Transcript
Pharmacogenomic in Neurology II:SJS/TEN caused by Carbamazepine,
Phenobarbital and Phenytoin
Lect. Nin Prapongsena, M.Ph.
Huachiew Chalermpraiet University
Outline
• Introduction SJS/TEN
– Clinical presentation
– Management
• Pharmacogenomic related to cutaneous ADR in CBZ, Phenytoin, Phenobarbital usage.
• Introduction of HLA type
• Which HLA type related to cutaneous ADR in CBZ, Phenytoin, Phenobarbital usage???
Drugs induced SJS/TEN
Antibiotics Sulphonamides, Vancomycin,Penicillins, Cephalosporins, Quinolones
Anticonvulsants CBZ, Phenytoin, Phenobarbital,Valporate, Lamotrigine
NSAIDs Piroxicam, Aspirin, Diclofenac
ARV NVP, ABC, Protease inhibitors
Anti-TB Isoniazid, Ethambutol
Anti-Gout Allopurinol
SJS/TEN Management (Drugs Therapy)
• Systemic steroids: “Pulse” High dose of dexamethasone
• Thalidomide: Anti-TNFα (No Benefit)
• Cyclosporine: 3-5 mg/kg oral/IV for 8-24 d or re-epithelialisation then taper off 2wk
• Cyclophosphamide: Should be benefit (small trials)
Pharmacogenomic and Cutaneous ADR
http://www.youtube.com/watch?v=VPvCekgPwRI
Case I (China)Feb 2005:•Female 61 y (Complex partial seizure 2-4 times/month)• On CBZ 200 mg 1*3: (10th day: Erythematous rashes, Maculopapular rashes and leucocyte increased)• Then off CBZ (1 week: rashes were clear)• On ValproateFeb 2010:• Tonic-clonic seizure: On Valproate 500 mg 1*2
+ OXC 900 mg OD (2wk later: skin rxn)• Off OXC (5d: rashes were clear)• Lab testing HLA-B*1502 (+)Nov 2010:Valproate 500 mg 1*2 + Levetiracetam 1000 mg OD (no symp)
Case II (China)March 2004:• Female 20 y (Complex partial seizure q 2-3 month)• EEG (+)• On Phenytoin 100 mg 1*1• 10d later: infected eyes, sore throat, erythematous rash (+), high fever (39.1), oral ulcer, maculopapule rashes >30% & leucocytosis• Off Phenytoin but On steroid and antihistamine:(Rash cleared)• Switched to Phenobarbital 90 mg OD• 2wk later rashes were recurrence• Switched to CBZ 100mg 1*3 and 300 mg 1*2, respectively• 2wk later rashes were recurrence• Now on topiramate 75 mg 1*2 (seizure free)• Lab testing: HLA-B*1502 (+)
Conclusion
• HLA-A*3101 Related to SJS/TEN of CBZ (In Europe)
• HLA-B*1502 Related to SJS/TEN of CBZ (In Thailand)Note: HLA-B*1502 cross-reacted to phenobarbital, phenytoin (case report)
top related