A 52-year-old Indian woman presents with a 3-week history of painful blisters and erosions in her mouth, followed by flaccid bullae on her chest and axillae. On examination, gentle pressure on apparently normal skin causes it to separate (positive Nikolsky sign). Intraoral examination reveals multiple erosions with a granular base. A skin biopsy shows intraepidermal acantholysis with a "tombstone" appearance of basal cells. Direct immunofluorescence reveals IgG and C3 deposits in an intercellular pattern. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Pemphigus Vulgaris ### Key Clinical Features **Key Point:** Pemphigus vulgaris is an autoimmune blistering disorder characterized by intraepidermal acantholysis (loss of cell-to-cell adhesion) due to IgG antibodies against desmoglein 3 (and often desmoglein 1). ### Diagnostic Criteria Present in This Case | Feature | Finding | Significance | | --- | --- | --- | | **Mucosal involvement** | Erosions in mouth first | Occurs in >90% of PV cases; often the presenting sign | | **Flaccid bullae** | Present on trunk/axillae | Rupture easily due to intraepidermal location | | **Nikolsky sign** | Positive | Indicates loss of epidermal cohesion | | **Histology** | Intraepidermal acantholysis, tombstone basal cells | Pathognomonic for pemphigus | | **Direct IF** | Intercellular IgG + C3 | Characteristic "chicken wire" or intercellular pattern | ### Pathophysiology 1. IgG autoantibodies bind to desmoglein 3 (mucosal dominant) ± desmoglein 1 (mucocutaneous) 2. Complement activation and loss of cell-to-cell adhesion (acantholysis) 3. Intraepidermal blister formation (suprabasal in mucosal disease) **High-Yield:** The combination of **oral erosions + flaccid bullae + positive Nikolsky sign + intercellular IgG on DIF** is diagnostic of pemphigus vulgaris. ### Why Oral Involvement Is Critical **Clinical Pearl:** Mucosal disease precedes cutaneous involvement in ~50% of pemphigus vulgaris cases. Painful erosions in the mouth should always raise suspicion for PV, especially when followed by trunk involvement. ### Histological Hallmark **Mnemonic:** **TOMBSTONE appearance** = basal cells remain attached to basement membrane while suprabasal cells separate (acantholysis). This is pathognomonic for pemphigus. ### Immunofluorescence Pattern - **Direct IF (DIF):** Intercellular IgG ("chicken wire" pattern) — diagnostic - **Indirect IF (IIF):** Circulating anti-desmoglein antibodies; titre correlates with disease activity [cite:Robbins 10e Ch 25]