Darier’s Disease


Key Points

  • Darier’s disease is a genodermatosis of autosomal dominant inheritance causing abnormalities of keratinization stemming from defects in calcium regulation in keratinocytes.
  • The classic skin manifestation is an eruption of hyperkeratotic papules, typically in a seborrheic distribution. Characteristic nail and mucous membrane involvement is common.
  • Superinfection of the skin lesions of Darier’s may result in clinical flares; important additional exacerbating factors include heat, humidity, UV light, perspiration, stress, and medications. Treatment should be adjusted accordingly and vigilant monitoring for superinfection is critical.

Introduction

Darier’s disease is a genodermatosis of autosomal dominant inheritance causing abnormalities of keratinization. The gene mutation associated with Darier’s is the ATP2A2 gene encoding SERCA-2, a calcium ATPase pump of the endoplasmic reticulum; the resulting disruption in calcium homeostasis in keratinocytes results in poor cell-cell adhesion with subsequent dyskeratosis affecting skin, nails, and mucous membranes. The hallmark skin lesion is a hyperkeratotic papule. The diagnosis of Darier’s disease is thus dependent on clinical features, family history and a characteristic histopathology.

Individuals affected by Darier’s disease typically develop manifestations of the disease in the first or second decade of life, not at birth. The classic eruption consists of hyperkeratotic, verrucous papules, classically in a seborrheic distribution: scalp, forehead, central face including the nasolabial folds, retroauricular neck, upper trunk, groin, and intergluteal cleft. Involvement of intertriginous sites can result in vegetative plaques. Other clinical variants include a cornifying variant, characterized by hypertrophic, vegetative lesions, primarily on the lower extremities, and localized forms in dermatomal, blaschkoid, or linear distribution, suggestive of somatic mosaicism. Some patients may have both variants simultaneously. The classic nail findings include V-shaped nicking, red and white streaking, or longitudinal ridging. Oral lesions, present in 13-50% of patients, include white umbilicated papules found on the palate, gingiva, and buccal mucosa (in order of frequency), sometimes coalescing into plaques with characteristic cobblestoned pattern.

The skin lesions of Darier’s are exacerbated by seasonal variation, especially by heat, humidity, UVB light; additional triggers include mechanical trauma, systemic lithium medication, and other chemical exposures. Superinfection by staphylococcal or streptococcal bacteria, or by herpes virus, can result in widespread flaring of the disease. Because the underlying genetic defect cannot yet be corrected, therapeutic strategies attempt to minimize the clinical consequences of abnormal keratinization and to treat the complications that result from the inherited defect. Systemic and topical retinoids are the mainstay. Because of seasonal exacerbations and partial remissions, therapy should be adjusted accordingly, and vigilant monitoring for superinfection with culture-directed antibiotic treatment as needed is critical. Because cutaneous squamous cell carcinoma is a rare complication of Darier’s disease, ongoing monitoring for malignancy is also required.

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