Inflammation Marker May Spot Atopic Dermatitis Risk Early in Childhood

Elevated levels of an inflammation marker in the skin during infancy doubled the likelihood that a child would develop atopic dermatitis by age 2 years, a prospective study in newborns showed.

The hazard ratio (HR) for atopic dermatitis at age 2 was 2.11 among children who had elevated levels of thymus and activation related chemokine (TARC) at 2 months. The HR increased almost five-fold in children who had moderate-to-severe atopic dermatitis at age 2. The association was more pronounced in children born at normal term but also was elevated in preterm children.

Elevated levels of interleukin (IL)-8 and IL-18 at 2 months also predicted an increased risk of atopic dermatitis by 2 years, reported Anne-Sofie Halling, MD, of Bispebjerg Hospital and the University of Copenhagen in Denmark, at the European Academy of Dermatology and Venereology (EADV) congress in Milan.

"It appears that the immune biomarker TARC plays an important role prior to any signs of atopic dermatitis," Halling said during a pre-meeting EADV press briefing. "This is actually in line with studies on active atopic dermatitis, as it is well recognized that TARC currently represents the best biomarker in patients with established atopic dermatitis."

"Importantly, we were able to predict atopic dermatitis occurring months after collection, which suggests that skin changes preceding atopic dermatitis could be instructional early in life," she added. "Hopefully, these findings will help identify children at the highest risk of atopic dermatitis in the future so preventive strategies can target these children early and decrease the incidence of this common disease, which so many children are suffering from."

The findings are stimulating, particularly the difference observed between children born at term and those who were born preterm, said press briefing moderator Dedee Murrell, MD, of the University of New South Wales in Sydney.

"Do you think [the difference] has anything to do with how infants are taken care of in the hospital, or some other reason?" she asked.

Newborns probably have some sort of maternal protection at birth and might require several months of exposure to the environment outside the hospital before the factors that influence the risk of atopic dermatitis come into play, said Halling.

Atopic dermatitis has a prevalence of 15%-20%, and the condition usually emerges early in life. Involving a combination of skin-barrier dysfunction and immune dysregulation, the condition persists into adulthood in about 50% of cases, Halling noted. The substantial physical, emotional, and social burden of atopic dermatitis has sparked considerable interest in prevention strategies, which have shown limited promise to date.

"Instead of using these strategies on all children, it is of high relevance to identify predictive biomarkers of atopic dermatitis so future strategies can target children with increased risk of developing atopic dermatitis and thereby improve the chances of preventing this disease," she said.

The investigators conducted a study to determine whether skin biomarkers can predict the risk of atopic dermatitis during the first 2 years of life. They enrolled 300 children born at term and 150 preterm children. At birth and at 2 months, each child had a skin examination, which included use of tape strips to remove samples of dead epidermal cells for biomarker analysis. Follow-up continued for 2 years.

The results showed that 34.6% of the term-birth children developed atopic dermatitis by 2 years as compared with 21.2% of the preterm children. Median time to onset of atopic dermatitis was 6 months in the term-birth group and 8 months in the preterm group. Median Eczema Area and Severity Index score (on 0-6 scale; 0=no active eczema in a region of the body) was 4.1 in the term-birth group and 1.6 in the preterm group.

Substantially more children in the term-birth group had moderate-to-severe atopic dermatitis (23.3% vs 8.0%), whereas twice as many preterm children had almost clear skin status (12.0% vs 6.0%).

The tape-strip results obtained at birth showed no association between any immune biomarker and subsequent development of atopic dermatitis. Among term-birth children, the 2-month results revealed a significant association between elevated TARC and atopic dermatitis at 2 years (95% CI 1.36-3.26, P=0.0008). After adjustment, the hazard remained significantly elevated (HR 1.85, 95% 1.18-2.89, P=0.007). An analysis of time to atopic dermatitis diagnosis showed an association with elevated TARC at all timepoints.

When investigators limited the analysis to children with moderate-to-severe atopic dermatitis, elevated TARC at 2 months was associated with a 4.97 atopic dermatitis hazard, decreasing slightly to 4.65 in an adjusted analysis (95% CI 1.91-11.31, P=0.0007).

Analysis of preterm children showed a more modest association with TARC, which exhibited a trend toward statistical significance after adjustment (HR 2.60, 95% CI 0.98-6.85, P=0.05).

Among children born at term, elevated IL-8 at 2 months had a significant association with atopic dermatitis at 2 years in the adjusted analysis (HR 3.01, 95% CI 1.24-7.31, P=0.02), as did IL-18 (HR 2.86, 95% CI 1.17-6.98, P=0.02).

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