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

Risk Factors

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

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.