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Transcutaneous Sensitization: The Real Skinny on Food-based Emollients and Skincare Products

By Rishabh Lohray, BS, and Peter A. Lio, MD

Introduction

The introduction of food proteins into the gastrointestinal tract early in life has been shown to induce tolerance and thus decrease the incidence of at least some food allergies. At the same time, there is convincing evidence that transcutaneous passage of food antigens through the skin, especially compromised skin, has the opposite effect and can result in a higher rate of sensitization. As such, children with atopic dermatitis (AD) are thought to be more susceptible to food allergies due to the transfer of allergens through their broken skin barrier. This theory has been tested in a few studies which have found that transcutaneous sensitization (TS) can occur in AD and, importantly, that aggressive management of AD can reduce the risk of developing food allergies in children.1-4

Historically, many natural products have been applied to the skin, some of which are also ingested as part of the diet. Common additives to numerous moisturizers, cleansers, and other cosmetic products include foods such as oat, wheat, sunflower, and coconut, causing concern for potential transcutaneous sensitization. This paper will examine the current research on transcutaneous sensitization and provide an overview of the evidence on using food-based emollients and skin-care products.

Mechanisms Behind Transcutaneous Sensitization

The two key immune mediators of TS are Thymic Stromal Lymphopoietin (TSLP) and interleukin(IL)-332,5,6. TSLP is a known activator of Langerhans cells which then promote T-cell activation and differentiation.2,7,8Children with AD have higher levels of TSLP in their stratum corneum.9 TSLP is also increased when food allergens are introduced to the skin.10 Similarly IL-33 is also increased in children with AD and it plays an important role in activating dendritic cells and driving IL-5, IL-13, and IgE production by polarized Th2 cells and B cells respectively.11 Like TSLP, IL-33 is also increased in the skin following transcutaneous ovalbumin sensitization.10, 12 Importantly, disruption of the skin barrier is not a requirement for inducing TS as studies have shown that peanut extract application on intact skin can cause a robust inflammatory response.13 Additionally, peanuts can cause bystander sensitization to other allergens: for example, when co-exposed to skin with peanut extract, milk can induce sensitization against milk proteins.13

The health of the skin microbiome can also determine the risk of TS. Factors such as vaginal birth, breastfeeding, outdoor activities, excessive antibiotic use, and ultra-sanitary lifestyles have all been implicated in the regulation of the microbiome and their relationship to atopy has been hypothesized.14 AD patients are known to have skin dysbiosis, and excessive staphylococcus aureus (S. aureus) colonization has been shown to affect disease severity. 15,16 The importance of the skin microbiome is further bolstered by a study that found skin bacteria transplantation from healthy individuals can decrease AD severity.17 Finally, high transepidermal water loss (TEWL) can also predispose to AD and TS. One study found that having a high TEWL (>9.3 g/m2/h) in the context of eczema and dry skin at 3 months was significantly associated with TS at 6 months.18

The Evidence on Food in Moisturizers

A population-based randomized clinical trial by Perkins et al found that there was a higher rate of food allergies and aeroallergen sensitization in those who moisturized more frequently in infancy.19 The most common food ingredient in these moisturizers was olive oil.19 Other foods included sunflower, almond, coconut, and vegetable oils.19 Another study found that application of peanut oil-based emollients to damaged skin in infancy is significantly associated with peanut allergy later in life.20 Interestingly, exposure to soy oils was also identified as a potential causal factor, likely secondary to cross-sensitization through similar epitopes.20 While oils can disrupt the barrier function of the skin and could potentially cause TS, it was unclear whether a significant portion of food-based products are indeed associated with a higher rate of TS in the cohort examined by Perkins et al.19,21

Oat (including oat starch, oat peptides, oatmeal, oat bran, oat kernel, and oat protein) and wheat (including wheat protein, wheat germ oil, wheat bran, wheat starch, and wheat gluten) are commonly used in a host of skin-care products due to their soothing, anti-inflammatory, and moisturizing properties.22 As observed in case reports, oat can trigger a type I or type IV hypersensitivity reaction in children with AD who were moisturized with oat-based emollients as infants.22-25. In a cohort of 302 patients with AD, 14.6% of the atopy patch tests and 9.2% of skin prick tests were positive for oat allergy.26 This was attributed to the application of oat-based cosmetics on an impaired skin barrier.26  Similarly, wheat-dependent exercise-induced anaphylaxis has been observed in those who used soap with hydrolyzed wheat protein.27-30

While there seems to be some evidence in the literature for TS to oat and wheat to warrant theoretical concern, practically it does not seem to be an issue for the vast majority of patients, especially given how commonly oat is added to products specifically designated for use in eczema. Irvine et. al reported that they surveyed all subjects in the STOP-AD trial and did not find a single patient with a significant reaction to oats despite a large percentage of the patients using oat-based products.31,32 They posit that peanut is likely a much more important sensitizer and is hence best avoided in skin care products for AD patients.32 Other oils like sunflower and almond oil have also been shown to be safe in independent cohorts of preterm infants, and they enhance the barrier function of the skin and can help in reducing nosocomial infections.33-35

Finally, an IgE-mediated reaction can not only be directed against epitopes on food but also towards similar epitopes on synthetic derivatives from food. One study examining the allergenicity and cross-reactivity of coconut oil derivatives found mildly significant cross-reactivity between those with an allergy to cocamidopropyl betaine (CABP–a coconut oil derivative) and TEA-PEG-3 cocamide sulfate (a coconut oil-derived surfactant).36 However, the study acknowledged that the reactions were doubtful and could be attributed to irritation.36 Despite the potential for cross-reaction with food derivatives, providers rarely screen for these in personal care products, which again suggests that the clinical risk of TS is low.

Finally, how can providers advise AD patients on which types of products to use? patients often face a deluge of marketing that adds to confusion with a host of products claiming to be “natural and safe.”  The word “natural” doesn’t necessarily mean good or safe. One study of Lithuanian skin-care products revealed that a third of products contained at least one well-known food allergen with almond, wheat, and soy being the most common culprits.37Products claiming to be “natural” and “ecological” were more likely to have food allergens in them.37 Another study done in Japan found that 4.3% of skin care products sold on Amazon in Japan have food allergens in them and most of them use language like “natural” and “organic” whereas products with terms like “hypoallergenic” attached to them were less likely to have food derivatives.38 However, as discussed, the risk of food-based products causing TS appears to be low. Additionally, many moisturizers are free from food-derived compounds and thus would be very safe choices in this regard.39

Conclusion

Despite conflicting viewpoints, the mentioned papers represent a valuable discussion on the use of food-based emollients. Coconut, wheat, sunflower, and oat-based products are commonly recommended for patients with compromised skin. Given that the risk of TS from these food-based or food-derived products is clinically very low, providers should feel comfortable suggesting these products to patients outside of those with existing allergies to the ingredients.

About the Authors

Rishabh Lohray is a fourth-year MD MBA candidate at Baylor College of Medicine and Rice University in Houston, TX.

Peter A. Lio, MD, is a Clinical Assistant Professor of Dermatology and Pediatrics at Northwestern University Feinberg School of Medicine and a partner at Medical Dermatology Associates of Chicago.

Disclosures:

Dr. Lio reports being on the speaker’s bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche-Posay/L’Oreal, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, Verrica; reports consulting/advisory boards for Alphyn Biologics (stock options), AbbVie, Almirall, Amyris, Arcutis, ASLAN, Bristol-Myers Squibb, Burt’s Bees, Castle Biosciences, Codex Labs (stock options), Concerto Biosci (stock options), Dermavant, Eli Lilly, Galderma, Janssen, LEO Pharma, Lipidor, L’Oreal, Merck, Micreos, MyOR Diagnostics, Regeneron/Sanofi Genzyme, Sibel Health, Skinfix, Suneco Technologies (stock options), Theraplex, UCB, Unilever, Verdant Scientific (stock options), Verrica, Yobee Care (stock options). In addition, Dr. Lio has a patent pending for a Theraplex product with royalties paid and is a Board member and Scientific Advisory Committee Member emeritus of the National Eczema Associati

Mr. Lohray has no relevant financial disclosures.

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