A 52-year-old woman from Delhi presents with painful erosions on the buccal mucosa for 3 weeks, followed by flaccid blisters on the chest and axillae. On examination, positive Nikolsky sign is elicited on the skin. She has no significant past medical history. What is the most appropriate next step in management?

Explanation

## Clinical Diagnosis and Confirmatory Testing This patient presents with the classic triad of pemphigus vulgaris (PV): oral mucosal involvement, flaccid blisters on flexural areas, and positive Nikolsky sign. While clinical suspicion is high, **diagnosis must be confirmed before initiating systemic immunosuppression**. ### Why Biopsy is the Next Step **Key Point:** Skin biopsy with both histopathology and direct immunofluorescence (DIF) is the gold standard for confirming pemphigus vulgaris and must precede systemic corticosteroid therapy. **High-Yield:** The diagnostic triad for PV confirmation: 1. **Histopathology** — acantholysis (loss of cell-to-cell adhesion), suprabasal cleft formation ("tombstone" appearance) 2. **Direct Immunofluorescence** — intercellular IgG and C3 deposition in a "chicken-wire" or "tombstone" pattern around keratinocytes 3. **Indirect Immunofluorescence or ELISA** — circulating anti-desmoglein 3 (and/or anti-desmoglein 1) antibodies ### Biopsy Technique - Take specimen from **perilesional skin** (edge of an active blister or erosion) for optimal acantholysis visualization - Include both epidermis and dermis - Send in **10% formalin** for histology and **Michel's transport medium** (or fresh, unfixed tissue) for DIF ### Clinical Pearl Positive Nikolsky sign indicates intraepidermal acantholysis and is highly suggestive of PV, but it is **not pathognomonic** — other pemphigus variants and bullous pemphigoid can occasionally show it. Histology and immunofluorescence are mandatory to differentiate and confirm the diagnosis before committing to long-term systemic corticosteroids. ### Rationale for Timing Starting corticosteroids before confirmation risks: - Masking the diagnosis if biopsy is delayed - Unnecessary immunosuppression if the diagnosis is different (e.g., bullous pemphigoid, linear IgA disease) - Inability to assess disease activity and antibody titers for prognostication [cite:Robbins 10e Ch 25]