1. Toxic Epidermal Necrolysis
Johns Hopkins Burn Center

2. • 20-30% mortality rate
• Incidence of 1-2 per million
• Most frequently incriminated are NSAIDs,
chemotherapics, antibiotics, and
anticonvulsants

3. Clinical Presentation
• Prodromal phase of fever, cough, malaise
• Nikolsky-positive macules (epidermal
separation induced by gentle lateral
pressure on skin surface)
• Mucosal surface often involved, systemic
involvement is variable (30% of cases have
respiratory involvement)

7. TEN vs. Stevens-Johnson?
1. TEN= > 30% of skin involvement
10-30%= SJS/TEN overlap
< 10% = Stevens-Johnson
Vs.
2. TEN = any degree of Nikolsky-positive
epidermal desquamation

8. Pathogenesis
• Large-scale apoptosis
--via TNF receptors in epidermis
--via imbalance between pro/anti apoptotic
proteins ex. granzyme
• TNF also found in blister PMNs, blood
PMNs, and macrophages

10. Fas ligand and more
• Fas ligand expressed on TEN keratinocytes
→apoptosis
• Drug-specific T-cell infiltrates
→express perforin & granzyme B

11. Initiating drug
↓
MHC immune response
↓
Expansion of CD8+ T cells
Keratinocyte amplification
apoptosis ↵

12. SCORTEN
• Severity of illness score
• Probability of hospital mortality
• Similar past formula was age + TBSA

13. Variables Odds Ratio p-value
Age (40 ≥ y old) 2.7 (1.0-7.5) 0.05
Heart Rate (≥ 120 bpm) 2.7 (1.0-7.3) 0.04
Cancer/hematologic malig. 4.4 (1.1-18.0) 0.04
BSA involved at day 1
< 10% 1
10-30% 2.9 (0.9-8.8) 0.04
> 30% 3.3 (1.2-9.6)
Serum urea level ( >10mmol) 2.5 (0.9-7.3) 0.09
Serum bicarb (<20 mmol/L) 4.3 (1.1-16.0) 0.03
Serum glucose (>14mmol/L) 5.3 (1.5-18.2) <0.01
SCORTEN 2.45 (2.26-5.25) <10-4

14. Mortality Rates and Relative Risks
SCORTEN # patients % mortality 95% CI Odds Ratio
0-1 31 3.2 (0.1-16.7) 1
2 66 12.1 (5.4-22.5) 4.1
3 34 35.3 (19.8-53.5) 14.6
4 24 58.3 (36.6-77.9) 42.0
≥5 10 90.0 (55.5-99.8) 270.0

15. Treatment
• Early withdrawal of suspect drug
CVVHD? Plasmapheresis?
• Supportive care in specialist unit
Similar to burn patients
No role for prophylactic abx
• Nutritional support and possible SSI
• Nebulized saline, bronchodilators
• Opthamology

16. Corticosteroids
+Modify inflammatory/immune response
+Downregulation of Fas ligand
- 9% TENS pts already on steroids
-Reported increased mortality
-Increased sepsis
= NO significant beneficial effect

17. Cyclosporin (3-5mg/kg daily)
• Blocks T-cell activation/proliferation
• CD8+ activation continuous vs.
full complement of activated cells by time
of presentation
• Inhibits apoptosis
• No higher risk of sepsis
• Shorter time to arrest of progression

18. IVIg
+Block keratinocyte Fas signalling
+Reported reduced mortality
-Wide batch-to-batch variation of anti-Fas
activity
-Conflicting study results

19. ???
• Insulin
Insulin-like growth factor is antiapoptotic
• Zinc
+Protects against apoptosis; critical for
function and integrity of cells;
immunosuppression in large doses (8x)
-Stimulates T-cells
• Granulocyte CSF adjunct for leukopenia