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Answering a burning question: what is the evolutionary cause of eczema?

By: Juliette Blais-Savoie


15-20% of children and 1-3% of adults globally suffer from eczema (1), many of them itching to know the true cause. Eczema, also known as atopic dermatitis, occurs when an allergic reaction of the skin (2) causes dry, red, and itchy patches to appear (3). Our bodies have immune reactions to defend us when we come into contact with something foreign that may be a threat. As useful as this trait is for getting rid of bacteria, viruses, and other harmful particles, our bodies aren’t always great at differentiating between a real threat and false alarm. This means that sometimes, harmless things like dust, pollen, or even our own cells can set off an allergic reaction. While trading the occasional false alarm for protection from a wide variety of infectious agents may sound like a pretty good deal, there’s an interesting new caveat to consider: the frequency of eczema cases appears to be rising over time (4).


Researchers have been trying to determine the root cause of this issue, and a common theory is related to the ‘hygiene hypothesis.’ This hypothesis states that we, as humans in modern society, are exposed to fewer microbes than our hunter-gatherer ancestors. Our immune systems evolved during this long nomadic period of human history, and they are therefore adapted for that kind of lifestyle. While some of the microbes that ancient humans would come into contact with were harmful, others were harmless – known as ‘old friends’ – and our immune systems adapted to function best with them present. When civilization and modern medicine allowed us to be exposed to fewer microbes, we kept the good out with the bad. This decrease in microbial exposure, particularly in childhood when the immune system is still developing, has caused our immune systems to become hyper-sensitive to possible threats. The hygiene hypothesis has been supported through experiments in which researchers exposed animals to different levels of microbes and found that allergic and autoimmune diseases increased after treatments to reduce microbial exposure (5).


Tsakok et al. (2) conducted a systematic review where they investigated the relationship between antibiotic exposure in early childhood and eczema. They took data from over 20 highly regarded studies on the subject and, by using statistical analysis, discovered that exposure to antibiotics in the first year of life significantly increases one’s risk of eczema (2). Because antibiotics reduce the number of ‘old friend’ bacteria in the human body, they hinder the immune development of infants, leading to an increased risk of allergic reactions as described in the hygiene hypothesis.


This trend is not just present with antibiotic use. When conducting a review containing results from over 27 studies for the hygiene hypothesis with regards to eczema, researchers found that early exposure to environments with more microbes, including daycare and households with pets, decreased risk of eczema (6). Because most cases of eczema in children fade before adulthood (7), it is also possible that the increased immune sensitivity caused by a lack of early microbial exposure decreases over time.


However, not everyone has bought into this theory. The Mayo Clinic (3) cites the primary risk factor for eczema as being “a personal or family history of eczema, allergies, hay fever, or asthma.” This is because researchers have found a link between a specific gene – KIF3A – and eczema (8), indicating that the disease is caused by a genetic variation, not environmental factors such as microbial exposure. However, this explanation does not account for why eczema rates are currently increasing.


The fact of the matter is that eczema is likely due to a mix of both of the aforementioned environmental and genetic factors, and perhaps some others that have yet to be discovered. The human immune system is highly complex, and a lot more research needs to be done to fully understand the root causes of hyper-inflammatory responses such as eczema. However, it appears that perhaps allowing our ‘old friends’ to give us a scratch on the back may go a long way in keeping us from scratching all over.


References


1. Allergy Asthma Network. Eczema Statistics. Accessed from: https://allergyasthmanetwork.org/what-is-eczema/eczema-statistics/.

2. Tsakok, T., et al. (2013). Does early life exposure to antibiotics increase the risk of eczema? A systematic review. British Journal of Dermatology 169: 983-991.

3. Mayo Clinic. Atopic dermatitis (eczema). Accessed from: https://www.mayoclinic.org/diseases-conditions/atopic-dermatitis-eczema/symptoms-cau ses/syc-20353273.

4. Williams, H., et al. (2008). Is eczema really on the increase worldwide? The Journal of Allergy and Clinical Immunology 121(4): 947-954.

5. Okada, H., et al. (2010). The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clinical and Experimental Immunology 160(1): 1-9.

6. Flohr, C., et al. (2005). Atopic dermatitis and the ‘hygiene hypothesis’: too clean to be true? British Journal of Dermatology 152: 202-216.

7. National Eczema Association. Eczema Stats. Accessed from: https://nationaleczema.org/research/eczema-facts/.

8. Stevens, M. L., et al. (2020). Disease-associated KIF3A variants alter gene methylation and expression affecting skin barrier and atopic dermatitis risk. Nature Communications 11: 4092.

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