Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe drug reactions characterized by extensive skin detachment. TEN involves over 30% of the body surface area detaching, while SJS is under 10%. Mortality rates are 1-5% for SJS and 25-35% for TEN. Prompt identification and removal of the causative drug leads to better survival. Common causes are certain medications like sulfonamides, allopurinol, and anti-seizure drugs. Treatment focuses on supportive care, IV fluids, stopping the offending drug, and occasionally corticosteroids or IVIg. Independent risk factors for worse prognosis include age over

1. Toxic Epidermal
Necrolysis
Carson R. Harris, MD
MELA International Acute Care Conference
March 2017
Acknowledgement: Scruggs, MD

2. SJS/TEN
• Severe mucocutaneous adverse drug reactions
• characterized by extensive epidermal detachment.
• The mortality rates
• 1% - 5% for Stevens-Johnson syndrome
• 25% - 35% for toxic epidermal necrolysis.
• Early recognition and prompt withdrawal of
the causative agent leads to increased patient
survival.

3. 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.

6. 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

7. 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

8. 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.

9. Etiologies
• Medications (Odds Ratio for exposure in hospitalized
patients):
• 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

10. 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

11. 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)

12. 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 Bullae
• Epidermolysis Bullosa
Acquisita

13. 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?

14. 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

15. 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.
• Palmieri TL, et al. A multicenter review of toxic epidermal
necrolysis treated in U.S. burn centers at the end of the
twentieth century. J Burn Care Rehabil. 2002;23:87–96.
• Alerhand, et al. Stevens-Johnson Syndrome and Toxic
Epidermal Necrolysis in the Pediatric Population: A Review.
Pediatr Emer Care 2016;32: 472–478