Hailey-Hailey disease (benign familial pemphigus) and Darier's disease both show acantholysis on histology but involve different molecular mechanisms. In Hailey-Hailey, acantholysis is caused by:

• A ATP2A2 mutation affecting SERCA2 pump in ER calcium homeostasis
• B Autoantibodies against desmoglein-1
• C ATP2C1 mutation affecting SPCA1 Golgi calcium/manganese pump ✓
• D Mutation in corneodesmosin causing premature desmosome dissolution

Explanation

Hailey-Hailey disease is caused by autosomal dominant mutation in ATP2C1, encoding secretory pathway Ca2+/Mn2+-ATPase 1 (SPCA1) located on the Golgi apparatus. This impairs Golgi calcium/manganese homeostasis, disrupting the glycosylation and trafficking of desmosomal proteins, leading to defective desmosome assembly and acantholysis. Darier's disease is caused by ATP2A2 mutation affecting SERCA2 (ER calcium pump). Both conditions flare with heat, friction, and secondary bacterial/viral infections.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.