Severe cutaneous adverse reactions to antiepileptic drugs in Asians

Department of Dermatology, Chang Gung University College of Medicine, Taipei, Taiwan.
Neurology (Impact Factor: 8.29). 11/2011; 77(23):2025-33. DOI: 10.1212/WNL.0b013e31823b478c
Source: PubMed


Ethnicity has been shown to be a contributing risk factor regarding antiepileptic drug (AED)-induced severe cutaneous adverse drug reactions (SCARs). To increase the clinical and epidemiologic information in Asians, we investigated the characteristics, outcome, and tolerability toward alternative drugs for AED-induced SCARs.
A total of 154 patients with AED-induced SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), were analyzed for demographic characteristics, causative AEDs, latent period, organ involvement, complications, and mortality. Tolerability toward alternative AEDs was followed for patients after AED-SCARs episodes.
Carbamazepine (CBZ) and phenytoin (PHT) were the most common causative AEDs for SJS/TEN (67.8%) and DRESS (43.6%), respectively. No SCARs case was caused by nonaromatic AEDs, e.g., valproic acid (VPA) and topiramate (TPM). The liver was the most frequently involved internal organ in AED-DRESS, whereas ocular complications were more commonly seen in AED-SJS/TEN. The mortality of AED-SJS/TEN and -DRESS was 6.1% and 7.7%, respectively. By following alternative AED usage of patients after AED-SCARs episodes, we noted that most patients were tolerant of nonaromatic AEDs. One case of oxcarbazepine-SJS had cross-hypersensitivity to lamotrigine (LTG) and further developed into DRESS.
CBZ, PHT, and LTG were the major causative AEDs for SCARs. The mortality of PHT-SCARs was higher than CBZ-SCARs due to complicated comorbidity in patients. Nonaromatic AEDs were safe alternatives for patients with aromatic AED-induced SCARs.

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    • "Antiepileptic drug induced hypersensitivity syndrome is a rare side effect of aromatic anticonvulsive drugs (e.g., PHB, phenytoin and carbamazepine). The drugs implicated most frequently are carbamazepine and phenytoin [5], but the reports of hypersensitivity syndrome to PHB are uncommonly seen. "
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    • "Genetic polymorphism in the cytochrome enzymes that metabolize phenytoin may be responsible for variable rates of metabolism and thus susceptibility to toxicity even in individuals taking appropriate doses.[6] A recent retrospective study of 154 patients in Taiwan with AED induced SCARs revealed that phenytoin is the most common cause for DRESS syndrome and the liver was the most frequently involved internal organ as compared to AED induced SJS/TEN.[7] "
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    ABSTRACT: A 32 year old Asian female on 300 mg per day of phenytoin following meningioma excision developed a fever with a diffuse maculopapular rash, lymphadenopathy and splenomegaly after12 days. A diagnosis of DRESS (Drug Rash Eosinophilia and Systemic Symptoms) syndrome was made. Patient was started on prednisolone at a dose of 1 mg/kg but since there was further deterioration in her condition, intravenous immunoglobulin was started. Clinical and blood parameters began to improve by the next day with liver functions returning to normal by the third week. DRESS syndrome is a drug hypersensitivity syndrome which can be fatal and therefore needs to be recognized early for the appropriate treatment to be started. The use of Intravenous immunoglobulins is anecdotal and the dramatic improvement noted in this case indicates that it is another treatment choice. The case and a brief review of the literature are discussed.
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