Adverse skin reactions to antiepileptic drugs - a review
DOI:
https://doi.org/10.12775/JEHS.2023.21.01.002Keywords
adverse skin reactions, antiepileptic drugs, dress, Stevens-Johnson Syndrome, toxic epidermal necrolysisAbstract
Introduction and objective: Treatment with antiepileptic drugs (AEDs) is frequently used all around the world. Just like in the course of all the drugs administration, side effects may appear, including characteristic side effects presenting on the skin. The aim of the study was to analyse adverse skin reactions to antiepileptic drugs, focusing on their epidemiology, symptoms and treatment.
Methods: Databases including PubMed and Google Scholar were browsed using keywords.
Description of the state of knowledge: The majority of adverse skin reactions (ASRs) constitute mild rashes and urticaria, however in about 10% cases severe reactions may occur, which can be life-threatening. They include Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Serum Sickness and Serum Sickness - like Reactions and Drug Induced Vasculitis. In the course of TEN mortality rates are highest, however all reactions can be dangerous and treatment should be applied immediately. In mild and moderate cases drug withdrawal is usually sufficient, however more severe cases need to be treated with immunosuppressive agents.
Summary: The awareness about possible adverse effects and their treatment is crucial as some can be life-threatening and immediate therapy increases the chance of recovery.
References
Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J, Pringsheim T, Lorenzetti DL, Jetté N. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies. Neurology. 2017 Jan 17;88(3):296-303. doi: 10.1212/WNL.0000000000003509.
Idris A, Alabdaljabar MS, Almiro A, Alsuraimi A, Dawalibi A, Abduljawad S, AlKhateeb M. Prevalence, incidence, and risk factors of epilepsy in arab countries: A systematic review. Seizure. 2021 Nov;92:40-50. doi: 10.1016/j.seizure.2021.07.031.
Guerrini R. Epilepsy in children. Lancet. 2006 Feb 11;367(9509):499-524. doi: 10.1016/S0140-6736(06)68182-8.
Beghi E. The Epidemiology of Epilepsy. Neuroepidemiology. 2020;54(2):185-191. doi: 10.1159/000503831.
Shorvon SD. The etiologic classification of epilepsy. Epilepsia. 2011 Jun;52(6):1052-7. doi: 10.1111/j.1528-1167.2011.03041.x.
Bauer D, Quigg M. Optimizing Management of Medically Responsive Epilepsy. Continuum (Minneap Minn). 2019 Apr;25(2):343-361. doi: 10.1212/CON.0000000000000709.
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.
Sedighi P, Khalili N, Khalili N, Doosti-Irani A, Moradi A, Moghadam S, Nemati M, Mohammadi Jorjafki S, Shervin Badv R, Sedighi I. Patterns of Antiepileptic Drug Reactions in Children: A Multicenter Study. Iran J Child Neurol. 2022 Summer;16(3):133-143. doi: 10.22037/ijcn.v16i3.32872.
Feliciani C, Verrotti A, Coscione G, Toto P, Morelli F, Di Benedetto A, Salladini C, Chiarelli F, Tulli A. Skin reactions due to anti-epileptic drugs: several case-reports with long-term follow-up. Int J Immunopathol Pharmacol. 2003 Jan-Apr;16(1):89-93. doi: 10.1177/039463200301600113.
Lehloenya RJ, Todd G, Wallace J, Ngwanya MR, Muloiwa R, Dheda K. Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons. Br J Dermatol. 2016 Jul;175(1):150-6. doi: 10.1111/bjd.14492.
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):64-68. doi: 10.12793/tcp.2019.27.2.64.
Tonekaboni SH, Jafari N, Mansouri M, Jabbehdari S, Eftekhari R, Chavoshzadeh Z, Abdollah Gorji F, Mesdaghi M. HLA-B*1502 in Iranian Children with Anticonvulsant Drugs-Induced Skin Reactions. Iran J Child Neurol. 2017 Spring;11(2):26-30.
Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia. 2007 Jul;48(7):1223-44. doi: 10.1111/j.1528-1167.2007.01041.x.
Du Y, Lin J, Shen J, Ding S, Ye M, Wang L, Wang Y, Wang X, Xia N, Zheng R, Chen H, Xu H. Adverse drug reactions associated with six commonly used antiepileptic drugs in southern China from 2003 to 2015. BMC Pharmacol Toxicol. 2019 Jan 14;20(1):7. doi: 10.1186/s40360-019-0285-y.
Fowler T, Bansal AS, Lozsádi D. Risks and management of antiepileptic drug induced skin reactions in the adult out-patient setting. Seizure. 2019;72:61-70. doi:10.1016/j.seizure.2019.07.003
Isaacs M, Cardones AR, Rahnama-Moghadam S. DRESS syndrome: clinical myths and pearls. Cutis. 2018 Nov;102(5):322-326.
Peter JG, Lehloenya R, Dlamini S, Risma K, White KD, Konvinse KC, Phillips EJ. Severe Delayed Cutaneous and Systemic Reactions to Drugs: A Global Perspective on the Science and Art of Current Practice. J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):547-563. doi: 10.1016/j.jaip.2017.01.025.
Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Seminars in Cutaneous Medicine and Surgery. 1996 Dec;15(4):250-257. doi: 10.1016/s1085-5629(96)80038-1.
Cardones AR. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Clin Dermatol. 2020 Nov-Dec;38(6):702-711. doi: 10.1016/j.clindermatol.2020.06.008
Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): An update in 2019. Allergol Int. 2019 Jul;68(3):301-308. doi: 10.1016/j.alit.2019.03.006
Pai SB, Sudershan B, Kuruvilla M, Kamath A, Suresh PK. Hydroxychloroquine-induced erythroderma. Indian J Pharmacol. 2017 Jan-Feb;49(1):132-134. doi: 10.4103/0253-7613.201027.
Lehloenya RJ, Peter JG, Copascu A, Trubiano JA, Phillips EJ. Delabeling Delayed Drug Hypersensitivity: How Far Can You Safely Go? J Allergy Clin Immunol Pract. 2020 Oct;8(9):2878-2895.e6. doi: 10.1016/j.jaip.2020.07.005.
Mizukawa Y, Hirahara K, Kano Y, Shiohara T. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms severity score: A useful tool for assessing disease severity and predicting fatal cytomegalovirus disease. J Am Acad Dermatol. 2019;80(3):670-678.e2. doi:10.1016/j.jaad.2018.08.052
Hama N, Abe R, Gibson A, Phillips EJ. Drug-Induced Hypersensitivity Syndrome (DIHS)/Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Clinical Features and Pathogenesis. J Allergy Clin Immunol Pract. 2022 May;10(5):1155-1167.e5. doi: 10.1016/j.jaip.2022.02.004.
Duong TA, Valeyrie-Allanore L, Wolkenstein P, Chosidow O. Severe cutaneous adverse reactions to drugs. Lancet. 2017 Oct 28;390(10106):1996-2011. doi: 10.1016/S0140-6736(16)30378-6.
Charlton OA, Harris V, Phan K, Mewton E, Jackson C, Cooper A. Toxic Epidermal Necrolysis and Steven-Johnson Syndrome: A Comprehensive Review. Adv Wound Care (New Rochelle). 2020 Jul;9(7):426-439. doi: 10.1089/wound.2019.0977.
Chung WH, Hung SI. Genetic markers and danger signals in stevens-johnson syndrome and toxic epidermal necrolysis. Allergol Int. 2010;59(4):325-332. doi:10.2332/allergolint.10-RAI-0261
Ostrov DA, Grant BJ, Pompeu YA, et al. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire. Proc Natl Acad Sci U S A. 2012;109(25):9959-9964. doi:10.1073/pnas.1207934109
Kaniwa N, Saito Y, Aihara M, et al. HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics. 2008;9(11):1617-1622. doi:10.2217/14622416.9.11.1617
Liotti L, Caimmi S, Bottau P, et al. Clinical features, outcomes and treatment in children with drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis. Acta Biomed. 2019;90(3-S):52-60. Published 2019 Jan 29. doi:10.23750/abm.v90i3-S.8165
Maity S, Banerjee I, Sinha R, Jha H, Ghosh P, Mustafi S. Nikolsky's sign: A pathognomic boon. J Family Med Prim Care. 2020;9(2):526-530. Published 2020 Feb 28. doi:10.4103/jfmpc.jfmpc_889_19
Shanbhag SS, Chodosh J, Fathy C, Goverman J, Mitchell C, Saeed HN. Multidisciplinary care in Stevens-Johnson syndrome. Ther Adv Chronic Dis. 2020;11:2040622319894469. Published 2020 Apr 28. doi:10.1177/2040622319894469
Yip LW, Thong BY, Lim J, et al. Ocular manifestations and complications of Stevens-Johnson syndrome and toxic epidermal necrolysis: an Asian series. Allergy. 2007;62(5):527-531. doi:10.1111/j.1398-9995.2006.01295.x
Ueta M. Results of Detailed Investigations Into Stevens-Johnson Syndrome With Severe Ocular Complications. Invest Ophthalmol Vis Sci. 2018;59(14):DES183-DES191. doi:10.1167/iovs.17-23537
Roujeau JC, Bricard G, Nicolas JF. Drug-induced epidermal necrolysis: Important new piece to end the puzzle. J Allergy Clin Immunol. 2011;128(6):1277-1278. doi:10.1016/j.jaci.2011.10.015
Paulmann M., Mockenhaupt M. Severe skin reactions: Clinical picture, epidemiology, etiology, pathogenesis, and treatment. Allergo J. Int. 2019;28:311–326. doi: 10.1007/s40629-019-00111-8.
Radić M, Martinović Kaliterna D, Radić J. Drug-induced vasculitis: a clinical and pathological review. Neth J Med. 2012;70(1):12-17.
Antiga, E., Verdelli, A., Bonciani, D., Bonciolini, V., Quintarelli, L., Volpi, W., et al. Drug-induced cutaneous vasculitides. G Ital Dermatol Venereol, 150(2), 203-210.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Michalina Gruszczyńska, Adam Jarzemski, Agnieszka Kolossa, Rafał Porzych
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 618
Number of citations: 0
