A 52-year-old Indian woman presents with a 3-week history of painful blisters and erosions on her buccal mucosa, palate, and gingiva. She reports that the oral lesions preceded skin involvement by 2 weeks. On examination, she has flaccid blisters on the flexural areas of the neck, axillae, and groin. Gentle pressure on an intact blister causes the blister roof to separate from the base (positive Nikolsky sign). Histopathology shows intraepidermal acantholysis with a "tombstone" appearance of basal cells. Immunofluorescence reveals IgG and C3 deposits in an intercellular pattern. What is the most likely diagnosis?

Explanation

## Diagnosis: Pemphigus Vulgaris ### Clinical Presentation **Key Point:** Pemphigus vulgaris classically presents with oral mucosal involvement (80–90% of cases) preceding cutaneous manifestations by weeks to months. The buccal mucosa, palate, and gingiva are the most common intraoral sites. **Clinical Pearl:** Flaccid blisters that rupture easily, leaving painful erosions, are characteristic. The blisters are fragile because they form within the epidermis (intraepidermal) rather than at the dermal-epidermal junction. ### Diagnostic Criteria | Feature | Pemphigus Vulgaris | Bullous Pemphigoid | Linear IgA Disease | |---------|-------------------|-------------------|--------------------| | **Blister location** | Intraepidermal | Subepidermal | Subepidermal | | **Blister type** | Flaccid, fragile | Tense, firm | Tense | | **Nikolsky sign** | Positive | Negative | Negative | | **Oral involvement** | Common (80–90%) | Rare (10–20%) | Rare | | **IgG pattern** | Intercellular | Linear (basement membrane) | Linear (basement membrane) | | **Acantholysis** | Present | Absent | Absent | ### Histopathology **High-Yield:** Intraepidermal acantholysis (loss of cell-to-cell adhesion) with the characteristic "tombstone" or "row of tombstones" appearance, where basal cells remain attached to the basement membrane while the suprabasal layer separates. ### Immunofluorescence **Key Point:** Direct immunofluorescence (DIF) shows **intercellular IgG and C3 deposits** in a "chicken-wire" or "honeycomb" pattern around keratinocytes. This is pathognomonic for pemphigus vulgaris. ### Pathophysiology Pemphigus vulgaris is an autoimmune disorder where IgG antibodies target **desmoglein 3** (mucosal dominant type) or both desmoglein 3 and desmoglein 1 (mucocutaneous type). Desmogleins are adhesion molecules in desmosomes, and their disruption leads to acantholysis. ### Nikolsky Sign **Clinical Pearl:** A positive Nikolsky sign (separation of the epidermis with gentle pressure) indicates intraepidermal pathology and is highly specific for pemphigus. It is negative in bullous pemphigoid and other subepidermal blistering disorders. **Mnemonic:** **PEMPHIGUS = Positive Nikolsky + Intraepidermal + Intercellular IgG** ### Treatment Approach 1. Systemic corticosteroids (first-line: prednisolone 1–1.5 mg/kg/day) 2. Steroid-sparing agents: azathioprine, mycophenolate mofetil 3. Topical corticosteroids for oral lesions 4. Rituximab (anti-CD20) for severe or steroid-resistant cases