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Darier disease

Daniel Hohl, MD
Section Editor
Jennifer L Hand, MD
Deputy Editor
Rosamaria Corona, MD, DSc


Darier disease, also known as Darier-White disease, keratosis follicularis, or dyskeratosis follicularis (MIM #124200), is a rare autosomal dominant genodermatosis characterized by a persistent eruption of red-brown, keratotic papules scattered to confluent in a seborrheic distribution, nail abnormalities, pitting of palms and soles, and mucosal changes [1]. The disease usually starts around puberty and runs a chronic course with exacerbations induced by sun exposure, heat, friction, or infections.

This topic will discuss the pathogenesis, clinical features, diagnosis, and management of Darier disease. Other acantholytic skin disorders, including Hailey-Hailey disease and Grover disease, are discussed separately. (See "Hailey-Hailey disease (benign familial pemphigus)" and "Grover's disease (transient and persistent acantholytic dermatosis)".)


Darier disease occurs worldwide with a prevalence of 1 to 4 per 100,000 [2,3]. The disease affects both sexes and all ethnic groups.


Mutations in the ATP2A2 gene that encodes a sarco/endoplasmic reticulum Ca2+-adenosine triphosphate (ATP)ase pump (SERCA2) lead to both acantholysis and apoptosis, accounting for the characteristic pathologic finding of acantholytic dyskeratosis in Darier disease [4]. SERCA2 actively transports calcium ions from the cytosol into the lumen of the endoplasmic reticulum to maintain a low cytoplasmic Ca2+ level. Specific mutations of SERCA2 induce defects in protein expression, ATP hydrolysis, calcium transport, and calcium binding and kinetics [5]. SERCA2 mutations also have been associated with impaired synthesis, folding, or trafficking of desmosomal proteins and abnormal cytokeratin expression [6-8].

Despite its ubiquitous expression, the lack of compensatory SERCA3 expression in keratinocytes may explain their particular vulnerability to SERCA2 deficiency. SERCA2 haploinsufficiency has been proposed to underlie the dominant transmission pattern by affecting Ca2+-mediated maturation of cellular adhesion proteins and desmosomes in the endoplasmic reticulum through a stress response, resulting in decreased strength of intercellular adhesion [9].

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Literature review current through: Sep 2017. | This topic last updated: Aug 24, 2017.
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