Darier Disease

Darier Disease

Irina Margaritescu, MD, DipRCPath

Photograph shows typical clinical features of Darier disease, namely greasy, crusted, keratotic, yellow-brown papules and plaques on seborrheic areas.

The histological hallmark of Darier disease is focal acantholytic dyskeratosis image.



  • Darier-White disease, keratosis follicularis



  • Mutations in gene ATP2A2

    • Located on 12q23-24.1

    • Encodes sarcoplasmic/endoplasmic reticulum Ca2+-ATPase isoform 2 protein (SERCA2)

    • > 113 familial and sporadic mutations identified

    • New mutations in ˜ 25% of cases


  • SERCA2 maintains low cytoplasmic Ca2+ level by transporting calcium ions from cytosol into lumen of endoplasmic reticulum

  • SERCA2 mutations cause alterations in cytosolic Ca2+ homeostasis that result in

    • Dyskeratosis due to reduced expression of antiapoptotic proteins Bcl-2, Bcl-x, and BAX

    • Acantholysis due to impaired trafficking of desmoplakin and abnormal desmosomal assembly

  • Heat, sweat, humidity, sunlight, UVB exposure, lithium, oral corticosteroids, mechanical trauma, and menstruation can exacerbate disease

    • UVB downregulates ATP2A2/SERCA2 expression via induction of COX-2 expression and subsequent increase of PGE(2) production in keratinocytes



  • Incidence

    • 4 new cases per 1 million over 10 years

  • Age

    • Typical onset in late childhood or adolescence

    • As early as age 4

    • Case of congenital keratosis follicularis reported

  • Gender

    • Males and females equally affected

  • Ethnicity

    • Worldwide distribution


  • Seborrheic areas such as forehead, temples, ears, nasolabial folds, scalp, upper chest, and back

  • Flexural areas including axillae, inframammary fold, groin, and perineum

  • Hands and nails

  • Mouth, anogenital mucosa, and sometimes pharynx, larynx, and esophagus


  • Symmetrical, greasy, crusted, keratotic, yellow-brown itchy papules and plaques

  • Flexural malodorous, hypertrophic, and vegetative plaques

  • Acrokeratosis verruciformis-like lesions on dorsum of hands and feet

  • Palmar pits

  • Longitudinal white &/or red nail streaks, subungual hyperkeratosis, longitudinal nail splitting with V-shaped notch at distal margin

  • White papules with cobblestone appearance on mucosa of cheeks, palate, and gums

  • Other clinical variants include hypertrophic, vesiculo-bullous, comedonal, hemorrhagic, linear, or segmental types

  • Neuropsychiatric abnormalities including epilepsy, bipolar disorder, and mental retardation have been described in some cases

Laboratory Tests

  • Gene sequencing can be used to confirm diagnosis

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Darier Disease

Full access? Get Clinical Tree

Get Clinical Tree app for offline access
%d bloggers like this: