Atopic dermatitis phenotypes may indicate outcomes

Children under two years old with signs of atopic dermatitis have an increased risk of developing asthma and food allergies, researchers report in JAMA Pediatrics. Once the food allergy sets in, the risk of developing asthma or allergic rhinitis heightens.

“This finding is of great importance because atopic dermatitis and food allergies are diseases appearing often in early childhood. The hypothesis is that children with atopic dermatitis are more prone to develop sensitization to food allergens owing to a defect of skin barrier among those children,” wrote researchers who were led by Caroline Roduit, M.D., of the University of Zurich in Switzerland.

The study, of 1,038 children from farm (47.7%) and other rural regions of Austria, Finland, France, Germany and Switzerland, describes four distinct clinical phenotypes for atopic dermatitis that are characterized by age of onset and the natural course of disease from birth to 6 years. The end-result was two early onset phenotypes (by age two years with persistent progression) and a late phenotype with onset after 24 months of age. The fourth phenotype included asymptomatic patients.

Atopic dermatitis affects more than 20 percent of children in industrialized countries and for more than 60 percent of these children, the condition is apparent by 24 months. Most children outgrow atopic dermatitis, but for others, it can linger into adulthood leading to eczema, food allergies, hay fever and asthma. In 2015, researchers questioned whether this “atopic march” could instead be explained by different subgroups depending on disease onset and the natural course of the disease.

“Children developing those diseases in early life might require special attention for prevention strategies of respiratory allergy,” researchers wrote. “It would be important to find immunologic markers for these clinical phenotypes of atopic dermatitis because it was suggested that among atopic children, there are different immunological phenotypes.”

THE PHENOTYPES

The four phenotypes that were identifed include:

• Early-transient with onset by 2 years old with resolution by 4 years old (n = 96, 9.2%).

• Early-persistent with onset by 2 years old persisting through 6 years old (n = 67; 6.5%).

• Late-onset with onset after 2 years old (n = 50; 4.8%).

• Never/infrequent phenotype (n = 825; 79.5%).

The prevalence of asthma and food allergy by six years old was increased in children with early phenotypes manifesting by two years, especially among children with persistent symptoms.

The number of children with the late phenotype who had asthma and food allergy “is even less than that observed for the never/infrequent phenotype. Yet, the study reports an association between the late phenotype and sensitization to food allergens at six years of age. This late phenotype appears to have unique molecular/immune features that are lacking in the other phenotypes, particularly in the early-persistent phenotype, which followed the atopic march as we would expect,” said Kanwaljit Brar, M.D., an assistant professor of pediatrics at National Jewish Health in Denver who reviewed the study for Dermatology Times.

See the related slideshow, "Atopic dermatitis phenotypes."

For children who developed atopic dermatitis after two years old, researchers identified an association with allergic rhinitis, but not asthma or food allergies.

“The onset of atopic dermatitis after the age of two had a unique lack of association with other allergic diseases. There was no asthma or food allergy association with the late phenotype of atopic dermatitis compared to the other three phenotypes,” Dr. Brar said.

Dr. Brar“This could have implications for the development of other diseases because the early-persistent type was the phenotype with the highest association to three other allergic diseases:  Asthma, food allergy and allergic rhinitis,” she said.

Having a family history of allergy was associated with all atopic dermatitis phenotypes, but especially for those with the early persistent phenotype. Children of parents with a history of allergies (53.4% of children in the study) were five to six times more likely to develop early persistent atopic dermatitis as compared to children whose parents did not have a history of allergies. And, parents with allergic rhinitis, asthma and atopic dermatitis were more likely to have children who developed atopic dermatitis by two years.

The study suggests that both “genetic and environmental factors influence the course of atopic dermatitis differently depending on the phenotype.”

Dr. Roduit and colleagues found that the introduction of yogurt during an infant’s first 12 months proved to be a protective factor against the early-persistent atopic dermatitis phenotype.

NEXT: Exposure to animals

EXPOSURE TO ANIMALS

Using the same study population, a previous study by Dr. Roduit and colleagues showed that prenatal exposure to farm animals was associated with a lower risk of atopic dermatitis. The new study showed that prenatal exposure to farm animals tended to protect against the development of all atopic dermatitis phenotypes.

But for household pets, that protective effect of prenatal exposure was seen only in children with the early persistent phenotype, specifically, among children with allergic parents.

For children who have a parent with a history of allergy, prenatal exposure to both a dog and a cat was found to be negatively associated with the early-persistent phenotype. This was surprising, Dr. Brar said, “because we typically think of cat allergies as being particularly bad due to the small molecular size and buoyancy of the allergen.”

STRENGTHS AND LIMITATIONS

Strengths of the study included its large birth cohort and its length:  Data was collected prospectively from birth to school age, which allowed researchers to use latent class analysis (LCA) to identify disease phenotypes by onset and progression. Also, SCORAD (Scoring atopic dermatitis) was performed to corroborate phenotype data in the study sample.

The study had some limitations. It did not focus on biomarkers which may have helped distinguish phenotypes, Dr. Brar said. Additionally, asthma and food allergies were diagnosed based on the parental report of a physician diagnosis.  “Food allergies were not verified by an observed food challenge, which is the gold standard for diagnosis, Dr. Brar said.

“We should expect to see more studies examining the relationship between atopic dermatitis and food allergy with a focus on prevention strategies such as the Learning Early About Peanut Allergy (LEAP) guidelines,” Dr. Brar says.

The study’s findings may not be generalizable to all populations because the study included data on only children from rural regions of Europe.

REFERENCE

Roduit C, Frei R, Depner M, et al. “Phenotypes of atopic dermatitis depending on the timing of onset and progression in childhood,” JAMA Pediatrics. July 1, 2017.  DOI:10.1001/jamapediatrics.2017.0556 Online at:  bit.ly/2k8Ki9g