A severe fatal case of Darier-White disease—an extreme phenotype or a new entity?

Abstract

Darier-White disease (DWD) is an autosomal-dominant skin disease characterized by warty keratotic papules and plaques in a primarily seborrheic distribution. Vegetating papules, erosions, or blisters may sometimes be present. Other findings may include varieties of nail abnormalities, “cobblestoning” of the oral mucosa, filiform keratoderma on the palms and soles, and hyperkeratosis verruciformis of Hopf. DWD has an unpredictable clinical course, and patients may present with variable extents of involvement and diverse morphologies at different body areas.1, 2 Neuropsychiatric abnormalities and immunologic aberrations have been reported in association with DWD.3, 4 Clinical subtypes reported to date include hypertrophic,5 vesicobullous, hypopigmented, cornifying, zosteriform or linear, and comedonal variants.6 DWD has recently been linked to mutations in the SERCA2 gene, which encodes the calcium ATPase pump in the sarcoendoplasmic reticulum. Alterations in calcium signaling cause aberrant keratinocyte differentiation. The result is characteristic dyskeratosis follicularis, demonstrated by the presence of typical dyskeratotic cells, such as, corps ronds and grains. Treatments may include emollients, topical retinoids, topical steroids, and intermittent courses of oral antibiotics and systemic retinoids. We present a unique case of DWD showing overlap between several clinical subtypes of the disease with a 20-year course and fatal outcome.