• A generalized hypersensitivity reaction, usually to a drug, in which skin and mucous membrane lesions are an early manifestation.
• Once considered to be the same as erythema multiforme major, a severe form of erythema multiforme in which >1 mucosal surface was involved, but many now consider it to be a different disease with a more difficult course and a more ominous prognosis.
• May progress to its more severe form, toxic epidermal necrolysis (TEN), which has a high morbidity and up to 70% mortality (1).
• System(s) affected: Cardiovascular; Hemic/Lymphatic/Immunologic; Nervous; Renal/Urologic; Skin/Exocrine
• Synonym(s): Ectodermosis erosiva pluriorificialis; Febrile mucocutaneous syndrome; Herpes iris; Erythema polymorphe; Toxic epidermal necrolysis (TEN).

ALERT

• Dangerous progression
• Patients with discrete skin lesions and >10% epidermal detachment are at risk of rapid progression to TEN.

Geriatric Considerations
Toxic epidermal necrolysis has a greater mortality in older patients.

Pediatric Considerations

• Rare in children <3 years
• More common in children and young adults

Pregnancy Considerations
Pregnancy is a possible predisposing condition.

Incidence

• Incidence/Prevalence in the US is difficult to estimate because there is no universally accepted definition of SJS.
• 1.1–7.1 and 0.4–1.2 cases per million person-years for SJS and TEN, respectively (1)

Prevalence

• Predominant age: SJS is more common in children and young adults.
• Predominant gender: Males > Females (2:1)
• Sex (% range of females): 33–62% for SJS and 61.3–64.3% for TEN (1)
• Age (average range): 25–47 years for SJS and 46–63 years for TEN (1)

• Previous history of SJS
• Patients with HIV infection may be predisposed to developing SJS in response to their medications:
  • HLA subtypes A, B, and D
  • Disease that cause immune compromise (deficiencies, malignancy, etc)
  • Possibly radiation therapy or UV light

Genetics
Possibly associated with HLA-B15, HLABw44, part of HLA-B12, and HLA-DQB1*0601

Secondary prevention may be possible by avoiding exposure to offending medications or chemical agents.

• Accumulation and binding of reactive drug metabolites to mucocutaneous epithelial cells as haptens. Drug-haptens signal T-lymphocyte and macrophages, which infiltrate and express IL-2, TNF-α, and interferon-γ expression.
• Erythematous papular lesions and keratinocyte necrosis is a consequence of cell-mediated immunity.
• Occurs 1–2 weeks after initial exposure to offending drugs and within 48 hours upon rechallenge.

• 50% of cases are idiopathic.
• Associated with metabolism of parent drugs and metabolites
• Sulfonamides are the drugs most strongly associated with SJS and TEN, then:
  • Cephalosporins
  • Quinolones
  • Aminopenicillins
  • Tetracyclines
  • Macrolides
  • Imidazole antifungals
  • Anticonvulsants
  • NSAIDs, especially oxicam
  • Vaccines—dPT, bCG, oral polio
  • Mycoplasma pneumonia infection

• TEN is a dangerous progression of Stevens-Johnson syndrome.
• Mycoplasma pneumonia may be an infectious precursor.