Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse reactions, which could be induced by a variety of drugs. It was proposed that human leukocyte antigen (HLA)-restricted presentation of antigens (drugs or their metabolites) to T lymphocytes initiates the immune reactions of SJS-TEN. The genetic susceptibility and the exact immunological pathogenesis were not clear until the recent studies. It was first identified that HLA-B*1502 is strongly associated with carbamazepine (CBZ)-induced SJS-TEN and HLA-B*5801 with allopurinol-SJS- TEN in Han Chinese. The same associations had been validated across different human populations. For the downstream danger signals, Fas-Fas ligand (FasL) and perforin -granzyme B had been advocated as cytotoxic mediators for keratinocyte death in SJS-TEN. However, expression levels of these cytotoxic proteins from the skin lesions were too low to explain the distinct and extensive epidermal necrosis. In recent study it was identified that the granulysin, a cytotoxic protein released from cytotoxic T cells or natural killer (NK) cells, is a key mediator for disseminated keratinocyte death in SJS-TEN. The article aims to provide an outlay of both of the genomic and immunologic perspectives of SJS-TEN. These studies give us a better understanding of the immune mechanisms, biomarkers for disease prevention and early diagnosis, as well as providing the therapeutic targets for the treatments of SJS-TEN.
Highlights
Adverse drug reactions (ADRs) account for 6–7% of all hospital admissions and remain a major clinical problem
CBZ is among the commonest antiepileptic drug (AED) that causes cutaneous adverse reactions[3] which includes the life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
The histopathology findings show that the significant feature of large portion epidermis separation from dermis is induced by massive keratinocyte apoptosis in SJS and TEN. 14 FasFasL interaction was previously considered to be the main effector in triggering apoptosis of keratinocytes, evidence suggests that the granulysin[1] is the one “turns on” apoptosis of keratinocyte.[15]
Summary
Adverse drug reactions (ADRs) account for 6–7% of all hospital admissions and remain a major clinical problem. Reports across Asia has shown that the prevalence of HLA B*1502 is high among Han Chinese (5-15%), Malays (12-15%), and Thais (8-27%), but low among Japan, Korea, Sri Lanka, and most ethnic groups in India These drugs include lamotrigine (LTG), carbamazepine (CBZ), phenytoin, phenobarbital, and oxcarbazepine are known anti-epileptic drugs to cause cutaneous drug reactions. CBZ is among the commonest AED that causes cutaneous adverse reactions (cADRs)[3] which includes the life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Both are characterized by a rapidly developing blistering exanthema of purpuric macules and target-like lesions accompanied by mucosal involvement and skin detachment to a varying extent[4]
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