xi
SUMMARY
Cutaneous adverse drug reactions (CADR) are very common to drugs these days. They
may appear after single dose or sometime after prolong administration. The severe
cutaneous adverse drug reactions are difficult to manage and need hospitalization. The
human leucocyte antigen (HLA) system is responsible for producing such allergic reactions
in response to foreign agents including drugs or drug metabolites. Carbamazepine is the
most prescribed drug in epileptic patients. . Though, carbamazepine and its metabolites
often immunogenic in nature and sensitize the immune system to evoke mild to severe
cutaneous adverse reactions. HLA-B*1502 allele is responsible in carbamazepine induced
cutaneous adverse drug reactions. HLA-B*1502 allele is combination of nine substitutions.
All these substitutions are present in exon 2 and 3 of HLA-B gene. According to previous
studies a strong association has been noted between HLA-B*1502 allele and
carbamazepine induced cutaneous adverse drug reactions. This allele is highly prevalent in
Southeast Asian countries. The prevalence of HLA-B*1502 allele is 100% in patients of
carbamazepine induced severe cutaneous adverse drug reaction, 3% in tolerant patients and
5 to 15% in normal subjects. Out of six phenotypically positive patients this allele was
observed in two patients. These two patients were known cases of Stevens- Johnson
syndrome. This allele was found in three normal subjects and one tolerant patient. The
present study investigated the same frequency of HLA-B*1502 allele in Pakistani
papulation. However, the frequency of this allele in other patient groups was variable. It
could be assumed that HLA-B*1502 allele is not associated with mild hypersensitive
reactions. It is consistent with the earlier studies that show this allele to be rare in
Caucasians but high in Asians. HLA-B gene is highly variable and many other mutations
have also been reported and observed in our patients. These mutations might be associated
in the generation of hypersensitive reactions specific to carbamazepine but this need to be
elucidated. To elucidate it further large scale potential studies are necessary.

SUMMARY

  • 1.
    xi SUMMARY Cutaneous adverse drugreactions (CADR) are very common to drugs these days. They may appear after single dose or sometime after prolong administration. The severe cutaneous adverse drug reactions are difficult to manage and need hospitalization. The human leucocyte antigen (HLA) system is responsible for producing such allergic reactions in response to foreign agents including drugs or drug metabolites. Carbamazepine is the most prescribed drug in epileptic patients. . Though, carbamazepine and its metabolites often immunogenic in nature and sensitize the immune system to evoke mild to severe cutaneous adverse reactions. HLA-B*1502 allele is responsible in carbamazepine induced cutaneous adverse drug reactions. HLA-B*1502 allele is combination of nine substitutions. All these substitutions are present in exon 2 and 3 of HLA-B gene. According to previous studies a strong association has been noted between HLA-B*1502 allele and carbamazepine induced cutaneous adverse drug reactions. This allele is highly prevalent in Southeast Asian countries. The prevalence of HLA-B*1502 allele is 100% in patients of carbamazepine induced severe cutaneous adverse drug reaction, 3% in tolerant patients and 5 to 15% in normal subjects. Out of six phenotypically positive patients this allele was observed in two patients. These two patients were known cases of Stevens- Johnson syndrome. This allele was found in three normal subjects and one tolerant patient. The present study investigated the same frequency of HLA-B*1502 allele in Pakistani papulation. However, the frequency of this allele in other patient groups was variable. It could be assumed that HLA-B*1502 allele is not associated with mild hypersensitive reactions. It is consistent with the earlier studies that show this allele to be rare in Caucasians but high in Asians. HLA-B gene is highly variable and many other mutations have also been reported and observed in our patients. These mutations might be associated in the generation of hypersensitive reactions specific to carbamazepine but this need to be elucidated. To elucidate it further large scale potential studies are necessary.