1. Pharmacogenomic in Neurology II:
SJS/TEN caused by Carbamazepine,
Phenobarbital and Phenytoin
Lect. Nin Prapongsena, M.Ph.
Huachiew Chalermpraiet University

2. 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???

3. 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

4. Translational Research 2012 Volume 159 Number 5

7. SJS vs TEN
Harr and French Orphanet Journal of Rare Diseases 2010, 5:39

8. SJS vs TEN
SJS SJS/TEN TEN
Occurred within
4 -28 days

9. SJS vs TEN (systemic sign)

10. Severity SJS/TEN Assessment

11. SJS/TEN Management (Supportive Care)

12. SJS/TEN Management (Supportive Care)

13. 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)

14. SJS/TEN Management (Continue)
• IVIG: High dose of IVIG (0.25-0.75 g/kg for 3-4 d)

15. Pharmacogenomic and Cutaneous ADR
http://www.youtube.com/watch?v=VPvCekgPwRI

17. Polymorphism of HLA type on MHC I
Related to Cutaneous ADR (SJS/TEN)

18. What’s polymorphism of HLA type that
Related to SJS/TEN in Anticonvulsant
• HLA-A*3101
• HLA-B*1502

19. HLA-A*3101

22. HLA-B*1502

25. HLA-B*1502

29. HLA-B*1502 Cross-reacted to Phenobarbital
and Phenytoin (Case Report)

31. 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 Valproate
Feb 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)

32. 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 (+)

35. 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)

36. Pharmacist’s role
• Interpreted Laboratory data of pharmacogenomic
that related to SJS/TEN
• Suggested doctor to avoid CBZ, Phenytoin and
Phenobarbital If patients are HLA-B*1502 (+)
• Suggested doctor to switch medication to
Topiramate/ Valproate/ Levetiracetam