Toxic Epidermal

Necrolysis
Kristine Scruggs, MD
AM Report
July 28, 2009

Definition

SJS/TEN:

Stevens-Johnson Syndrome:

Lesions: Small blisters on dusky purpuric macules or

atypical targets
Mucosal involvement common
Prodrome of fever and malaise common
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.

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

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

Risk Factors:

Mortality:

SJS: 5%
TEN: 30%

HIV infection
Genetic factors

Concomitant viral infections

Underlying immunologic
diseases
Physical factors

Certain HLA types

Slow acetylators
Polymorphisms in IL4
receptor gene

UV light, radiation therapy

Malignancy
Higher doses of known
offenders

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.

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

Differential Diagnosis for

Vesicular or Bullous Rash
Bullous
Pemphigoid
Often affects
the elderly

Dermatitis Herpetiformis
Associated with gluten intolerance

Pemphigus
Affects middle-aged or elderly

Cicatricial Pemphigoid
Mucosal involvement, sometimes cutaneous

Differential Diagnosis, cont.

Linear IgA Disease

Itchy, ring-shaped, no internal disease

Herpes Simplex Virus

Varicella/Zoster Virus

Hand-Foot-Mouth
Disease
(Enteroviruses)

Contact Dermatitis

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

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?

Prognosis

Independent Prognosis Factors

Weight

Age

>/= 40 years

Malignancy

Yes

BSA Detached

>/= 10%

Tachycardia

>/= 120/min

Serum urea

>10 mmol/l

Serum glucose

>14 mmol/l

Serum bicarbonate

<20 mmol/l

SCORTEN #

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. Harrisons 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.