• An acute self-limited hypersensitivity reaction involving the skin and sometimes the mucus membranes:
  • Erythema multiforme (also called the erythema multiforme Hebra) is a mild disease that appears as a pleomorphic rash and includes target lesions, but not large vesicles or petechia, affecting the skin with or without involving 1 mucus membrane site.
  • Three clinical subgroups have been identified:
    • Classical: A single episode as described;
    • Recurrent: Episodes recur, usually in synchrony with herpes simplex outbreaks
    • Persistent: Rare; only 23 cases having been reported in the world literature
• Acceptance of the diagnostic criteria for erythema multiforme is not universal. Much of the literature consists of reports of 1 or 2 cases with “an erythema multiform-like rash.” Many authors refer to episodes of Stevens-Johnson syndrome as erythema multiforme, or erythema multiforme major, and others describe patients with oral lesions but no rash as “atypical erythema multeforme.” Some authors consider erythema multeforme to be a mild form of Stevens-Johnson syndrome, but there appears to be a growing consensus that the 2 are unrelated (11).
• System(s) affected: Skin/Exocrine
• Synonym(s): Erythema exudativum multiforme

Incidence
The incidence in the US is not known. In Germany, the incidence of erythema multiforme major, Stevens Johnson syndrome, and toxic epidermal necrolysis combined appears to be 0.189/100,000 persons per year.

Prevalence

• Predominant age: Peak incidence in 20s and 30s; rare < age 3 and > age 50
• Predominant sex: Male > Female (3:2)

Previous history of erythema multiforme

Genetics
Possibly associated with HLA-B15

• Known or suspected etiologic agents should be avoided.
• Acyclovir may help prevent herpes-related erythema multiforme.
• Tamoxifen has been shown to prevent premenstrual-related disease.

• Most cases appear to be due to a preceding infection. Viral infections, particularly herpes simplex; also Epstein-Barr, Coxsackie, echovirus, varicella, mumps, and poliovirus
• Bacterial infections, including brucellosis, diphtheria, borreliosis
• Mycoplasma appears to more often precede Stevens-Johnson syndrome.
• Protozoan infections
• Fungal infection, including Trichophyton rubrum
• Collagen vascular diseases
• Malignancy
• Pregnancy
• Premenstrual hormone changes
• Consumption of beer
• Reiter syndrome
• Sarcoidosis
• Vaccines: Tetanus/Diphtheria, bacillus Calmette-Guérin, oral polio vaccine
• Medications: Drugs seem to be an infrequent cause of erythema
• The list of drugs that have been reported as being involved includes sulfonamides, penicillins, anticonvulsants, and salicylates, but most of these were actually associated with Stevens Johnson syndrome when it was considered to be a type of erythema nodosum major.

• Any of the infections or diseases listed under “Etiology”
• Alert skin biopsy

ALERT
Pregnancy Considerations
Reported as a possible etiologic condition