It itches, it stings, it weeps: Atopic dermatitis (neurodermatitis) is one of the most common inflammatory skin diseases. One fifth of all children in Europe suffer from it. In addition to neurodermatitis, they often suffer from hay fever or asthma as well. Experts surmise a liaison of several genetic factors and environmental reasons to cause this disease. Preliminary mutation analyses have drawn the attention to different genes. But those were not always reproducible in following studies. The researcher had to go back to starters time and again.
A protein as cause
An important new hint now came from Ichthyosis vulgaris, an inherent skin disease with excessive dander and dryness of the skin. The fish scale disease is based on a mutation in the Filaggrin-gene causing a decrease of the protein in the outer layers of the skin. Filaggrin develops from Profillagrin during the process of skin cornification. By this mutation, the outer layers of skin contain less filaggrin. Since an Ichthyosis vulgaris comes along with an atopic dermatitis in one third of the cases, it was obvious for the scientists at the Medical University of Innsbruck to start looking for filaggrin defects in neurodermatitis as well. This lead to the conclusion, that half of the patients with atopic dermatitis have that particular gene defect.
Barrier function of the skin missing
The localization of filaggrin in the outer layers of skin indicates that this protein has something to do with the barrier function of the skin towards the environment. This function is the basis for the survivability of man, since it prevents evaporation of body fluids thus establishing the prerequisite for the regulation of the hydrologic balance. In addition it is relevant for the protective function of the skin against dangers from outside. This function is crucially impaired in patients with atopic dermatitis. “The weakened barrier might enable an easier penetration of allergens and cause the higher inflammatory disposition of atopic skin. How exactly this is functioning and to what extent other factors of the immune system and the environment play a role, currently is subject to further research efforts”, explains Univ.-Prof. Dr. Matthias Schmuth of the Innsbruck Hautklinik. Those efforts are made in coordination with the European Epidermal Barrier Research Network. For research, the results loom large, since the accessibility of the skin immune system by allergens plays a decisive role in the genesis of atopy.
The key to complex dieseases
“Now that the difficult sequencing of the filaggrin gene is possible, extensive epidemiologic studies of larger groups of patients can explore its relevance in atopic dermatitis”, reckons Univ.-Prof. Dr. Janecke of the Sektion für Klinische Genetik der Medizinischen Universität Innsbruck (department for clinical genetics). Those results are an example for how the examination of rare monogenetic diseases might bring important key findings for education of complex diseases. Researches in Innsbruck were made in cooperation with research groups in Scotland, the Netherlands, Japan and the US and published in the European Journal of Human Genetics and the professional journal Nature Genetics. It also turned out that certain mutations are common in different geographic regions, while others are only found in specific regions. For example one mutation was discovered during the examinations which is only found in Tirol.