Research suggests that early-, mid-, and late-onset pediatric AD may be clinically distinct disease subtypes and that age of onset could be used to risk stratify patients.
The disease course of atopic dermatitis in children can vary significantly according to the timing of its onset, and now research published in the Journal of the American Academy of Dermatology has suggested that early-, mid-, and late-onset pediatric AD may be clinically distinct disease subtypes and that age of onset could be used to risk stratify patients.1
The study used data from the Pediatric Eczema Elective Registry (PEER), which was set up to evaluate the post-marketing malignancy risk associated with pimecrolimus (Elidel, Novartis), a topical calcineurin inhibitor for treating mild-to-moderate atopic dermatitis. Patients included in the study enrolled between November 2004 and September 2018 at a median age of 6.6 years.
Researchers collected patient information on demographics, atopic dermatitis disease and treatment history, including the age of disease onset, on enrollment. Patients or their caregivers were surveyed about atopic disease control and treatment use every six months for up to 10 years.
While previous studies in British and Dutch children showed similar results for any atopic dermatitis activity,2,3 this study also evaluated the level of disease control.
A total of 8,015 patients (53.3% were female) were included in the study for which data on 41,934 person-years of follow-up were available. This data came from 70,841 follow-up surveys - an average of 8.8 surveys per patient. The median age of atopic dermatitis onset was 0.75 years; 5,770 (72.0%) children were classified as having early-onset with the condition beginning before two years of age; 1,492 (18.6%) children were classified has having mid-onset, with the condition beginning between two and eight years of age; and 712 (8.9%) children were classified as having late-onset atopic dermatitis.
Patients with mid- and late-onset atopic dermatitis were more likely to have good or complete disease control at the time of enrolment, while those with early-onset disease were more likely to have limited control or uncontrolled disease.
For each additional year of age at disease onset, the adjusted odds ratio (aOR) for poorer control was 0.93, meaning a child whose atopic dermatitis began at age 10 had a 44% lower odds of worse control over time compared to one whose atopic dermatitis began at age 2.
While complete control was more likely to be reported in patients of increasing age in all groups, it was more likely to be reported in the late-onset group than in the mid-onset and early-onset groups, and differences were most distinct in the second and third decades of life.
The odds of persistent atopic dermatitis was significantly lower for each additional year of age at onset (adjusted odds ratio 0.84). A child whose atopic dermatitis began at age 10 years, therefore, had a 75% lower odds of persistent disease over time compared to one whose condition began at age two years.
“Earlier onset atopic dermatitis was associated with worse disease control and greater persistence over time, independent of sociodemographic characteristics and atopic comorbidities,” Joy Wan, M.D., department of dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, says. “Our findings suggest that atopic dermatitis onset age differentiates clinically distinct forms of the disease.”
In all three groups, the proportion of subjects reporting persistent atopic dermatitis generally declined with older age, and differences among the three onset groups were most pronounced from early adolescence onward, with a subset of patients with early-onset atopic dermatitis experiencing disease resolution, she adds.
“In our early-onset group, a continuous decline in reports of persistent atopic dermatitis occurs in early childhood and nadirs at age 13, likely reflecting those individuals whose atopic dermatitis resolved,” Dr. Wan says.
Previous studies have shown that earlier onset atopic dermatitis is associated with a greater risk for asthma, allergic rhinitis, and food allergies as well as the presence of genetic risk variants for atopic dermatitis, which suggests that the timing of atopic dermatitis onset is driven, in part, by genetics and is associated with not only atopic dermatitis severity and persistence but also atopic burden overall.
“From a clinical perspective, the age of atopic dermatitis onset may be helpful for risk stratifying and counselling patients about their expected disease course. Although more precise subtypes of atopic dermatitis may be identified by combining clinical, genetic, and biomarker data, a simple approach to atopic dermatitis sub-classification remains clinically useful,” Dr. Wan says.
“The timing of disease onset is normally assessed as part of the clinical history for patients with atopic dermatitis while genetic and laboratory tests are not routinely performed. By considering the framework of early-onset or late-onset disease, we can identify those patients at greater risk for persistent or poorly controlled atopic dermatitis and whom may benefit from more intensive treatment or monitoring,” she says.
1. Wan J, Mitra N, Hoffstad OJ, Yan AC, Margolis DJ. Longitudinal atopic dermatitis control and persistence vary with timing of disease onset in children: a cohort study. J Am Acad Dermatol. 2019.
2 Lee E, Lee SH, Kwon JW, et al. Atopic dermatitis phenotype with early onset and high serum IL-13 is linked to the new development of bronchial hyperresponsiveness in school children. Allergy. 2016;71(5):692-700.
3 Seo E, Yoon J, Jung S, Lee J, Lee BH, Yu J. Phenotypes of atopic dermatitis identified by cluster analysis in early childhood. J Dermatol. 2019;46(2):117-123.