{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T05:25:18Z","timestamp":1762925118957,"version":"3.45.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Zonisamide (ZNS), a sulfonamide-derived anticonvulsant, is increasingly used for epilepsy but remains an underrecognized cause of severe cutaneous adverse reactions (SCARs). This study reports the first documented case in China of ZNS-induced drug rash with eosinophilia and systemic symptoms (DRESS), which initially presented as painful papules and herpetiform lesions on the lumbar, abdominal, and facial regions. The patient also exhibited a potential risk of progression to Stevens-Johnson syndrome (SJS) in the context of acute liver failure. Notably, the patient\u2019s latency period was 57\u202fdays, representing the second-longest interval reported in the literature. Furthermore, we provide a comprehensive review of ZNS-induced hypersensitivity reactions, including the clinical presentation, complications, management, and prognosis. Our systematic review of 30 ZNS-SCARs cases revealed key characteristics including a Japanese predominance (80%), a median latency of 23\u202fdays, and frequent hepatic involvement (26.7%), with human herpesvirus 6 reactivation confirmed in 66.7% of tested cases. Overall, 75% of patients improved following glucocorticoid-based therapies. This study aims to enhance awareness of SCARs associated with ZNS\u2014including DRESS, SJS, and toxic epidermal necrolysis (TEN)\u2014to support early recognition and timely clinical interventions.<\/jats:p>","DOI":"10.3389\/fmed.2025.1708376","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T05:20:16Z","timestamp":1762924816000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Zonisamide-induced DRESS syndrome with progression toward SJS: the first Chinese case and review of the literature on ZNS-associated SCARs"],"prefix":"10.3389","volume":"12","author":[{"given":"Juan","family":"Wen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Difang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruohong","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baogang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijuan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haohao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1016\/j.seizure.2004.04.016","article-title":"Zonisamide: chemistry, mechanism of action, and pharmacokinetics","volume":"13","author":"Leppik","year":"2004","journal-title":"Seizure"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1517\/14656566.2011.622268","article-title":"Zonisamide in the treatment of epilepsy","volume":"12","author":"Holder","year":"2011","journal-title":"Expert Opin Pharmacother"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1111\/epi.12749","article-title":"Long-term safety and efficacy of zonisamide versus carbamazepine monotherapy for treatment of partial seizures in adults with newly diagnosed epilepsy: results of a phase iii, randomized, double-blind study","volume":"55","author":"Baulac","year":"2014","journal-title":"Epilepsia"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta25750","article-title":"Lamotrigine versus levetiracetam or zonisamide for focal epilepsy and valproate versus levetiracetam for generalised and unclassified epilepsy: two sanad ii non-inferiority rcts","volume":"25","author":"Marson","year":"2021","journal-title":"Health Technol Assess"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1136\/ejhpharm-2020-002387","article-title":"Drug rash with eosinophilia and systemic symptoms (dress) syndrome in a paediatric patient taking zonisamide","volume":"29","author":"Trivedi","year":"2022","journal-title":"Eur J Hosp Pharm"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1111\/jgh.14685","article-title":"Gastrointestinal: a case of zonisamide-induced esophageal and small intestinal injury","volume":"34","author":"Ihara","year":"2019","journal-title":"J Gastroenterol Hepatol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1002\/ccr3.1288","article-title":"Stevens-Johnson syndrome\/toxic epidermal necrolysis associated with zonisamide","volume":"6","author":"Vivar","year":"2018","journal-title":"Clin Case Rep"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"AB42","DOI":"10.1016\/j.jaci.2015.12.139","article-title":"A case report of dress with prolonged latency period related to zonisamide in a child","volume":"137","author":"Khan","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1111\/pde.12657","article-title":"Pediatric toxic epidermal necrolysis: experience of a tertiary burn center","volume":"32","author":"Rizzo","year":"2015","journal-title":"Pediatr Dermatol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"229","DOI":"10.2340\/00015555-1863","article-title":"Dihs\/dress with remarkable eosinophilic pneumonia caused by zonisamide","volume":"95","author":"Shibuya","year":"2015","journal-title":"Acta Derm Venereol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/2045-7022-4-S3-P14","article-title":"A case of toxic epidermal necrolysis with extensive intestinal involvement","volume":"4","author":"Nishimura","year":"2014","journal-title":"Clin Transl Allergy"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.2217\/pgs.13.180","article-title":"Specific hla types are associated with antiepileptic drug-induced stevens-Johnson syndrome and toxic epidermal necrolysis in japanese subjects","volume":"14","author":"Kaniwa","year":"2013","journal-title":"Pharmacogenomics"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1111\/j.1468-3083.2012.04547.x","article-title":"Clinical course of drug-induced hypersensitivity syndrome treated without systemic corticosteroids","volume":"27","author":"Uhara","year":"2013","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"E2277","DOI":"10.1210\/jc.2012-2054","article-title":"High frequency of hla b62 in fulminant type 1 diabetes with the drug-induced hypersensitivity syndrome","volume":"97","author":"Onuma","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1542\/peds.2010-3322","article-title":"Recurrence and outcomes of Stevens-Johnson syndrome and toxic epidermal necrolysis in children","volume":"128","author":"Finkelstein","year":"2011","journal-title":"Pediatrics"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1111\/j.1346-8138.2010.01147.x","article-title":"Case of drug rash with eosinophilia and systemic symptoms induced by zonisamide and reactivation of human herpes virus 7","volume":"38","author":"Murata","year":"2011","journal-title":"J Dermatol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"409","DOI":"10.2169\/internalmedicine.49.2451","article-title":"Acute kidney injury caused by zonisamide-induced hypersensitivity syndrome","volume":"49","author":"Fujita","year":"2010","journal-title":"Intern Med"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"225","DOI":"10.2336\/nishinihonhifu.72.225","article-title":"Drug-induced hypersensitivity syndrome (dins) due to zonisamide (excegran) showing only reactivation of cytomegalovirus","volume":"72","author":"Kyo","year":"2010","journal-title":"Nishi Nihon Hifuka"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"584","DOI":"10.2336\/nishinihonhifu.71.584","article-title":"A case of drug-induced hypersensitivity syndrome with the features of toxic epidermal necrolysis","volume":"71","author":"Kenji","year":"2009","journal-title":"Nishi Nihon Hifuka"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1001\/archdermatol.2007.48","article-title":"Toxic epidermal necrolysis due to zonisamide associated with reactivation of human herpesvirus 6","volume":"144","author":"Teraki","year":"2008","journal-title":"Arch Dermatol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.4088\/JCP.v65n1219a","article-title":"A cautionary note when using zonisamide in youths: a case report of association with toxic epidermal necrolysis","volume":"65","author":"Majeres","year":"2004","journal-title":"J Clin Psychiatry"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1159\/000063818","article-title":"Protein-losing cytomegalovirus gastritis in a patient with Stevens-Johnson syndrome","volume":"65","author":"Yoshioka","year":"2002","journal-title":"Digestion"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1111\/j.1600-0625.2008.00748.x","article-title":"Predicting possible zonisamide hypersensitivity syndrome","volume":"17","author":"Neuman","year":"2010","journal-title":"Exp Dermatol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.amjmed.2011.01.017","article-title":"The dress syndrome: a literature review","volume":"124","author":"Cacoub","year":"2011","journal-title":"Am J Med"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.alit.2019.03.006","article-title":"Drug-induced hypersensitivity syndrome (dihs)\/drug reaction with eosinophilia and systemic symptoms (dress): an update in 2019","volume":"68","author":"Shiohara","year":"2019","journal-title":"Allergol Int"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"895","DOI":"10.3390\/medicina57090895","article-title":"Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of diagnosis and management","volume":"57","author":"Frantz","year":"2021","journal-title":"Medicina (Kaunas)"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.24748.1","article-title":"Recent advances in managing and understanding stevens-Johnson syndrome and toxic epidermal necrolysis","volume":"9","author":"Hasegawa","year":"2020","journal-title":"F1000Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1001\/archderm.1993.01680220104023","article-title":"Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme","volume":"129","author":"Bastuji-Garin","year":"1993","journal-title":"Arch Dermatol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.pharep.2014.11.009","article-title":"Antiepileptic drugs and adverse skin reactions: an update","volume":"67","author":"Blaszczyk","year":"2015","journal-title":"Pharmacol Rep"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1177\/1535759719835672","article-title":"Making rash decisions in epilepsy: evaluating hypersensitivity reactions to anti-seizure medications","volume":"19","author":"Bermeo-Ovalle","year":"2019","journal-title":"Epilepsy Curr"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.clineuro.2012.01.019","article-title":"Antiepileptic drug-induced skin reactions: a retrospective study and analysis in 3793 chinese patients with epilepsy","volume":"114","author":"Wang","year":"2012","journal-title":"Clin Neurol Neurosurg"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1056\/NEJMoa022963","article-title":"Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics","volume":"349","author":"Strom","year":"2003","journal-title":"N Engl J Med"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1046\/j.1440-1592.2003.00309.x","article-title":"Human herpesvirus infection in drug-induced hypersensitivity syndrome, toxic epidermal necrolysis and stevensjohnson syndrome","volume":"53","author":"Aihara","year":"2004","journal-title":"Allergol Int"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1002\/(sici)1096-9071(200003)60:3<284::aid-jmv6>3.0.co;2-8","article-title":"Reactivation of human herpesvirus 6 by infection of human herpesvirus 7","volume":"60","author":"Tanaka-Taya","year":"2015","journal-title":"J Med Virol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"3872","DOI":"10.1073\/pnas.91.9.3872","article-title":"Cd4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus","volume":"91","author":"Lusso","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1111\/j.1365-2133.2007.08167.x","article-title":"Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome","volume":"157","author":"Tohyama","year":"2007","journal-title":"Br J Dermatol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"100673","DOI":"10.1016\/j.waojou.2022.100673","article-title":"Dress syndrome: a literature review and treatment algorithm","volume":"16","author":"Calle","year":"2023","journal-title":"World Allergy Organ J"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1111\/j.1398-9995.2007.01553.x","article-title":"Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity: dependence on its timing and the type of drug eruption","volume":"62","author":"Kano","year":"2007","journal-title":"Allergy"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"D783","DOI":"10.1093\/nar\/gkz1029","article-title":"Allele frequency net database (afnd) 2020 update: gold-standard data classification, open access genotype data and new query tools","volume":"48","author":"Gonzalez-Galarza","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3349\/ymj.2016.57.1.118","article-title":"Hla allele frequencies in 5802 Koreans: varied allele types associated with SJS\/TEN according to culprit drugs","volume":"57","author":"Park","year":"2016","journal-title":"Yonsei Med J"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/nrneurol.2011.90","article-title":"Epilepsy: HLA alleles linked to carbamazepine hypersensitivity","volume":"7","author":"Striano","year":"2011","journal-title":"Nat Rev Neurol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1001\/archderm.148.4.dlt120002-c","article-title":"Poor benefit\/risk balance of intravenous immunoglobulins in dress","volume":"148","author":"Janela","year":"2012","journal-title":"Arch Dermatol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1708376\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T05:20:18Z","timestamp":1762924818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1708376\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":42,"alternative-id":["10.3389\/fmed.2025.1708376"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1708376","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"article-number":"1708376"}}