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Key Features

Essentials of Diagnosis

  • Erythema multiforme

    • Herpes simplex is the most common cause

    • Cutaneous lesions are true three ring targets

    • Presents on the extensor surfaces, palms, soles, or mucous membranes

    • Disease remains localized

  • Stevens-Johnson syndrome

    • Medications are the most common cause

    • Cutaneous lesions are targetoid, but often not true three ring targets

    • Favors the trunk

    • Involves two or more mucous membranes

    • May progress on to have significant body surface involvement and may be life-threatening

General Considerations

  • Erythema multiforme

    • An acute inflammatory skin disease due to multiple causes

    • May also present as recurring oral ulceration and diagnosed by oral biopsy, with skin lesions present in only half of the cases

    • Was traditionally divided into minor and major types based on the clinical findings

      • Because ~90% of erythema multiforme minor follow outbreaks of herpes simplex, the preferred term is "herpes-associated erythema multiforme"

      • The term "erythema multiforme major" has been abandoned

  • Stevens-Johnson syndrome is defined as atypical targetoid lesions involving < 10% body surface area (BSA) skin loss

  • Toxic epidermal necrolysis is present when there is skin loss of > 30% BSA

  • SJS/TEN overlap is used to describe cases with between 10% and 30% BSA skin denudation

  • The abbreviation SJS/TEN is often used to refer to these three variants of what is considered one syndrome

  • All of these clinical scenarios are characterized by toxicity and involvement of two or more mucosal surfaces (often oral and conjunctival)

Clinical Findings

Symptoms and Signs

  • Classic target lesion, as in herpes-associated erythema multiforme, consists of three concentric zones of color change, and is most often found acrally on the hands and feet

  • Drug-associated bullous eruptions in the SJS/TEN spectrum present with raised target-like lesions, with only two zones of color change and a central blister, or as nondescript reddish or purpuric macules

  • Pain may occur on eating, swallowing, or urination

  • Blisters are always worrisome and dictate the need for consultation

Differential Diagnosis

  • Herpes-associated erythema multiforme

    • Drug eruption

    • Urticaria

    • Individual lesions of true urticaria itch, should come and go within 24 hours, and are usually responsive to antihistamines


    • Autoimmune bullous diseases (including pemphigus and pemphigoid)

    • Acute generalized exanthematous pustulosis

    • Pustular psoriasis (rarely)


Laboratory Tests

  • Blood tests are unhelpful


  • Presence of a blistering eruption requires biopsy

  • Skin biopsy is diagnostic (direct immunofluorescence studies are negative)



Table 6–2.Useful topical dermatologic therapeutic agents.

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