A 52-year-old Indian woman presents with a 3-week history of painful oral ulcers and blistering lesions on the inner cheeks and palate. She reports that the blisters rupture easily, leaving painful erosions. Over the past 10 days, similar flaccid blisters have appeared on her chest and axillae. On examination, gentle pressure on apparently normal skin results in separation of the epidermis (positive Nikolsky sign). Intraoral examination shows extensive erosions with a red, denuded 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 throughout the epidermis. What is the most likely diagnosis?

Explanation

## Diagnosis: Pemphigus Vulgaris ### Clinical Presentation **Key Point:** Pemphigus vulgaris classically presents with painful oral erosions preceding cutaneous involvement by weeks to months. - **Mucosal involvement:** Nearly 90% of cases begin with oral ulcers and erosions on the buccal mucosa, palate, and gingiva - **Cutaneous lesions:** Flaccid blisters that rupture easily, leaving painful erosions on the chest, axillae, groin, and flexural areas - **Positive Nikolsky sign:** Gentle lateral pressure on normal-appearing skin causes intraepidermal separation — pathognomonic for acantholytic disorders ### Histopathology **High-Yield:** The "tombstone" appearance (also called "row of tombstones") is a hallmark finding: - Intraepidermal acantholysis (loss of cell-to-cell adhesion) - Basal cells remain attached to the basement membrane, appearing as isolated cells at the base - Suprabasal acantholysis in pemphigus vulgaris (vs. subcorneal in pemphigus foliaceus) ### Immunofluorescence Pattern **Mnemonic:** **IIF** (Intercellular IgG in Pemphigus) - **Direct immunofluorescence (DIF):** IgG and C3 in an **intercellular pattern** throughout the epidermis ("chicken wire" or "honeycomb" pattern) - This reflects antibodies against desmoglein 3 (mucosal type) and desmoglein 1 (mucocutaneous type) ### Pathophysiology 1. Autoantibodies (IgG) bind to desmoglein 3 → loss of cell-to-cell adhesion 2. Complement activation and inflammatory cascade 3. Intraepidermal acantholysis with blister formation 4. Oral mucosa affected first due to higher expression of desmoglein 3 ### Diagnostic Criteria Met in This Case | Feature | Present | Significance | |---------|---------|---------------| | Oral erosions | Yes | Early/primary involvement | | Flaccid blisters | Yes | Easily ruptured, painful | | Positive Nikolsky sign | Yes | Intraepidermal pathology | | Suprabasal acantholysis | Yes | Pemphigus vulgaris subtype | | Intercellular IgG/C3 | Yes | Pathognomonic for pemphigus | **Clinical Pearl:** The sequence of involvement (oral → cutaneous) and the ease of blister rupture distinguish pemphigus vulgaris from bullous pemphigoid, where blisters are tense and cutaneous lesions often precede mucosal involvement.