Hailey-Hailey Disease

Hailey-Hailey disease (familial benign chronic pemphigus) is an autosomal dominant genodermatosis from mutations in ATP2C1 (encoding the SPCA1 calcium and manganese pump), causing impaired keratinocyte adhesion and acantholysis.

• Prevalence is 1 in 50,000. Onset in the second to fourth decade, typically in the intertriginous areas.
• Triggers: heat, sweating, friction, skin infection (Staphylococcus, Candida, HSV), obesity, and UV exposure.
• Chronic, relapsing course with spontaneous improvement in some, and rare squamous cell carcinoma in chronic lesions.
• Variable penetrance; family history in two thirds.

• Recurrent vesicles and flaccid blisters that break quickly to form malodorous, macerated, eroded, and fissured plaques in the neck, axillae, groins, inframammary, and perianal folds.
• Painful linear fissures in the skin folds ("crumbled wall" pattern).
• Longitudinal white bands on the nails; mucosal involvement is uncommon.
• Secondary infection with bacterial, candidal, and herpetic organisms is frequent.

• Clinical, with skin biopsy: widespread suprabasal acantholysis with a "dilapidated brick wall" appearance and little dyskeratosis.
• DIF negative (differentiates from pemphigus).
• Genetic testing: ATP2C1 variants.
• Swabs for bacteria, fungi, and HSV PCR for suspected infection.
• Exclude pemphigus vegetans, Darier disease, intertrigo, inverse psoriasis, candidiasis, and extramammary Paget disease.

• Reduce friction and sweating: weight loss, loose cotton clothing, cool environment, moisture wicking fabrics, and antiperspirants.
• Topical: moderate to potent steroids (e.g., clobetasol 0.05% for 2 weeks then step down), tacrolimus 0.1% ointment, calcipotriol, and antiseptic or antifungal combinations (clotrimazole, mupirocin, fusidic acid).
• Oral antibiotics for flares or infection: doxycycline 100 mg twice daily, flucloxacillin 500 mg four times daily; valaciclovir 500 mg to 1 g twice daily for HSV.
• Systemic therapy for persistent disease: low dose naltrexone 1.5 to 4.5 mg daily (up to 50 mg in some regimens), methotrexate 10 to 25 mg weekly, acitretin 0.25 to 0.5 mg/kg, dapsone 50 to 100 mg, oral prednisolone for short courses, apremilast 30 mg twice daily, and alitretinoin.
• Procedures: botulinum toxin injection (reduces sweating and friction), CO2 laser ablation or Er:YAG, dermabrasion, photodynamic therapy, and surgical excision with skin grafting.
• Genetic counselling and long term follow up for secondary infection and rare malignancy.