Keratosis follicularis

From Ganfyd

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^[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:
  • Trunk
  • Flexures
  • Scalp
• 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.

Rare acute presentations have been reported^[2]. Acantholytic dyskeratotic nevi are a variant and acrokeratosis verruciformis can be caused by other mutations of the ATP2A2 gene.

Aetiology

This is not yet fully understood.^[3] 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.^[4]. There is a relationship to an inherited bullous disorder, benign chronic pemphigus, which is caused by deficits of the Golgi SERCA pump.

Treatment

All the classic treatments for hyperkeratosis have been tried with variable, sometimes mild success.

Histology

• Clefts may form just above the basal layer of the epidermis (suprabasal acantholysis).
• Corp ronds or grains.
• Hyperkeratosis
• Parakeratosis

References