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.


TERMINOLOGY



Synonyms



  • Darier-White disease, keratosis follicularis



ETIOLOGY/PATHOGENESIS


Etiology



  • 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


Pathophysiology



  • 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


CLINICAL ISSUES


Epidemiology



  • 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


Site



  • 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


Presentation



  • 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
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