What is Darier disease?
Darier disease is an autosomal dominant genetic disorder classified as a hereditary acantholytic dermatosis. Darier disease typically presents with scaly crusted papules in a seborrhoeic distribution and in skin folds.
Also known as Darier–White disease, Darier disease was previously called ‘keratosis follicularis’, but this is incorrect because the scaly papules do not arise from hair follicles.
Who gets Darier disease?
The onset of skin changes is usually in adolescence. Darier disease is inherited in an autosomal dominant pattern, which means that a single gene passed from one parent causes the condition. The chance of a child inheriting the abnormal gene if one parent is affected is 1 in 2 (50%) but not all people with the abnormal gene will develop clinical features of the disease.
What is the cause of Darier disease?
The abnormal gene in Darier disease has been identified as ATP2A2, found on chromosome 12q23-24.1. This gene codes for the SERCA enzyme or pump (SarcoEndoplasmic Reticulum Calcium-ATPase) that is required to transport calcium within the cell. The exact mechanism by which this abnormal gene causes the disease is still under investigation but it appears that the way in which skin cells join together may be disrupted. The skin cells (keratinocytes) stick together via structures called desmosomes and it seems the desmosomes do not assemble properly if there is insufficient calcium.
How is Darier disease diagnosed?
Usually, Darier disease is diagnosed by its appearance and family history, but it is often is mistaken for other skin problems.
Diagnosis may require a skin biopsy. The histology is characteristic, known as focal acantholytic dyskeratosis associated with varying degrees of papillomatosis. The pathological features are similar to transient acantholytic dermatosis (Grover disease).
What are the clinical features of Darier disease?
The symptoms and signs of Darier disease vary markedly between individuals. Some have very subtle signs that are asymptomatic and found only on careful inspection. Others have extensive lesions which can cause considerable distress to the affected individual. In an affected person the severity of the disease can fluctuate over time.
The skin lesions are characterised by persistent, greasy, scaly papules. Affected sites include:
- Seborrhoeic areas of the face (scalp margins, forehead, ears, around the nostrils and sides of nose, eyebrows, and beard area)
- Scalp and neck
- Central chest and back
- Skin folds, such as armpits, groin, under the breasts, and between the buttocks
The papules have a firm, harsh feel like coarse sandpaper and may be skin-coloured, yellow-brown, or brown in colour. If several of the small papules grow together they may form larger warty lesions which can become quite smelly within skin folds. There may be a heavily crusted rash similar to seborrhoeic dermatitis.
Other skin signs may include:
- Small pits on the palms and soles
- Bleeding under the skin.
Atypical presentations of Darier disease are common.
- Flat, freckle-like lesions
- Blistered papules
- Large, raised, warty lesions
- A linear pattern, with papules following the lines of embryonal development of the skin (segmental distribution)
Acne conglobata (cystic acne) is associated with Darier disease in some individuals.
Warty papules on the dorsum of hands are known as acrokeratosis verruciformis.
A localised variant of Darier disease, in which papules on hands and feet are the main feature is called acrokeratosis verruciformis of Hopf.
Nail signs of Darier disease
Most patients with Darier disease will have longitudinal broad red and/or white stripes in some or all fingernails. A V-shaped nick at the free edge of the nail is very suggestive of Darier disease.
Darier disease of palms and nails
Lesions affecting the mucous membranes
Mucous membranes are the red, moist linings of body surfaces (mouth, oesophagus, rectum, vulva, vagina). Patients with Darier disease may uncommonly have a white cobblestone pattern of small papules affecting the mucous membranes. Overgrowth of the gums may also occur.
Prognosis and complications of Darier disease
Most affected patients develop signs of Darier disease before the age of 20 years.
- Many have mild and unnoticed Darier disease.
- More severe disease may have a chronic relapsing-remitting pattern.
- The signs may clear up altogether.
Flare-ups may be caused by any of the following factors.
- Exposure to sunlight or heat.
- Topical steroid use
- Bacterial infection, usually Staphylococcus aureus
- Herpes simplex infection – including severe Kaposi varicelliform eruption (see eczema herpeticum).
In most patients, general health remains good regardless of the severity of the disease. However it can have a major impact on psychosocial functioning.
Kaposi varicelliform eruption in Darier disease
What is the treatment of Darier disease?
Treatment of Darier disease is required only if there are troublesome symptoms. Mild disease can be managed with:
Localised Darier disease can be treated by:
Darier disease and effect of acitretin