What are the histopathological features of pemphigus foliaceus?

Histopathological Features of Pemphigus Foliaceus

The defining histopathological feature of pemphigus foliaceus is superficial acantholysis with cleavage and blister formation within the granular layer of the epidermis, which must be confirmed by direct immunofluorescence showing intercellular IgG and complement deposition between keratinocytes. 1, 2

Primary Histological Findings

Acantholysis Location and Pattern:

• Superficial acantholysis occurs specifically within or just below the granular layer of the epidermis, distinguishing pemphigus foliaceus from pemphigus vulgaris which shows deep suprabasal acantholysis 3, 1, 2
• Subcorneal blister formation results from loss of intercellular connections (acantholysis) between keratinocytes in the upper epidermis 1
• The basal cell layer remains intact, with basal cells maintaining attachment to the basement membrane 4

Cellular Changes:

• Acantholytic keratinocytes (rounded, separated cells) are present within the blister cavity 3
• Dyskeratotic cells may be observed in the affected layers 4

Early Ultrastructural Changes (Pre-Acantholysis)

Before complete blister formation develops, electron microscopy reveals:

• Intercellular space widening between desmosomes, starting in lower epidermal layers and progressing upward 5
• Decreased number of desmosomes throughout the epidermis 5
• Hypoplastic desmosomes that appear partially or completely torn off from opposing cells (pseudo-half-desmosomes) 5
• Reduction of peripheral tonofilaments in epidermal cells 4
• Aggregates of electron-dense granular material in intercellular spaces, potentially representing antigen-antibody complexes 4

Essential Immunopathological Confirmation

Direct Immunofluorescence (DIF) - Mandatory for Diagnosis:

• Intercellular IgG and complement (C3) deposits in a cell surface pattern between keratinocytes throughout the epidermis 6, 7, 3
• This intercellular "chicken wire" pattern distinguishes pemphigus from pemphigoid disorders which show linear basement membrane zone deposits 7
• DIF must be performed on perilesional intact skin or clinically uninvolved skin 6, 7

Critical Diagnostic Algorithm

When evaluating suspected pemphigus foliaceus:

1. Obtain biopsy from an early blister or erosion for routine histology - look for superficial (granular layer) acantholysis, not deep suprabasal splitting 2
2. Obtain separate perilesional skin biopsy for DIF - must show intercellular IgG/C3 deposits to confirm diagnosis 6, 7, 3
3. Histopathology showing superficial acantholysis remains the most reliable criterion for distinguishing pemphigus foliaceus from pemphigus vulgaris 2

Important Diagnostic Pitfalls

• Histopathology alone is insufficient - the intercellular immunofluorescence pattern must be demonstrated to distinguish pemphigus from other acantholytic disorders 6, 3
• Indirect immunofluorescence (IIF) detects circulating antibodies in only 43% of pemphigus foliaceus cases, making it less sensitive than DIF 2
• ELISA for anti-desmoglein-1 antibodies may be confirmatory but detects antibodies in only 71% of cases and can be positive in some pemphigus vulgaris patients 2
• The level of acantholysis (superficial vs. deep) is the key histological distinction from pemphigus vulgaris, which shows suprabasal acantholysis 6, 2