Erythema multiforme (EM) is a rare, acute hypersensitivity reaction most commonly triggered by herpes simplex virus (HSV) infections. Other triggers include M. pneumoniae infection, certain drugs, and immunizations. EM is mainly seen in adults between 20–40 years of age. Clinical features include a rash of varied appearance, beginning as macules and papules, which evolve into characteristic target lesions. The rash first appears on the dorsal aspect of the hands and feet then extends proximally. If mucous membrane involvement and systemic symptoms occur, the condition is defined as EM major. The diagnosis is often clear on history and physical examination, whereas serology for underlying infectious causes and/or skin biopsy may be necessary in doubtful or recurrent cases. EM is usually self-limiting and resolves spontaneously within a month; symptomatic treatment with NSAIDs, antihistamines, and topical steroids is generally sufficient. In severe cases of EM major, hospitalization to treat dehydration, severe pain, and possible bacterial superinfection may be necessary.
- Incidence: < 1% per year
- Age: mainly adults 20–40 years
- Sex: slight male predominance
Epidemiological data refers to the US, unless otherwise specified.
Erythema multiforme is a type IV hypersensitivity reaction; which can be triggered by the following.
- Infections: (most common): herpes simplex virus (HSV), Mycoplasma pneumoniae, and fungal infections
- Drugs: : e.g., barbiturates, phenytoin; , NSAIDs, beta-lactam antibiotics (e.g., penicillins); , and sulfonamides
- Immunizations (rare): e.g., after diphtheria, tetanus, influenza, hepatitis B vaccination
- Acute onset, with progression from erythematous macules to papules and vesicles to target lesions
- Characteristic of EM, appear a few days after the onset of rash, may be absent in some patients
- Target lesions have 3 zones: an inner dark red/brown zone, surrounded by a pale zone, and an outer erythematous ring
- Epithelial necrosis is present in the inner zone
- May be asymptomatic or cause pruritus and painful burning
- Nikolsky sign is negative
- Symmetrical distribution
- Affects backs of hands and feet first → spreads proximally and can affect the entire body, including palms and soles
- Mucous membrane involvement
- Further symptoms: fever, myalgia, and arthralgia in cases of EM major
The diagnosis is mainly clinical and should be suspected (especially) if there is a history of recurrent labial herpes, recent drug intake, or immunizations.
- Serology or PCR testing: in patients with suspected HSV/M. pneumoniae infections (see also herpes simplex virus infections, atypical pneumonia, and pneumonia for diagnostic procedures)
- Skin biopsy: indicated only in doubtful cases (e.g., no target lesions, recurrent EM)
- Stevens-Johnson syndrome: In comparison to EM, skin involvement in SJS is more severe and usually triggered by drugs.
- Urticaria: The lesions of urticaria are transient, disappearing within a few hours, while those of EM last up to a month; target lesions are uncommon.
- Prodrome phase of bullous pemphigoid: Prodromal rash resembles that of urticaria/EM; oral involvement is rare.
Fixed drug eruption
- Definition: hypersensitivity reaction to specific drugs occurring within 8 hours of exposure
- Clinical features
- Well-defined, erythematous, pruritic lesions (often solitary)
- Oral mucosa may be affected; atypical target lesions may be present
- Resolves spontaneously on stopping the offending drug; may cause postinflammatory hyperpigmentation
- Diagnosis: provocation tests (oral challenge test/skin patch test)
- For details, see “Overview of annular skin lesions.”
The differential diagnoses listed here are not exhaustive.
In most cases of EM, no treatment is necessary because the condition is self-limiting.
- General: stop the offending drug or treat the underlying infection
Mild cases: symptomatic treatment
- Analgesics, NSAIDs
- Antihistamines (for pruritus)
- Topical steroids and saline (gargling) solutions
- Topical lubricants (for eye involvement)
- Severe cases: (EM major): hospitalize and treat as thermal burns
- Recurrent EM: oral acyclovir for 4 months; if no recurrence, then taper and stop
- EM is usually self-limiting; rash spontaneously disappears within a month
- Some patients may have a recurrence of EM.