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Darier’s Disease

What are the aims of this leaflet?

This leaflet has been written to help you understand more about Darier’s disease.   It tells you what it is, what causes it, what can be done about it, and where you can find out more about it.

What is Darier’s disease?

It is a rare inherited skin condition, in which the skin in certain areas develops numbers of small brownish warty bumps.

What causes Darier’s disease?

It runs in certain families, being inherited in a pattern known as 'dominant inheritance' - which means that there is a 1 in 2 (50:50) chance that each child of an affected parent will inherit the problem.  It affects both men and women.  It is not contagious (catching) or due to an allergy.

In normal skin, the skin cells are held together like bricks cemented in a wall. In Darier's disease the sticky junctions that hold the skin cells together are not made properly, and the skin may become scaly or lumpy or even form blisters.  Fuller details of recent discoveries in this field are given in the Appendix at the end of this leaflet.

Is it hereditary?

Yes, see the paragraph above.  Its severity may vary considerably within a single family; and the fact that one person is badly affected does not mean that other family members who inherit the condition will also get severe disease.

What are the symptoms of Darier’s disease?

Itching is very common.  The affected skin may smell unpleasant, particularly in moist areas. This is probably caused by increased numbers of ordinary skin bacteria growing in the affected skin.  The appearance of the rash, and its smell, can be embarrassing.

What does it look like?

The first signs of the condition usually appear somewhere between the ages of 6 and 20. Little brownish, rough-topped bumps develop on the skin. The severity of the condition varies a lot and is unpredictable. The rash is often on the chest, neck or upper back at the start but warty bumps may occur on any part of the body including the flexures and skin under the breasts. It is unusual for people to have much trouble on the face except for the skin on the forehead near the hairline.

The fingernails are usually affected. They tend to be rather fragile, split easily and look as if they have been bitten or appear dirty. There may be very obvious long red or white lines running the length of the nails. Nail changes and/or flat "warts" on the backs of the hands are often present in childhood, well before there are any other skin changes. Pits or small "corns" occur on the palms of the hands and less often the soles of the feet. Occasionally there may be small spots inside the mouth and these may give the roof of the mouth a rough feeling.

A quarter of patients notice that the condition improves as they get older.  Some women notice that it worsens around the time of their period.

How will it be diagnosed?

The diagnosis can often be made on the basis of the look of the rash and fact that it runs in families.  To confirm it, a small sample of skin (a biopsy) can be removed under a local anaesthetic and examined under the microscope in the laboratory.

Can Darier’s disease be cured?

No, there is no switch-off cure, but there are many ways of helping it (see below) 

How can Darier’s disease be treated?

·       The itching: Creams like Calmurid, E45 or aqueous cream may relieve some of the irritation. Sometimes corticosteroid creams are helpful if the skin is very itchy and these are often prescribed in a mix with an antibiotic to prevent skin infection.

·       The smell.  This is part of the skin condition and does not mean that the skin is dirty. Careful washing is important but, in addition, antiseptic solutions for the bath, antiseptic creams or antibiotics may help.

·       The use of retinoid tablets.  These are derived from Vitamin A (the current one that is used is called acitretin or Neotigason) and will improve the skin in most patients, but they can have several important side effects. If women take retinoids when they are pregnant, the medicine is likely to damage the developing baby. Therefore retinoids can only be prescribed for women of childbearing age who have been sterilised or who are using an effective contraceptive e.g. the contraceptive pill.  Retinoids also cause drying of the lips, eyes and nose.  Used long term, they may also have effects on bones and fat levels in the blood.  Patients with mild skin disease often find they would rather live with their disease than put up with these side effects.

·       Infections.  There is an increased chance of developing skin infections if you have the condition.  Infection with the same sort of bacteria that infects cuts or grazes is common and may make the condition more active - this may require treatment with antibiotics from your doctor.  The "cold sore" virus (herpes simplex) sometimes causes widespread skin infections in people with Darier's disease. If the condition suddenly gets worse and is much more painful than usual this may be a sign of a herpes simplex infection. Contact your GP or dermatologist urgently if this happens.

What can I do?

Most people with Darier’s disease lead full, normal lives and have no other medical problems.  Less than a quarter need any time off work or school because the skin is a problem.  However a number of things seem to make the skin worse, particularly heat, sweating and wool or nylon clothing. Some patients find that sun causes the skin disease to flare up. It is sensible to try to avoid these triggers.

Where can I get more information about Darier’s disease?
 

Web links to detailed leaflets:
www.emedicine.com/derm/topic209.htm
www.dermnetnz.org/dna.darier/darier.html

Appendix

Recent scientific advances in our understanding of Darier’s disease.

Darier’s disease is now known to be caused by a change (mutation) in a gene on chromosome 12. Researchers have discovered that this gene makes a protein pump called SERCA2.

What does SERCA2 do?

The SERCA2 protein is a “calcium pump” that is found within the cells of the skin (keratinocytes). Cells use calcium to produce signals that tell the complicated “machinery” inside the cell what to do and when to do it. Cells store calcium in tiny containers inside the cell. The containers are called the sarcoplasmic or endoplasmic reticulum. The SERCA2 pumps sit in the wall of these containers. (SERCA2 stands for sarco-endoplasmic reticulum calcium ATPase 2).

The cell makes signals by letting calcium out of the containers and using SERCA2 to pump the calcium back into the containers. Changes in the amount of calcium as it is released and then pumped back into the container can be measured. The rapid changes in calcium are measured as a number of tiny spikes. The pattern of spikes makes a very complicated signal, but we do not know exactly what the changes in calcium spikes say. It is rather like hearing Morse code but not understanding what the dots and dashes mean. We need “code breakers” so we can unravel exactly how the calcium messages switch the machinery on and off.

We know that calcium-signalling controls the  “machinery” that makes the sticky junctions (desmosomes) that hold skin cells together. If the “machinery” does not work properly, the sticky junctions may not be made correctly. In Darier’s disease, the SERCA2 pumps in skin cells do not work properly. We suspect that faulty signals affect the skin cells so that the sticky junctions are not made correctly, the cells do not hold together and the skin forms little rough bumps.

How will this discovery help treatment of Darier’s disease?

This discovery is a very important step because once we understand exactly what is going wrong we will be in a much better position to put things right. We are still a long way from finding a better treatment but we are getting closer.

Will extra calcium help Darier’s disease?

No. Your body is not short of calcium. It will make no difference to the signalling if you eat more calcium or if you rub a cream containing calcium on your skin.

Next Steps.

Clinical scientists would like to understand:

·         Exactly how the SERCA2 pumps work inside skin cells.

·         How signals affect the machinery in the cells.

·         What happens to the signalling in Darier’s disease.

·         Why sunburn, heat and sweating make Darier’s disease worse.

·         How retinoids (e.g. Neotigason) affect the SERCA2 pumps.

(While every effort has been made to ensure that the information given in this leaflet is accurate, not every treatment will be suitable or effective for every person. Your own doctor will be able to advise in greater detail)