. phenytoin, which may lead to life-threatening symptoms!

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Good prognosis if anticonvulsant drugs are stopped immediately; if hypersensitivity is not recognized, foudroyant course with lethal outcome in multiorgan failure!

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  1. Aihara Y et al (2003) Carbamazepine-induced hyperyensitivita syndrome associated with transient hypogammaglobulinaemia and reactivation of human herpesvirus 6 infection demonstrated by real-time quantitative polymerase chain reaction. Br J Dermatol 149: 165-169
  2. Baba M et al (2003) The anticonvulsant hypersensitivity syndrome. J Eur Acad Dermatol Venereol. 17: 399-401
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  5. Huang YL et al (2003) Fatal sodium valproate-induced hypersensitivity syndrome with lichenoid dermatitis and fulminant hepatitis. J Am Acad Dermatol 49: 316-319
  6. Niketic V, Ristic S, Saicic ZS et al (1995) Activities of antioxidant enzymes and formation of the glutathione adduct of hemoglobin (Hb ASSG) in epileptic patients with long-term antiepileptic therapy. Farmaco 50: 811-813
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  9. Petter G, Haustein UF (1999) Stevens-Johnson syndrome with transition to toxic epidermal necrolysis after carbamazepine administration, heroin and alcohol abuse. dermatologist 50: 884-888
  10. Verrotti A (2002) Anticonvulsant hypersensitivity syndrome in children: incidence, prevention and management. CNS Drugs 16: 197-205


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Last updated on: 29.10.2020