Abstracts

Rationale: Patients with epilepsy after encephalitis/encephalopathy (EAE) often have refractory seizures, resulting in polytherapy with the risk of adverse reactions due to anti-epileptic drugs (AEDs). Among the adverse reactions caused by AEDs in patients with EAE, we focused on the characteristics of cutaneous adverse reaction (CAR). Methods: In this retrospective study, the medical records of 67 patients who were diagnosed as having EAE in our hospital between February 1996 and May 2009 were reviewed and the clinical characteristics were analyzed. Immunological biomarkers including cytokines, chemokines, granzyme B, soluble tumor necrosis factor receptor 1 (s-TNFR 1), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured in 22 patients. Results: CARs attributed to AEDs were observed in 16 of 67 EAE patients (23.9 %) (CAR group). High CAR rates were observed with phenytoin (8 of 32 patients), lamotrigine (2 of 8 patients), phenobarbital (5 of 35 patients), and carbamazepine (6 of 54 patients), but CARs were never observed with zonisamide, clobazam, clonazepam, and gabapentin. Severe CARs (Steven-Johnson syndrome, and drug induced hypersensitivity syndrome) were found in three of 67 patients (4.5%). The frequencies of CARs were significantly higher in patients with encephalitis onset older than five years of age (p = 0.018). CAR occurred only in patients who had onset of EAE within 6 months after encephalitis. The durations from acute encephalitis to CARs were within one year for almost all AEDs, except lamotrigine, and 61% of patients with EAE had CARs within 1 month after encephalitis. Three patients were successfully restarted on the AEDs that had been discontinued because of CARs. IL-1?, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, FGF basic, G-CSF, GM-CSF, IP10, MCP-1, MIP1a, MIP1b, IFN?, eotaxin, MMP-9, TIMP-1, granzyme B were not significantly different between CAR group and non-CAR group. The proportion of patients with serum RANTES levels higher than the upper limit of normal range was significantly higher in CAR group than in non-CAR group (p=0.017). Conclusions: Patients in the early stage of EAE and patients with encephalitis onset older than five years of age may be at higher risk of CARs to AEDs, especially to phenytoin, lamotrigine, phenobarbital, and carbamazepine. RANTES may be a biomarker for susceptibility to CARs in EAE patients.