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Toxic Epidermal Necrolysis

Toxic Epidermal Necrolysis is a topic covered in the 5-Minute Clinical Consult.

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A severe T-cell–mediated immunologic reaction resulting in extensive epidermal detachment that requires immediate drug withdrawal (if inciting medication present) and admission to a burn/ICU unit


  • Toxic epidermal necrolysis (TEN) is a severe dermatologic condition marked clinically by extensive epidermal detachment of skin and mucous membranes.
  • On the same spectrum as Stevens-Johnson syndrome (SJS) with TEN defined as >30% body surface area (BSA) epidermal detachment. SJS is <10% BSA involvement, whereas SJS/TEN overlap is 10–30% BSA involvement.
  • Most often the result of an adverse drug reaction: secondary to inappropriate immune response/activation to drug or drug metabolites
  • System(s) affected: skin/mucosa, respiratory, gastrointestinal (GI), genitourinary, ocular involvement
  • Synonym(s): toxic erythema necrosis; Lyell syndrome (1)


  • Incidence of 0.4 to 1.9 cases per million per year worldwide; with the highest incidence in Africa, Asia, and India
  • Affects all ages; males and females are affected equally.
  • Special consideration in the geriatric population, immunosuppressed and HIV patients (risk 1:1,000), and those with malignancy
  • The risk of mortality increases with surface area involved, and meta-analyses of the literature shows the risk to be between 16% and 55% (2).

Etiology and Pathophysiology

  • TEN is characterized by widespread keratinocyte apoptosis that leads to epidermal detachment from the dermis.
  • Pathologic mechanism has not been fully established, although immune mechanisms and altered drug metabolism have been suggested:
    • Recognition of offending drug triggers HLA class 1 molecule-initiated CD8+ cytotoxic T-cell activation (CD8+ T cells). T cell and natural killer (NK) cell induce damage via perforin/granzyme/granulysin damage or Fas/Fas ligand (FasL) interaction.
    • Tumor necrosis factor-α (TNF-α) and reactive nitric oxide have also been implicated in keratinocyte damage (3).
  • >80–90% of TEN is drug-induced. >100 drugs have been found to cause SJS/TEN. Commonly implicated medications include the following:
    • Antibacterial and antifungal agents (sulfonamides, penicillins, cephalosporins, tetracycline, terbinafine)
    • Anticonvulsants (hydantoins, barbiturates, carbamazepine, lamotrigine)
    • Nonantibiotic sulfonamides (sulfasalazine)
    • Analgesics, oxicam-NSAIDs
    • Allopurinol
    • Nevirapine


Certain HLA haplotypes predispose to increased susceptibility to SJS/TEN with particular drug use:

  • HLA-B*1502 has been associated with carbamazepine-induced SJS in the Han Chinese population; the FDA recommends genotyping of all Asian patients for HLA-B*1502 before initiating carbamazepine treatment.
  • HLA-B*5801 has been linked to allopurinol-induced SJS. HLA-B85701, HLADR7, and HLA-DQ3 are associated with abacavir-induced hypersensitivity.
  • HLA-A*0206 and HLA-B12 may be a marker of increased ocular complications in SJS/TEN in Japanese and Caucasian patients, respectively (1).

Risk Factors

  • Immunosuppression, including HIV/AIDS, specific HLA haplotypes, and malignancy (1)
  • Multiple concurrent medications increase risk.

General Prevention

  • Always ask patients about prior adverse drug events.
  • Be aware of medications with higher incidence of cutaneous drug reactions.

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Stephens, Mark B., et al., editors. "Toxic Epidermal Necrolysis." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688192/all/Toxic_Epidermal_Necrolysis.
Toxic Epidermal Necrolysis. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688192/all/Toxic_Epidermal_Necrolysis. Accessed March 24, 2019.
Toxic Epidermal Necrolysis. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688192/all/Toxic_Epidermal_Necrolysis
Toxic Epidermal Necrolysis [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 March 24]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688192/all/Toxic_Epidermal_Necrolysis.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Toxic Epidermal Necrolysis ID - 1688192 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688192/all/Toxic_Epidermal_Necrolysis PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -