Ten

1. Toxic Epidermal Necrolysis
Kristine Scruggs, MD
AM Report
July 28, 2009

2. Definition
 SJS/TEN:
 Lesions: Small blisters on dusky purpuric macules or
atypical targets
 Mucosal involvement common
 Prodrome of fever and malaise common
 Stevens-Johnson Syndrome:
 Rare areas of confluence.
 Detachment </= 10% BSA
 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.

4. Presentation
 Fever (often >39) and flu-like illness 1-3 days
before 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
exposure

5. Epidemiology
 2-7/million people/year
 SJS: age 25-47, TEN: age
46-63
 Women: >60%
 Poor prognosis:
 Intestinal/Pulmonary
involvement
 Greater extent of
detachment
 Older age
 Mortality:
 SJS: 5%
 TEN: 30%
 Risk Factors:
 HIV infection
 Genetic factors
 Certain HLA types
 “Slow acetylators”
 Polymorphisms in IL4
receptor gene
 Concomitant viral infections
 Underlying immunologic
diseases
 Physical factors
 UV light, radiation therapy
 Malignancy
 Higher doses of known
offenders

6. Pathogenesis
 Secondary to cytotoxicity and delayed hypersensitivity reaction
to 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
hospitalized 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
exposure, Herbal medicines, Foods

8. Differential Diagnosis for Vesicular or
Bullous 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)

10. Differential Diagnosis, cont.
 Erythema Multiforme
 Staphylococcal Scalded Skin Syndrome
 Bullous Impetigo
 Toxic Shock Syndrome
 Paraneoplastic Pemphigus
 Cutaneous emboli
 Diabetic Bullae
 Porphyria Cutanea Tarda
 Porphyria Variegata
 Pseudoporphyria
 Bullous dermatosis of Hemodialysis
 Coma Bulloae
 Epidermolysis Bullosa Acquisita

11. Treatment
 Early diagnosis - biopsy
 Immediate discontinuation of offending agent
 Supportive care – pay close attention to ocular
complications
 IV hydration (e.g. Parkland formula)
 Antihistamines
 Analgesics
 Local v. systemic corticosteroids
 Think about nursing requirements!
 Possible treatment in burn unit, wound care
 IVIg?

12. Prognosis
Independent Prognosis Factors Weight
Age >/= 40 years 1
Malignancy Yes 1
BSA Detached >/= 10% 1
Tachycardia >/= 120/min 1
Serum urea >10 mmol/l 1
Serum glucose >14 mmol/l 1
Serum bicarbonate <20 mmol/l 1
SCORTEN # 7

13. Resources:
 Cooper, et al. The Washington Manual of Medical
Therapeutics, 32nd Edition. 2007.
 High, et al. Stevens-Johnson syndrome and toxic
epidermal necrolysis: Management, prognosis, and
long-term sequelae. Up To Date. 2009.
 Kasper, et al. Harrison’s Principles of Internal
Medicine, 16th Edition. 2005.
 Nirken, et al. Stevens-Johnson syndrome and toxic
epidermal necrolysis: Clinical manifestations,
pathogenesis, and diagnosis. Up To Date. 2009.