Antiepileptic Medication-induced Severe Cutaneous Adverse Reactions in Hospitalized Children: A Retrospective Study
-
Bahareh Abtahi-Naeini
,
Reza Makhmali
,
Niloufar Amini
,
Mohammad Reza Maracy
,
Nikta Nouri
,
Tooba Momen
Abstract
Background: There are limited data on severe cutaneous adverse reactions (SCARs) associated with antiepileptic medications. The current study aims to investigate the clinical and epidemiological characteristics of antiepileptic medication-induced SCARs in hospitalized children.
Materials and Methods: The current five-year retrospective study was conducted at Isfahan University of Medical Sciences, Iran. This study included all children with a definite diagnosis of SCARs secondary to the use of antiepileptic medications based on the world health organization (WHO) definition. In our study SCARs were categorized into three fields: Hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).
Results: Among 259 children with SCARs induced by antiepileptic medications, 199 (76.83%), 42 (16.22%), and 18 (6.95%) had hypersensitivity syndrome, DRESS, and SJS/TEN, respectively. Phenobarbital was the most common offending drug in all types of SCARs. The multinomial logistic regression model revealed that lymphadenopathy increased the occurrence of DRESS by 35 times compared to hypersensitivity syndrome (P < 0.001). Girls were at risk of SJS/TEN approximately 6 times more than boys (P = 0.027). Age (P = 0.021), weight (P = 0.036), and mucosal involvement (P < 0.001) affected the hospitalization duration in children with SCARs related to antiepileptic medication.
Conclusion: There are some similarities and differences in the clinical and epidemiological features of Iranian children suffering from antiepileptic medication-induced SCARs.
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3. Chia FL, Leong KP. Severe cutaneous adverse reactions to drugs. Curr Opin Allergy Clin Immunol. 2007;7(4):304–9.
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10. Ye YM, Thong BYH, Park HS. Hypersensitivity to antiepileptic drugs. Immunol Allergy Clin North Am. 2014;34(3):633–43.
11. Chadwick D. Safety and efficacy of vigabatrin and carbamazepine in ne wly diagnosed epilepsy: a multicentre randomised double-blind study. Lancet. 1999;354:13–9.
12. Guerrini R. Epilepsy in children. Lancet. 2006;367:499–524.
13. Rafati MR, Ahmadi A. Report of thirty one admissions due to adverse drug reactions in Bo-Ali Sina hospital, Sari, Iran. J. Maz. Univ. Med. Sci. 2009; 19(72): 67–70.
14. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(5):239-45.
15. Shiohara T, Iijima M, Ikezawa Z, Hashimoto K. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol. 2007;156(5):1083–4.
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17. Oh HL, Kang DY, Kang HR, Kim S, Koh YI, Kim SH, et al. Severe cutaneous adverse reactions in Korean pediatric patients: a study from the Korea SCAR Registry. Allergy Asthma Immunol Res. 2019;11(6):241–53.
18. Arif H, Buchsbaum R, Weintraub D, Koyfman S, Salas-Humara C, Bazil CW, et al. Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology. 2007;68(20):1701–9.
19. Błaszczyk B, Szpringer M, Czuczwar SJ, Lasoń W. Single centre 20 year survey of antiepileptic drug-induced hypersensitivity reactions. Pharmacol Rep. 2013;65(2):399–409.
20. Primisawitri PP, Mawardi P. The Correlation of Neutrophil–Lymphocyte Ratio and Eosinophil Count with SCORTEN in SJS/TEN. Clin. Cosmet. Investig. Dermatology. 2022;15:547–56.
21. Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T. Current perspectives on Stevens-Johnson syndrome and toxic epidermal necrolysis. Clin Rev Allergy Immunol. 2018;54(1):147–76.
22. Koh MJA, Tay YK. Stevens-Johnson syndrome and toxic epidermal necrolysis in Asian children J Am Acad Dermatol. 2010;62(1):54–60.
23. Forman R, Koren G, Shear NH. Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a review of 10 years’ experience. Drug Saf. 2002 25(13):965–72.
24. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol. 2005;94(4):419–36.
25. Bedouelle E, Said BB, Tetart F, Milpied B, Welfringer-Morin A, Maruani A, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): series of 49 French pediatric cases. J Allergy Clin Immunol Pract. 2022;10(1):267–74.
26. Chen HC, Wang RC, Tsai HP, Medeiros LJ, Chang KC. Morphologic Spectrum of Lymphadenopathy in Drug Reaction With Eosinophilia and Systemic Symptoms SyndromeA Case Series With Literature Review. Arch Pathol Lab Med. 2022; 146(9):1084–93.
27. Misirlioglu ED, Guvenir H, Bahceci S, Abul MH, Can D, Guc BEU, et al. Severe cutaneous adverse drug reactions in pediatric patients: a multicenter study. J Allergy Clin Immunol Pract. 2017;5(2):757–63.
28. Metterle L, Hatch L, Seminario-Vidal L. Pediatric drug reaction with eosinophilia and systemic symptoms: A systematic review of the literature. Pediatr Dermatol. 2020;37(3):124–9.
29. Gilbert M, Scherrer LA. Efficacy and safety of cyclosporine in Stevens–Johnson syndrome and toxic epidermal necrolysis. Dermatol Ther. 2019;32:e12758.
30. Morita C, Yanase T, Shiohara T, Aoyama Y. Aggressive treatment in paediatric or young patients with drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with future development of type III polyglandular autoimmune syndrome. BMJ Case Rep. 2018;bcr-2018-225528.
31. Tsironi S, Koulierakis G. Factors associated with parents’ levels of stress in pediatric wards. J Child Health Care. 2018;22(4):175–85.
32. Bequignon E, Duong TA, Sbidian E, Valeyrie-Allanore L, Ingen-Housz-Oro S, Chatelin V, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: ear, nose, and throat description at acute stage and after remission. JAMA Dermatol. 2015;151(14):302–7.
2. Roujeau JC, Haddad C, Paulmann M, Mockenhaupt M. Management of nonimmediate hypersensitivity reactions to drugs. Immunol Allergy Clin North Am. 2014;34(3):473–87.
3. Chia FL, Leong KP. Severe cutaneous adverse reactions to drugs. Curr Opin Allergy Clin Immunol. 2007;7(4):304–9.
4. Bellón T. Mechanisms of severe cutaneous adverse reactions: recent advances. Drug Saf. 2019;42(8):973–92.
5. Copaescu AM, Trublano JA. The assessment of severe cutaneous adverse drug reactions. Aust Prescr. 2022;45(2):43-8.
6. Tempark T, John S, Rerknimitr P, Satapornpong P, Sukasem C. Drug-Induced Severe Cutaneous Adverse Reactions: Insights Into Clinical Presentation, Immunopathogenesis, Diagnostic Methods, Treatment, and Pharmacogenomics. Front. Pharmacol. 2022;13.
7. Cho YT, Chu CY. Treatments for severe cutaneous adverse reactions. J. Immunol. Res. 2017;2017:1-9.
8. Horcajada-Reales C, Pulido-Pérez A, Suárez-Fernández R. Severe cutaneous drug reactions: do overlapping forms exist? Actas Dermosifiliogr. 2016;107(1):23-33.
9. Gouveia MP, Gameiro A, Coutinho I, Pereira N, Gonçalo M. Overlap between maculopapular exanthema and DRESS among cutaneous adverse drug reactions in a dermatology ward (2008-2012). Clin Transl Allergy. 2014;4(3).
10. Ye YM, Thong BYH, Park HS. Hypersensitivity to antiepileptic drugs. Immunol Allergy Clin North Am. 2014;34(3):633–43.
11. Chadwick D. Safety and efficacy of vigabatrin and carbamazepine in ne wly diagnosed epilepsy: a multicentre randomised double-blind study. Lancet. 1999;354:13–9.
12. Guerrini R. Epilepsy in children. Lancet. 2006;367:499–524.
13. Rafati MR, Ahmadi A. Report of thirty one admissions due to adverse drug reactions in Bo-Ali Sina hospital, Sari, Iran. J. Maz. Univ. Med. Sci. 2009; 19(72): 67–70.
14. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(5):239-45.
15. Shiohara T, Iijima M, Ikezawa Z, Hashimoto K. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol. 2007;156(5):1083–4.
16. Abtahi-Naeini B, Dehghan Ms, Paknazar F, Shahmoradi Z, Faghihi G, Sabzghabaee AM, et al. Clinical and epidemiological features of patients with drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Iran: different points of children from adults. Int J Pediatr. 2022;2022:1-10.
17. Oh HL, Kang DY, Kang HR, Kim S, Koh YI, Kim SH, et al. Severe cutaneous adverse reactions in Korean pediatric patients: a study from the Korea SCAR Registry. Allergy Asthma Immunol Res. 2019;11(6):241–53.
18. Arif H, Buchsbaum R, Weintraub D, Koyfman S, Salas-Humara C, Bazil CW, et al. Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology. 2007;68(20):1701–9.
19. Błaszczyk B, Szpringer M, Czuczwar SJ, Lasoń W. Single centre 20 year survey of antiepileptic drug-induced hypersensitivity reactions. Pharmacol Rep. 2013;65(2):399–409.
20. Primisawitri PP, Mawardi P. The Correlation of Neutrophil–Lymphocyte Ratio and Eosinophil Count with SCORTEN in SJS/TEN. Clin. Cosmet. Investig. Dermatology. 2022;15:547–56.
21. Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T. Current perspectives on Stevens-Johnson syndrome and toxic epidermal necrolysis. Clin Rev Allergy Immunol. 2018;54(1):147–76.
22. Koh MJA, Tay YK. Stevens-Johnson syndrome and toxic epidermal necrolysis in Asian children J Am Acad Dermatol. 2010;62(1):54–60.
23. Forman R, Koren G, Shear NH. Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a review of 10 years’ experience. Drug Saf. 2002 25(13):965–72.
24. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol. 2005;94(4):419–36.
25. Bedouelle E, Said BB, Tetart F, Milpied B, Welfringer-Morin A, Maruani A, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): series of 49 French pediatric cases. J Allergy Clin Immunol Pract. 2022;10(1):267–74.
26. Chen HC, Wang RC, Tsai HP, Medeiros LJ, Chang KC. Morphologic Spectrum of Lymphadenopathy in Drug Reaction With Eosinophilia and Systemic Symptoms SyndromeA Case Series With Literature Review. Arch Pathol Lab Med. 2022; 146(9):1084–93.
27. Misirlioglu ED, Guvenir H, Bahceci S, Abul MH, Can D, Guc BEU, et al. Severe cutaneous adverse drug reactions in pediatric patients: a multicenter study. J Allergy Clin Immunol Pract. 2017;5(2):757–63.
28. Metterle L, Hatch L, Seminario-Vidal L. Pediatric drug reaction with eosinophilia and systemic symptoms: A systematic review of the literature. Pediatr Dermatol. 2020;37(3):124–9.
29. Gilbert M, Scherrer LA. Efficacy and safety of cyclosporine in Stevens–Johnson syndrome and toxic epidermal necrolysis. Dermatol Ther. 2019;32:e12758.
30. Morita C, Yanase T, Shiohara T, Aoyama Y. Aggressive treatment in paediatric or young patients with drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with future development of type III polyglandular autoimmune syndrome. BMJ Case Rep. 2018;bcr-2018-225528.
31. Tsironi S, Koulierakis G. Factors associated with parents’ levels of stress in pediatric wards. J Child Health Care. 2018;22(4):175–85.
32. Bequignon E, Duong TA, Sbidian E, Valeyrie-Allanore L, Ingen-Housz-Oro S, Chatelin V, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: ear, nose, and throat description at acute stage and after remission. JAMA Dermatol. 2015;151(14):302–7.
| Files | ||
| Issue | Vol 23 No 2 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v23i2.15320 | |
| Keywords | ||
| Adverse drug reactions Allergy and immunology Antiepileptic drug Drug reaction with eosinophilia and systemic symptoms | ||
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How to Cite
1.
Abtahi-Naeini B, Makhmali R, Amini N, Reza Maracy M, Nouri N, Momen T. Antiepileptic Medication-induced Severe Cutaneous Adverse Reactions in Hospitalized Children: A Retrospective Study. Iran J Allergy Asthma Immunol. 2024;23(2):139-148.
