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Darier disease

Jonathan A Dyer, MD
Section Editor
Jeffrey Callen, MD, FACP, FAAD
Deputy Editor
Rosamaria Corona, MD, DSc


Darier disease, also known as Darier-White disease or keratosis follicularis (MIM #1242000), is a rare autosomal dominant genodermatosis. It is characterized by a persistent eruption of greasy hyperkeratotic papules in seborrheic areas, nail abnormalities, 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.


Darier disease is caused by mutations in the ATP2A2 gene on 12q23-24.1 that encodes the sarcoplasmic/endoplasmic reticulum Ca2+-ATP isoform 2 protein (SERCA2), which is a calcium pump [4]. SERCA2 actively transports calcium ions from the cytosol into the lumen of the endoplasmic reticulum to maintain a low cytoplasmic Ca2+ level. One study showed that in Darier disease SERCA2-controlled Ca²+-dependent keratinocyte adhesion and differentiation is mediated by sphingolipid signaling [5]. In addition, keratinocytes in Darier disease display a constitutive endoplasmic reticulum stress response with immature adherens junctions and desmosomes, resulting in decreased strength of intercellular adhesion [6].

The molecular mechanisms by which specific ATP2A2 mutations alter the function of the SERCA2 protein and cause loss of desmosomal adhesion (acantholysis) and abnormal keratinization (dyskeratosis) are not known. In in vitro models, specific mutations of ATP2A2 induce defects in protein expression, ATP hydrolysis, calcium transport, and calcium binding and kinetics [7]. ATP2A2 mutations also have been associated with impaired synthesis, folding, or trafficking of desmosomal proteins and abnormal cytokeratin expression [8-10].


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Literature review current through: Apr 2017. | This topic last updated: Mar 26, 2015.
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