Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis is a topic covered in the Select 5-Minute Pediatrics Topics.

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Basics

Description

  • Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, potentially fatal, mucocutaneous drug reactions characterized by epidermal necrosis involving skin and at least 2 mucous membranes.
  • The cutaneous necrosis leads to widespread epidermal detachment and loss of skin barrier function.
  • Given the potential risk for infection and fluid and electrolyte imbalances with widespread denudation, SJS and TEN are considered medical emergencies.

Epidemiology

Incidence

  • Overall annual risk of 0.5–1.9 per million in the general population
  • The precise incidence in children is unknown.
  • Patients with HIV have a 1,000-fold increased risk.

Risk Factors

  • Exposure to inciting medications
  • Infection with Mycoplasma pneumoniae, HIV
  • Genetic background
  • Coexistence of cancer
  • Concomitant radiotherapy

Genetics

  • Recently, strong associations have been made between HLA alleles and SJS/TEN.
  • Associations are ethnic population–specific and therefore universal screening of HLA alleles is rarely recommended.
  • The FDA recommends checking for HLA-B*1502 in Asian populations where this HLA subtype is highly prevalent before prescribing carbamazepine.

General Prevention

Once SJS/TEN has occurred, the inciting medication and any cross-reacting medications should be avoided.

Pathophysiology

  • Widespread keratinocyte and mucosal cell death occurs secondary to CD8+ T-cell–mediated apoptosis via Fas and Fas ligand pathways and/or direct granulysin secretion. Fas receptors are located on keratinocytes and, when activated with Fas ligand, induce apoptosis and therefore necrosis of epidermal cells. Granulysin is released from cytotoxic T cells and induces apoptosis by creating holes in target cell membranes.
  • The exact mechanism by which the implicated drug or infection triggers activation of cytotoxic T cells and the upregulation of the Fas/FasL pathway is unknown.
  • Soluble Fas ligand is increased in patients with SJS/TEN.
  • IVIG theoretically acts to block the Fas–FasL connection, thereby interrupting keratinocyte death and epidermal necrosis. Trials that show a benefit of IVIG use demonstrate improvement of disease severity but not complete abolition of symptoms; this incomplete effect may be due to IVIG being started too late in the disease progression or due to a potential alternative pathway to keratinocyte destruction.

Etiology

  • <5% of cases have no known cause.
  • Medications
    • Over 100 medications have been implicated in causing SJS/TEN.
    • High-risk drugs include aromatic amine anticonvulsants such as carbamazepine, phenobarbital and phenytoin, lamotrigine, β-lactam antibiotics, sulfa medications (including trimethoprim-sulfamethoxazole and sulfasalazine), minocycline, cephalosporins, quinolones, NSAIDs (especially peroxicam and meloxicam), allopurinol, and nevirapine.
  • Acetaminophen (very rare)
    • Recently, the FDA issued a warning about the risk of acetaminophen-related SJS/TEN.
    • Although SJS/TEN is a very rare occurrence in patients taking acetaminophen, the ubiquity of acetaminophen in prescription and OTC products prompted the requirement for new labeling.
  • A greater risk of developing SJS/TEN is seen in the first 8 weeks of treatment with these medications, with the highest risk being 1–3 weeks after exposure.
  • M. pneumoniae
    • A well-established nondrug cause of SJS/TEN
    • More commonly implicated in children and adolescents
  • There is scant evidence that vaccines, neoplastic syndromes, and autoimmune disease such as SLE may play a role in etiology.
  • Herpes simplex virus–associated erythema multiforme (EM) was historically categorized on the spectrum with SJS and TEN, but new classification schemes place it as a separate entity.

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Citation

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TY - ELEC T1 - Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis ID - 14066 Y1 - 2015 PB - Select 5-Minute Pediatrics Topics UR - https://im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14066/all/Stevens_Johnson_Syndrome_and_Toxic_Epidermal_Necrolysis ER -