Experts on genetic skin disorders at the University of Dundee conducted the research with collaborators in Dublin, Glasgow, Seattle and Copenhagen.

Currently, only symptomatic treatment of eczema is possible with topical ointments designed to prevent the skin drying out or with drugs that target inflammation. Now that the underlying gene defect behind this disorder is known, it will be possible to design new, more effective therapies to tackle the root cause of the problem. The Dundee group is already working on developing methods to treat and even prevent these diseases.

Impaired Formation of Skin Barrier

The gene in question produces a protein called filaggrin which is normally found in large quantities in the outermost layers of the skin. This protein is essential for skin barrier function, helping to form a protective layer at the surface of the skin that keeps water in and keeps foreign organisms out.

Reduction or complete absence of this important protein leads to impaired formation of the skin barrier. As a result, the skin dries out too easily and in addition, the outer layers of the skin are poorly formed and constantly flake off. As well as keeping water in, the skin barrier normally keeps foreign substances out of the skin.

In people with filaggrin mutations, foreign substances can easily enter the skin and be seen by the immune system. This explains the development of inflamed skin characteristic of eczema. In some people, priming of the immune system through the "leaky" skin appears to lead to asthma when foreign substances later enter the lungs.

The first study, led by geneticists Professor Irwin McLean and Dr Frances Smith in Dundee and their dermatology colleague, Dr Alan Irvine, Our Lady's Hospital for Sick Children, Dublin, discovered that about 10 percent of European people carry a type of genetic mutation that switches off the filaggrin gene, and this causes a very common dry, scaly skin condition, known as ichthyosis vulgaris.

About 5 million people in the UK alone make only 50 percent of the normal amount of filaggrin protein and have a milder form of the disorder where the skin is dry and flaky. About 1 in 500 people, or 120,000 people in the UK, have both copies of the gene knocked out by genetic mutations and have no filaggrin protein whatsoever in the skin. These individuals have a severe and persistent form of the disease, often requiring specialist treatment.

60 Million People Affected Worldwide

A second study showed that many people with ichthyosis vulgaris also have eczema. Further research then showed a link between ichthyosis vulgaris, eczema and asthma. McLean, Smith and Irvine, in collaboration with Drs. Colin Palmer and Somnath Mukhopadhyay of the Dundee BREATHE study, and Professor Hans Bisgaard in Copenhagen, showed in four independent experiments that these common mutations in the filaggrin gene are a major predisposing factor in the development of eczema and the form of asthma associated with eczema:

About 5 million people in the UK carry one of the filaggrin mutations and consequently, have dry skin and are predisposed to eczema and to a lesser extent, asthma.

Worldwide, about 60 million people are estimated to carry these particular gene defects and more than 1 million are predicted to have the severe form of the disease as a consequence of these mutations alone.

The Dundee group already have evidence for the presence of different filaggrin mutations in other ethnic populations and it seems that reduction or absence of filaggrin in the skin is likely to be a major cause of dry skin and eczema worldwide.