Asthma and food allergies associated with early-onset AD

Children with early-onset atopic dermatitis (AD) have an increased risk of developing asthma and food allergies by age 6 years, especially those with persistent dermatitis symptoms. This is a key finding of a recently published study that looked at whether subtypes of AD in children are associated with greater risk of developing other allergic diseases.¹

The study identified 4 phenotypes of AD depending on the onset and course of the disease. Two of these phenotypes, those associated with early-transient and early-persistent AD, were found to place children at greatest risk of developing respiratory allergy and food allergy. Children with early persistent disease were at the highest risk.

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According to Bernard A. Cohen, MD, professor of Pediatrics and of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, the findings of the study confirm what previously published data² already support, namely, that “kids with earlier onset, more severe, and persistent AD are more likely to develop other atopic phenomena.”

Here is a closer look at the study.

PASTURE study

Designed to assess the risk and preventive factors for atopic diseases, the Protection Against Allergy Study in Rural Environments (PASTURE) is a birth cohort study that includes children from rural areas in Austria, Finland, France, Germany, and Switzerland. Between August 2002 and March 2005, pregnant women during their pregnancies were recruited to participate in the study.

The women were divided into 2 groups: the farm group (women who lived on family-run farms with livestock) and the reference group (women in the same rural areas not living on a farm).

The study included 1038 children from this cohort of women with data on AD from birth to age 6 years. Of these children, 495 (47.7%) were children from women in the farm group and 543 (52.3%) were children from the reference (or nonfarm) group. Of these children, 551 (53.4%) had at least 1 parent with a history of allergies.

To identify different phenotypes of AD and whether some are related to a greater risk of developing other allergic diseases, the investigators used a statistical method called the latent class analysis (LCA) to first identify phenotypes of AD. Using LCA, the investigators identified 4 phenotypes (Table 1).

Among the children in the study, 96 (9.2%) had early-transient phenotype, 67 (6.5%) had early-persistent phenotype, 50 (4.8%) had late phenotype, and 825 (79.5) had never/ infrequent phenotype.

Looking at whether exposure during pregnancy or during the first year of life was associated with the identified phenotypes, the investigators found a strong association between early phenotypes (particularly the early-persistent phenotype) in children with a parent with a history of allergies. The study found that if both parents had a history of allergy, the child had a nearly 6-fold increased risk of developing early-persistent AD compared with children with parents that had no history of allergies.

However, prenatal exposure to an increased number of different farm animals showed a protective effect against developing all phenotypes of AD. In addition, a negative association with developing the early-persistent phenotype of AD was found in children exposed to pets, such as cats and dogs. In particular, this protective benefit was seen in children with at least 1 parent with a history of allergies.

Prior data also has shown the protective benefit of early life exposure to furry pets,³ which, says Cohen, may be the “American equivalent of farm animals.”

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“The lower risk of AD and other atopic phenomena in kids whose mothers were exposed to farm animals during pregnancy supports data generated regarding the hygiene hypothesis,” Cohen says. “Kids exposed to animal poop in the first year of life and share their microbiome with parents and friends are less likely to develop features of the atopic march.”

When looking at whether the phenotypes were associated with other allergic diseases, the study found that early-onset phenotypes were associated with other allergic diseases compared with children with the never/infrequent phenotype (Table 2).

The investigators highlight that these data indicate that both early-transient and early-persistent phenotypes are positively associated with other allergies, with a stronger association with the early-persistent phenotype. In particular, the investigators highlight that the data show a strong association between early phenotypes of AD and the development of food allergies. In addition, the data show that children with both asthma and allergic rhinitis are at the highest risk of developing respiratory allergy.

Take-home message

A key take-home message for clinicians, according to the investigators, is to pay special attention to children with early-onset and early-persistent AD to help prevent the development of respiratory and food allergies in these high-risk children.

“Children with early phenotypes, especially with persistent symptoms, have an increased risk of developing other allergic diseases, and having additional food allergy substantially increases this risk,” state the investigators.

Saying that these findings suggest ways for developing future prevention strategies, such as using precision medicine approaches, the investigators also provide a simple strategy suggested by data showing the benefit of introducing yogurt into the diet during the first year of life.

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“One simple strategy could be based on diet, such as recommendation of introduction of yogurt in first year of life,” state the investigators. The study found that yogurt introduced in the first year of life in children decreased the risk of developing early-onset and early-persistent AD.

However, Cohen emphasizes that data are mixed on the benefit of probiotic exposure and to date do “not support the use of yogurt in at-risk children.”⁴

REFERENCES

1. Roduit C, Frei R, Depner M, et al. Phenotypes of atopic dermatitis depending on the timing of onset and progression in childhood. JAMA Pediatr. 2017;171(7):655-662.

2. Kantor R, Silverberg JI. Environmental risk factors and their role in the management of atopic dermatitis. Expert Rev Clin Immunol. 2017;13(1):15-26.

3. Flohr C, Yeo L. Atopic dermatitis and the hygiene hypothesis revisited. Curr Probl Dermatol. 2011;41:1-34.

4. van der Aa LB, Heymans HS, van Aalderen WM. Sprikkelman AB. Probiotics and prebiotics in atopic dermatitis: review of the theoretical background and clinical evidence. Pediatr Allergy Immunol. 2010;21(2 pt 2):e355-e36.