Erythema multiforme - Oral Mucosal Lesion
In the past, the conditions EM, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) were considered a continuum, but EM is now considered a distinct hypersensitivity eruption that does not progress to SJS/TEN. It can be distinguished from SJS/TEN based on the presence of typical target lesions (as opposed to atypical targetoid lesions) and papular (rather than macular) lesions.
In adults, the primary trigger for EM is herpes simplex virus (HSV), which is estimated to incite about 90% of cases. Mycoplasma is another common trigger. In children, important additional triggers to consider include drugs (particularly penicillin), group A Streptococcus, and Epstein-Barr virus among other viruses and bacteria.
Typically, all cutaneous lesions appear within 24-72 hours and persist for 2 weeks before fading. The eruption recurs on repeated exposure to the inciting agent.
EM demonstrates classical target lesions, raised atypical target lesions, or both concomitantly on the skin.
The following points should be kept in mind when a diagnosis of EM is being considered:
- Herpes labialis may precede, develop concomitantly, or manifest after the onset of EM. In almost half of all cases, herpes labialis precedes EM.
- Classical target lesions are well-defined circular lesions that are less than 3 cm in diameter, have 3 distinct color zones, and a central zone that has a bulla or crust.
- Atypical target lesions are palpable, poorly defined, circular lesions that have 2 distinct color zones. Raised atypical targets are a subtype of atypical targets that have a vesicle or bulla centrally.
- EM is not considered within the same disease spectrum as SJS/TEN and confers no risk in progressing to TEN.
- EM major refers to the presence of significant mucosal involvement in a case of EM, whereas in EM minor, mucosal involvement is absent or minimal.
- In EM major, painful intraoral and lip erosions eventuate from vesicles or bullae. Secondary crusting, including hemorrhagic crusting, then develops.
L51.9 – Erythema multiforme, unspecified
22972008 – Erythema multiforme, dermal type
- Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) – Clinically, look for irregularly shaped, dusky red necrotic macules on the trunk, face, and palms / soles. A positive Nikolsky sign can be found. Oral involvement in SJS/TEN parallels that of EM; there is mucosal involvement, including the eyes, lips, mouth, and genitalia. Look for hemorrhagic crusts and intraoral erosions. Precipitating factors are usually medications.
- Reactive infectious mucocutaneous eruption (RIME) – Usually occurs secondary to mycoplasma infection (as evidenced by clinical pneumonia, imaging studies, and/or mycoplasma serologies) although Chlamydia pneumoniae, human parainfluenza virus 2, rhinovirus, adenovirus, enterovirus, human metapneumovirus, and influenza B virus have more recently been recognized to cause a similar clinical picture. There is pronounced oral and ocular mucositis with absent, spare, or mild cutaneous involvement. Cutaneous lesions are most often tense vesiculobullae. Target or targetoid lesions may be present. Nikolsky sign is negative. Acute and convalescent mycoplasma titers may be employed to help to establish this diagnosis in the correct clinical scenario.
- Fixed drug eruption – May involve the lips. Has a characteristic round shape.
- Herpes simplex virus
- Lichen planus – Whitish reticulated plaques may be seen on the lips and oral mucosa. Erosive intraoral forms are less frequently seen.
- Pemphigus vulgaris – Lips are usually spared.
- Mucous membrane pemphigoid – This condition mostly affects the mucosa and almost always the gingiva, although other sites may be involved.
- Bullous pemphigoid – Intraoral erosions may be seen.
- Epidermolysis bullosa acquisita – Intraoral vesicles or bullae and ulcers occur in a minority of patients.
- Aphthous stomatitis
- Kawasaki disease
- Autoimmune progesterone dermatitis
- Paraneoplastic pemphigus