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.
- 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
- Target lesions
- May be asymptomatic or cause pruritus and painful burning
- Nikolsky sign is negative
- 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 , , and for diagnostic procedures)
- Skin biopsy: indicated only in doubtful cases (e.g., no target lesions, recurrent EM)
- : In comparison to EM, skin involvement in SJS is more severe and usually triggered by drugs.
- : 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 : 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
- 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
- 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.