Sivakumar, M R (2012) Genetic Susceptibility to Carbamazepine-Induced Cutaneous Adverse Drug Reactions. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.
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Abstract
Adverse drug reactions (ADRs) are a major clinical problem. According to a widely cited meta-analysis, ADRs was ranked between the fourth and sixth most common cause of death (Lazarou1 et al., 1998), and cause 6-7% of hospitalization (JAMA, 2006). Potentially serious cutaneous ADRs account for about 2-3% of all hospital admissions [Bigby, et al., 1986]. Although drug eruptions may be mild to moderate, such as maculopapular rash, erythema multiforme (EM), urticaria, and fixed drug eruption, more severe cutaneous ADRs such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN; Lyell's syndrome) are lifethreatening and frequently result in death. There is a high prevalence HLA-B*1502 allele in South Indian epileptic population on Carbamazepine (18.20%) when compared to the non-epileptic population (7%). This is being reported for the first time in the world literature and further studies have to be done in other centers in India and in other countries in different races to look for this difference. The mechanisms underlying this difference have to be elucidated. In our study, the presence of the HLA-B*1502 allele was strongly correlated to the development of SJS/TEN. The Positive Predictive Value for development of SJS/TEN on exposure to CBZ was 81.82 % with a very high Negative Predictive Value of 99.30%. The Sensitivity of HLA-B*1502 Test was 96.43% with a Specificity of 95.95%. There is a strong association (100%) of HLA–B*1502 allele and the development of SJS in South Asians. This observation is similar to that reported in Chinese, Malay and Thai populations in South East Asia. In conclusion, HLA-B*1502 has recently been linked to CBZ-induced SJS/TEN in some Asian groups. Screening of HLA-B*1502 in these ethnic groups before use of CBZ is recommended. Determination of prevalence of HLA-B*1502 allele and its association with CBZ-induced SJS/TEN in the different ethnic groups is thus of high priority for epilepsy care in India and South East Asia.
| Item Type: | Thesis (Doctoral) |
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| Uncontrolled Keywords: | Genetic Susceptibility, Carbamazepine, Induced, Cutaneous Adverse Drug Reactions. |
| Subjects: | Respiratory Medicine > General Medicine > Respiratory Medicine > General Medicine |
| Depositing User: | Subramani R |
| Date Deposited: | 18 Jun 2017 14:04 |
| Last Modified: | 24 Oct 2022 14:01 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/104 |
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