Random Dermatology MCQ - Pemphigus vulgaris

A 45-year-old woman presents with painful flaccid bullae and erosions on her scalp, trunk, and oral mucosa. A Nikolsky sign is positive. Direct immunofluorescence of perilesional skin shows intercellular deposition of IgG and C3 throughout the epidermis. ELISA testing is positive for antibodies against desmoglein 3. Which of the following is the most likely diagnosis?

A) Bullous pemphigoid
B) Pemphigus vulgaris
C) Paraneoplastic pemphigus
D) Pemphigus foliaceus
E) Linear IgA disease

Correct Answer: B) Pemphigus vulgaris

Explanation

This patient has pemphigus vulgaris (PV), a potentially fatal autoimmune blistering disorder characterized by acantholysis.

Key Diagnostic Features:

1. Clinical:

   • Flaccid bullae that easily rupture, leaving painful erosions.

   • Mucosal involvement (oral, conjunctival, genital) is common and often the initial presenting sign.

   • A positive Nikolsky sign (lateral pressure on perilesional skin causes epidermal separation) is a classic finding.

2. Immunopathology:

   • Direct immunofluorescence (DIF): Shows a fishnet-like pattern of intercellular IgG and C3 deposition throughout the epidermis. This is the hallmark finding.

   • Serology: Circulating antibodies against desmoglein 3 (Dsg3) are present. In mucocutaneous disease, antibodies against both Dsg1 and Dsg3 are often detected.

3. Histopathology:

   • Suprabasal acantholysis leading to an intraepidermal blister. "Tombstoning" of basal keratinocytes is a characteristic feature.

Why Not Other Options?

• (A) Bullous pemphigoid: Features tense bullae on urticated plaques, negative Nikolsky sign, and linear IgG/C3 deposition at the basement membrane zone.

• (C) Paraneoplastic pemphigus: Has severe stomatitis and is associated with an underlying neoplasm (e.g., lymphoma). DIF shows intercellular and basement membrane zone deposition. Antibodies are against plakin proteins (e.g., desmoplakins).

• (D) Pemphigus foliaceus: Affects only the skin (superficial blisters, often on seborrheic areas) with no mucosal involvement. Antibodies are against desmoglein 1.

• (E) Linear IgA disease: Shows linear IgA deposition at the basement membrane zone on DIF, not intercellular IgG.

Management:

• First-line: Systemic corticosteroids (e.g., prednisone 1 mg/kg/day).

• Steroid-sparing agents: Rituximab (now first-line in many guidelines), azathioprine, or mycophenolate mofetil.

Prognosis: Historically fatal without treatment; with modern immunosuppressive therapy, mortality has significantly decreased.