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Ann Indian Acad Neurol. 2019 Oct-Dec;22(4):377-383. doi: 10.4103/aian.AIAN_492_18. Epub 2019 Oct 25.

Diagnostic Utility of Human Leukocyte Antigen B*15:02 Screening in Severe Carbamazepine Hypersensitivity Syndrome.

Author information

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.

Abstract

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.

KEYWORDS:

Carbamazepine; human leukocyte antigen-B*15:02; hypersensitivity; meta-analysis; screening

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