Antiepileptic drug hypersensitivity Z 88.8

Antiepileptic drugs are used both to treat the acute epileptic seizure and to prevent further seizures in the period without symptoms. Treatment with antiepileptic drugs can be associated with unforeseeable adverse events.

The hypersensitivity reactions are generally regarded as T-cell-mediated allergy. Immediate type reactions with anaphylactic symptom pattern are rare.

Delayed skin reactions are therefore typical. They range from maculo-papular (non-urticarial) exanthema, which occurs 4-6 weeks after the start of therapy (they subside after a few days after discontinuation of medication - Blaszcyk B et al. 2013) to severe skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN).

The following active substances are assigned to the active substance group "antiepileptic drugs":

• Brivaracetam
• Carbamazepine
• Clobazam
• Clomethiazole
• Clonazepam
• Diazepam
• Eslicarbazepine
• Ethosuximide
• Felbamat
• Gabapentin
• Lacosamide
• Lamotrigine
• Levetiracetam
• Nitrazepam
• Oxcarbazepine
• Perampanel
• Phenobarbital
• Phenytoin
• Pregabalin
• Primidone
• Sultiam
• Topiramate
• Valproic acid
• Zonisamide

Genetic predisposition: Antiepileptic drug hypersensitivity may be associated with the presence of certain HLA alleles. This association is particularly significant for carbamazepine (Tangamornsuksan W et al. 2013). This is especially true for Chinese of Han Chinese and Thai descent. Here the human leukocyte antigen (HLA)-B1502 is so closely related to SJS/TEN that its determination should be carried out before starting carbamazepine therapy.

After the ADR has healed, an allergological clarification by means of epicutaneous testing is recommended (for most antiepileptic drugs, 10% concentrations in a vaseline base are considered non-irritative!). and, if necessary, a lymphocyte transformation test. Important: the sensitivity of the tests is not sufficient to rule out an allergy in case of negative reactions! If no positive reaction can be detected, the active ingredients in question can be re-tested in the case of slight index reactions (Schnyder B 2018). In case of severe skin or skin system reactions, the drugs in question should be strictly avoided. Clinically and in tests, there are often cross-reactions within aromatic antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, oxacarabazepine, primidone, felbamate, zonisamide, lamotrigine)

The term "antiepileptic drug hypersensitivity" is not used uniformly. Many authors use the term "hypersensitivity reaction".

1. Błaszczyk B et al. (2013) Single centre 20 year survey of antiepileptic drug-induced hypersensitivity reactions. Pharmacol Rep. 2013;65(2):399-409.
2. Schnyder B (2018) Antiepileptic drug-induced hypersensitivity reactions. Allergo J 27: 16-18
3. Tangamornsuksan W et al (2013) Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol 149:1025-1032.