Treatment of Hailey-Hailey Disease
For Hailey-Hailey disease, begin with topical corticosteroids and topical antimicrobials as first-line therapy, escalating to oral antibiotics for refractory cases, with procedural interventions (botulinum toxin A, excisional procedures, or photodynamic therapy) reserved for severe or treatment-resistant disease. 1
First-Line Topical Management
Topical corticosteroids (mild-to-moderate potency) represent the treatment with the strongest evidence base and should be applied to affected intertriginous areas (neck, axillae, groin, perianal regions) during active flares 1, 2
Topical antimicrobials are equally well-supported as first-line therapy to address secondary bacterial, viral, or fungal superinfections that frequently complicate the macerated erosions characteristic of this disease 1, 2
Patients must avoid friction and excessive sweating by wearing light cotton clothing, and practice strict sun avoidance with SPF 50 sunscreen, as ultraviolet radiation is a known trigger 3, 4
Second-Line Systemic Therapy for Refractory Disease
When topical therapy fails after 4-8 weeks, escalate to:
Oral antibiotics (such as tetracyclines) show the most benefit for refractory disease and should be the next step before considering more aggressive interventions 1, 4
Oral retinoids (acitretin 25 mg daily) have demonstrated dramatic improvement over 6 months in cases refractory to conservative management, likely through effects on epidermal differentiation and calcium homeostasis 5
Hydroxyurea (1000-1500 mg orally daily) has shown complete durable response in severe relapsing disease, with one case demonstrating 4-year remission without relapses 4
Oral dapsone, cyclosporine, azathioprine, or methotrexate can control mild-to-moderate disease but typically fail in severe chronic or relapsing forms 4, 6
Procedural Interventions for Severe Disease
For disease unresponsive to topical and systemic medical therapy:
Botulinum toxin A injections and excisional procedures have the strongest evidence among procedural options for refractory Hailey-Hailey disease 1
Photodynamic therapy (PDT) with aminolevulinic acid (ALA) and red light is recommended by the British Journal of Dermatology, showing histological clearance with no recurrences at 19-25 months in a small case series 7
Topical liposomal chlorin photosensitizer PDT has also demonstrated successful treatment 3
Laser therapy can be considered, though evidence is limited compared to other procedural options 2
Surgical skin grafting represents the last resort for resistant localized disease that has failed all other interventions 4
Critical Management Principles
The therapeutic approach must focus on three simultaneous targets: controlling exacerbating factors (sweating, weight gain, trauma, pregnancy), treating secondary infections aggressively, and suppressing cutaneous inflammation 3, 2
A major pitfall is attempting systemic corticosteroids as monotherapy - while they may provide temporary relief, they do not address the underlying calcium pump abnormality (ATP2C1 gene mutation) and fail to prevent the characteristic relapsing-remitting pattern 4
No single regimen works for all patients due to the variable expressivity of this autosomal dominant condition, requiring clinicians to systematically escalate through the treatment ladder outlined above 1, 2
The disease follows a chronic relapsing course with spontaneous remissions and multiple recurrences, and severe cases can cause major psychological and social impact requiring aggressive management 2