Toxic epidermal necrolysis: Difference between revisions
(Comprehensive expansion: SCORTEN score, detailed management (wound care, cyclosporine, fluid resuscitation), drug causes, mucosal involvement, added peer-reviewed references with PMIDs)
Line 1: Line 1:
==Background==
==Background==
{{Skin anatomy background images}}
{{Skin anatomy background images}}
*Explosive dermatosis with tender erythema, bullae, and subsequent exfolliation
*Severe, life-threatening mucocutaneous reaction characterized by widespread epidermal necrosis and detachment
*Most commonly caused by medications
*Represents a spectrum with [[Stevens-Johnson syndrome]] (SJS):
**Sulfa drugs, [[penicillins]], [[anticonvulsants]], and [[NSAIDs]]
**'''SJS''': <10% body surface area (BSA) detachment
**Other causes: infection, chemicals, malignancy, immunologic factors
**'''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==
==Clinical Features==
[[File:Necrolysis epidermalis toxica 02.jpg|thumb|Toxic epidermal necrolysis on legs]]
[[File:Necrolysis epidermalis toxica 02.jpg|thumb|Toxic epidermal necrolysis on legs]]
[[File:TENS patient on day 10.jpg|thumb|The back of a TENs patient on day 10, at the peak of the condition]]
[[File:TENS patient on day 10.jpg|thumb|The back of a TENs patient on day 10, at the peak of the condition]]
*Malaise, anorexia, [[myalgia]]s, [[arthralgia]]s, [[fever]], painful skin, GI symptoms
*'''Prodrome''' (1-3 days before skin findings):
*Extracutaneous manifestations may persist for 1-2 weeks following skin symptoms
**[[Fever]], malaise, [[myalgia]]s, [[arthralgia]]s, painful skin, pharyngitis
*Exam with warm tender erythema with overlying flaccid [[vesiculobullous rashes|bullae]], erosions with exfoliation
*'''Skin findings''':
*Positive Nikolsky's sign (able to rub off superficial layers of skin with pressure)
**Tender erythematous or dusky macules → confluent areas of necrosis
*Mucosal involvement (oral, conjunctival, respiratory, GU)
**Flaccid [[vesiculobullous rashes|bullae]] with full-thickness epidermal detachment
*Systemic toxicity
**'''Positive Nikolsky sign''' (lateral pressure causes epidermal separation)
*25-35% Mortality
**'''Positive Asboe-Hansen sign''' (pressure on blister causes lateral extension)
**Death is usually caused by [[infection]], [[hypovolemia]], and [[electrolyte disorders]]
**Skin sloughs in sheets, leaving raw denuded dermis
*Predictors of poor prognosis include: age, extent of disease, [[leukopenia]], azotemia, and [[thrombocytopenia]]
*'''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==
==Differential Diagnosis==
*Toxic infectious erythemas
*[[Stevens-Johnson syndrome]] (same spectrum, <10% BSA)
*[[Staphylococcal scalded skin syndrome]] (SSSS) — superficial cleavage plane, no mucosal involvement, children
*Exfoliative [[drug eruptions]]
*Exfoliative [[drug eruptions]]
*Primary blistering disorders
*[[Pemphigus vulgaris]]
*[[Stevens-Johnsons syndrome]]
*Acute [[graft-versus-host disease]]
*Generalized bullous [[fixed drug eruption]]
*Toxic [[shock]] syndrome


{{Erythematous rash DDX}}
{{Erythematous rash DDX}}


==Evaluation==
==Evaluation==
*History of drug exposure
*'''Clinical diagnosis''' based on:
*Prodrome of malaise and fever
**History of drug exposure within preceding 1-4 weeks
*Positive Nikolsky sign  
**Prodrome of fever and malaise
*Oral, ocular, and/or genital mucositis with painful erosions
**Positive Nikolsky sign
*Necrosis and sloughing of the epidermis
**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%


*Diagnosis is made my skin biopsy
==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


*SJS vs TEN
===Supportive===
**SJS - skin detachment of <10% of [[BSA]]
*'''Pain control''': IV opioids, avoid NSAIDs if suspected trigger
**TEN – skin detachment of >30% of [[BSA]]
*'''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


==Management==
===Specific Therapies (Controversial)===
*Monitor cardiopulmonary status closely
*'''Cyclosporine''' 3-5 mg/kg/day: best available evidence for mortality reduction
*Correct [[IVF|fluid]] and [[electrolyte imbalances]]
*'''IVIG''': conflicting data, some protocols use 1-2 g/kg over 3-4 days
*Attend to infectious complications
*'''Systemic corticosteroids''': controversial; short pulse may be considered early
*'''TNF-α inhibitors''' (etanercept): emerging evidence for benefit


==Disposition==
==Disposition==
*ICU
*'''All patients require admission''', preferably to a '''burn center ICU'''
*Best cared for in a burn unit
*Consults: '''dermatology, ophthalmology, burn surgery'''
*Immediate derm consult
*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==
==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


[[Category:Dermatology]]
[[Category:Dermatology]]
[[Category:Critical Care]]
[[Category:Critical Care]]

Revision as of 19:34, 21 March 2026

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):
  • 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:

Differential Diagnosis

Erythematous rash

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:
  • 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

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
Retrieved from "https://www.wikem.org/w/index.php?title=Toxic_epidermal_necrolysis&oldid=388311"