🎯 Erythema Multiforme (EM) is an acute, self-limiting, type IV hypersensitivity skin reaction. 🦠 Trigger: 90% are triggered by infections (70% are HSV). Drugs are a rare cause (<10%). ⚠️ NICE/BAD Note: EM is now considered distinct from SJS/TEN. EM rarely progresses to SJS.

ℹ️ Pathophysiology

Mechanism: Cell-mediated immune reaction against keratinocytes expressing foreign (viral or drug) antigens.
Classification:
- EM Minor: Skin involvement only; no or minimal mucosal involvement.
- EM Major: Involvement of one or more mucosal sites (oral, genital, or ocular).

🩺 Clinical Features (The "Three-Zone" Rule)

True Target Lesions: Must have 3 distinct zones:
1. Center: Dusky, blistered, or crusty (dark).
2. Middle: Paler pink/edematous ring.
3. Outer: Bright red erythematous margin.
Distribution: Symmetrical and centripetal (starts on backs of hands/feet and spreads toward the trunk).
The "Fixed" Rule: Unlike urticaria, EM lesions stay in the same place for 7 days+ and do not "migrate."
Mucosal (EM Major): Painful erosions/bullae. Check the eyes—ocular involvement is a medical emergency.

🦠 Common Triggers

Viral (Most Common): Herpes Simplex (HSV-1 & 2) is the #1 cause. Often appears 10–14 days after the cold sore.
Bacterial: Mycoplasma pneumoniae (often presents with severe mucosal involvement/EM Major).
Drugs (Rare for EM): NSAIDs, Sulfonamides, Antiepileptics, Penicillins. (If drug-induced, consider if it's actually SJS).

🔍 Differentials (NICE Red Flags)

Condition	Distinguishing Feature
Urticaria	Lesions are itchy, "wheal and flare," and disappear within 24 hours (transient).
SJS / TEN	Skin pain is disproportionate to the rash; positive Nikolsky sign (skin peels with pressure); mostly trunk/face.
Granuloma Annulare	Chronic, no "target" center, usually ring-shaped nodules on hands.

💊 Management (NICE/BAD Guidance)

Supportive: Most cases resolve in 2–4 weeks without treatment.
Symptomatic:
- Topical steroids (mild/moderate potency) for itch.
- Antihistamines (non-sedating during day, sedating at night).
- Antiseptic/anaesthetic mouthwashes (e.g., Difflam) for oral EM Major.
Specific Treatment:
- HSV: Oral Aciclovir does not treat the current EM but is used for prophylaxis if the patient gets >5 episodes of HSV-EM per year.
- Mycoplasma: Treat with Macrolides (e.g., Clarithromycin) if active pneumonia.

⚠️ When to Refer (Urgent)

Ophthalmology: Any eye involvement (redness, pain, discharge) requires immediate same-day review to prevent scarring/blindness.
Dermatology: If diagnosis is uncertain, lesions are bullous (blistering), or there is extensive mucosal involvement.

📌 Clinical Tips

Tip 1: Always check the mouth, eyes, and genitals in any patient with a target-like rash.
Tip 2: If the lesions are itchy, it’s more likely to be EM; if the skin is exquisitely painful to the touch, think SJS.
Tip 3: A biopsy is rarely needed for EM—the diagnosis is almost always clinical based on the "three-zone" target.

📚 References

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Erythema Multiforme ✅