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Allergic sensitization, the role of the skin barrier
- 10min
- May. 2022
- Supported by
The traditional view of allergy holds that sensitization occurs at the site of symptoms: skin allergies are triggered through skin contact, food allergies are triggered by ingesting the offending substance and respiratory allergies are triggered via inhalation. This model is strongly challenged today.
The skin, a major route to all types of allergy
Already in 2003, a clinical study conducted in a cohort of 13,971 preschool children showed that the use of skin preparations containing peanut oil (e.g. diaper rash creams) increased the risk of peanut allergy by 6.8-fold vs no use.1
Later, studies using mouse model of allergy suggested that the skin may be a relevant source of allergen sensitization.
- Cutaneous exposure generates the highest levels of allergen-specific IgE, compared with gut, sublingual, nasal or cutaneous routes.2
- Intestinal food allergy is shown to be dependent on basophils infiltration of the skin, leading to antigen-specific Th2 cytokine responses.3
As it has been suggested that the skin may serve as a site for sensitization to allergens even when allergic skin inflammation is absent, it is proposed today that it may be an important site in the initiation of the atopic march.4
Impaired skin barrier function, a key part of the process
When this critical barrier is disrupted, allergens pass into the dermis and come in contact with the immune cells of this skin, and this contact can cause sensitization.
For reasons that are complex and not yet fully elucidated, the immune cells may overreact, treating the allergen as a harmful substance and triggering the production of allergen-reactive cells in the lymph nodes.
The strength and the integrity of the stratum corneum, as well as the cutaneous permeability regulation, are mainly driven by filaggrin (FLG). FLG null mutations are responsible of an impairment of the skin barrier function allowing antigen to penetrate and promoting water evaporation.5
They are also strongly associated with risk for atopic dermatitis (AD), for food allergies and asthma.4
Clinically speaking, increased allergy risk is linked to skin barrier impairment as showed in infants with or without clinical symptoms of atopic dermatitis but with an increased trans-epidermal water loss (TEWL), a marker of skin barrier defects.6,7
And, of course, an impaired skin barrier as it exists in atopic dermatitis increases the risk of food allergy, for example risk of peanut allergy, which incidence was found to be 2-fold higher in children with AD (incidence), and even more so when AD is severe.8
Adults can also become sensitized via the skin:
- Risk of developing allergic rhinitis increased in adults with eczema exposed to mice.9
- Allergy to wheat protein in foods induced by wheat-containing skin products in adults.10
Protect or restore the skin barrier function by emollients: a chance to prevent skin sensitization
In a context where allergy prevention is shifting from allergen avoidance to tolerance, emollients could provide protection from environmental factors by improving the skin barrier function.11
Emollients provide lipids to the stratum corneum, which in turn, improves skin hydration by trapping water.11,12
This skin barrier enhancement prevents skin dryness and cracking, as well as inhibiting irritant and allergen penetration into the epidermis, which are potential initiators of skin inflammation.12
Emollients have been found to correct subclinical skin barrier dysfunction and early inflammation in predisposed infants before atopic dermatitis development by improving skin hydration and reducing skin permeability.12
This early skin protection with emollients could help slow the allergic march by preventing sensitization and associated food allergy, asthma or allergic rhinitis.13
Bibliography
- Lack G., Fox D., Northstone K., et al. Factors associated with the development of peanut allergy in childhood. N EnglJ Med. 2003;348(11):977-85.
Link to abstract - Dunkin D, Berin C., Mayer L. Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner. J Allergy Clin Immunol. 2011;128(6):1251-1258.e2.
Link to full publication - Noti M., Kim B.S., Siracusa M.C., et al. Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis. J Allergy Clin Immunol. 2014;133(5):1390-9, 1399.e1-6.
Link to full publication - Han H.H., Roan F., Ziegler S.F. The atopic march: current insights into skin barrier dysfunction and epithelial cell-derived cytokines. ImmunolRev. 2017;278(1):116-30.
Link to full publication - Brough H.A., Simpson A., Makinson K., et al. Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations. J Allergy Clin Immunol. 2014;134(4):867-875.e1.
Link to full publication - Kelleher M.M., Dunn-Galvin A., Gray C., et al. Skin barrier impairment at birth predicts food allergy at 2 years of age. J Allergy Clin Immunol. 2016;137(4):1111-1116.e8.
- Kelleher M.M., Dunn-Galvin A., Horihane J.O’B., et al. Skin barrier dysfunction measured by trans epidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year. J Allergy Clin Immunol.2015;135:930-5.
Link to full publication - Brough H.A., Liu A.H., Sicherer S., et al. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy. J Allergy Clin Immunol. 2015;135(1):164-70.
Link to full publication - Grant T., Dantzer J., Keet C., et al. Physician-diagnosed eczema is an independent risk factor for incident mouse skin test sensitization in adults. Allergy Asthma Proc. 2018;39(4):311-5.
Link to full publication - Yokooji T., Kurihara S., Murakami T., et al. Characterization of causative allergens for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat proteins in facial soap. Allergol Int. 2013;62(4):435-45.
Link to full publication - Chalmers J.R., Haines R.H., Mitchell E.J., et al. Effectiveness and cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children (The BEEP trial): protocol for a randomized controlled trial. Trials. 2017;18(1):343.
Link to full publication - Simpson E.L., Chalmers J.R., Hanifin J.M., et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy ClinImmunol. 2014;134(4):818-23.
Link to full publication - Natsume O., Ohya Y. Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction. Allergol Int. 2018;67(1):24-31.