Zonisamide-Induced DRESS Syndrome with Progression TowardSJS: The First Chinese Case and Review of the Literature on ZNS-Associated SCARs

Juan Wen¹Kang Du²Difang Shi³Yue Wang²Ruohong Xue⁴Baogang Huang²Xi Liang²Huijuan Fan²Haohao Wu^2*Fengming Xu^2*

• ¹Department of Neurology, Guizhou Panjiang Investment Holding (Group) General hospital, Guizhou, China
• ²Kunming Medical University Affiliated Qujing Hospital, Qujing, China
• ³Yunnan Cancer Hospital, Kunming, China
• ⁴First Affiliated Hospital of Kunming Medical University, Kunming, China

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' s latency period was 57 days, 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 days, 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—including DRESS, SJS, and toxic epidermal necrolysis (TEN)—to support early recognition and timely clinical interventions.