Annals of Indian Academy of Neurology
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Diagnostic utility of human leukocyte antigen B*15:02 screening in severe carbamazepine hypersensitivity syndrome


1 Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy, Rabat Institute University Mohamed V, Rabat, Morocco
2 Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Rabat Institute University Mohamed V, Rabat, Morocco

Correspondence Address:
Youssef Moutaouakkil,
Faculty of Medicine and Pharmacy, Laboratory of Pharmacology-Toxicology, Rabat Institute, Mohamed V University, Rabat
Morocco
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.AIAN_492_18

Background: Despite many studies suggesting an association between human leukocyte antigen (HLA)-B*15:02 and carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions essentially toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS), the evidence of association in different populations and the degree of association remain uncertain. Materials and Methods: The primary analysis was based on population control studies. Data were pooled by means of a random-effects model, and sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−), diagnostic odds ratios (DOR), and areas under the summary receiver operating characteristic curve (AUC) were calculated. Results: In 23 population control studies, HLA-B*15:02 was measured in 373 patients with CBZ-induced TEN/SJS and 3452 patients without CBZ-induced TEN/SJS. The pooled sensitivity, specificity, LR+, LR−, DOR, and AUC were 0.67 (95% confidence interval [CI] = 0.63–0.72), 0.98 (95% CI = 0.98–0.99), 19.73 (95% CI = 10.54–36.92), 0.34 (95% CI = 0.23–0.49), 71.38 (95% CI = 34.89–146.05), and 0.96 (95% CI = 0.92–0.98), respectively. Subgroup analyses for Han Chinese, Thai, and Malaysian populations yielded similar findings. Specifically, racial/ethnic subgroup analyses revealed similar findings with respect to DOR for Han Chinese (99.28; 95% CI = 22.20–443.88), Thai (61.01; 95% CI = 23.05–161.44), and Malaysian (30; 95% CI = 7.08–126.68) populations, which are similar to the pooled DOR for the relationship between the HLA-B*15:02 allele and CBZ-induced TEN/SJS across all populations (71.38; 95% CI = 34.89–146.05). Conclusions: The present study reveals that CBZ is the leading cause of TEN/SJS in many countries. Screening of HLA-B*15:02 may help patients to prevent the occurrence of CBZ-induced TEN/SJS, especially in populations with a higher (≥5%) risk allele frequency.


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    -  Moutaouakkil Y
    -  Adouani B
    -  Cherrah Y
    -  Lamsaouri J
    -  Bousliman Y
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