Darier disease

Darier disease, also known as Darier-White disease, keratosis follicularis, or dyskeratosis follicularis, is a rare inherited skin disorder caused by mutations in the ATP2A2 gene, which encodes the SERCA2 calcium pump essential for cell-to-cell adhesion in the skin. The disease is characterized by a disruption in the normal process of keratinization, leading to loss of adhesion between skin cells (acantholysis) and abnormal keratinization (dyskeratosis). The hallmark clinical features include greasy, warty, skin-colored or brownish papules that tend to coalesce into plaques, primarily affecting seborrheic areas such as the chest, back, scalp, forehead, and skin folds (groin, axillae). These lesions often have a distinctive unpleasant odor due to secondary bacterial infection. Nail abnormalities are very common and include longitudinal red and white streaks, V-shaped nicking at the free edge of the nail, and subungual hyperkeratosis. Small pits or punctate keratoses on the palms and soles (palmar pits) are another characteristic finding. Mucous membranes, particularly the oral mucosa, may also be affected with whitish papules. The disease typically worsens with heat, humidity, sun exposure, friction, and sweating. Some patients also experience neuropsychiatric manifestations, including mood disorders, epilepsy, and learning difficulties, though the relationship to the underlying genetic defect is still being studied. There is currently no cure for Darier disease. Management focuses on symptom control and prevention of flares. Mild cases may be managed with emollients, sun protection, and avoidance of triggers such as heat and friction. Topical retinoids and topical corticosteroids can be helpful for localized disease. For moderate to severe cases, oral retinoids such as acitretin or isotretinoin are the mainstay of treatment and can significantly reduce the severity of skin lesions. Secondary bacterial, viral (particularly herpes simplex), and fungal infections are common complications that require prompt treatment. Genetic counseling is recommended for affected individuals and their families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Darier disease