You’re cruising through a derm q-bank and you hit a classic: “target lesions” after a recent infection. Erythema multiforme (EM) is one of those diagnoses that feels obvious… until the answer choices start blending into Stevens-Johnson syndrome (SJS), urticaria, and pemphigus. This post breaks down a high-yield EM vignette and—more importantly—why every distractor is tempting (and how to kill it fast on USMLE.
Tag: Dermatology > Skin Disorders
The Clinical Vignette (Q-Bank Style)
A 19-year-old man presents with a 2-day history of a mildly pruritic rash on his hands and forearms. He had “a cold sore” on his lip about a week ago. Exam shows multiple targetoid lesions with three concentric zones (dusky center, pale edematous ring, peripheral erythematous halo) on the dorsal hands and extensor forearms. No skin pain. No fever. Oral mucosa is normal. Nikolsky sign is negative.
Most likely diagnosis?
A. Erythema multiforme
B. Stevens-Johnson syndrome
C. Urticaria
D. Bullous pemphigoid
E. Pemphigus vulgaris
F. Toxic epidermal necrolysis
G. Allergic contact dermatitis
Correct Answer: Erythema Multiforme (EM)
Why this is EM
This vignette screams EM minor:
- Classic target lesions (3 zones) on acral/extensor surfaces (hands/forearms)
- Often triggered by HSV (especially HSV-1)
- Minimal or no mucosal involvement in EM minor (mucosa can be involved in EM major)
- Patients are often not systemically ill
- Nikolsky negative (helps separate from SJS/TEN)
Pathophysiology (high-yield)
- Type IV (T-cell–mediated) hypersensitivity
- In HSV-associated EM, immune response targets viral antigens in keratinocytes → interface dermatitis
Management (Step-friendly)
- Treat the trigger:
- If recurrent HSV-associated EM: consider acyclovir/valacyclovir prophylaxis
- Supportive care:
- Topical steroids, antihistamines, analgesia
- If significant mucosal involvement (EM major): may need hydration, pain control; admit if unable to maintain PO
High-Yield EM Cheat Sheet
| Feature | Erythema multiforme | SJS/TEN |
|---|---|---|
| Typical trigger | HSV, Mycoplasma | Medications (sulfa, anticonvulsants, allopurinol, NSAIDs) |
| Lesion type | True target (3 zones), often acral | Atypical target + widespread dusky macules, bullae |
| Pain | Often mild pruritus or burning | Painful skin |
| Mucosal involvement | None/minor (EM minor), can occur (EM major) | Prominent (oral/ocular/genital) |
| Nikolsky sign | Negative | Positive |
| Body surface area detachment | Minimal | SJS <10%, TEN >30% |
Now: Why Each Distractor Is Wrong (and How They Trap You)
B. Stevens-Johnson Syndrome (SJS)
Why it’s tempting: “Target lesions” + scary mucocutaneous disease gets conflated with EM.
Why it’s wrong here:
- SJS is usually drug-induced and patients look toxic (fever, malaise)
- Lesions are often painful, with prominent mucosal erosions
- Atypical targets (less crisp, more diffuse) rather than classic 3-zone targets
- Often positive Nikolsky
USMLE kill shot: If the stem emphasizes skin pain, mucositis, and recent new med, think SJS/TEN—not EM.
C. Urticaria
Why it’s tempting: Pruritic rash that can look “ringed” or annular.
Why it’s wrong here:
- Urticarial wheals are transient—each lesion lasts <24 hours
- They’re migratory and blanching, not fixed “target” lesions with dusky centers
- No classic association with HSV
USMLE kill shot: Ask yourself: “Do lesions come and go within a day?” If yes → urticaria.
D. Bullous Pemphigoid
Why it’s tempting: Blisters and autoimmune buzzwords.
Why it’s wrong here:
- Typically elderly patients
- Tense bullae on erythematous/urticarial base, often very pruritic
- Not classic target lesions; distribution is more generalized (trunk, flexures)
Key pathology to remember:
- Autoantibodies against hemidesmosomes (BP180/BP230)
- Subepidermal blister
- Linear IgG/C3 along basement membrane on DIF
USMLE kill shot: Age + tense bullae + subepidermal split = pemphigoid, not EM.
E. Pemphigus Vulgaris
Why it’s tempting: Mucosal disease + bullae can blur with other blistering disorders.
Why it’s wrong here:
- Usually flaccid bullae that rupture easily → erosions
- Mucosal involvement is common and early
- Nikolsky positive
- Not target lesions; think “painful erosions” more than “targets”
Key pathology to remember:
- Autoantibodies against desmoglein 3 (and sometimes desmoglein 1)
- Intraepidermal acantholysis
- “Row of tombstones” basal layer on histology
USMLE kill shot: Flaccid bullae + oral mucosa + Nikolsky+ = pemphigus vulgaris.
F. Toxic Epidermal Necrolysis (TEN)
Why it’s tempting: Sometimes q-banks lump it with SJS and show a rash picture.
Why it’s wrong here:
- TEN is the severe end of SJS/TEN spectrum with >30% BSA detachment
- Patients are very ill with skin tenderness, widespread necrosis, mucosal sloughing
- Strongly linked to medications
USMLE kill shot: Extensive epidermal sloughing + systemic toxicity + drug exposure → TEN.
G. Allergic Contact Dermatitis
Why it’s tempting: Itchy rash on hands/forearms is a common exposure pattern.
Why it’s wrong here:
- Usually well-demarcated, eczematous plaques/vesicles in area of contact
- Often linear streaks (poison ivy) or geometric patterns
- Not classic target lesions, and HSV history would be a red herring here
High-yield immunology:
- Type IV hypersensitivity (like EM), but morphology and exposure pattern differ
USMLE kill shot: Contact dermatitis follows contact geography; EM follows target lesion morphology.
Rapid-Fire USMLE Pearls (What They Love to Ask)
EM vs SJS/TEN: fastest differentiators
- EM: HSV trigger, true targets, acral distribution, patient not toxic, Nikolsky negative
- SJS/TEN: new med, painful rash, mucositis, epidermal detachment, Nikolsky positive
“Target lesions” aren’t all equal
- True target (3 zones) → think erythema multiforme
- “Targetoid”/dusky macules with sloughing → think SJS/TEN
EM associations
- Most common: HSV
- Also: Mycoplasma pneumoniae (especially in children/adolescents), other infections
Takeaway: How to Win This Question in 10 Seconds
- See true target lesions + acral distribution → EM.
- Check for skin pain + mucosal erosions + drug exposure → if yes, pivot to SJS/TEN.
- If lesions are transient (<24h) → urticaria, not EM.
Frequently Asked Questions
How do you tell erythema multiforme from Stevens-Johnson syndrome or toxic epidermal necrolysis on a question stem?
Erythema multiforme is suggested by true 3-zone target lesions on acral or extensor surfaces, a recent HSV infection, little or no mucosal involvement, and a negative Nikolsky sign. Stevens-Johnson syndrome and toxic epidermal necrolysis are more often drug-induced and feature painful skin, prominent mucosal erosions, systemic illness, atypical targets, and a positive Nikolsky sign. TEN also has extensive epidermal detachment.
Why does a recent cold sore point toward erythema multiforme?
A recent cold sore points toward erythema multiforme because HSV, especially HSV-1, is a classic trigger. In HSV-associated erythema multiforme, the process is a type IV T-cell-mediated hypersensitivity reaction in which the immune response targets viral antigens in keratinocytes, producing interface dermatitis. That trigger pattern helps separate EM from medication-driven disorders like SJS or TEN.
What are the classic skin findings in erythema multiforme?
The classic finding is a true target lesion with three concentric zones: a dusky center, a pale edematous ring, and a peripheral erythematous halo. These lesions commonly appear on acral or extensor surfaces such as the dorsal hands and forearms. Patients often have mild pruritus or burning rather than severe pain, and EM minor usually has minimal or no mucosal involvement.
How do you distinguish erythema multiforme from urticaria or allergic contact dermatitis?
Erythema multiforme has fixed target lesions with dusky centers, often after HSV, whereas urticaria causes transient, migratory, blanching wheals that last less than 24 hours per lesion. Allergic contact dermatitis instead produces well-demarcated eczematous plaques or vesicles in a contact pattern, often linear or geometric. The key distinction is morphology and distribution: EM follows target-lesion morphology, not contact geography.
What is the management for erythema multiforme?
Management focuses on treating the trigger and giving supportive care. For recurrent HSV-associated erythema multiforme, acyclovir or valacyclovir prophylaxis can be considered. Supportive treatment includes topical steroids, antihistamines, and analgesia. If there is significant mucosal involvement, patients may need hydration and pain control, and admission is appropriate if they cannot maintain oral intake.