Erythema Multiforme Clinical Presentation

Updated: Feb 20, 2020
  • Author: Jose A Plaza, MD; Chief Editor: William D James, MD  more...
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In addition to characterizing skin and mucous membrane lesions of erythema multiforme (EM), a complete history should document recent constitutional symptoms, previous history of or current herpes simplex (HSV) or Mycoplasma pneumoniae infection, and all use of prescription and over-the-counter (OTC) medications, with particular attention to those started in the previous 2 months. Patients may have a history of anxiety.


Prodromal symptoms are usually absent or mild in persons with erythema multiforme minor, consisting of a mild, nonspecific upper respiratory tract infection. The abrupt onset of a rash usually occurs within 3 days, starting on the extremities symmetrically, with centripetal spreading. Pruritus is generally absent

In erythema multiforme major, 50% of patients have prodromes similar to an influenzalike prodrome, including moderate fever, general discomfort, cough, sore throat, vomiting, chest pain, and diarrhea (secondary to gastrointestinal [GI] tract ulceration). These symptoms have a classic time course of development and are usually present for 1-14 days before the cutaneous eruption occurs. The lesions begin on the acral areas and spread similarly to the distribution of erythema multiforme minor (ie, usually symmetrical and extend from the face and torso to the trunk and proximal extremities).

Prominent mucosal involvement may also occur in erythema multiforme major. Erosions of the oral mucosa may result in difficulty in eating, drinking, or opening the mouth. Conjunctival involvement may cause lacrimation, photophobia, burning eyes, or visual impairment. Genital lesions are painful and may result in urinary retention; painful micturition due to genitourinary tract ulceration may also occur. Shortness of breath or difficulty in breathing may occur due to tracheobronchial epithelial involvement.

A localized form of erythema multiforme has been reported at the site of marrow aspiration. Half the children with erythema multiforme have a history of herpes labialis or genitalis. Although the onset usually precedes erythema multiforme by 3-14 days, it may still be present at the onset of erythema multiforme.


Physical Examination

The hallmark of erythema multiforme (EM) is a target lesion with variable mucous membrane involvement.

Skin lesions

The initial lesion is a dull-red, purpuric macule or urticarial plaque that expands slightly to a maximum of 2 cm over 24-48 hours. In the center, a small papule, vesicle, or bulla develops, flattens, and then may clear. An intermediate ring develops and becomes raised, pale, and edematous. The periphery gradually changes to become cyanotic or violaceous and forms a typical concentric, “target” lesion. Some lesions consist of only 2 concentric rings (see the first image below). Polycyclic or arcuate lesions may occur (see second image below). Some lesions appear at areas of previous trauma (Koebner phenomenon). Postinflammatory hyperpigmentation or hypopigmentation may occur. The Nikolsky sign is negative (ie, top layers of the skin do not slip away from the lower layers when slightly rubbed).

Target lesion of erythema multiforme. Target lesion of erythema multiforme.
Raised atypical targets and arcuate lesions. Raised atypical targets and arcuate lesions.

Skin distribution

The lesions are symmetrical, predominantly on the acral extensor surfaces of the extremities, and they spread centripetally to involve the abdomen and back. Lesions may also coalesce and become generalized. The palms, neck, and face are frequently involved. Lesions of the soles and flexural aspects of the extremities are less common. A zosteriform distribution may be present.

Mucosal lesions

Mucosal lesions usually heal without sequelae. The mucosal involvement in Stevens-Johnson syndrome is more severe and more extensive than that of erythema multiforme major. Generalized lymphadenopathy often accompanies erythema multiforme major.

Other findings

Mild temperature elevation is usually noted. Hyperventilation and mild hypoxia may result from anxiety or tracheobronchial involvement.

Dehydration may range from mild to massive as a result of the following factors:

  • Evaporation through open skin lesions

  • Poor oral intake secondary to oropharyngeal mucous membrane involvement

  • Profuse diarrhea from involvement of bowel mucosa

  • Increased insensible losses secondary to elevated core body temperature



Most patients with erythema multiforme (EM) have an uncomplicated course, with the exception of hosts who are immunocompromised and those with secondary bacterial infections of the skin or the mucosa. Healing of the mucosal areas is usually complete.

Scars and strictures of the esophageal, urethral, vaginal, and anal mucosa rarely occur. However, severe oral involvement may be accompanied by difficulty in consuming food and fluid and can result in dehydration, and vaginal and urethral erosions may cause urinary retention and phimosis. Hematocolpos is the result of genital lesions in teenage females. Severe scarring of the genitourinary tract may cause vaginal and urethral stenosis.

Severe eye complications (20%), such as purulent conjunctivitis, anterior uveitis, panophthalmitis, scarring of the conjunctivae, symblepharon, may result in permanent blindness. Other ocular sequelae may include the following:

  • Epiphora secondary to obstruction of the lacrimal ducts

  • Sjögren-like sicca syndrome of dry eyes, punctate keratitis, corneal pannus, and mucin deficiency in tears

  • In-turned eyelashes, corneal scarring, corneal and conjunctival neovascularization, epithelial proliferation with squamous metaplasia, photophobia, burning eyes, visual impairment

Other complications include the following:

  • Patchwork appearance of the skin, with hypopigmented regions and potential hypertrophic scarring

  • Pneumonia / acute respiratory distress syndrome (ARDS)

  • Dehydration and electrolyte disturbances

  • Possible gastrointestinal (GI) hemorrhage, nephritis, and renal failure