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For further information, see CMDT PART 6-32: REACTIVE ERYTHEMAS

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 (SJS) and toxic epidermal necrolysis (TEN)

    • 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 to significant body surface area (BSA) involvement and may be life-threatening

      • SJS is defined as atypical targetoid lesions involving < 10% BSA skin loss

      • TEN is present when skin loss is > 30% BSA

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

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

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

  • SJS/TEN is 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

  • SJS/TEN presents 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

  • Urticaria and drug eruptions are the chief entities that must be differentiated from erythema multiforme

  • In true urticaria, lesions are not purpuric or bullous, last less than 24 hours, and respond to antihistamines

  • Urticaria multiforme is a distinct eruption in infants and young children where patients present with fever and targetoid urticarial plaques


    • Autoimmune bullous diseases (including pemphigus and pemphigoid)

    • Acute generalized exanthematous pustulosis

    • Pustular psoriasis (rarely)


  • Blood tests are unhelpful

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


General Measures

  • Discontinue the offending medication

  • Move patients with > 25–30% BSA involvement to an appropriate acute care environment

  • Nutritional and fluid support and high vigilance for infection are important aspects of care



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