Carbamazepine
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Reactions 1283 - 9 Jan 2010 S Carbamazepine DRESS syndrome: case report A 18-year-old boy developed drug rash with eosinophilia and systemic symptoms (DRESS) syndrome during treatment with carbamazepine for epilepsy. The boy presented with fever of 10 days duration, nausea, abdominal pain, and a 2-day history of maculopapular rash and facial oedema. Before admission, he had treated himself with amoxicillin. He had been receiving valproate for the treatment of grand mal epilepsy and carbamazepine had been added 3 weeks prior to the onset of fever [dosage not stated]. On admission, generalised lymphadenopathy, hepatomegaly, and splenomegaly were observed. He had a body temperature of 39.5°C and X-rays revealed infiltration in the right cardiophrenic angle. He had a leucocyte count of 19.9 × 10 9 /L with 12% of atypical lymphocytes and an eosinophil count of 1611 × 10 9 /L. ESR and fibrinogen were normal. Procalcitonin was highly elevated to 2.64 ng/mL (normal <0.1) and C-reactive protein to 59 mg/L (normal <5). Elevated levels of transaminase, alkaline phosphatase, GGT, lactate dehydrogenase, and bilirubin (AST 108 U/L, ALT 444 U/L, ALP 197 U/L, GGT 318 U/L, LDH 1136 U/L, bilirubin 41.3 µmol/L) were observed. The boy was initially presumed to have sepsis and was treated with broad- spectrum antibiotics and paracetamol [acetaminophen] while carbamazepine was continued. Five days later, he developed a fever of 40-41°C and severe hepatitis with further elevation of AST, ALT, LDH, total bilirubin, procalcitonin and C-reactive protein. He experienced frequent seizures during fever spikes and altered mental status. Carbamazepine was replaced with phenobarbital due to suspected hepatotoxicity. One week after admission, he was diagnosed with DRESS. Phenobarbital and valproate were discontinued and replaced with topiramate and diazepam. Treatment was initiated with methylprednisolone and topical emollients and steroids. Procalcitonin levels reduced to 0.8 ng/mL 3 days later and valproate was reintroduced 1 week later. After 7 days, methylprednisolone was replaced with prednisone which was gradually tapered and switched to alternate day therapy after 4 weeks. He completely recovered two months after carbamazepine discontinuation, leaving slightly elevated ALT and AST levels. Positive results were obtained from patch testing performed 6 months later with carbamazepine 10% w/w in white petrolatum. Author comment: "[Carbamazepine] is primary metabolized via cytochrome P450 . . . to reactive epoxides - arene oxides responsible for direct cytotoxicity. Arene oxides are detoxified mainly by epoxide hydrolase and by conjugation with glutathione. Valproate inhibits epoxide hydrolase, while paracetamol, by depleting hepatic glutathione, increases [carbamazepine] toxicity . . . [T]he additional use of valproate and paracetamol could have contributed to the severe clinical presentation in our patient." Bonaci-Nikolic B, et al. High procalcitonin in a patient with drug hypersensitivity syndrome. Internal Medicine 48: 1471-1474, No. 16, 2009 - Serbia 801158221 1 Reactions 9 Jan 2010 No. 1283 0114-9954/10/1283-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
Transcript of Carbamazepine
Reactions 1283 - 9 Jan 2010
SCarbamazepine
DRESS syndrome: case reportA 18-year-old boy developed drug rash with eosinophilia
and systemic symptoms (DRESS) syndrome duringtreatment with carbamazepine for epilepsy.
The boy presented with fever of 10 days duration,nausea, abdominal pain, and a 2-day history ofmaculopapular rash and facial oedema. Before admission,he had treated himself with amoxicillin. He had beenreceiving valproate for the treatment of grand mal epilepsyand carbamazepine had been added 3 weeks prior to theonset of fever [dosage not stated]. On admission,generalised lymphadenopathy, hepatomegaly, andsplenomegaly were observed. He had a body temperatureof 39.5°C and X-rays revealed infiltration in the rightcardiophrenic angle. He had a leucocyte count of19.9 × 109/L with 12% of atypical lymphocytes and aneosinophil count of 1611 × 109/L. ESR and fibrinogen werenormal. Procalcitonin was highly elevated to 2.64 ng/mL(normal <0.1) and C-reactive protein to 59 mg/L (normal<5). Elevated levels of transaminase, alkaline phosphatase,GGT, lactate dehydrogenase, and bilirubin (AST 108 U/L,ALT 444 U/L, ALP 197 U/L, GGT 318 U/L, LDH 1136 U/L,bilirubin 41.3 µmol/L) were observed. The boy was initiallypresumed to have sepsis and was treated with broad-spectrum antibiotics and paracetamol [acetaminophen]while carbamazepine was continued. Five days later, hedeveloped a fever of 40-41°C and severe hepatitis withfurther elevation of AST, ALT, LDH, total bilirubin,procalcitonin and C-reactive protein. He experiencedfrequent seizures during fever spikes and altered mentalstatus. Carbamazepine was replaced with phenobarbitaldue to suspected hepatotoxicity.
One week after admission, he was diagnosed withDRESS. Phenobarbital and valproate were discontinued andreplaced with topiramate and diazepam. Treatment wasinitiated with methylprednisolone and topical emollientsand steroids. Procalcitonin levels reduced to 0.8 ng/mL3 days later and valproate was reintroduced 1 week later.After 7 days, methylprednisolone was replaced withprednisone which was gradually tapered and switched toalternate day therapy after 4 weeks. He completelyrecovered two months after carbamazepinediscontinuation, leaving slightly elevated ALT and ASTlevels.
Positive results were obtained from patch testingperformed 6 months later with carbamazepine 10% w/w inwhite petrolatum.
Author comment: "[Carbamazepine] is primarymetabolized via cytochrome P450 . . . to reactive epoxides -arene oxides responsible for direct cytotoxicity. Arene oxidesare detoxified mainly by epoxide hydrolase and byconjugation with glutathione. Valproate inhibits epoxidehydrolase, while paracetamol, by depleting hepaticglutathione, increases [carbamazepine] toxicity . . . [T]headditional use of valproate and paracetamol could havecontributed to the severe clinical presentation in our patient."Bonaci-Nikolic B, et al. High procalcitonin in a patient with drug hypersensitivitysyndrome. Internal Medicine 48: 1471-1474, No. 16, 2009 - Serbia 801158221
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Reactions 9 Jan 2010 No. 12830114-9954/10/1283-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
