Transcript Toxic Epidermal Necrolysis

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
Mortality:


SJS: 5%
TEN: 30%

Risk Factors:


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
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.