A 28-year-old woman presents with fever, mucosal erosions, and a rapidly spreading erythematous rash with target lesions involving >30% of body surface area. She had started cotrimoxazole 5 days ago for a urinary tract infection. Which investigation is most specific for confirming the diagnosis of Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (SJS/TEN)?

Explanation

## Investigation of Choice for SJS/TEN Diagnosis **Key Point:** Skin biopsy with histopathology is the gold standard and most specific investigation for confirming SJS/TEN, as clinical presentation alone can overlap with other severe cutaneous adverse reactions (SCAR). ### Why Skin Biopsy is Diagnostic **High-Yield:** Histopathology shows: - Full-thickness epidermal necrosis (hallmark of TEN) - Subepidermal blister formation with minimal dermal inflammation - Keratinocyte apoptosis (scattered or confluent) - Distinction from other SCAR (e.g., DRESS, AGEP) which show different inflammatory patterns **Clinical Pearl:** The histologic finding of **epidermal necrosis with sparse dermal infiltrate** is pathognomonic for SJS/TEN and differentiates it from drug reaction with eosinophilia and systemic symptoms (DRESS), which shows dense dermal inflammation with eosinophils. ### Timing of Biopsy - Should be taken from an **active lesion** (not a blister roof) - Ideally from the **edge of an erythematous area** for best yield - Early biopsy (within 48–72 hours of onset) shows clearer apoptotic changes ### Diagnostic Criteria Using Histology The **RegiSCAR scoring system** incorporates histopathology as a key criterion: - Epidermal necrosis: +3 points (most specific) - Sparse dermal infiltrate: +1 point - Eosinophils: −2 points (argues against SJS/TEN) **Mnemonic:** **NECROSIS** — **N**ecrosis of **E**pidermis is the **C**onfirming **R**esult; **O**ther **S**evere **I**nflammatory **S**kin diseases show different patterns. ## Why Other Investigations Are Not Confirmatory | Investigation | Utility | Limitation | | --- | --- | --- | | **Direct Immunofluorescence (DIF)** | Rules out autoimmune blistering (pemphigus, bullous pemphigoid) | Non-specific for SJS/TEN; may show IgM/C3 deposition but not diagnostic | | **Viral Serology** | Identifies viral triggers (HSV, EBV) in some SJS cases | Does not confirm SJS/TEN diagnosis; serology can be false-positive; virus is not the cause in drug-induced cases | | **Patch Testing** | Identifies contact allergen in contact dermatitis | Contraindicated during active SJS/TEN; cannot be performed acutely; not used for drug-induced SJS/TEN |