Eczema

The Biology of Eczema

Posted on : 07.05.2019

When you think of eczema, you probably picture a red rash around the wrists, elbows or maybe the cheeks. If you suffer from it yourself, it’s more likely the itch that you associate with the condition. Being able to recognise and manage eczema is one thing, but understanding what’s happening at a cellular or molecular level is a little trickier, and we still don’t have all the answers.

Who gets eczema, and why?

Eczema is most common in people with what’s called ‘atopic tendency’, which groups together three closely linked conditions: asthma, hay fever and atopic eczema.[1] For a long time, we’ve known there was a genetic factor involved, but recent research has shed some more light on one aspect, showing that around 16% of children with eczema have a mutation in the gene responsible for producing filaggrin.[2] More on this later.

A weakened skin barrier

One of the main features of eczema-prone skin is a weakened skin barrier that loses water more quickly than normal skin.[3] The skin barrier is made up of flattened, dead cells called corneocytes (I like to picture them as corn flakes) that are held together by intercellular lipids (imagine a nice, smooth peanut butter). When everything is as it should be, the peanut butter holds the cornflakes in place, creating a strong, even barrier that keeps water in and irritants out. But just like real peanut butter, sometimes the consistency isn’t right—it can be dry, lumpy, difficult to spread. When this happens to your skin lipids, the corneocytes flake away more easily, a characteristic of dry skin, leaving gaps in the barrier. A vital component of the skin lipids are ceramides (a family of molecules crucial for the healthy functioning of the skin) and studies have shown that in eczema-prone skin, ceramide 1 is reduced, while a lack of ceramide 3 is linked to increased water loss from the skin.[4] Without these key ceramides, the lipid portion of the barrier is disrupted.

Another contributing factor in some people with eczema-prone skin is a mutation to the gene responsible for producing filaggrin. Filaggrin’s role is to help bind corneocytes together, but it’s also broken down and recycled to create the skin’s Natural Moisturising Factor, a mix of ingredients that, you guessed it, help keep skin moisturised.[4] This mutation results in less filaggrin produced, and as a result, less moisturising factor in the skin.[5]

One unanswered question is how, or if, low filaggrin levels are associated with low ceramide levels. Ceramide production is known to be affected by pH, and while filaggrin breakdown changes the skin’s pH, it’s not yet clear if there’s a link between the two.[6] Surprisingly, recent studies have shown no significant differences in the skin lipids (including ceramides) between eczema sufferers with the filaggrin mutation and those without it, indicating that the process must be more complex.[7]

Why does eczema itch?

The main cause of itch is the stimulation of nerve endings, called C-fibres in the top layer of the skin. Some known triggers are external irritants, chemical mediators in the skin, and dry skin. I delve much deeper into the fascinating topic of itch in this article, but in a nutshell the problem for people with eczema-prone skin seems to come from a combination of a dry, weakened skin barrier, and a greater density of these C-fibres, resulting in an itch that, at times, won’t let up.[8]

How can moisturisers help?

For most people, it’s the incessant itch that can make eczema seem so unbearable. But as we’ve seen, that itch is often caused or made worse by dry skin as a result of a weakened skin barrier, so one of the most important management strategies is to try to address the issue of dry skin. Moisturisers can’t fix the skin barrier, but like a tarp over a leaking roof, they can help support the barrier by holding moisture where it’s needed. Regular and liberal use of moisturisers is vital for people with eczema prone skin.[9]

Filling in the gaps

The recent discovery of the filaggrin gene mutation and its link to eczema has revealed a new piece to the puzzle, but the fact that not all people with eczema have this mutation means there’s still something we’re missing. We know that ceramides are key players in the skin barrier so it’s possible there are other genetic factors that affect ceramide production just waiting to be discovered.

References

  1. Stanway A. Atopic dermatitis | DermNet NZ [Internet]. DermNet NZ2004 [cited 2019 Apr 17];Available from: https://www.dermnetnz.org/topics/atopic-dermatitis/
  2. Margolis DJ, Apter AJ, Gupta J, Hoffstad O, Papadopoulos M, Campbell LE, et al. The persistence of atopic dermatitis and filaggrin (FLG) mutations in a US longitudinal cohort. J Allergy Clin Immunol 2012;130(4):912–7.
  3. Yosipovitch G. Dry skin and impairment of barrier function associated with itch – new insights. Int J Cosmet Sci 2004;26(1):1–7.
  4. Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol 1998;78(1):27–30.
  5. Kezic S, Kemperman PMJH, Koster ES, Jongh CM de, Thio HB, Campbell LE, et al. Loss-of-Function Mutations in the Filaggrin Gene Lead to Reduced Level of Natural Moisturizing Factor in the Stratum Corneum. J Invest Dermatol 2008;128(8):2117–9.
  6. Jungersted JM, Agner T. Eczema and ceramides: an update. Contact Dermatitis 2013;69(2):65–71.
  7. Jungersted JM, Scheer H, Mempel M, Baurecht H, Cifuentes L, Høgh JK, et al. Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema. Allergy 2010;65(7):911–8.
  8. Homey B, Steinhoff M, Ruzicka T, Leung DYM. Cytokines and chemokines orchestrate atopic skin inflammation. J Allergy Clin Immunol 2006;118(1):178–89.
  9. Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol 2018;32(5):657–82.

Questions & Answers

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How do I reduce or remove dark spots on my skin ?

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I have recently had an actinic keratosis removed and am now desperately want to get my skin protection right…any advice please?

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