On the Role of the Epidermal Differentiation Complex in Ichthyosis Vulgaris, Atopic Dermatitis and Psoriasis

S. Hoffjan; S. Stemmler


The British Journal of Dermatology. 2007;157(3):441-449. 

In This Article

Conclusions and Future Prospects

In conclusion, FLG loss-of-function mutations have been implicated convincingly in the pathogenesis of ichthyosis vulgaris and AD, and there is strong evidence that EDC variation might also play a role in psoriasis. Interestingly, the FLG mutations that result in impaired barrier function have a comparatively high frequency in the European population (carrier frequency of ∼5%). This fact raises the question of whether there might be some kind of evolutionary advantage for heterozygote individuals. Irvine and McLean recently offered a tempting explanation: they speculated that a minor barrier dysfunction could promote repeated low-level exposure to pathogens like a 'natural vaccination' and thus result in strengthened immunity.[62] This hypothesis is in line with the so-called hygiene hypothesis, suggesting that low-level exposure to pathogens in early childhood might prevent the development of allergic disease by stimulating innate immunity.[63]

The highly significant and consistent correlations between FLG mutations and ichthyosis vulgaris as well as AD emphasize the important role of an impaired skin barrier function for the development of both skin disease and allergic disease. Especially for AD, the consistent association with FLG mutations has paved the way for a new understanding of the underlying pathogenesis. Instead of interpreting AD primarily as an allergic disease mediated by dysregulated IgE responses, the hypothesis is now rather that an impaired skin barrier function in the first place might promote transepidermal entry of allergens and thus secondary development of allergic disease. Although the exact pathogenic mechanisms are still unclear, these findings open up a new field for therapeutic targeting or prevention of allergic disease. Correcting or improving barrier dysfunction will certainly constitute an important therapeutic strategy for allergic diseases in the future.

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