Hailey-Hailey disease (familial benign chronic pemphigus) is caused by mutation in which gene, and what is the main histopathological difference from pemphigus vulgaris?

• A Desmoglein-3 mutation; both show suprabasal acantholysis
• B ATP2A2 mutation; both show corps ronds and corps grains
• C ATP2C1 (SPCA1 pump) mutation; Hailey-Hailey shows full-thickness acantholysis throughout the epidermis ('dilapidated brick wall'), unlike suprabasal acantholysis in PV ✓
• D KRT1 mutation; blistering is intraepidermal at the same level as PV

Explanation

Hailey-Hailey disease is caused by loss-of-function mutations in ATP2C1, encoding the Golgi-localized secretory pathway Ca2+/Mn2+-ATPase (SPCA1). Impaired calcium signaling disrupts desmosomal assembly. Histopathology shows widespread full-thickness acantholysis — the classic 'dilapidated brick wall' or 'row of tombstones' pattern where acantholysis extends throughout all layers of the epidermis. In contrast, pemphigus vulgaris shows acantholysis confined to the suprabasal layer, with an intact basal layer ('tombstone' pattern). ATP2A2 mutations cause Darier's disease (SERCA2).

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

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