Keratosis follicularis (Darier-White disease, Darier disease, Darier's disease) is an autosomal dominant disorder with variable penetrance often caused by mutations in the ATP2A2 gene at 12q23-q24.1 encoding the SERCA2 Ca2+-ATPase. This appears to affect epidermal cell adhesion with resulting abnormal keratinisation.
Affected patients develop, usually by their 30s:
- Warty papules and plaques in seborrhoeic areas such as:
- Palmoplantar pits
- Haemorrhage into acantholytic vesicles on the palms can give black pits
- Nail abnormalities, usually thickening.
Sun, heat, and sweating exacerbate it and it is difficult to treat, especially in its more severe forms. Superinfection is common including Kaposi varicelliform eruption.
This is not yet fully understood. Keratinocytes, unlike most cells, use Ca2+ release into the cytosol from both the Golgi apparatus and endoplasmic reticulum for efficient Ca2+-mediated signalling. In the case of Darier's disease, SERCA pumps maintain the normally low cytosolic Ca2+ concentration by pumping Ca2+ into the endoplasmic reticulum.. There is a relationship to an inherited bullous disorder, benign chronic pemphigus, which is caused by deficits of the Golgi SERCA pump.
All the classic treatments for hyperkeratosis have been tried with variable, sometimes mild success.
- Clefts may form just above the basal layer of the epidermis (suprabasal acantholysis).
- Corp ronds or grains.
This article is a work in progress. Please feel free to contribute to it.
- ↑ Sakuntabhai A, Ruiz-Perez V, Carter S, Jacobsen N, Burge S, Monk S, Smith M, Munro CS, O'Donovan M, Craddock N, Kucherlapati R, Rees JL, Owen M, Lathrop GM, Monaco AP, Strachan T, Hovnanian A. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nature genetics. 1999 Mar; 21(3):271-7.(Link to article – subscription may be required.)
- ↑ Fishman HC. Acute, eruptive Darier disease (keratosis follicularis). Archives of dermatology. 1975 Feb; 111(2):221-2.
- ↑ Byrne CR. The focal nature of Darier's disease lesions: calcium pumps, stress, and mutation? The Journal of investigative dermatology. 2006 Apr; 126(4):702-3.(Link to article – subscription may be required.)
- ↑ Godic A. Darier disease: a guide to the physician. Journal of medicine. 2004; 35(1-6):5-17.