24 Oct Drug Hypersensitivity to Dapsone HLA Association

MedicalResearch.com Interview with:
Dr. Jian-Jun Liu
Shangdong Provincial Institute of Dermatology and Venereology

MedicalResearch.com: What are the main findings of the study?

Answer:
·      HLA-B*13:01 is associated with the development of dapsone hypersensitivity syndrome.
·      Carrying one copy of HLA-B*13:01 increases one’s risk by 34 times of getting DHS, while carrying two copies increases risk by 100 times as compared to not carrying this allele.
·      HLA-B*13:01 has a sensitivity and specificity of above 85% in predicting the risk of DHS, theoretically reducing the risk of DHS by 7 fold when implemented in clinical screening.

MedicalResearch.com: Were any of the findings unexpected?

Answer:

·      Many drug-adverse hypersensitivity reactions are immunologically mediated, whose risks have been reported to be associated with HLA molecules. Hence, the association between HLA-B*13:01 and dapsone hypersensitivity syndrome is not completely unexpected.
·      However, we found that certain patients with DHS (about 14%) do not carry the HLA-B*13:01, which is unexpected and suggests that other genetic variants might also play an important role in DHS development.  Further study will be needed to identify these additional genetic risk variants for DHS.

MedicalResearch.com: What should clinicians and patients take away from your report?
Answer:

·      Our findings have provided evidence that the risk for the adverse-effect of dapsone is largely influenced by HLA-B*13:01 and can be prevented in the future by testing the carrier status of HLA-B*13:01.
·      By implementing clinical test for HLA-B*13:01, the effectiveness of dapsone in treating infection and inflammation can be used to its maximum potential and at the same time with better assurance of patient’s safety.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Answer:

·      Development and clinical validation of a diagnostic kit for HLA-B*13:01 can be the next step of reducing the burden of dapsone hypersensitivity reactions.
·      Further studies will be needed for identifying additional genetic risk variants for dapsone hypersensitivity syndrome.

Citation:

HLA-B*13:01 and the Dapsone Hypersensitivity Syndrome

F.-R. Zhang, H. Liu, A. Irwanto, X.-A. Fu, Y. Li, G.-Q. Yu, Y.-X. Yu, M.-F. Chen, H.-Q. Low, J.-H. Li, F.-F. Bao, J.-N. Foo, J.-X. Bei, X.-M. Jia, J. Liu, H. Liany, N. Wang, G.-Y. Niu, Z.-Z. Wang, B.-Q. Shi, H.-Q. Tian, H.-X. Liu, S.-S. Ma, Y. Zhou, J.-B. You, Q. Yang, C. Wang, T.-S. Chu, D.-C. Liu, X.-L. Yu, Y.-H. Sun, Y. Ning, Z.-H. Wei, S.-L. Chen, X.-C. Chen, Z.-X. Zhang, Y.-X. Liu, S.L. Pulit, W.-B. Wu, Z.-Y. Zheng, R.-D. Yang, H. Long, Z.-S. Liu, J.-Q. Wang, M. Li, L.-H. Zhang, H. Wang, L.-M. Wang, P. Xiao, J.-L. Li, Z.-M. Huang, J.-X. Huang, Z. Li, J. Liu, L. Xiong, J. Yang, X.-D. Wang, D.-B. Yu, X.-M. Lu, G.-Z. Zhou, L.-B. Yan, J.-P. Shen, G.-C. Zhang, Y.-X. Zeng, P.I.W. de Bakker, S.-M. Chen, and J.-J. Liu

N Engl J Med 2013; 369:1620-1628
October 24, 2013DOI: 10.1056/NEJMoa1213096

Last Updated on October 24, 2013 by Marie Benz MD FAAD