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• W2290786543 abstract "Levetiracetam (LEV) has rarely been associated with skin rashes. We managed two patients who developed skin rashes following LEV administration. In this communication we report these patients to highlight the occurrence of skin rashes with LEV. A 19-year-old woman had secondary generalized seizures for 18 months due to a calcified parietal granuloma. She was treated with phenytoin (PHT) and sodium valproate. PHT was replaced with LEV 500 mg twice daily because of a recurrence of seizures. Having taken LEV for 10 days, she developed a generalized maculopapular itchy rash which spared the mucous membranes. LEV was stopped and she was prescribed oral cetirizine, ranitidine, and clobazam. Sodium valproate was continued. The skin rash improved over the next 5 days, but she had break through seizures. LEV was restarted at a dose of 750 mg twice daily. On day 7 of LEV administration, she again developed a maculopapular rash this time also affecting the mucus membranes. The skin rash involved more than 70% of body surface area. Her Naranjo score was nine, suggesting a definite association between LEV and skin rash. The patient was managed in intensive care and required nasogastric tube feeding. She was given oxygen by face mask and LEV and sodium valproate was stopped. She received intravenous immunoglobulin 200 mg/kg daily for 5 days, topical steroid ointment, artificial tear and levocetirizine 10 mg daily. After 1 month of hospital treatment, her rash had healed sufficiently for her to be discharged. She remained seizure free for next 1 year on clobazam 15 mg twice daily. The patient was admitted to our hospital because of recurrence of secondary generalized seizures. On examination, she had healed scar marks from her previous rash on face, trunk and extremities (Fig. 1). She was prescribed gabapentin 100 mg once daily which was increased to 300 mg twice daily in addition to clobazam. She has been seizure for last 4 months. A 29-year-old male had been experiencing seizures and diagnosed with idiopathic generalized epilepsy 2 years previously. Seizures usually occurred at night. The patient had a history of febrile seizures. His seizures were controlled with PHT 200 mg daily but 3 months prior to admission he had two seizures in the context of adherence problems. He was prescribed oxcarbazepine 600 mg daily and PHT was increased to 300 mg. Three months later, he developed an urticarial skin rash all over his body. Phenytoin and oxcarbazepine were stopped and he was referred to our hospital. On examination, he had fading skin rash. He was prescribed LEV 500 mg twice daily but on day 9 of LEV administration, he again developed a morbilliform pruritic rash. Levetiracetam was replaced with clobazam 10 mg daily. One month later, he had a generalized tonic clonic seizure for which LEV 1000 mg daily was prescribed by his local physician. On the third day of LEV treatment, he developed an extensive morbilliform rash. His Naranjo score was seven (Fig. 1E and F). The patient was managed symptomatically. LEV was replaced with sodium valproate controlled release 400 mg twice daily and clobazam was continued. At 2 months follow-up, there was no recurrence of seizures or rash. Both patients had LEV induced skin rashes. The skin rash was due to LEV because there was no other cause for skin rash, the rash recurred on drug challenge and the Naranjo score was suggestive. Antiepileptic drug related skin rashes may occur following PHT, carbamazepine, oxcarbazepine, phenobarbitone, primidone, zonisamide, lamotrigine, and may have cross reactivity despite differences in the chemical structures of these agents [1Arif H. Buchsbaum R. Weintraub D. Koyfman S. Salas-Humara C. Bazil C.W. et al.Comparison and predictors of rash associated with 15 antiepileptic drugs.Neurology. 2007; 68: 1701-1709Crossref PubMed Scopus (204) Google Scholar, 2Zaccara G. Franciotta D. Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs.Epilepsia. 2007; 48: 1223-1244Crossref PubMed Scopus (279) Google Scholar]. In contrast, valproate, topiramate, gabapentin, tiagabine and LEV, are rarely associated with skin rashes. Only 0.8% of patients newly started on LEV developed a skin rash [[1]Arif H. Buchsbaum R. Weintraub D. Koyfman S. Salas-Humara C. Bazil C.W. et al.Comparison and predictors of rash associated with 15 antiepileptic drugs.Neurology. 2007; 68: 1701-1709Crossref PubMed Scopus (204) Google Scholar]. To date, only five patients with LEV-associated skin reactions have been reported (Table 1) [[3]Jones R.T. Evans W. Mersfelder T.L. Kavanaugh K. Rare red rashes: a case report of levetiracetam-induced cutaneous reaction and review of the literature.Am J Ther. 2014; ([Epub ahead of print])Google Scholar]. Idiosyncratic drug reactions can be attributed to several immunologic mechanisms [[2]Zaccara G. Franciotta D. Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs.Epilepsia. 2007; 48: 1223-1244Crossref PubMed Scopus (279) Google Scholar]. Drug reactions can be life-threatening or a source of considerable morbidity. On rechallenge, the rash usually appears within 2 days [[2]Zaccara G. Franciotta D. Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs.Epilepsia. 2007; 48: 1223-1244Crossref PubMed Scopus (279) Google Scholar]. In our patients the drug rashes appeared on the third or seventh day of a LEV rechallenge respectively. The pathogenesis of Stevens–Johnson syndrome and toxic epidermal necrolysis is not fully understood but is believed to be immune-mediated because rechallenge with the responsible chemical trigger results in rapid recurrence of fulminant skin reactions. Immune-mediated drug reactions are thought to be dose-independent, but some reports have discussed the possible role of the dose of the offending drug in immune-mediated reactions [[2]Zaccara G. Franciotta D. Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs.Epilepsia. 2007; 48: 1223-1244Crossref PubMed Scopus (279) Google Scholar]. If the drug is started in a very low dose and gradually increased, the risk of allergic reaction is reduced, because of desensitization. The relationship between starting dose and titration rate in cutaneous drug reaction is particularly notable with lamotrigine, PHT and carbamazepine [[4]Chadwick D. Shaw M.D. Foy P. Rawlins M.D. Turnbull D.M. Serum anticonvulsant concentration and the drug induced skin eruptions.J Neurol Neurosurg Psych. 1984; 47: 642-644Crossref PubMed Scopus (98) Google Scholar]. The skin rash following carbamazepine is commoner in Asians compared to Europeans and American patients because of pharmacogenetic susceptibility due to HLA-B*1502 and HLA-A*3101 alleles [[2]Zaccara G. Franciotta D. Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs.Epilepsia. 2007; 48: 1223-1244Crossref PubMed Scopus (279) Google Scholar]. The genetic and epigenetic aspects of LEV related skin rash need further evaluation.Table 1Cases of levetiracetam induced skin rash with review of literature.Serial no of patientsAuthor/year of publicationAge (in years)/sexPrimary disease and associated conditionType of skin rashOn which day rash appearDosage of LEVNaranjo score#Naranjo scoring is as follows: definite adverse drug reaction (score – 9); probable (score 5–8); possible (score 1–4); and doubtful (score 0).Challenge of LEVOther AED during rashOutcome after stopping LEV1Zou et al. (2012) in Jones et al. (2014)2.25/FCongenital heart disease, post-operative cardiopulmonary arrestSJS930 mg/kg/dayNANot donePBT, OXCImproved2Yesilova et al. (2013) in Jones et al. (2014)27/FEpilepsyErythema multiforme151000 mg/dayNANot doneNoImproved3Duong et al. (2013) in Jones et al. (2014)20/FHead injuryTEN26NA3Not doneNoImproved429/FHIV 1 +ve, cerebral tuberculoma, Aspergillusniger otitis externaTEN19NA3Not doneClobazamImproved5Jones et al. (2014)64/MLeft basal ganglia mass.EBV and CMV +Morbilliform7500 mg BID × IV7Not doneNoImproved6Our patient19/FSeizure, NeurocysticercosisMorbilliform- initialTEN-Re-exposure10 days – initial exposure7 days – re-exposure500 mg BID × oral750 mg BID9Yes, SJSPHT, VPAImproved729/MSeizure disorderMorbilliform9 days – initial exposure3 days – re-exposure500 mg BID × oral7YesClobazamImprovedAbbreviations: LEV – levetiracetam, PBT – phenobarbitone, OXC – oxcarbamazepine, AED – antiepileptic drugs, EBV – Epstein Barr virus, CVM – cytomegalovirus, TEN – toxic epidermal necrolysis, SJS – Stevens–Johnson syndrome, BID – twice daily, IV – intravenous route, NA – not available.# Naranjo scoring is as follows: definite adverse drug reaction (score – 9); probable (score 5–8); possible (score 1–4); and doubtful (score 0). Open table in a new tab Abbreviations: LEV – levetiracetam, PBT – phenobarbitone, OXC – oxcarbamazepine, AED – antiepileptic drugs, EBV – Epstein Barr virus, CVM – cytomegalovirus, TEN – toxic epidermal necrolysis, SJS – Stevens–Johnson syndrome, BID – twice daily, IV – intravenous route, NA – not available. LEV potentially causes skin toxicity. Especially when previous possible rashes have been reported with LEV, rechallenge should only be undertaken after consideration of alternative treatments and with great caution." @default.
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• W2290786543 title "Skin rash following levetiracetam" @default.
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