Pharmacogenomics for Treatment Response in Patients With Stevens-Johnson Syndrome: An Updated Review

  • Henry Budiawan Prasetya Universitas Ahmad Dahlan
  • Lalu Muhammad Irham Universitas Ahmad Dahlan
  • Wirawan Adikusuma Departement of Pharmacy, University of Muhammadiyah Mataram, Mataram, Indonesia
  • Danang Prasetyaning Amukti universitas ahmad dahlan
  • Maulida Mazaya Research Centre for Computing, Research Organisation for Electronics and Informatics, National Research and Innovation Agency (BRIN), Cibinong Science Center, Cibinong, Indonesia
  • Rockie Chong Department of Chemistry and Biochemistry, University of California, Los Angeles, USA
  • Rina Mutiara Department of Pharmacy, RSUPN Dr Cipto Mangunkusumo, Jakarta, Indonesia
  • Darmawi Darmawi Department of Histology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
  • Sabiah Khairi School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan.
  • Made Ary Sarasmita Pharmacy Study Program, Faculty of Science and Mathematics, Udayana University, Bali, Indonesia
  • Barkah Djaka Purwanto Faculty of Medicine, University of Ahmad Dahlan, Yogyakarta, Indonesia
  • Lalu Muhammad Harmain Siswanto Mataram Training Health Center, Indonesia Ministry of Health, Indonesia
  • Faizul Hasan Faculty of Nursing, Chulalongkorn University, Bangkok, Thailand
  • Rahmat Dani Satria Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Daraporn Rungprai Department of Pharmaceutical Care, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand
DOI: https://doi.org/10.5937/scriptamed56-53722
Keywords: Stevens-Johnson syndrome, Toxic epidermal necrolysis, Pharmacogenetics, Computational biology

Abstract


Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are dermatological emergencies characterised by widespread epidermal necrolysis and sloughing. SJS is defined as the shedding of skin on less than 10 % of the body surface area, whereas TEN involves the shedding of skin on more than 30 %. The pathogenesis of SJS is identified by the occurrence of apoptosis of keratinocytes, which is spread throughout the body. The binding of the molecule to the human leukocyte antigen (HLA) peptide is one of the basic triggering mechanisms for SJS due to an autoimmune reaction. This study aims to predict genetic predictive markers for the prevention and pharmacological treatments of SJS/TEN. The PharmGKB website was used to gather information regarding the relationship among drugs, genes and the SJS condition. Results revealed notable gene variants (eg HLA-A, HLA-B, HLA-B, HLA-C, CYP2B6) predisposing individuals to a toxic response, instigating the SJS reaction. Implicated drugs included allopurinol, antiepileptics such as carbamazepine, lamotrigine, oxcarbazepine and phenytoin, as well as methazolamide and nevirapine, identified as potential risk factors. As a result, this study can provide information and facilitate precision medicine, which focuses on individual genetic variations as a means of prevention and treatment, enabling early prognosis and optimising patient care in preventing SJS/TEN.

References

Frantz R, Huang S, Are A, Motaparthi K. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of diagnosis and management. Medicina (Kaunas). 2021 Aug 28;57(9):895. doi: 10.3390/medicina57090895.

Zizi N, Elmrahi A, Dikhaye S, Fihmi N, Alami Z. Stevens Johnson syndrome-toxic epidermal necrolysis overlap induced by sulfasalazine treatment: a case report. Tunis Med. 2015 Jul;93(7):413-5. PMID: 26757493.

Khan FI, Rehman MT, Sameena F, Hussain T, AlAjmi MF, Lai D, et al. Investigating the binding mechanism of topiramate with bovine serum albumin using spectroscopic and computational methods. J Mol Recognit. 2022 Jul;35(7):e2958. doi: 10.1002/jmr.2958.

Trivedi BS, Darji NH, Malhotra SD, Patel PR. Antiepileptic drugs-induced Stevens-Johnson syndrome: A case series. J Basic Clin Pharm. 2016 Dec;8(1):42-4. doi: 10.4103/0976-0105.195130.

Kodliwadmath A. Phenytoin-induced Stevens-Johnson syndrome with myocarditis: a rare case report. Int Med Case Rep J. 2017 Jul 10;10:229-31. doi: 10.2147/IMCRJ.S135643.

van Nispen C, Long B, Koyfman A. High risk and low prevalence diseases: Stevens Johnson syndrome and toxic epidermal necrolysis. Am J Emerg Med. 2024 Jul;81:16-22. doi: 10.1016/j.ajem.2024.04.001.

Neerukonda VK, Stagner AM. Stevens Johnson syndrome: A review of a vision and life-threatening mucocutaneous disease including histopathology with updates on pathogenesis and genetic risk factors. Semin Ophthalmol. 2021 May 19;36(4):270-81. doi: 10.1080/08820538.2021.1893764.

Ali J, Rahman M, Ahmad A, Khattak Z, Shahzad MA. Toxic epidermal necrolysis secondary to metronidazole. Cureus. 2021 Aug 11;13(8):e17101. doi: 10.7759/cureus.17101.

Łoboda J, Dudzik A, Chomyszyn-Gajewska M. [Stevens-Johnson syndrom and toxic epidermal necrolysis--based on literature]. Przegl Lek. 2015;72(1):35-7. Polish. PMID: 26076576.

Yang MS, Lee JY, Kim J, Kim GW, Kim BK, Kim JY, et al. Incidence of Stevens-Johnson Syndrome and toxic epidermal necrolysis: a nationwide population-based study using national health insurance database in Korea. PLoS One. 2016 Nov 11;11(11):e0165933. doi: 10.1371/journal.pone.0165933.

Hung YT, Chen YW, Huang Y, Lin YJ, Chen CB, Chung WH. Acute graft-versus-host disease presenting as Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective cohort study. J Am Acad Dermatol. 2023 Apr;88(4):792-801. doi: 10.1016/j.jaad.2022.10.035.

Houschyar KS, Tapking C, Borrelli MR, Nietzschmann I, Puladi B, Ooms M, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: a 10-year experience in a burns unit. J Wound Care. 2021 Jun 2;30(6):492-6. doi: 10.12968/jowc.2021.30.6.492.

Fahmy D, Kandil H, Khelifi A, Yaghi M, Ghazal M, Sharafeldeen A, et al. How AI can help in the diagnostic dilemma of pulmonary nodules. Cancers (Basel). 2022 Apr 6;14(7):1840. doi: 10.3390/cancers14071840.

St-Pierre J, Ruel I, Genest J. The essential role of primary caregiver in early detection of familial hypercholesterolemia and cardiovascular prevention. Curr Pediatr Rev. 2017;13(4):260-4. doi: 10.2174/1573396314666180221162556.

Sivagourounadin K, Rajendran P, Selvarajan S, Ganesapandian M. Agreement among different scales for causality assessment in drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis. Curr Drug Saf. 2022;17(1):40-6. doi: 10.2174/1574886316666210611160123.

Jawaro T, Kumar A, Pistun O, Dixit D. Stevens-Johnson syndrome associated with chlordiazepoxide. J Pharm Technol. 2018 Apr;34(2):82-5. doi: 10.1177/8755122517753595.

Usui T, Naisbitt DJ. Human leukocyte antigen and idiosyncratic adverse drug reactions. Drug Metab Pharmacokinet. 2017 Feb;32(1):21-30. doi: 10.1016/j.dmpk.2016.11.003.

Noe MH, Micheletti RG. Diagnosis and management of Stevens-Johnson syndrome/toxic epidermal necrolysis. Clin Dermatol. 2020 Nov-Dec;38(6):607-12. doi: 10.1016/j.clindermatol.2020.06.016.

Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY, et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med. 2008 Dec;14(12):1343-50. doi: 10.1038/nm.1884.

Jimbo H, Nagai H, Fujiwara S, Shimoura N, Nishigori C. Fas-FasL interaction in cytotoxic T cell-mediated vitiligo: The role of lesional expression of tumor necrosis factor-α and interferon-γ in Fas-mediated melanocyte apoptosis. Exp Dermatol. 2020 Jan;29(1):61-70. doi: 10.1111/exd.14053.

Kim HJ, Noh JW, Amarsanaa K, Jeon SC, Yang YS, Hwang NH, et al. Peripheral pain modulation of Chrysaora pacifica jellyfish venom requires both Ca2+ influx and TRPA1 channel activation in rats. Neurotox Res. 2020 Dec;38(4):900-13. doi: 10.1007/s12640-020-00282-1.

Gong L, Whirl-Carrillo M, Klein TE. PharmGKB, an integrated resource of pharmacogenomic knowledge. Curr Protoc. 2021 Aug;1(8):e226. doi: 10.1002/cpz1.226.

Okamoto-Uchida Y, Nakamura R, Sai K, Imatoh T, Matsunaga K, Aihara M, et al. Effect of infectious diseases on the pathogenesis of Stevens-Johnson syndrome and toxic epidermal necrolysis. Biol Pharm Bull. 2017;40(9):1576-80. doi: 10.1248/bpb.b17-00207.

Whirl-Carrillo M, Huddart R, Gong L, Sangkuhl K, Thorn CF, Whaley R, et al. An evidence-based framework for evaluating pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2021 Sep;110(3):563-72. doi: 10.1002/cpt.2350.

Ordoñez L, Salgueiro E, Jimeno FJ, Manso G. Spontaneous reporting of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with antiepileptic drugs. Eur Rev Med Pharmacol Sci. 2015;19(14):2732-7. PMID: 26221907.

Tunuguntla MN, Chanti P, Kesani T, Yarapathineni K, Kukkadapu P. Phenytoin-induced toxic epidermal necrolysis. Cureus. 2023 Jul 29;15(7):e42654. doi: 10.7759/cureus.42654.

Ferdiana A, Fachiroh J, Oktarina DAM, Irwanto A, Mahendra C, Febriana SA, Soebono H. Allopurinol-induced Stevens-Johnson Syndrome in Javanese men with positive HLA-B*58:01. Front Genet. 2022 Jun 13;13:839154. doi: 10.3389/fgene.2022.839154.

Kim EY, Kim MY, Park CS, Choi JH, Ghim JL, Kim HS, Shin JG. Antiepileptic drug-induced severe cutaneous adverse reactions and HLA alleles: A report of five cases with lymphocyte activation test. Transl Clin Pharmacol. 2019 Jun;27(2):64-8. doi: 10.12793/tcp.2019.27.2.64.

Kim HK, Kim DY, Bae EK, Kim DW. Adverse skin reactions with antiepileptic drugs using Korea adverse event reporting system database, 2008-2017. J Korean Med Sci. 2020 Feb 3;35(4):e17. doi: 10.3346/jkms.2020.35.e17.

Błaszczyk B, Lasoń W, Czuczwar SJ. Antiepileptic drugs and adverse skin reactions: An update. Pharmacol Rep. 2015 Jun;67(3):426-34. doi: 10.1016/j.pharep.2014.11.009.

Chomean S, Nakkam N, Tassaneeyakul W, Attapong J, Kaset C. Development of label-free electrochemical impedance spectroscopy for the detection of HLA-B*15:02 and HLA-B*15:21 for the prevention of carbamazepine-induced Stevens-Johnson syndrome. Anal Biochem. 2022 Dec 1;658:114931. doi: 10.1016/j.ab.2022.114931.

Zhang N, Su T, Yan J, Zhang M, Zhao S, Liu C, et al. Case report: Successful immunomodulators combined with electromagnetic field therapy in a patient with methazolamide-induced Steven Johnson syndrome/toxic epidermal necrolysis overlap. Front Med (Lausanne). 2023 May 25;10:1192920. doi: 10.3389/fmed.2023.1192920.

Yu KH, Yu CY, Fang YF. Diagnostic utility of HLA-B*5801 screening in severe allopurinol hypersensitivity syndrome: an updated systematic review and meta-analysis. Int J Rheum Dis. 2017 Sep;20(9):1057-71. doi: 10.1111/1756-185X.13143.

Li X, Zhao Z, Sun SS. Association of human leukocyte antigen variants and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A meta-analysis. Am J Health Syst Pharm. 2017 May 1;74(9):e183-e192. doi: 10.2146/ajhp160243.

Published
2025/06/30
Issue
Vol. 56 No. 3 (2025): May-Jun
Section
Current topic
Authors who publish with this journal agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).