Erythema Multiforme
Dermatology
Illness script · Dermatology
Erythema Multiforme
Acute, self-limited immune-mediated hypersensitivity reaction producing classic target skin lesions, most commonly triggered by HSV infection.
This illness script for Erythema Multiforme covers predisposing factors, classic presentation, mechanism, workup, management, and the clinical pivots that separate it from look-alikes—written for USMLE Step 1 and clerkship reasoning.
01
Predisposing factors
- Young adults 20–40 years; slight male predominance
- HSV-1 or HSV-2 is the most common trigger (~90% of recurrent cases)
- Mycoplasma pneumoniae — leading trigger in children
- Medications (less common than in SJS/TEN — sulfonamides, NSAIDs)
- Immunocompromised states increase severity
- Recurrent EM is nearly always HSV-driven
02
Presentation
- Classic target lesion: 3 concentric zones — central dusky/necrotic blister, pale edematous ring, outer erythematous ring
- Lesions are FIXED (persist >7 days at the same site)
- Symmetric acral distribution — palms, soles, dorsal hands predominate, spreading centripetally
- EM minor: skin only; EM major: ≥1 mucosal surface (oral most common) involved
- Prodrome: HSV outbreak 1–2 weeks before skin eruption
- Mild fever and malaise in EM major; systemic toxicity is minimal compared to SJS
03
Pathophysiology
- Type IV (cell-mediated) hypersensitivity reaction
- HSV DNA fragments deposited in keratinocytes → CD4+ T-cell infiltration and epidermal apoptosis
- Immune complex deposition in superficial dermal vessels causes vasodilation and edema
- Results in the characteristic 3-zone target lesion morphology
04
Diagnostics
- Primarily a CLINICAL diagnosis based on target lesion morphology and distribution
- Skin biopsy (if uncertain): interface dermatitis, satellite cell necrosis, lichenoid lymphocytic infiltrate
- HSV PCR/culture or serology to confirm trigger and guide prophylaxis
- Mycoplasma IgM titers or PCR in pediatric or atypical cases
- No pathognomonic labs; Nikolsky sign is NEGATIVE (distinguishes from TEN)
05
Management
- EM minor: supportive — antihistamines, topical corticosteroids, analgesics
- Treat active HSV trigger with acyclovir/valacyclovir; azithromycin if Mycoplasma
- Recurrent HSV-triggered EM: daily suppressive valacyclovir (500–1000 mg/day) is definitive
- EM major: oral rinses, ophthalmology referral for ocular involvement, possible short systemic steroids (controversial)
- Discontinue any potential drug trigger; self-resolves in 2–6 weeks
06
Clinical pivots
How to separate this script from the look-alikes that show up on exams and on the wards.
Stevens-Johnson Syndrome (SJS)
SJS is drug-induced with atypical flat/dusky targets, ≥2 mucosal sites, epidermal detachment, and systemic toxicity — EM has classic 3-zone targets and is HSV-triggered.
Urticaria
Urticarial wheals are transient (<24 h), migratory, and intensely pruritic — EM target lesions are fixed, persist >7 days, and burn more than itch.
Fixed Drug Eruption
Fixed drug eruption recurs at the EXACT same site(s) with each re-exposure to a drug; EM has acral-predominant, widespread symmetric new lesions after HSV.
Bullous Pemphigoid
Bullous pemphigoid affects elderly patients with tense bullae on urticarial plaques, lacks classic target morphology, and shows IgG anti-BP180/BP230 on immunofluorescence.
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Educational use only. This illness script is a study framework, not medical advice. Confirm decisions with current guidelines and your clinical supervisors.