Case report Toxic epidermal necrolysis with combination lamotrigine and valproate in bipolar disorder Chuan-Chia Chang a , I-Shin Shiah a,b, * , Hsin-An Chang a , San-Yuan Huang a,b a Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan b National Defense Medical Center, Taipei, Taiwan Accepted 26 August 2005 Available online 12 October 2005 Abstract Toxic epidermal necrolysis (TEN) is the most severe and potentially life-threatening cutaneous reaction associated with lamotrigine. The risk of developing TEN during lamotrigine therapy is low and previously reported cases most involved epileptic patients. However, the risk of TEN with combination lamotrigine and valproate is greater than with monotherapy. We present here the emergence of TEN in a 32-year-old bipolar woman who was concomitantly treated with lamotrigine and valproate. The patient developed high fever, pharyngitis, cervical lymphadenopathy, mucosal sloughing, generalized erythematous eruptions and more than 40% epidermal detachment of the total body surface area (TBSA) after we added lamotrigine to her medications of valproate and trazodone. The patient’s illness course was protracted and accompanied with hepatitis, pneumonitis and hematologic abnormalities. In the beginning of her illness course, our patient did not respond to antihistamine treatment. However, she made a full recovery without any sequela after she had received systemic corticosteroid and intensive resuscitation. Our case suggests that early use of systemic corticosteroid might be beneficial in treating TEN patients, if there is not any clinical contraindication. D 2005 Elsevier Inc. All rights reserved. Keywords: Anticonvulsants; Bipolar disorder; Lamotrigine; Toxic epidermal necrolysis; Valproate 1. Introduction Toxic epidermal necrolysis (TEN) is a rare, severe, and life-threatening exfoliative skin disorder, which is character- ized by a high fever, malaise, skin blistering or crusting and extensive epidermal necrosis (Warnock and Morris, 2003). This disorder has been considered as a maximal variant of Stevens-Johnson syndrome (SJS), depending on the amount of epidermal detachment (Bastuji-Garin et al., 1993). In TEN, there is greater than 30% total body surface area (TBSA) involvement, whereas SJS is usually defined as having less than 30% TBSA involvement (Bastuji-Garin et al., 1993). The pathogeness of both disorders is still unclear; however, over 80% of TEN cases are specific medication related, as opposed to 50% with SJS (Warnock and Morris, 2003). Over 100 drugs have been implicated in the development of TEN and SJS, most commonly anticonvulsants, antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs) (Clennett and Hosking, 2003). The estimated mortality rate for SJS is approximately 10% while that for TEN is as high as 45%, with death mainly due to sepsis and homodynamic failure (Warnock and Morris, 2003). Lamotrigine is a relatively new anticonvulsant. It is effective in treating and preventing bipolar depression, and has been recently approved by the U.S. Food and Drug Administration (FDA) as a maintenance treatment for bipolar disorder (Yatham, 2004). The frequency of SJS and TEN in patients treated with lamotrigine is estimated to be 1 : 1000 for adults and 3 : 1000 for children (Messenheimer, 1998; Guberman et al., 1999). However, most reported cases of lamotrigine- associated TEN involved epileptic patients (Wadelius et al., 1996; Schlienger et al., 1998; Rzany et al., 1999; Clennett and Hosking, 2003; Hashim et al., 2004). Furthermore, the risk of TEN with combination lamotrigine and valproate is greater 0278-5846/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2005.08.025 Abbreviations: CRP, C-reactive protein; FDA, Food and Drug Administra- tion; NSAIDs, non-steroidal anti-inflammatory drugs; SJS, Stevens-Johnson syndrome; TBSA, total body surface area; TEN, toxic epidermal necrolysis. * Corresponding author. Department of Psychiatry, Tri-Service General Hospital, No. 325, Sec. 2, Cheng-Kung RD., Neihu District, 114, Taipei, Taiwan. Tel.: +886 2 87927431; fax: +886 2 87912161. E-mail address: ishiah@ms45.hinet.net (I.-S. Shiah). Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 147 – 150 www.elsevier.com/locate/pnpbp