Darier disease: Current insights and challenges in pathogenesis and management

Area of Science:

• Dermatology
• Genetics
• Immunology

Background:

• Darier disease is a rare autosomal dominant genodermatosis linked to ATP2A2 gene mutations.
• It presents as chronic, relapsing keratotic papules and plaques, primarily in seborrheic areas.
• Patients experience frequent bacterial and viral superinfections due to epidermal barrier defects and inflammation.

Purpose of the Study:

• To review the pathogenesis, clinical features, diagnosis, and treatment of Darier disease.
• To highlight the role of chronic inflammation and potential therapeutic targets.

Main Methods:

• Literature review of Darier disease pathogenesis, clinical presentation, and therapeutic strategies.
• Discussion of current and emerging treatment options, including symptomatic care, retinoids, and immunomodulatory therapies.

Main Results:

• Limited long-term therapeutic options exist, with systemic retinoids being the most effective for extensive lesions.
• Chronic inflammation, involving Th17 cells, is a key feature.
• Blocking the IL-23/IL-17 axis demonstrated improvement in therapy-resistant cases.

Conclusions:

• Darier disease management requires addressing chronic inflammation and superinfections.
• Targeting the IL-23/IL-17 axis represents a promising therapeutic avenue for severe, refractory cases.
• A comprehensive understanding of pathogenesis is crucial for developing effective treatments.