A 78-year-old woman presents with 6 weeks of intensely pruritic urticarial plaques on her trunk and flexural forearms, evolving into large, tense, fluid-filled bullae 1–3 cm in diameter. The bullae remain intact for days and rupture to leave non-extending erosions. Nikolsky sign is negative. Punch biopsy shows subepidermal blister formation with an eosinophil-rich infiltrate. Direct immunofluorescence of perilesional skin demonstrates a linear band of IgG and C3 along the epidermal basement membrane zone. The structure marked **A** in the diagram represents this clinical and immunological presentation. Which of the following best explains the mechanism of blister formation in this condition?

Question

Accepted Answer

A. IgG antibodies against BP180 fix complement, recruit eosinophils and neutrophils, and trigger proteolytic destruction of hemidesmosomal anchoring complexes, causing subepidermal separation. ## Why option 1 is correct

The structure marked **A** represents bullous pemphigoid with its characteristic tense subepidermal bullae, negative Nikolsky sign, and linear IgG/C3 at the basement membrane zone. The pathogenic mechanism is anti-BP180 (BPAG2, collagen XVII) IgG antibodies that fix complement, recruit eosinophils and neutrophils, and trigger proteolytic destruction of hemidesmosomal anchoring complexes bonding basal keratinocytes to the lamina lucida. This results in the deep, subepidermal cleavage plane that produces durable, tense bullae characteristic of this disease (Bolognia Dermatology 5e Ch 30; Schmidt Lancet 2013).

## Why each distractor is wrong

- **Option 2**: This describes pemphigus vulgaris (anti-DSG3), which causes intraepidermal acantholysis, flaccid bullae, and a positive Nikolsky sign — the opposite of the structure marked **A**. This corresponds to label B in the diagram.
- **Option 3**: This describes dermatitis herpetiformis or linear IgA disease, characterized by neutrophilic microabscesses at dermal papillae and annular vesicles — not the subepidermal blister with eosinophil infiltrate seen in **A** (label C).
- **Option 4**: This describes epidermolysis bullosa acquisita (anti-collagen VII), which causes acral hemorrhagic bullae after trauma and anchoring fibril disruption — a different pathophysiology and clinical presentation from **A** (label D).

**High-Yield:** Bullous pemphigoid = anti-BP180 → complement fixation → eosinophil/neutrophil recruitment → hemidesmosomal destruction → tense subepidermal bullae with negative Nikolsky sign.

[cite: Bolognia Dermatology 5e Ch 30; Schmidt Lancet 2013]

Answer

B. Circulating immune complexes deposit at the dermal–epidermal junction and activate complement, leading to neutrophilic microabscesses in dermal papillae

Answer

C. IgG antibodies against desmoglein 3 cause loss of cell-to-cell adhesion within the epidermis, resulting in intraepidermal acantholysis

Answer

D. IgG antibodies against type VII collagen disrupt anchoring fibrils in the sub-basal lamina zone, causing trauma-induced blistering

Explanation

Why option 1 is correct

Why each distractor is wrong

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