COMPARATIVE ANALYSIS OF STEVENS-JOHNSON SYNDROME INCIDENCE AMONG SEIZURE PATIENTS ON DIFFERENT ANTIEPILEPTIC DRUGS

Authors

  • JITENDER SHARMA Department of Neurology, Army College of Medical Sciences, New Delhi, India
  • ANMOL SHARMA Department of General Medicine, Army College of Medical Sciences, New Delhi, India.
  • SINDHU SINGH Department of Neurology, Sawai Man Singh Medical College, Jaipur, Rajasthan, India

DOI:

https://doi.org/10.22159/ajpcr.2024v17i12.53471

Keywords:

Stevens-Johnson syndrome, Antiepileptic drugs, HLA-B*1502 allele, Drug hypersensitivity

Abstract

Objectives: Steven-Johnson syndrome (SJS) is a severe, immune-mediated hypersensitivity reaction which is often triggered by medications, notably antiepileptic drugs (AEDs). AEDs such as phenytoin, carbamazepine, and sodium valproate are reported to be commonly offending drugs, particularly in individuals with genetic factors such as HLA-B*1502. A retrospective analysis of 1000 seizure patients revealed variability in SJS incidence among AEDs, highlighting levetiracetam as relatively safer but not risk-free. Early detection and tailored treatment can improve outcomes and mitigate risks.

Methods: This retrospective study (2019–2024) at a tertiary care center examined the incidence of SJS in epilepsy patients aged ≥18 years treated with phenytoin, carbamazepine, sodium valproate, or levetiracetam for ≥6 months. Using electronic health records, patient demographics, AED patterns, and genetic predispositions (HLA-B*1502 allele) were analyzed. The study identified SJS rates and potential risk factors. For statistical analysis, p<0.05 was taken as significant.

Results: An overall SJS incidence of 3.0%. Phenytoin (4.8%) and carbamazepine (3.6%) had significantly higher SJS rates than sodium valproate (2.4%) and levetiracetam (1.2%) (p<0.01). HLA-B*1502 allele strongly correlated with SJS, especially for phenytoin and carbamazepine. Age and comorbidities were not statistically significant risk factors. Genetic predisposition was the primary determinant of SJS risk, emphasizing personalized treatment strategies.

Conclusion: There was a higher risk of SJS with phenytoin and carbamazepine compared to sodium valproate and levetiracetam, with levetiracetam being the safest option. Genetic screening for HLA-B*1502 in at-risk populations is essential to prevent SJS.

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References

Frantz R, Huang S, Are A, Motaparthi K. Stevens-Johnson syndrome and toxic epidermal necrolysis: Areview of diagnosis and management. Medicina (Kaunas). 2021 Aug 28;57(9):895. doi: 10.3390/ medicina57090895. PMID: 34577817; PMCID: PMC8472007

Zimmerman D, Dang NH. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN): Immunologic reactions. Oncol Crit Care. 2019 Jul 9:267-80. doi: 10.1007/978-3-319-74588-6_195. PMCID: PMC7122590

Ferrell PB Jr., McLeod HL. Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008 Oct;9(10):1543-6. doi: 10.2217/14622416.9.10.1543. PMID: 18855540; PMCID: PMC2586963

Aggarwal R, Sharma M, Modi M, Garg VK, Salaria M. HLA-B∗ 1502 is associated with carbamazepine induced Stevens-Johnson syndrome in North Indian population. Hum Immunol. 2014 Nov;75(11):1120-2. doi: 10.1016/j.humimm.2014.09.022. PMID: 25305458

Lyseng-Williamson KA. Levetiracetam: Areview of its use in epilepsy. Drugs. 2011 Mar 5;71(4):489-514. doi: 10.2165/11204490-000000000- 00000. PMID: 21395360

Perucca E, Tomson T. The pharmacological treatment of epilepsy in adults. Lancet Neurol. 2011 May;10(5):446-56. doi: 10.1016/S1474- 4422(11)70047-3. PMID: 21511198

Shanbhag SS, Koduri MA, Kannabiran C, Donthineni PR, Singh V, Basu S. Genetic markers for Stevens-Johnson syndrome/toxic epidermal necrolysis in the Asian Indian population: Implications on prevention. Front Genet. 2021 Jan 12;11:607532. doi: 10.3389/fgene.2020.607532. PMID: 33510770; PMCID: PMC7837290

Harden C. Safety profile of levetiracetam. Epilepsia. 2001;42 Suppl 4:36-9. PMID: 11564124

French J, Edrich P, Cramer JA. A systematic review of the safety profile of levetiracetam: A new antiepileptic drug. Epilepsy Res. 2001 Nov;47(1-2):77-90. doi: 10.1016/s0920-1211(01)00296-0. PMID: 11673023

Locharernkul C, Loplumlert J, Limotai C, Korkij W, Desudchit T, Tongkobpetch S, et al. Carbamazepine and phenytoin induced Stevens- Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia. 2008 Dec;49(12):2087-91. doi: 10.1111/j.1528- 1167.2008.01719.x. Erratum in: Epilepsia. 2009 Apr;50(4):971. PMID: 18637831

Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9861-6. doi: 10.1073/pnas.0308208101. PMID: 15210974; PMCID: PMC470764

Puri P, Aslam ZM, Komal F, Prachi F, Sardana P, Chitkara A. Phenytoin-associated Stevens-Johnson syndrome and toxic epidermal necrolysis overlap in focus: A case report. Cureus. 2023 Sep 27;15(9):e46075. doi: 10.7759/cureus.46075. PMID: 37900419; PMCID: PMC10604504

Pannu BS, Egan AM, Iyer VN. Phenytoin induced Steven-Johnson syndrome and bronchiolitis obliterans - case report and review of literature. Respir Med Case Rep. 2016 Jan 20;17:54-6. doi: 10.1016/j. rmcr.2016.01.006. PMID: 27222786; PMCID: PMC4821333

Montanez K, Berninger T, Willis M, Harding A, Lutgendorf MA. Genetic testing costs and compliance with clinical best practices. J Genet Couns. 2020 Dec;29(6):1186-1191. doi: 10.1002/jgc4.1285. PMID: 32356909

Sander JW. The use of antiepileptic drugs--principles and practice. Epilepsia. 2004;45 Suppl 6:28-34. doi: 10.1111/j.0013- 9580.2004.455005.x. PMID: 15315513

Ueta M. Genetic predisposition to Stevens-Johnson syndrome with severe ocular surface complications. Cornea. 2015 Nov;34 Suppl 11:S158-65. doi: 10.1097/ICO.0000000000000605. PMID: 26448174

Chung WH, Hung SI. Genetic markers and danger signals in Stevens- Johnson syndrome and toxic epidermal necrolysis. Allergol Int. 2010 Dec;59(4):325-32. doi: 10.2332/allergolint.10-RAI-0261. PMID: 20962567

Borowicz-Reutt K, Czernia J, Krawczyk M. Genetic background of epilepsy and antiepileptic treatments. Int J Mol Sci. 2023 Nov 14;24(22):16280. doi: 10.3390/ijms242216280. PMID: 38003469; PMCID: PMC10671416

Catt CJ, Hamilton GM, Fish J, Mireskandari K, Ali A. Ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis in children. Am J Ophthalmol. 2016 Jun;166:68-75. doi: 10.1016/j.ajo.2016.03.020. Epub 2016 Mar 24. PMID: 27018234

Manolio TA, Hutter CM, Avigan M, Cibotti R, Davis RL, Denny JC, et al. Research directions in genetic predispositions to Stevens- Johnson Syndrome/toxic epidermal necrolysis. Clin Pharmacol Ther. 2018 Mar;103(3):390-394. doi: 10.1002/cpt.890. PMID: 29105735; PMCID: PMC5805563

Published

07-12-2024

How to Cite

JITENDER SHARMA, ANMOL SHARMA, and SINDHU SINGH. “COMPARATIVE ANALYSIS OF STEVENS-JOHNSON SYNDROME INCIDENCE AMONG SEIZURE PATIENTS ON DIFFERENT ANTIEPILEPTIC DRUGS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 17, no. 12, Dec. 2024, pp. 232-5, doi:10.22159/ajpcr.2024v17i12.53471.

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