Neurology Department, Federal University of Paraná, Curitiba, Brazil, Pequeno Príncipe School of Medicine, Curitiba, Brazil.
Immunogenetics Laboratory, Cajuru University Hospital, Curitiba, Brazil.
Epileptic Disord. 2021 Jun 1;23(3):466-475. doi: 10.1684/epd.2021.1288.
To describe the clinical characteristics of cutaneous adverse reactions and cross-sensitivity induced by antiseizure medications and compare the pattern of use of antiseizure medications in patients with epilepsy according to skin rash history.
We analysed patients with a history of skin rash presenting for up to 12 weeks after initiating antiseizure medication. The history of skin rash was verified by medical charts, interviews, and identification of skin lesions by patients based on illustrative images. The minimum follow-up period was eight months. The control group comprised epilepsy patients with regular antiseizure medication use for at least 12 weeks without skin rash. We included 109 cases and 99 controls.
The median (interquartile range) period from the index rash was six years (2-11). Carbamazepine was the trigger medication in 48% of cases and induced skin rashes in all patients with cross-sensitivity and carbamazepine exposure. Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reactions with eosinophilia and systemic symptoms affected 36% of cases. Carbamazepine- or oxcarbazepine-induced maculopapular exanthema occurred earlier (median: one week) than that induced by other antiseizure medications (median: three weeks) (p=0.006). Cross-sensitivity was more common in patients with at least one episode of Stevens-Johnson syndrome (29%) and Stevens-Johnson/toxic epidermal necrolysis overlap (50%) than in patients with maculopapular exanthema (8%) (p=0.01). Although most cases were mild, the pattern of antiseizure medication use differed from that of controls, with a lower proportion of antiseizure medication typically associated with severe cutaneous adverse reactions (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and lamotrigine) (p<0.001). Most cases exposed to high-risk medication, however, did not develop cross-sensitivity.
Cutaneous adverse reaction history may influence antiseizure medication use. Cross-sensitivity is more common in severe cases and most patients are affected by mild, self-limited skin rashes. Further research should consider the relevance of mild skin rashes in lifelong epilepsy treatment.
描述抗癫痫药物引起的皮肤不良反应和交叉过敏的临床特征，并根据皮疹病史比较癫痫患者抗癫痫药物的使用模式。
我们分析了皮疹发作后 12 周内就诊的有皮疹病史的患者。皮疹病史通过病历、访谈和患者根据说明图像识别皮损进行验证。最小随访时间为 8 个月。对照组为至少使用抗癫痫药物 12 周且无皮疹的癫痫患者。共纳入 109 例病例和 99 例对照。
中位（四分位距）皮疹出现至就诊时间为 6 年（2-11）。卡马西平是 48%病例的触发药物，且所有交叉过敏和卡马西平暴露患者均出现皮疹。史蒂文斯-约翰逊综合征、中毒性表皮坏死松解症或药物反应伴嗜酸性粒细胞增多和全身症状占 36%的病例。卡马西平或奥卡西平引起的斑丘疹性发疹比其他抗癫痫药物（中位：3 周）更早（中位：1 周）出现（p=0.006）。至少有 1 次史蒂文斯-约翰逊综合征和史蒂文斯-约翰逊/中毒性表皮坏死松解症重叠史的患者比有斑丘疹性发疹史的患者更常见交叉过敏（29%比 8%）（p=0.01）。尽管大多数病例为轻度，但抗癫痫药物的使用模式与对照组不同，与严重皮肤不良反应相关的抗癫痫药物比例较低（卡马西平、苯妥英钠、苯巴比妥、扑米酮、奥卡西平和拉莫三嗪）（p<0.001）。然而，大多数接触高风险药物的患者并未发生交叉过敏。
皮肤不良反应史可能影响抗癫痫药物的使用。交叉过敏在严重病例中更为常见，大多数患者受轻度、自限性皮疹的影响。进一步的研究应考虑轻度皮疹在癫痫终身治疗中的相关性。
