The skin barrier is the outermost layer of the skin, the stratum corneum: flattened cells set in a matrix of ceramides, cholesterol and free fatty acids that holds water in and keeps irritants out. In eczema that matrix is built wrong and the cells set in it are often short of filaggrin, so the barrier leaks before any immune response begins.
What the skin barrier is
The stratum corneum is made of flattened dead cells called corneocytes, held together by a lipid mixture filling the spaces between them. Dermatologists call it bricks and mortar: corneocytes the bricks, lipids the mortar.
The same structure does two jobs. It holds water in, measured as transepidermal water loss, and keeps irritants, allergens and microorganisms out. A barrier that leaks water also lets things through.
The mortar is a mixture, and the proportions matter
Three lipid classes make up the mortar: ceramides, cholesterol and free fatty acids (Janssens et al, 2012). None builds a working barrier alone, which is why a product can contain a genuine barrier lipid and still do very little.
Man and colleagues tested that in 1996, tracking recovery in damaged skin under different lipid combinations. One or two of the three delayed recovery. An equimolar mixture of all three restored the normal rate, and repair ran faster still when one lipid was raised up to threefold above the others. The work was murine, and "preliminary results were obtained in damaged human skin" (Man et al, 1996). Elias, Man and Darmstadt gave the 2022 version: a 3:1:1 molar ratio accelerates recovery, and an unbalanced mixture aggravates the defect it was meant to fix. The measured numbers, and how to read a label, are in ceramides and eczema.
What goes wrong in eczema
The best understood cause is a loss-of-function variant in FLG, the gene for filaggrin. Filaggrin bundles keratin filaments so corneocytes flatten into a tight overlapping layer, then breaks down into urocanic acid, pyrrolidone carboxylic acid and other small molecules that make up much of natural moisturising factor and keep the surface acidic. Between 20 and 40% of European and Asian patients with moderate to severe eczema carry an FLG variant, and carriers showed higher water loss than healthy controls, with stratum corneum pH raised in those carrying two variants (Winge et al, 2011).
The second defect is in the mortar. Janssens and colleagues found shorter ceramides in eczema-prone skin: more very short chains, fewer very long ones, a reduced average chain length. The shift appeared in skin that looked unaffected, and regardless of FLG status, so it is a separate mechanism, not a consequence of filaggrin loss. The skin is making ceramides but not finishing them.
Both defects push surface pH upward, which is not cosmetic. Elias and colleagues note that keeping surface pH below 5 attenuates the development of atopic dermatitis, and that a lower pH raises production of the skin's antimicrobial peptides (Elias et al, 2022).
Is eczema an autoimmune disease?
Not in the strict sense, and the distinction is more than pedantry. An autoimmune disease is one in which the immune system attacks the body's own healthy tissue. In type 1 diabetes the target is the insulin-producing cells of the pancreas. In rheumatoid arthritis it is the synovial membrane of the joints. In both, the immune system has produced antibodies or immune cells aimed at self-tissue.
Eczema does not work that way. The inflammation is real, but it is not directed at your own cells. It is a response to what comes through the gap described above: allergens, irritants and microorganisms crossing a barrier that should have kept them out. The more accurate label is an immune-mediated inflammatory disease with a primary barrier defect. The response that follows is Th2-biased, driven by the cytokines IL-4, IL-13 and IL-31, the last of which acts on nerve endings and accounts for much of the itch.
That immune bias runs in families, which is why eczema rarely arrives on its own. It sits in the atopic triad alongside asthma and allergic rhinitis. Many people with eczema have one or both of the other two, or close relatives who do. The shared thread is a tendency towards Th2 responses and IgE-mediated reactions to environmental allergens, not an attack on the self.
The picture is not perfectly clean. Auto-antibodies have been found in a subset of people with long-standing eczema. Whether they drive anything, or are a by-product of years of chronic inflammation, is not yet settled, and no treatment decision currently turns on the answer.
What does follow from the classification is an order of operations. Barrier repair comes first, because the barrier defect comes first. Topical steroids and the newer biologics act on the immune response, which is the consequence rather than the cause.
Why this matters for treatment
Emollient therapy is the layer everything else sits on, and NHS advice for atopic eczema is to apply emollients "as often as possible (at least 2 times a day)". Topical steroids reduce inflammation but do not rebuild the mortar. They suppress the response, and while the barrier stays permeable the triggers keep arriving and inflammation returns when the steroid stops. Starting that emollient routine at birth, before any eczema exists, is a different proposition: a large UK trial tested it in high-risk babies and did not find the prevention everyone expected (emollient in the first year).
What damages the barrier further
Hot water strips lipids from the matrix. Soap removes lipids and pushes the surface away from the acidity filaggrin breakdown products maintain. Fragrance is a direct irritant. Wool and synthetic fabrics cause friction that disrupts the surface layer. Low humidity accelerates transepidermal water loss, which is why eczema typically worsens in winter.
How to support barrier repair
Timing first. Apply emollient in the minutes after washing, while the skin is still damp and the lipids have just been stripped.
Composition second. Ceramides alongside cholesterol and a fatty acid source match the mixture that repaired barriers in Man's work; ceramides on their own are the incomplete kind. The trial evidence, covered in the ceramides post, supports regular use rather than any one formulation, so texture and tolerability are reasonable grounds for choosing and a large price premium is not.
Occlusion third, for badly broken skin. Covering emollient with a damp layer holds water against the stratum corneum for hours rather than minutes, the principle behind wet wrap therapy and the reason it is reserved for severe flares.
References
- Man MQ, Feingold KR, Thornfeldt CR, Elias PM. Optimization of physiological lipid mixtures for barrier repair. Journal of Investigative Dermatology, 1996, 106:1096-1101. https://hero.epa.gov/reference/7012768/
- Elias PM, Man MQ, Darmstadt GL. Optimised emollient mixture for skin barrier repair: applications to global child health. Journal of Global Health, 2022. https://jogh.org/2022/jogh-12-03019
- Janssens M, van Smeden J, Gooris GS, et al. Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients. Journal of Lipid Research, 2012, 53:2755-2766. https://pmc.ncbi.nlm.nih.gov/articles/PMC3494247/
- Winge MCG, Hoppe T, Berne B, et al. Filaggrin genotype determines functional and molecular alterations in skin of patients with atopic dermatitis and ichthyosis vulgaris. PLoS One, 2011, 6:e28254. https://pmc.ncbi.nlm.nih.gov/articles/PMC3229525/
- NHS. Atopic eczema. https://www.nhs.uk/conditions/atopic-eczema/