In the previous report, I explained that a food elimination diet is not wholly effective in prevention of food allergies. Then, how do food allergies develop? Recent studies have revealed that eczema and atopic dermatitis are closely related to the onset of food allergies in infants. In the case of infants, the onset of atopic dermatitis generally occurs before the onset of food allergies.

According to a UK study targeting 619 babies who were three months old and completely breast-fed, it was revealed that there was a high sensitization rate to food allergens (egg, cow's milk, and peanut) in those with atopic dermatitis. Moreover, increased severity of eczema is associated with a higher sensitization rate.

Furthermore, according to our prospective birth cohort study (neonatal follow-up research) conducted at the National Center for Child Health and Development, infants who had developed eczema by 12 months of age had a higher risk of developing food allergies at three years of age ¹. More precisely, and interestingly, it was revealed that infants who developed eczema during the first 1-2 months after birth had the highest risk of developing food allergies.

These findings from epidemiology studies indicate that children who developed atopic dermatitis during early infancy have a higher risk of developing food allergies. Moreover, if there is a high degree of eczema severity, the onset of food allergies is more likely. Then, the next question is, why do children with atopic dermatitis have a higher risk of developing food allergies? The answer is the "primary function of the skin."

The skin serves as a barrier function that separates the body from its external environment. This protects the body from external irritant substances and keeps the bodily fluids within the body. In addition, immune cells in the skin detect and attempt to eliminate foreign substances (such as bacteria and viruses), which may enter the body through a cut or other similar channels. Atopic dermatitis/eczema impairs the skin's barrier function, and as a result, allergens (foreign proteins that cause allergies) can enter the body through the skin. When immune cells in the skin identify allergens as dangerous, they will produce IgE antibodies to counter these "enemies" (epicutaneous sensitization). Once IgE antibodies are produced, they will bind together immediately if the same allergens enter the body a second time and counter them. This is called "allergic reaction."

Common allergens include foodstuffs, dust mites, pet dander/hair, molds, and pollens. Dr. Gideon Lack et al. in the UK first proposed food allergen sensitization (epicutaneous sensitization) through an impaired skin barrier. They conducted a research survey targeting children who had developed a peanut allergy. According to the survey, children who developed eczema by six months of age have a higher risk of developing a peanut allergy. In particular, children who have been subjected to skin preparations containing peanut oil have a significantly higher risk ².

Another survey reported that the amount of peanut protein in house dust is related to an increased risk of peanut sensitization in children. There are various kinds of food components to be found inside the home environment, reflecting the foodstuffs consumed by each family.

In addition, according to a research survey in Japan targeting 94 children aged three years, egg protein was identified in all dust samples collected from the bedsheets of target children at the time of home visits. The proportion of egg protein was significantly higher than the proportion of dust mite protein ³.

Food allergens found inside the home environment can vary, depending on the foodstuffs consumed by the family, cooking methods, the type of food protein, and other factors. The type of foods responsible for food allergies is different according to country and region, reflecting the differences in food cultures.

Then, why do children develop atopic dermatitis during their early infancy stage, which may cause food allergies later? According to some studies, one of the factors that cause atopic dermatitis is a filaggrin gene defect. Filaggrin is a protein that plays a key role in the skin barrier function. Filaggrin gene defects may bring about a shortage of natural moisturizing factors and increase the risk of atopic dermatitis onset ⁴. Furthermore, it is revealed that, for children who developed atopic dermatitis, although no filaggrin gene defect was found, their skin barrier function was more likely to be impaired at two days of age for some reasons.

Based on these findings, it was assumed that such an innate impairment of the skin barrier function, which may cause the onset of atopic dermatitis, can be resolved by adequate treatments during early infancy. To verify this assumption, a randomized controlled trial (RCT) was conducted. This can provide a high level of evidence, to verify the effects of moisturizing care starting from the neonatal stage in preventing the onset of atopic dermatitis ⁵.

In this trial, we randomly assigned 118 infants within the first week of life to two groups. They were born at the National Center for Child Health and Development and had a family history of atopic dermatitis (i.e., high-risk infants). For those infants assigned to an intervention group, a moisturizer was applied to their entire body surface after bathing, on a daily basis. For those assigned to a control group, Vaseline was applied only to dry skin areas as necessary. We compared the cumulative incidence rates of atopic eczema in these two groups during the first 32 weeks of life.

The results show that the percentage of infants who had itchy eczema for more than two weeks and were diagnosed with atopic dermatitis by dermatologists was 47.5% in the control group and 32.2% in the intervention group. There was a significant difference between the two groups: those in the intervention group were approximately 30% fewer than those in the control group. This proves our assumption that the application of moisturizing agents from the neonatal stage can reduce the risk of developing atopic dermatitis.

Another RCT was conducted by researchers from the UK and the US targeting 124 high-risk infants. In this study, a full-body emollient therapy was applied to infants assigned to the intervention group starting within three weeks of birth, while no therapy was applied to infants assigned to the control group. As a result, the cumulative incidence of atopic dermatitis in those infants in the intervention group was significantly lower than that of those infants in the control group at six months of age (relative risk: 0.5; 95% confidence interval: 0.28-0.90) ⁶.

With regard to the prevention of egg white sensitization in our study, however, no effect of moisturizing care starting from the neonatal stage was confirmed in the intervention group.

According to an observation study, more patients who developed atopic dermatitis had a higher risk of developing food allergies if the period between the onset of atopic dermatitis and the commencement of therapy was longer. This is probably because the development of epicutaneous sensitization is more likely to occur when eczema continues over a longer period of time.

A multi-institution study is currently under way to verify the hypothesis that effective therapy for atopic dermatitis beginning in early infancy can prevent the onset of food allergies (the PACI Study) ⁷. It is expected that new findings that can contribute to the prevention of food allergies will be released from Japan. Please watch for future information.

References Cited

• 1. Shoda T, Futamura M, Yang L, Yamamoto-Hanada K, Narita M, Saito H, et al. Timing of eczema onset and risk of food allergy at 3 years of age: A hospital-based prospective birth cohort study. Journal of Dermatological Science 2016;84:144-8.
• 2. Lack G, Fox D, Northstone K, Golding J, Avon Longitudinal Study of P, Children Study T. Factors associated with the development of peanut allergy in childhood. N Engl J Med 2003;348:977-85.
• 3. Kitazawa H, Yamamoto-Hanada K, Saito-Abe M, Ayabe T, Mezawa H, Ishitsuka K, et al. Egg antigen was more abundant than mite antigen in children's bedding: Findings of the pilot study of the Japan Environment and Children's Study (JECS). Allergology International 2019;68:391-3.
• 4. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature genetics 2006;38:441-6.
• 5. Horimukai K, Morita K, Narita M, Kondo M, Kitazawa H, Nozaki M, et al. Application of moisturizer to neonates prevents development of atopic dermatitis. J Allergy Clin Immunol 2014;134:824-30 e6.
• 6. Simpson EL, Chalmers JR, Hanifin JM, Thomas KS, Cork MJ, McLean WH, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol 2014;134:818-23.
• 7. Yamamoto-Hanada K, Kobayashi T, Williams HC, Mikami M, Saito-Abe M, Morita K, et al. Early aggressive intervention for infantile atopic dermatitis to prevent development of food allergy: a multicenter, investigator-blinded, randomized, parallel group controlled trial (PACI Study)-protocol for a randomized controlled trial. Clin Transl Allergy 2018;8:47.