Erythema Multiforme (EM)

EM is an acute, self-limiting immune-mediated mucocutaneous blistering condition characterized by the presence of symmetrically distributed target or iris lesion on the trunk and extremities.15 Oral manifestations occur in more than 70% of EM cases, often affording the oral healthcare professional the opportunity to establish a prompt diagnosis. Accurate epidemiologic information is lacking, but the incidence of EM appears to be well under 1%.15

EM has been attributed to a T lymphocyte-mediated type IV cytotxic reaction targeting blood vessels of the skin and mucosa.16 Numerous triggering factors have been identified and include infectious agents, drugs, immune conditions, toxins, and chemicals (Table 2). Infectious agents are implicated in up to 90% of cases, with herpes representing about 75% of such cases. The most commonly implicated drug triggers are the sulfonamides.15

Table 2. Some Potential Triggers for Erythema Multiforme.
Infectious Drugs
Herpes viruses Sulfonamides
Adenoviruses NSAIDs
Enteroviruses Penicillins
Mycoplasma pneumoniae Anticonvulsants (barbiturates, carbamazepine)
Corynebacterium diphtheriae Hydantoids
Hemolytic streptococci Valproic acide
Legionella pneumophila Allorpurinol

The oral lesions of EM can affect any area of the mouth and present a varied clinical appearance ranging from diffuse erythema to multifocal superficial ulcerations and bullae. Lip lesions often present a characteristic hemorrhagic crusting (Figure 3). The oral pain may impair the patient’s ability to speak, drink, and eat.15

Figure 3. Erythema Multiforme 70-year-old Female.

Image of erythema multiforme 70-year-old female.

Skin lesions can present in various forms, hence the term multiforme. The classic skin lesions present as concentric erythematous rings separated by rings of near normal color with lesions size ranging from 2 to 20 mm. These lesions are known as target or iris lesions. Cutaneous manifestations of EM tend to start on the hands and move towards the trunk in a symmetric pattern.

It should be noted that the most serious variants of the EM spectrum, Steven-Johson syndrome (SJS) and toxic epidermal necrolysis (TEN), are now considered to be distinct conditions based on their different clinical presentations, patient demographics and potential causes.15-17

Table 3. SJS, SJS/TEN, TEN.
SJS Skin: 2% - < 10%
Mucosa: Oral plus genital and / or conjunctival
Mortality rate: 1% - 5%
SJS/TEN Skin: 10% - 30%
Mucosa: Oral plus genital and / or conjunctival
TEN Skin: > 30%
Mucosa: Multisite
Mortality rate: 25% - 35%

Therapeutic Strategies

The management of EM is dictated by the severity of the clinical presentation. However, an essential element of treatment is the identification of potential initiating factors.15,16 The patient’s physician should be consulted to discontinue potentially offending drugs.

Therapy for mild cases of EM with limited cutaneous and mucosal involvement is symptomatic and supportive. Topical steroids, anesthetics, and analgesics may be beneficial and maintenance of nutritional and fluid intake is mandatory. The use of an extemporaneous rinse of equal parts diphenhydramine 12.5 mg/5 mL, nystatin suspension, Maalox, and water as a swish and spit out, up to four times a day may be prescribed.15

Gel formulations of topical steroids to promote lesion resolution may be useful, especially for early stage disease. For all cases, frequent monitoring for resolution is essential. Prophylactic antiviral (e.g., acyclovir, valacyclovir, famcyclovir) therapy to reduce the risk of EM attributable to HSV should be considered.15 A comprehensive discussion of anti-HSV chemotherapy is presented elsewhere.18 Patients with progressing EM or signs and symtoms of SJS or TEN warrant immediate medical referal.