Eczema - What Causes It and What Do We Know About It

What is it

Eczema or atopic dermatitis is a pretty common skin condition that is chronic, can lead to infections and poor quality of life. For the people who suffer from it though, they experience dry and itchy skin which results in scratching which creates rashes all over the body of different severities.^1.0 While there is much more to be understood about Eczema, one school of thought is that eczema has something to do with genetics and environmental factors. Family histories with allergies, eczema, and asthma are common especially including those with skin barrier components and an involvement by the immune system.^1.1

Filaggrin

One of the largest genetic factors to be aware of is a mutation of the filaggrin (FLG) gene which provides instructions to build structural proteins in the stratum granulosum and stratum corneum (the middle and surface layers of the epidermis). This helps to hold keratinocytes together which are the cells that make up 90% of the epidermis which consists of five sublayers. As keratinocytes move from the base layer (stratum, basale) to the surface layer (stratum corneum) they go through keratinisation where they accumulate more and more of the protein keratin. As they move up the layers they are further from the blood supply so become less active and eventually die to create the dead skin cells on the surface of the skin. If the production of the structural proteins is affected it can comprise the skin barrier, lead to moisture loss and perhaps allow penetration of allergens into the skin.^2.0 (p. 186 -191). There were 2 important studies that took place in 2006, the first linked loss of function mutations in the filaggrin gene to causing ichthyosis vulgaris.^4.0 The second study discusses 2 filaggrin gene mutations that have strong predisposing factors for atopic dermatitis.^5.0 For a while atopic dermatitis was thought to be primarily a problem with the immune system with skin symptoms being a secondary symptom. But now due to the outside-inside hypothesis the main driver is thought to be the impaired skin barrier which allows allergens to enter the body which triggers allergic reactions in the epidermis which is already in an enflamed state resulting in the overall atopic dermatitis situation. The thinking behind this is all the evidence of the link between loss of function mutations of the filaggrin gene and atopic dermatitis.^6.0

Functions Of The Skin

As the outermost layer of the body, skin is there to protect and defend the body from the outside environment. It’s functions are to regulate transepidermal water loss (TEWL), protect against physical and chemical agents and protect from external microbes. Filaggrin is a protein that is made from pro-filaggrin by the keratinocytes in the epidermis.^3.0 Certain amino acids are present between the cells in the epidermis such as arginine, glutamine, and histadine. They provide natural moisturising factors (NMF) for the skin which support the stratum corneum (the outer most layer of keratinocytes within the epidermis).^3.1

Conclusion

Other genes may be involved but filaggrin is the highest genetic risk factor for atopic dermatitis with around half of atopic dermatitis patients having a filaggrin mutation.^6.1 The epidermal differentiation complex (EDC) is a group of genes on chromosome 1 which are needed for epidermal barrier formation^7.0 but of these genes filaggrin is the one that is susceptible to variation.^6.2 Atopic Dermatitis is a complicated disease with many different factors working in combination such as genetics, environment, the skin microbiome and the immune system. I will be writing about these aspects and more in future. But for now I wonder, what if anything can be done about genetics when it comes to eczema, and why isn't this knowledge mainstream?

References

1.↑ ^{1.0 1.1} Nemeth, V., Syed, H. A., & Evans, J. (2024, March 1). Eczema. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK538209/

2.↑ ^2.0 Tortora, G. J., Derrickson, B., Burkett, B., Cooke, J., Pietro, F. D., Diversi, T. (2022). Principles of Anatomy and Physiology, Asia-Pacific Edition, 3rd Edition.

3.↑ ^{3.0 3.1} Zaniboni, M. C., Samorano, L. P., Orfali, R. L., & Aoki, V. (2016). Skin barrier in atopic dermatitis: beyond filaggrin. Anais Brasileiros De Dermatologia, 91(4), 472–478. https://doi.org/10.1590/abd1806-4841.20164412

4.↑ ^4.0 Smith, F. J. D., Irvine, A. D., Terron-Kwiatkowski, A., Sandilands, A., Campbell, L. E., Zhao, Y., Liao, H., Evans, A. T., Goudie, D. R., Lewis-Jones, S., Arseculeratne, G., Munro, C. S., Sergeant, A., O’Regan, G., Bale, S. J., Compton, J. G., DiGiovanna, J. J., Presland, R. B., Fleckman, P., & McLean, W. H. I. (2006). Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nature Genetics, 38(3). https://doi.org/10.1038/ng1743

5.↑ ^5.0 Palmer, C. N. A., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S. P., Goudie, D. R., Sandilands, A., Campbell, L. E., Smith, F. J. D., O’Regan, G. M., Watson, R. M., Cecil, J. E., Bale, S. J., Compton, J. G., DiGiovanna, J. J., Fleckman, P., Lewis-Jones, S., Arseculeratne, G., . . . McLean, W. H. I. (2006). Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics, 38(4). https://doi.org/10.1038/ng1767

6.↑ ^{6.0 6.1 6.2} Gupta, J., & Margolis, D. J. (2020). Filaggrin Gene Mutations with Special Reference to Atopic Dermatitis. Current Treatment Options in Allergy, 7(3), https://doi.org/10.1007/s40521-020-00271-x

7.↑ ^7.0 Leśniak, W. (2024). Dynamics and epigenetics of the Epidermal differentiation complex. Epigenomes, 8(1), 9. https://doi.org/10.3390/epigenomes8010009