Chaichon Locharernkul

Carbamazepine and phenytoin induced Stevens‐Johnson syndrome is associated with HLA‐B*1502 allele in Thai population

Purpose:  Previous studies found a strong association between HLA‐B*1502 and carbamazepine (CBZ)‐induced Stevens‐Johnson syndrome (SJS) in Han Chinese, but not in Caucasian populations. Even in Han Chinese, the HLA‐B*1502 was not associated with CBZ‐induced maculopapular eruptions (MPE). This study seeks to identify whether HLA‐B*1502 is associated with CBZ‐ or phenytoin (PHT)‐induced SJS or MPE in a Thai population.

Pharmacogenetic screening of carbamazepine-induced severe cutaneous allergic reactions

Recent studies associated the HLA-B 1502 allele with carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in patients from China, Thailand and Malaysia. No association has been found in patients from Europe or Japan. Linkage summary reports from East and South-east Asia predict a highly significant odds ratio (OR) of 84.75 (95% confidence interval [CI]=42.53-168.91; p=8.96×10[-15]) with sensitivity and negative predictive values of 92% and 98%, respectively. The higher prevalence of HLA-B 1502 allele among certain Asian populations (10-15%) compared to Caucasians (1-2%) may explain a 10-fold to 25-fold higher incidence of CBZ-SJS/TEN in patients from Asia. Screening for HLA-B 1502 before using CBZ can prevent SJS/TEN in certain populations, but screening may be less beneficial in populations with low HLA-B 1502 allele frequency and in patients exposed to CBZ for more than 2 months. A retrospective study demonstrated that the costs of HLA-B 1502 screening were less than those of SJS treatment. This article reviews possible benefits and concerns of HLA-B 1502 screening in clinical practice.

HLA-B* 1502 screening: Time to clinical practice

may explain this discrepancy. Our work analyzed trials with five AEDs assessed in both adults and children with partial epilepsy, whereas Beyenburg et al. compared the pooled effect of 14 AEDs in adults with that of only 5 AEDs studied in children with different epilepsy syndromes. In addition, we assessed responder rates in an intentionto-treat (ITT) analysis over the whole treatment period, whereas Beyenburg et al. in Figure 2 seem to have used in many trials a modified ITT or a per-protocol analysis. Beyenburg et al. used risk differences, whereas we used relative risk, which provides more robust estimates than absolute measures (Deeks, 2002). In fact, the heterogeneity between the same five pediatric trials was greater in the model of Beyenburg et al. (I = 62%) than in our model (I = 31%), which might indicate inadequate model fit (Deeks, 2002). Overall, we believe that meta-analyses should be performed on datasets comparable in terms of effective (or most effective) doses, seizure type, and efficacy endpoints. Efficacy data should ideally focus on completers to avoid the bias deriving from LOCF analysis, and editorial policies should be standardized to ensure that authors disclose in their publications those datasets that are most meaningful clinically.

Outcome of temporal lobectomy for hippocampal sclerosis in older patients

Patients of 50 years or older account for a small but significant portion of the patient population that receives surgical treatment for epilepsy. There have been few studies reporting surgical outcomes from temporal lobectomy in older patients. We examined seizure outcome and surgical complications after anterior temporal lobectomy for temporal lobe epilepsy with pathological evidence of unilateral hippocampal sclerosis. Two patient groups were compared in this study: patients 50 years or older (mean age 55.5 years old, n=16) and patients less than 50 years old (mean age 32.9 years old, n=184). After a minimum of one year follow up, younger patients (79.4%, n=146) were significantly more likely to be seizure-free (p=0.041) compared to older patients (56.3%, n=9). There was no significant difference (p=0.404) between the two age groups in the percentage of patients withdrawn from medication following surgery. Surgical complications were significantly higher in the older age group compared to the younger age group (p=0.009), although there was no permanent morbidity. Thus, while surgical treatment of temporal lobe epilepsy with unilateral hippocampal sclerosis is still beneficial in older patients who are refractory to medical therapy, surgical treatment should be considered at as early an age as possible, to maximize the chance for a better outcome with fewer complications.