Pemphigus Vulgaris

Rare autoimmune bullous disease, the most common (80%) subtype of the pemphigus group (includes 4 blistering autoimmune diseases that affect the skin and mucous membranes)

Epidemiology

• Rare disease (≈0.5–3 cases per 100,000/year)

• Peak onset: 40–60 years

• No strong gender predilection

• Higher prevalence in certain ethnic groups (Mediterranean, Middle Eastern, Ashkenazi Jewish)

• Associated with HLA-DR4 and HLA-DR14

Aetiology

Autoimmune Mechanism

• Autoantibodies (IgG, mainly IgG4) target:
• Desmoglein 3 (Dsg3) → mucosal involvement
• Desmoglein 1 (Dsg1) → skin involvement

• Leads to acantholysis (loss of keratinocyte cohesion)

Desmoglein Compensation Theory

Pathophysiology

• Type II hypersensitivity - IgG4 antibodies against desmosomal — desmoglein 1 and 3 — proteins lead to loss of keratinocyte adhesion (acantholysis - lysis of intercellular adhesion sites) in the skin and mucous membranes

• This causes superficial (intra-epidermal) blisters, erosions and mucosal ulcers

Clinical presentation

Skin Lesions

• Flaccid bullae on normal-appearing skin

• Bullae rupture easily → painful erosions

• Nikolsky sign positive

• Lesions heal without scarring

Mucosal Involvement (Hallmark)

• Occurs in >90% of patients

• Oral mucosa most common (buccal, gingiva, palate)

• Painful, persistent erosions

• May precede skin lesions by months

Distribution

• Scalp

• Face

• Trunk

• Intertriginous areas

Investigations

Histopathology (Gold standard)

• Suprabasal acantholysis

• “Row of tombstones” appearance of basal keratinocytes

Immunofluorescence

Management

First-line Therapy

• Systemic corticosteroids
• Prednisone 0.5–1 mg/kg/day for 2-3 months
• Then, 40 mg/day tappering off for 4-9 months → until 5 mg every 2 days

Steroid-sparing Agents (Adjuvants)

Biologic Therapy

• Rituximab 0.4 g/kg/day (anti-CD20) – now considered first-line in moderate–severe PV
• High remission rates

Supportive Care

• Wound care

• Infection prevention

• Pain control