Toxic Epidermal Necrolysis

Kristine Scruggs, MD
AM Report
July 28, 2009
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.
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  Risk Factors:
 SJS: age 25-47, TEN: age  HIV infection
46-63  Genetic factors
 Women: >60%  Certain HLA types
 “Slow acetylators”
 Poor prognosis:
 Polymorphisms in IL4
 Intestinal/Pulmonary receptor gene
involvement
 Concomitant viral infections
 Greater extent of
 Underlying immunologic
detachment
diseases
 Older age
 Physical factors
 Mortality:  UV light, radiation therapy
 SJS: 5%  Malignancy
 TEN: 30%  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 Subepidermal split with cell-poor bullous.
secretion Epidermis shows full thickness necrosis.
 fas-ligand expression (cell death receptor)
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 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
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.