Oral Ulceration - Erythema Multiforme

Aetiology

Although the aetiology is unclear in most patients, in some it is precipitated by infections (such as herpes simplex or mycoplasma), drugs (sulphonamides, barbiturates, hydantoins and others) or a range of other triggers such as hormonal changes.

Clinical features

The oral lesions often recur but the condition usually resolves after six or seven episodes. Usually attacks occur for 10 to 14 days once or twice a year but the periodicity can vary from weeks to years. Erythema multiforme may affect the mouth alone, or skin and/or other mucosa.

The major form (Stevens-Johnson syndrome) causes widespread lesions affecting mouth, eyes, skin and genitals, with fever and toxicity, bullous and other rashes, pneumonia, arthritis, nephritis or myocarditis. Toxic epidermal necrolysis (TEN) presents similarly but is usually drug-related.

The minor form of erythema multiforme is much more common and affects only one site.

Oral lesions include:

Lips – cracked, bleeding, crusted, swollen
Ulcers – diffuse and widespread. Oral lesions progress through macules to blisters and ulceration, typically most pronounced in the anterior parts of the mouth. Extensive oral ulceration may be seen.

Other lesions:

Rashes – various but typically ‘iris’ or ‘target’ lesions or bullae on extremities
Ocular changes: resemble those of mucous membrane pemphigoid, and dry eyes and symblepharon may result
Genital lesions: balanitis, urethretitis and vulval ulcers

Management

Specialist referral is indicated, particularly in patients with major forms such as Steven-Johnson syndrome, who may need hospital care.

Biopsy may well be indicated but pathology can be variable because there may be subepithelial or intra-epithelial vesiculation, and immunostaining is not specific – showing fibrin and C3 at the basement membrane zone, and perivascular IgM, C3 and fibrin. Differentiation from acute herpetic stomatitis can be difficult; virolological studies may thus be indicated.

Precipitating factors, when identified, should be treated. Aciclovir or periciclover may be indicated in erythema multiforme related to herpes simplex infection.

Oral hygiene should be improved with 0.2% aqueous chlorhexidine mouthbaths. In addition, major erythema multiforme should be treated with systemic corticosteroids and/or azathioprine or other immunomodulatory drugs. Specialist care is indicated and some patients need hospitalization. Levamisole and thalidomide have been used to some effect on occasion. Minor erythema multiforme may respond to symptomatic treatment and topical corticosteroids, but systemic steroids may still be required.