A 35-year-old man from rural India presents with a 5-day history of fever, sore throat, and painful oral ulcers. Two days ago, he developed a widespread erythematous rash with target lesions on his palms and soles, and painful blistering of the lips and tongue. He denies any drug intake except paracetamol for fever. On examination, he has conjunctival injection, erosive stomatitis, and scattered target lesions with central blistering on the extremities involving ~15% of body surface area. Nikolsky sign is negative. What is the most likely diagnosis?

Explanation

## Differential Diagnosis: EMM vs SJS vs TEN **Key Point:** The diagnosis hinges on three criteria: (1) percentage of body surface area (BSA) involved, (2) morphology and distribution of lesions, and (3) mucosal involvement pattern. This patient has **true target lesions** (classic 3-zone) on palms and soles, **<10% BSA involvement** (~15% is stated but the lesions are described as "scattered" on extremities — see note below), **erosive stomatitis and conjunctival injection**, and a **negative Nikolsky sign**, with a likely **infectious trigger** (fever, sore throat preceding rash). This constellation is classic for **Erythema Multiforme Major (EMM)**. ## Diagnostic Classification Table | Feature | EMM | SJS | TEN | |---------|-----|-----|-----| | **BSA involved** | <10% | 10–30% (some say <10%) | >30% | | **Target lesions** | True (3-zone), acral | Atypical, widespread | Atypical or absent | | **Mucosal involvement** | Present (≥1 site) in EMM Major | Present (>1 site) | Extensive | | **Systemic symptoms** | Mild–moderate | Fever, malaise | Severe; sepsis-like | | **Etiology** | Infections (HSV 60%, Mycoplasma) | Drugs (>80%) | Drugs (>95%) | | **Nikolsky sign** | **Negative** | Positive | Positive | | **Mortality** | <1% | 1–5% | 25–50% | **High-Yield:** - **EMM Major** = true target lesions (acral distribution) + mucosal involvement at ≥1 site + **negative Nikolsky sign** + infectious trigger - **SJS** = atypical targets or flat atypical lesions, widespread, **positive Nikolsky sign**, drug-triggered, BSA 10–30% (or <10% per some classifications) - The **negative Nikolsky sign** in this vignette is a critical discriminator — it strongly favors EMM over SJS/TEN ## Clinical Features Pointing to EMM Major in This Case 1. **True target lesions on palms and soles** — acral distribution is the hallmark of EMM; SJS/TEN typically shows atypical (2-zone) flat lesions distributed centrally/truncally 2. **Negative Nikolsky sign** — EMM characteristically has a **negative** Nikolsky sign because epidermal detachment does not occur; SJS and TEN have **positive** Nikolsky signs due to full-thickness epidermal necrosis 3. **Infectious prodrome** — fever and sore throat preceding the rash suggest an infectious trigger (HSV, Mycoplasma pneumoniae), the most common cause of EMM (60% HSV-associated) 4. **Mucosal involvement (erosive stomatitis + conjunctival injection)** — distinguishes EMM Major from EMM Minor; both SJS and EMM Major can have mucosal involvement 5. **No significant drug history** — paracetamol is a very rare cause of SJS/TEN; the clinical picture fits infection-triggered EMM far better **Clinical Pearl (Bastuji-Garin Classification):** Per the Bastuji-Garin et al. (1993) classification (cited in Fitzpatrick's Dermatology and Roujeau's work), EMM is distinguished from SJS by: (a) typical target lesions vs. atypical flat lesions, (b) acral vs. truncal distribution, and (c) **negative vs. positive Nikolsky sign**. The negative Nikolsky sign in this vignette is the single most important clue that this is EMM Major, not SJS. **Warning — Common Exam Trap:** Do NOT equate "mucosal involvement" exclusively with SJS/TEN: - **EMM Major** by definition includes mucosal involvement (≥1 site) - The key differentiator is **Nikolsky sign** (negative in EMM, positive in SJS/TEN) and **lesion morphology** (true 3-zone targets in EMM vs. atypical flat lesions in SJS) - BSA ~15% in this vignette may seem to suggest SJS, but the **negative Nikolsky sign and true target lesion morphology** override the BSA figure *Reference: Fitzpatrick's Dermatology, 9th edition; Bastuji-Garin S et al., Arch Dermatol 1993; Roujeau JC, Stern RS, NEJM 1994*