Agreement Among Different Scales for Causality Assessment in Drug-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

BACKGROUND AND OBJECTIVE: Identification of the offending drug is crucial and challenging in cases of severe cutaneous adverse drug reactions (CADR) like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Poor reproducibility and varying levels of agreement have been observed among different causality assessment tools (CATs) in assessing severe CADRs. This study was conducted to examine the agreement among four different CATs in assessing cases of drug-induced SJS, TEN and SJS/TEN overlap. METHODS: All cases of drug-induced SJS, TEN and SJS/TEN overlap, which were reported between January 2012 and January 2020, were identified from the ADR register at an ADR monitoring centre. Causality assessment was done in these reported cases using the following CATs: The World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale, Naranjo algorithm, Liverpool algorithm and Algorithm of drug causality for epidermal necrolysis (ALDEN). Weighted kappa (κw) test was used to evaluate the agreement among four CATs. RESULTS: A total of 30 cases of drug-induced SJS, TEN and SJS/TEN overlap were included in our analyses. The most common offending groups of drugs were anticonvulsants (46.7%), antimicrobials (40%) and nonsteroidal anti-inflammatory drugs (13.3%). Of the anticonvulsants, phenytoin (13.3%), carbamazepine (10%), and valproate (10%) were the commonly reported offending drugs. Poor agreement was observed among the four different causality assessment scales. CONCLUSION: Discrepancies were observed among four different CATs in assessing drug-induced SJS and TEN. A CAT, which is more specific to drug-induced SJS and TEN, simple, user-friendly with limited subjective interpretation, incorporating new immunological and pharmacogenetic markers, is necessary.

Hepatitis B Vaccine and Immunoglobulin: Key Concepts.

Hepatitis B virus (HBV) immunization is safe and has been accepted worldwide as a routine practice. The target of such vaccination is to induce the immune response in the host, resulting in the prevention of replication of HBV. There are several immunological and clinical factors which determine the clinical efficacy and safety of the HBV vaccine. In this article we have highlighted the response of the host immune system to HBV vaccination (immunogenicity), efficacy, and safety of the vaccine, issues with booster dosing, paths of development (preclinical and clinical) of the HBV vaccine, novel and upcoming strategies for improvement of HBV vaccination, and the concept of therapeutic HBV vaccination. The different aspects and regulatory recommendations pertaining to HBV vaccine development are also discussed. The new strategies for improvement of HBV vaccination include pre-S1 and pre-S2 portions of the HBV surface antigen, increasing the antigen dose, accelerated vaccination schedules, alternative vaccination route, use of adjuvants like immunostimulatory DNA sequences, etc. Therapeutic vaccination is being explored for initiation of a multifunctional and multispecific T cell response against the major HBV antigens and also effective activation of humoral immunity for viral control.

Influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphism on dose-adjusted plasma levels of carbamazepine in epileptic patients in South Indian population.

AIM: The aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 (CYP3A5)* 3 genotypes. SUBJECTS AND METHODS: The study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma CBZ levels were measured using reverse-phase high-performance liquid chromatography method, and genotyping of CYP3A5 was done using real-time polymerase chain reaction method. RESULTS: Patients inheriting CYP3A5*3/*3 variant (nonexpressers) had an increased plasma concentration of CBZ (4.86 µg/ml) when compared to patients inheriting either CYP3A5*1/*1 or CYP3A5*1/*3 (expressers) (4.3 µg/ml, P = 0.004). Nonexpressers had significantly increased plasma concentrations of CBZ when adjusted for dose and weight when compared to expressers (P < 0.002 and P < 0.001, respectively). The frequency of adverse reactions in expressers and nonexpressers was 12% and 9%, respectively. CONCLUSION: There is a significant influence of CYP3A5*3 genetic polymorphism (6986A>G) on dose-adjusted plasma levels of CBZ in epileptic patients in the South Indian population.