Antiepileptic drugs hypersensitivity

Schlienger RG, Shear NH. Antiepileptic drug hypersensitivity syndrome. Epilepsia 1998 39(Suppl 7) S3-7. 

Eland lA, Dofferhoff AS, Vink R, Zondervan PE, Strieker BH. Cohtis may be part of the antiepileptic drug hypersensitivity syndrome. Epilepsia 1999 40(12) 1780-3. 

Scheuerman O, Nofech-Moses Y, Rachmel A, A ikenazi S. Successful treatment of antiepileptic drug hypersensitivity syndrome with intravenous immune globulin. Pediatrics (2001) 107, E14. 

Hematologic Agranulocytosis has been observed as an unexpected progression from a phenytoin-associated antiepileptic drug hypersensitivity syndrome [248 ]. 

Cross-sensitivity among aromatic antiepileptic drugs occurs in about 50% of patients with a hypersensitivity reaction. It has previously been described on first exposure to each of the offending drugs (57). However, this patient developed an allergic rash on his second exposure to phenytoin, having previously tolerated it for 6 months. This suggests that carbamazepine may have altered his response to phenytoin. 

Klassen BD, Sadler RM. Induction of hypersensitivity to a previously tolerated antiepileptic drug by a second antiepileptic drug. Epilepsia 2001 42(3) 433-5. 

In a retrospective cohort study in 83 patients with primary brain tumors who were treated with procarbazine, 20 patients had procarbazine hypersensitivity reactions (4). There was a significant association between exposure to antiepileptic drugs and the development of procarbazine hypersensitivity reactions. The authors suggested that this association may have been due to a reactive intermediate generated by induction of CYP3A. 

Leeder JS (1998) Mechanisms of idiosyncratic hypersensitivity reactirais to antiepileptic drugs. Epilepsia 39(Suppl 7) S8-S16... 

Patients with Stevens—Johnson syndrome or toxic epidermal necrolysis due to antiepileptic drugs have been compared with patients with antiepileptic drug-related hypersensitivity syndrome the results are shown in Table 1 [79 ]. The authors concluded that these cutaneous syndromes may share some clinical and laboratory features. 

Liver The pathogenesis and clinical characteristics of drug-induced liver injury associated with antiepileptic drugs has been reviewed [41 ]. Reactive metabolites can, in some cases, lead to direct cytotoxicity and liver cell necrosis, whereas in other cases they can cause neoantigen formation, inducing immunoallergic mechanisms. In fact, hypersensitivity features are found in more than 70% of patients with pheny-toin-induced liver injury, whereas this is only observed in 30% of carbamazepine-associated hepatotoxicity and very rarely with valproate-induced liver injury. No specific therapy is of proven value in these cases. However, carnitine, which is an important co-factor in mitochondrial beta-oxidation of fatty acids, is recommended in valproate-associated liver injury, and N-acetylcysteine is an appropriate treatment in patients with liver injury due to pheny-toin and carbamazepine. Liver transplantation may be required for patients with the most severe liver reactions. 

Hypersensitivity to barbiturates can result in a life-threatening syndrome called the Drug, Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome with a mortality of 10%. In persons developing hypersensitivity to barbiturates, there is a potential of cross-sensitivity with other aromatic antiepileptics, such as phenytoin and carbamazepine. 

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