Anticonvulsant hypersensitivity syndrome: lymphocyte toxicity assay for the confirmation of diagnosis and risk assessment.
OBJECTIVE
To report a case of anticonvulsant hypersensitivity syndrome (AHS) precipitated by exposure to phenobarbital.


METHODS
An 11-year-old girl receiving phenobarbital developed fever, exfoliative skin rash, mucous membrane lesions, alopecia, and hepatic inflammation. Investigations ruled out an infectious etiology; an adverse event following phenobarbital administration was considered. Applying the Naranjo probability scale for objective causality assessment showed the adverse reaction was probably due to phenobarbital. The diagnosis was confirmed by in vitro lymphocyte toxicity assay, which demonstrated increased cell death following exposure to phenobarbital, as well as other aromatic anticonvulsants and lamotrigine.


CONCLUSIONS
AHS is a rare, potentially fatal event with multisystem manifestations. It is reported following exposure to aromatic antiepileptics. The mechanism proposed for AHS is accumulation of toxic arene oxide metabolites due to a defect in epoxide hydrolase-mediated detoxification. Despite the difference in chemical structure of lamotrigine, in vitro susceptibility to AHS was demonstrated in our patient.


CONCLUSIONS
Although AHS is a rare event, it should be suspected in patients who develop unexplained systemic manifestations following exposure to aromatic antiepileptics. The potential of lamotrigine to cause AHS should be remembered when this drug is used in subjects who have developed AHS on exposure to phenobarbital and other first-line antiepileptic agents.
Seth GS Medical College and KEM Hospital, Mumbai, India.
Sandeep B
SB
Bavdekar
Mamta N
MN
Muranjan
Nithya J
NJ
Gogtay
Vishakha
V
Kantharia
Nilima A
NA
Kshirsagar
D000927:Anticonvulsants / Q000009:adverse effects*; D002648:Child; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D010634:Phenobarbital / Q000009:adverse effects*; D018570:Risk Assessment; D012640:Seizures / Q000188:drug therapy
D000927:Anticonvulsants; D010634:Phenobarbital