What are pemphigus bullae?

What is Pemphigus Bullae?

Pemphigus bullae are intraepithelial blisters caused by IgG autoantibodies attacking desmosomal adhesion proteins (primarily desmoglein 1 and 3), leading to acantholysis—the loss of cell-to-cell adhesion between keratinocytes. 1, 2

Disease Mechanism and Pathophysiology

Pemphigus is fundamentally different from other blistering diseases because the autoimmune attack occurs within the epidermis itself rather than at the basement membrane zone. 1, 3

Key Pathological Features:

• Suprabasal acantholysis creates the characteristic intraepithelial split, where keratinocytes lose their connections and separate from each other 1, 4
• IgG autoantibodies bind to the intercellular spaces between keratinocytes, specifically targeting desmoglein proteins that normally hold skin cells together 1, 2
• The binding of these autoantibodies to desmogleins induces the separation of neighboring keratinocytes through acantholysis 2, 3

Clinical Presentation of Pemphigus Bullae

Pemphigus Vulgaris (Most Common Form):

• Oral mucosa is the first site in the majority of cases, with painful erosions that may precede skin involvement by an average of 4 months 1, 4
• Oral lesions consist of small blisters or erosions found mainly on the palatal mucosa 1
• Flaccid blisters develop on skin that rupture easily, leaving painful erosions 1
• Almost all patients eventually develop oral erosions, even if skin lesions appear first 1, 4

Pemphigus Foliaceus:

• Exclusively cutaneous with superficial blisters and crusting 2, 3
• No mucosal involvement 2
• Lesions typically affect seborrheic areas (scalp, face, upper trunk) 3

Diagnostic Confirmation

Essential Laboratory Tests:

• Direct immunofluorescence (DIF) of perilesional skin shows IgG deposition in the intercellular spaces of the epidermis—this is the gold standard diagnostic finding 1, 4
• Histology demonstrates suprabasal acantholysis and blister formation 1, 4
• ELISA testing for anti-desmoglein 1 and anti-desmoglein 3 antibodies provides direct measurement and is superseding indirect immunofluorescence 1, 2

Antibody Patterns Determine Clinical Phenotype:

• Anti-Dsg3 alone: predominantly mucosal pemphigus vulgaris 1, 4
• Anti-Dsg3 plus anti-Dsg1: mucocutaneous pemphigus vulgaris (50-60% of PV patients) 1, 4
• Anti-Dsg1 alone: pemphigus foliaceus with only skin involvement 2, 3

Critical Distinction from Bullous Pemphigoid

Pemphigus bullae form WITHIN the epidermis (intraepithelial), while bullous pemphigoid creates blisters BELOW the epidermis (subepidermal). 1

Key Differences:

• Pemphigus: Flaccid blisters, suprabasal split, IgG in intercellular spaces, targets desmogleins 1, 2
• Bullous pemphigoid: Tense blisters, subepidermal split, linear IgG at basement membrane zone, targets BP180/BP230 1

Prognosis and Severity

• Historical mortality before corticosteroids was approximately 75%, primarily from dehydration or secondary infections 1, 4
• Current mortality varies by phenotype: 1-17% for predominantly mucosal disease versus 34-42% for mucocutaneous disease 1, 4
• Peak incidence occurs in the third to sixth decades of life 1, 4

Common Diagnostic Pitfalls

• Delayed diagnosis occurs when oral lesions precede cutaneous involvement by months, and pemphigus may be misdiagnosed as other oral conditions like aphthous stomatitis or herpes 4
• DIF must be performed on perilesional, intact skin—not from the blister itself—to demonstrate the characteristic intercellular IgG pattern 1
• Biopsy and immunofluorescence can be performed after treatment initiation, though prolonged treatment reduces positive results 1