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 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

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 PemphigoidOften affects

the elderly

Dermatitis HerpetiformisAssociated with gluten intolerance

Cicatricial PemphigoidMucosal involvement, sometimes cutaneous

PemphigusAffects middle-aged or elderly

Differential Diagnosis, cont.

Linear IgA DiseaseItchy, ring-shaped, no internal disease

Contact Dermatitis

Varicella/Zoster Virus

Herpes Simplex Virus

Hand-Foot-Mouth Disease (Enteroviruses)

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.