Darier’s disease

Darier's disease is a rare, chronic, autosomal dominant condition, that usually arises in adolescence, and is characterised by scaly papules, most frequent on the upper trunk. 

This chapter is set out as follows:

• Darier's disease is inherited as autosomal dominant, meaning that a single gene passed from one parent causes the condition. The chance of a child inheriting gene if one parent is affected is 1 in 2 but not all people with the abnormal gene will develop symptoms of the disease
• The gene in Darier's disease has been identified as ATP2A2 at chromosome 12q24.1, an abnormality in this gene affects desmosome function, which results in reduced cell-to-cell adhesion

• Symptoms tend to first present in the second decade of life
• Heat and sunlight can exacerbate symptoms
• Extensive, malodorous and painful skin can impact on social interaction, work or school

Distribution

• The seborrhoeic areas of the trunk and face (ie more central), along with the scalp, hairline, temples and ears are the most commonly affected sites
• The flexures are also commonly involved 
• Less commonly Darier's can have a Blaschkoid distribution 

Morphology

• There can be significant variation between individuals, with some having very mild skin changes, while others have extensive lesions
• The characteristic lesion is a persistent, greasy-looking, firm, rough papule, which is skin-coloured or yellow-brown. Lesions can coalesce to form large warty plaques, which if arise in the flexures can be very malodorous
• The scalp is often heavily crusted, and has a rough feel
• Less common presentations include multiple pale macules, especially in darker-skinned individuals, and nodular acne 

Other cutaneous features

•     Lesions on the hands and nails
• Small pits on the palms and soles are very characteristic
• Flat-topped papules on the dorsa of the hands and feet can be a very early sign 
• Most patients will have white or red longitudinal bands affecting the nails, often ending in a characteristic V-shaped notch at the free edge of the nail  

• Mucous membranes
• Mucous membrane involvement is uncommon
• Ocular manifestations include hyperkeratotic plaques and seborrhoeic debris at the eyelid margin. The chronic blepharitis is associated with dry eyes and occasionally corneal erosion

• Secondary infection
• Impetiginisation and eczematisation are common, and patients have an increased susceptibility to infection with herpes simplex and herpes zoster, severe infections may be disseminated or fatal

Non-cutaneous features

• Neuropsychiatric features - depression, bipolar disorder, epilepsy and intellectual difficulties have been reported 

• Darier's disease is usually diagnosed clinically 
• Occasionally a skin biopsy is required, showing focal acantholytic dyskeratosis (disordered cell adhesion)

General management principles

• Provide a patient information leaflet on Darier's disease
• Supply appropriate quantities (ie 500g) of an emollient to use as a moisturiser. Given the increased incidence of skin infection consider using an emollient with an antiseptic property eg the Dermol ® range 
• Moderately potent to super-potent topical steroids can be used on sore / inflamed skin - if associated with recurrent infections then use a combined treatment of topical steroids with antifungals / antibiotics 
• If herpetic infection is suspected stop topical steroids and treat with oral antivirals, eg aciclovir

More severe disease - refer

• Oral retinoids (acitretin 0.25–0.5 mg/kg/day or isotretinoin 0.5 mg/kg/day) are usually effective treatments but are teratogenic 
  
• Pulse ciclosporin can be used to manage severe flares 

Prognosis

• Although persistent, many patients with Darier's disease are relatively mildly affected
• Patients with more severe disease have a chronic relapsing-remitting pattern
• Spontaneous resolution is uncommon