Completing the jigsaw puzzle: an important piece is in place. 

What causes Hailey-Hailey disease?

The condition is caused by a change (mutation) in a gene on chromosome 3. Now researchers in the UK and USA have discovered that this gene makes a “calcium pump”.

What does the pump do?

This “calcium pump” is found within the cells of the skin (keratinocytes). Cells use calcium to produce signals that tell a complicated “machinery” inside the cell what to do and when to do it. Cells store calcium in tiny containers inside the cell. We believe that the pump sits in the wall of a container – called the Golgi apparatus.

The cell makes signals by letting calcium out of 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-signaling 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 Hailey-Hailey disease, the pumps in skin cells to 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 raw areas or blisters.

How will this discovery help treatment of Hailey-Hailey 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 Hailey-Hailey disease?

No. Your body is not short of calcium. It will make no difference to the signaling 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 pumps work inside skin cells
• how signals affect the machinery in the cells
• what happens to the signaling in Hailey-Hailey disease
• why infections make Hailey-Hailey disease worse
• how steroid creams affect the pumps

Thank you

Clinical scientists and dermatologists would like to thank all the families and individuals who have and are continuing to help with this work. These advances would not have been possible without your co-operation.

Susan Burge DM FRCP