Toxic epidermal necrolysis

Background

Normal dermal anatomy.

• Severe, life-threatening mucocutaneous reaction characterized by widespread epidermal necrosis and detachment
• Represents a spectrum with Stevens-Johnson syndrome (SJS):
  • SJS: <10% body surface area (BSA) detachment
  • SJS-TEN overlap: 10-30% BSA detachment
  • TEN: >30% BSA detachment
• Medications are the cause in 80-95% of cases
  • Most common: sulfonamides, anticonvulsants (carbamazepine, phenytoin, lamotrigine), allopurinol, NSAIDs, penicillins
  • Typically occurs 1-3 weeks after drug initiation
• Other triggers: Mycoplasma pneumoniae infection (especially in children), HIV, malignancy
• Mortality: 25-35% for TEN, 1-5% for SJS
• HLA-B*5801 (allopurinol) and HLA-B*1502 (carbamazepine) associated with increased risk

Clinical Features

Toxic epidermal necrolysis on legs

The back of a TENs patient on day 10, at the peak of the condition

• Prodrome (1-3 days before skin findings):
  • Fever, malaise, myalgias, arthralgias, painful skin, pharyngitis
• Skin findings:
  • Tender erythematous or dusky macules → confluent areas of necrosis
  • Flaccid bullae with full-thickness epidermal detachment
  • Positive Nikolsky sign (lateral pressure causes epidermal separation)
  • Positive Asboe-Hansen sign (pressure on blister causes lateral extension)
  • Skin sloughs in sheets, leaving raw denuded dermis
• Mucosal involvement (present in >90% of cases):
  • Oral (painful erosions, inability to eat/drink)
  • Ocular (conjunctivitis, corneal erosions — ophthalmology emergency)
  • Genitourinary (dysuria, urinary retention)
  • Respiratory (tracheobronchial sloughing may cause respiratory failure)
• Systemic complications:
  • Sepsis (leading cause of death)
  • Hypovolemia and electrolyte disorders
  • Acute kidney injury
  • DIC

Differential Diagnosis

• Stevens-Johnson syndrome (same spectrum, <10% BSA)
• Staphylococcal scalded skin syndrome (SSSS) — superficial cleavage plane, no mucosal involvement, children
• Exfoliative drug eruptions
• Pemphigus vulgaris
• Acute graft-versus-host disease
• Generalized bullous fixed drug eruption
• Toxic shock syndrome

Erythematous rash

• Positive Nikolsky’s sign
  • Febrile
    • Staphylococcal scalded skin syndrome (children)
    • Toxic epidermal necrolysis/SJS (adults)
  • Afebrile
    • Toxic epidermal necrolysis
• Negative Nikolsky’s sign
  • Febrile
    • Toxic shock syndrome
    • Kawasaki disease
    • Scarlet fever
    • DRESS syndrome
    • Cellulitis
    • Acute generalized exanthematous pustulosis
  • Afebrile
    • Alcohol intoxication
    • Anaphylaxis
    • Cellulitis
    • Dermatitis (multiple types)
    • Drug rash
    • Erysipelas
    • Erythema multiforme
    • Exfoliative erythroderma
    • Scombroid
    • Vancomycin infusion reaction

Evaluation

• Clinical diagnosis based on:
  • History of drug exposure within preceding 1-4 weeks
  • Prodrome of fever and malaise
  • Positive Nikolsky sign
  • Mucosal erosions with skin detachment
• Labs:
  • CBC (leukopenia and thrombocytopenia = poor prognosis)
  • BMP (acute kidney injury, electrolyte derangements)
  • LFTs (hepatic involvement in ~10%)
  • Coagulation studies (DIC screening)
  • Blood cultures (if febrile)
  • Lactate
• Skin biopsy: full-thickness epidermal necrosis (distinguishes from SSSS)
• SCORTEN severity score (assess within first 24 hours):
  • Age >40, malignancy, HR >120, initial BSA detachment >10%, BUN >28, glucose >252, bicarb <20
  • Score ≥3 = mortality >35%; Score ≥5 = mortality >90%

Management

Immediate

• Discontinue ALL suspected causative medications immediately
  • Early drug withdrawal (within 24h of blister onset) improves survival
• Manage as a burn patient — transfer to burn center when stable
• Fluid resuscitation:
  • Less than typical burn (use 2/3 Parkland formula or ~2-3 mL/kg/%BSA/day)
  • Target UOP 0.5-1 mL/kg/hr
• Wound care:
  • Minimize handling; leave intact bullae when possible
  • Non-adherent dressings (e.g., Aquacel, petrolatum gauze)
  • Do NOT debride attached skin
• Temperature regulation: raise ambient temperature to 30-32°C

Supportive

• Pain control: IV opioids, avoid NSAIDs if suspected trigger
• Nutrition: early enteral nutrition via NG tube if unable to eat
• DVT prophylaxis
• Eye care: urgent ophthalmology consult, preservative-free lubricating drops, amniotic membrane grafting for severe involvement
• Mouth care: antiseptic mouthwash, viscous lidocaine
• Infection monitoring: avoid prophylactic antibiotics (increases resistance); culture if signs of sepsis
• Foley catheter if GU involvement

Specific Therapies (Controversial)

• Cyclosporine 3-5 mg/kg/day: best available evidence for mortality reduction
• IVIG: conflicting data, some protocols use 1-2 g/kg over 3-4 days
• Systemic corticosteroids: controversial; short pulse may be considered early
• TNF-α inhibitors (etanercept): emerging evidence for benefit

Disposition

• All patients require admission, preferably to a burn center ICU
• Consults: dermatology, ophthalmology, burn surgery
• Patients may require weeks-months of wound care and rehabilitation
• Long-term complications: skin scarring, ocular sequelae (symblepharon, blindness), genital stenosis
• Document causative drug allergy prominently in medical record

See Also

• Stevens-Johnson syndrome
• Drug eruptions
• Erythema multiforme
• Staphylococcal scalded skin syndrome
• Burns

References

• Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis. Part I: Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69(2):173.e1-13. PMID 23866878
• Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis. Part II: Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol. 2013;69(2):187.e1-16. PMID 23866879
• Sekula P, et al. Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. J Invest Dermatol. 2013;133(5):1197-1204. PMID 23389396
• Gonzalez-Herrada C, et al. Cyclosporine use in epidermal necrolysis is associated with an important mortality reduction. J Allergy Clin Immunol. 2017;139(2):607-615. PMID 27448444
• Bastuji-Garin S, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115(2):149-153. PMID 10951229