COMMENTARY

Slowly But Surely, Seizure Therapy Gets Personalized

Andrew N. Wilner, MD

Disclosures

November 05, 2014

Phenytoin Cutaneous Adverse Reactions

I saw a woman many years ago in the hospital with fever, lymphadenopathy, and liver function abnormalities associated with phenytoin. Her case has stuck with me, probably because her EEG/video monitoring demonstrated nonepileptic seizures and not epilepsy. She suffered from a serious complication of phenytoin, a drug she didn't even need!

Of all the antiepileptic drugs (AEDs), phenytoin is associated with the highest rate of rashes (5.9%), followed by lamotrigine (4.8%) and carbamazepine (3.7%).[1] Although usually mild, drug rashes can be life-threatening if they take the form of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug reactions with eosinophilia and systemic symptoms (DRESS).[2]

A recent study[3] revealed that phenytoin-related severe cutaneous adverse reactions are associated with CYP2C9*3 missense variants on chromosome 10 in an Asian population. This case-controlled study included 105 cases of phenytoin-related severe cutaneous adverse reactions (61 SJS or TEN, 44 DRESS); 78 cases of maculopapular exanthema; 130 phenytoin-tolerant control individuals; and 3655 population control individuals from Japan, Malaysia, and Taiwan. A genome-wide association study (GWAS) included 60 cases with severe phenytoin-related reactions and 412 Taiwanese controls. The results were validated in Taiwanese, Japanese, and Malaysian populations.

GWAS identified a cluster of 16 single nucleotide polymorphisms in CYP2C genes on chromosome 10 (10q23.33). Of these, the missense variant rs1057910 (CYP2C9*3) had the highest association (odds ratio, 12) with phenytoin-related severe cutaneous adverse reactions.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....