2. Definition
Toxic Epidermal Necrolysis:
Confluent erythema is common.
Outer layer of epidermis separates easily from basal layer
with lateral pressure.
Large sheet of necrotic epidermis often present.
>30% BSA involved.
3.
4. Presentation
Fever (often >39) and flu-like illness 1-3 days befo
re mucocutaneous lesions appear
Confluent erythema
Facial edema or central facial involvement
Lesions are painful
Palpable purpura
Skin necrosis, blisters and/or epidermal detachment
Mucous membrane erosions/crusting, sore throat
Visual Impairment (secondary to ocular involvement)
Rash 1-3 weeks after exposure, or days after 2nd ex
posure
5. Epidemiology
2-7/million people/year
SJS: age 25-47, TEN: age 4
6-63
Women: >60%
Poor prognosis:
Intestinal/Pulmonary involve
ment
Greater extent of detachmen
t
Older age
Mortality:
TEN: 30%
Risk Factors:
HIV infection
Genetic factors
Certain HLA types
“Slow acetylators”
Polymorphisms in IL4 recept
or gene
Concomitant viral infections
Underlying immunologic dise
ases
Physical factors
UV light, radiation therapy
Malignancy
Higher doses of known offen
ders
6. Pathogenesis
Secondary to cytotoxicity and delayed hypersensitivity reaction t
o the offending agent.
Antigen is either the implicated drug or a metabolite.
Histopathology:
Granulysin (cytolytic protein produced
by cytotoxic T cells and NK cells)
Expression of HLA-DR and
intracellular adhesion molecule
(ICAM)-1 by
Keratinocytes
CD4 cells (in dermis)
CD8 T cells (in epidermis)
Apoptosis of keratinocytes
facilitated by
TNF-alpha, perforin and granzyme
secretion
fas-ligand expression (cell death receptor)
Subepidermal split with cell-poor bullous.
Epidermis shows full thickness necrosis.
7. Etiologies
Medications (Odds Ratio for exposure in hospitalize
d pts):
Sulfonamide antibiotics (172)
Allopurinol (52)
Amine antiepileptics
Phenytoin (53)
Carbamazepine (90)
Lamotrigine
NSAIDs (72)
Infections (e.g. Mycoplasma pneumonia)
Other: Vaccinations, Systemic diseases, Chemical e
xposure, Herbal medicines, Foods
8. Differential Diagnosis for Vesicular or Bul
lous Rash
Bullous
Pemphigoid
Often affects
the elderly
Dermatitis Herpetiformis
Associated with gluten intolerance
Cicatricial Pemphigoid
Mucosal involvement, sometimes cutaneous
Pemphigus
Affects middle-aged or elderly
9. Differential Diagnosis, cont.
Linear IgA Disease
Itchy, ring-shaped, no internal disease
Contact Dermatitis
Varicella/Zoster Virus
Herpes Simplex Virus
Hand-Foot-Mouth
Disease
(Enteroviruses)
11. Treatment
Early diagnosis - biopsy
Immediate discontinuation of offending agent
Supportive care – pay close attention to ocular com
plications
IV hydration (e.g. Parkland formula)
Antihistamines
Analgesics
Local v. systemic corticosteroids
Think about nursing requirements!
Possible treatment in burn unit, wound care
IVIg?
13. Resources:
Cooper, et al. The Washington Manual of Medical T
herapeutics, 32nd Edition. 2007.
High, et al. Stevens-Johnson syndrome and toxic ep
idermal necrolysis: Management, prognosis, and lon
g-term sequelae. Up To Date. 2009.
Kasper, et al. Harrison’s Principles of Internal Medici
ne, 16th Edition. 2005.
Nirken, et al. Stevens-Johnson syndrome and toxic
epidermal necrolysis: Clinical manifestations, pathog
enesis, and diagnosis. Up To Date. 2009.