The "Practice Pointer" about Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis(TEN) gave a good overview of the presentation, clinical features, aetiology, and management of this rare but life-threatening type of T cell-mediated drug reaction (1). However one important omission, in my opinion, was information about HLA associations associated with these types of severe cutaneous adverse reactions.
HLA polymorphism has a strong association in drug-induced SJS/ TEN. An example of this is the association between HLA-B*1502 and the development of SJS on exposure to carbamazepine. This HLA subtype is highly prevalent in the populations of China, Vietnam, Thailand, Malaysia, and Indonesia and is thought to be the reason why carbamazepine-induced SJS has an incidence of 0.25% in these populations compared to 0.005% in non-European Caucasians. (2)
Allopurinol is another drug implicated in many cases of SJS, and this is particularly seen in the Han Chinese population, again mediated through HLA association (HLA-B*5801). (2)
The associations are so strong in these particular ethnic groups that some guidelines have recommended either avoiding these drugs completely if at all possible in these populations or considering HLA subtyping prior to commencing the drug. (4)
I think a note for the clinician to consider patient ethnicity would have been an important point to include in box 3, "Red flags to consider", in the article.
(1) Creamer D, Lumb, T, Tibbles CD & Lee HY. Practice Ponter. Stevens-Johnson syndrome/toxic epidermal necrolysis: initial assessment. BMJ 2024;386:e079986 http://dx.doi.org/10.1136/bmj-2024-079986
(2) Lisanne M. et al. Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines. Frontiers in Pharmacology Volume 11 - 2020 | https://doi.org/10.3389/fphar.2020.567048).
(3) Dean L, Kane M. Allopurinol Therapy and HLA-B*58:01 Genotype. 2013 Mar 26 [Updated 2020 Dec 9]. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK127547/
(4) Kloypan, C.; Koomdee, N.; Satapornpong, P.; Tempark, T.; Biswas, M.; Sukasem, C. A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine. Pharmaceuticals 2021, 14, 1077. https://doi.org/10.3390/ph14111077
Rapid Response:
Re: Stevens-Johnson syndrome/toxic epidermal necrolysis: initial assessment
Dear Editor
The "Practice Pointer" about Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis(TEN) gave a good overview of the presentation, clinical features, aetiology, and management of this rare but life-threatening type of T cell-mediated drug reaction (1). However one important omission, in my opinion, was information about HLA associations associated with these types of severe cutaneous adverse reactions.
HLA polymorphism has a strong association in drug-induced SJS/ TEN. An example of this is the association between HLA-B*1502 and the development of SJS on exposure to carbamazepine. This HLA subtype is highly prevalent in the populations of China, Vietnam, Thailand, Malaysia, and Indonesia and is thought to be the reason why carbamazepine-induced SJS has an incidence of 0.25% in these populations compared to 0.005% in non-European Caucasians. (2)
Allopurinol is another drug implicated in many cases of SJS, and this is particularly seen in the Han Chinese population, again mediated through HLA association (HLA-B*5801). (2)
The associations are so strong in these particular ethnic groups that some guidelines have recommended either avoiding these drugs completely if at all possible in these populations or considering HLA subtyping prior to commencing the drug. (4)
I think a note for the clinician to consider patient ethnicity would have been an important point to include in box 3, "Red flags to consider", in the article.
(1) Creamer D, Lumb, T, Tibbles CD & Lee HY. Practice Ponter. Stevens-Johnson syndrome/toxic epidermal necrolysis: initial assessment. BMJ 2024;386:e079986 http://dx.doi.org/10.1136/bmj-2024-079986
(2) Lisanne M. et al. Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines. Frontiers in Pharmacology Volume 11 - 2020 | https://doi.org/10.3389/fphar.2020.567048).
(3) Dean L, Kane M. Allopurinol Therapy and HLA-B*58:01 Genotype. 2013 Mar 26 [Updated 2020 Dec 9]. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK127547/
(4) Kloypan, C.; Koomdee, N.; Satapornpong, P.; Tempark, T.; Biswas, M.; Sukasem, C. A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine. Pharmaceuticals 2021, 14, 1077. https://doi.org/10.3390/ph14111077
Competing interests: No competing interests