Darier disease

Author: Dr Amy Stanway MBChB, Registrar, Department of Dermatology, Waikato Hospital, Hamilton, New Zealand, 2002. Updated by Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, October 2016.

What is Darier disease?

Darier disease is a rare genetic disorder that is manifested predominantly by scaly or crusted papules. Like benign familial pemphigus (Hailey-Hailey disease), Darier disease is classified as a hereditary acantholytic dermatosis.

Darier disease was previously also known as ‘keratosis follicularis’, but this is incorrect because the scaly papules do not arise from hair follicles.

Who gets Darier disease?

Onset of skin changes is usually in adolescence and the disease is usually chronic. 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 symptoms 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 the 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 (skin thickening). The pathology is similar in Grover disease (transient acantholytic dermatosis).

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:

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.  

Atypical presentations of Darier disease are common.

 Acne conglobata (cystic acne) is associated with Darier disease in some individuals.  

Acrokeratosis verruciformis

Warty papules on the dorsum of hands are known as acrokeratosis verruciformis or keratosis follicularis.  Other signs may include:

A localised variant of Darier disease, in which papules on hands and feet are the main feature is called acrokeratosis verruciformis of Hopf.

Most patients with Darier disease will have longitudinal broad stripes of white and reddish colour on some or all fingernails. A V-shaped nick at the free edge of the nail is also very suggestive of Darier disease.

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 30 years.

Flare-ups may be caused by any of the following factors.

In most patients, general health remains good regardless of the severity of the 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:

Secondary bacterial infection (usually due to Staphylococcus aureus) should be treated with antibiotics. Herpes simplex is treated with aciclovir or valaciclovir.

Severe Darier disease is usually treated with oral retinoids, either acitretin or isotretinoin. Ciclosporin has been reported to be effective in a few patients.

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