Erythema multiforme !
A short-lived skin reaction, usually after a cold sore (herpes) infection, with target-shaped spots on the hands, arms and legs.
Updated 2026-11-01
Structures involved
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Why it happens
What it is
An acute immune-mediated reaction of the skin and sometimes mucosae, characterised by typical target lesions that appear mainly on the extremities. Most cases follow herpes simplex virus infection, and it is distinct from Stevens-Johnson syndrome.
Who gets it
Affects mainly young adults between 20 and 40 years, somewhat more men. Recurrent episodes are usually linked to recurrent herpes simplex. It is uncommon in children.
Causes
- Herpes simplex virus (HSV-1 and HSV-2) infection: the most common trigger
- Mycoplasma pneumoniae infection, especially in children (often with more mucosal involvement)
- Drugs in a minority of cases (for example sulfonamides, anticonvulsants, NSAIDs)
- Other infections and, rarely, systemic diseases
Risk factors
- Recurrent herpes labialis or genital herpes
- Young adult age
- Recent Mycoplasma infection
Pathophysiology
Fragments of viral DNA carried to the skin trigger a cell-mediated (T-cell) immune response against infected keratinocytes. The resulting damage at the dermal-epidermal junction creates the concentric zones of the target lesion: a dark or blistered centre, a pale oedematous ring and an outer red ring.
Classification
- Erythema multiforme minor: typical targets on the skin with little or no mucosal involvement
- Erythema multiforme major: targets plus involvement of one or more mucosae, often with fever
- Recurrent erythema multiforme, usually linked to herpes simplex
Symptoms and signs
- Sudden appearance of round, well-defined target lesions with three zones
- Symmetric distribution on the backs of the hands, forearms, palms, feet and limbs, spreading towards the trunk
- Lesions stay fixed in place for at least a week (unlike urticaria)
- Mild burning or itching
- In the major form: oral erosions, lip crusts, eye or genital lesions, fever and malaise
- Cold sore a few days to two weeks before the rash
Diagnosis
- Clinical
- Diagnosis is clinical: typical raised target lesions mainly on the extremities, with a recent cold sore or infection.
- Tests
- Usually none. PCR or serology for herpes simplex, Mycoplasma testing in children or with chest symptoms, and skin biopsy when the diagnosis is uncertain (interface dermatitis with necrotic keratinocytes).
- Imaging
- Chest X-ray if Mycoplasma pneumonia is suspected.
Differential diagnosis
- Stevens-Johnson syndrome and toxic epidermal necrolysis (drug-induced, widespread, atypical flat targets, skin detachment)
- Urticaria (lesions move and resolve within hours)
- Fixed drug eruption
- Bullous pemphigoid and pemphigus vulgaris
- Urticarial vasculitis and cutaneous lupus
Goal of treatment
Relieve symptoms, treat or remove the trigger, protect the mucosae and eyes, and prevent recurrences when they are frequent.
Treatment
- Conservative
- Self-limited: oral antihistamines and topical corticosteroids for itching and burning; mouthwashes and soft diet for oral lesions.
- Medical
- Stop any suspected drug; antivirals for herpes-associated disease, and continuous suppressive antiviral therapy for frequent recurrences.
- Medical
- Systemic corticosteroids may be considered in severe mucosal disease; treatment of Mycoplasma infection when present.
- Follow-up
- Monitor fluid intake and eye involvement; refer to ophthalmology if the eyes are affected.
Complications
- Dehydration from painful oral lesions
- Eye involvement with scarring in severe mucosal disease
- Post-inflammatory changes in skin colour
- Frequent recurrences linked to herpes simplex
Prognosis
Usually resolves in two to six weeks without scarring. Recurrences are common in herpes-associated cases but respond to suppressive antiviral therapy.
Prevention
- Suppressive antiviral therapy for frequent herpes-associated recurrences
- Sun protection of the lips, since UV can reactivate herpes labialis
- Avoid a drug that caused a previous episode
Test yourself
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What is the most common trigger of erythema multiforme?
Herpes simplex virus infection.
What does the classic lesion look like?
A raised target with three concentric zones: dark or blistered centre, pale oedematous ring, outer red ring.
Where are the lesions mostly located?
Symmetrically on the extremities, including the backs of the hands, palms and soles, spreading towards the trunk.
How is erythema multiforme distinguished from Stevens-Johnson syndrome?
EM is usually infection-triggered, with typical raised targets on the limbs and little skin detachment; SJS is usually drug-induced, with flat atypical lesions on the trunk, epidermal detachment and severe mucosal involvement.
Related conditions
- Genital herpes (herpes simplex infection)
- Stevens–Johnson syndrome and toxic epidermal necrolysis
- Cutaneous drug reactions and DRESS
- Pemphigus vulgaris
- Community-acquired pneumonia
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Erythema multiforme: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
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