Worsening Severity of AD in Children Associated With Increased Comorbidity Onset Risk

This article was originally published by Contemporary Pediatrics®. It has been lightly edited.

In addition to an association between the worsening severity of atopic dermatitis (AD) and an increased risk of comorbidity onset, children with AD have an increased risk of developing multiple comorbid conditions, according to a study published in the Journal of The European Academy of Dermatology & Venereology.

AD presents a substantial clinical burden for children. Consequently, investigators in Sweden sought to assess the clinical burden of disease in children with AD compared to children without AD by comparing time to onset of a variety of comorbidities via a population-based, nationwide cohort study.

According to the study authors, a growing amount of data supports AD as a systemic disease, potentially linked to comorbid conditions via inflammation or shared risk factors. Previous observational studies evaluating the clinical burden of AD are not complete regarding comorbidity assessment, potentially causing suboptimal treatment.

The study featured children aged younger than 18 years with AD, identified between 2007 and 2017. The inclusion period ended on December 31, 2017, with a follow-up to December 31, 2018. The AD cohort was matched at a 1:1 ratio with replacement to non-AD individuals (non-AD reference cohort).

The study evaluated the time to first diagnosis for a variety of comorbid conditions in both the AD cohort and the non-AD reference cohort. All patients were classified with either mild to moderate (M2M) or severe AD at the start of follow-up.

The researchers noted that they analyzed a number of conditions individually, including hypersensitivity and allergic disorders, psychiatric disorders, neurological disorders, infections, immunological and inflammatory disorders, type 1 diabetes (T1D), type 2 diabetes (T2D), ocular disorders, skeletal disorders, and malignancies.

“Descriptive statistics were computed for patients at risk, stratified by severity and compared with the non-AD reference cohort as mean and standard deviation (SD) for continuous variables and number and percentage for categorical variables," the authors wrote.

Cumulative incidence curves, forest plots, and analysis using Cox proportional hazards models displayed the association between time to the start of a clinically managed condition and the presence of AD.

Child with AD

Image credit: Марина Терехова - stock.adobe.com

There were 165,145 patients in the AD cohort, of which 120,684 (73%) were classified with M2M disease (mean age, 4.64 years; 47.25% females) and 44,461 (27%) were classified with severe AD (mean age, 7.52 years; 48.01% females).

At baseline, the greatest differences in the prevalence of conditions were observed for hypersensitivity, allergic disorders, and infections, all of which were higher in the AD cohort compared to the non-AD reference cohort.

In the AD cohort, less than 20% of patients used systemic treatments during follow-up, while approximately 50% of these patients received their first systemic treatments before age 7.

Of patients in the AD cohort, 36.6% developed at least 1 comorbidity amid follow-up compared to 28.5% in the non-AD reference cohort, and “of those patients who developed at least [1] comorbidity, 27.1% and 19.7% developed multiple comorbidities (≥2) in the AD cohort and the non-AD reference cohort, respectively.”

Hypersensitivity and allergic disorders were the most common comorbidities as they occurred in 18.55% of patients in the AD cohort (95% CI, 18.31-18.80) and 10.03% of patients in the non-AD reference cohort (95% CI, 9.88-10.18).

Infections were the second most common comorbidities in the AD cohort, occurring in 18.35% (95% CI, 18.12-18.59) of patients in the AD cohort and 5.29% (95% CI, 5.18-5.41) in the non-AD reference cohort.

The third most common comorbidity between groups was skeletal disorders, occurring in 13.20% (95% CI, 13.02-13.39) of patients in the AD cohort and 9.65% (95% CI, 9.51-9.80) of the non-AD reference cohort.

Compared with the reference cohort, patients with AD displayed a higher risk of developing comorbid conditions for all investigated categories other than T1D and skeletal disorders.

Also, compared to the reference group, the highest risk was observed for hypersensitivity and allergic disorders (hazard ratio [HR], 3.87), which was followed by malignancies (HR, 2.53) and immunological and inflammatory disorders (HR, 2.36).

Comorbidity onset increased with AD severity, and those with AD had a higher risk of developing multiple comorbidities. Compared to patients in remission, the investigators concluded that those with active AD were associated with an increased comorbidity risk.

Reference:

Kobyletzki L, Henrohn D, Ballardini N, et al. Comorbidities in childhood atopic dermatitis: A population‐based study. Acad Dermatol Venereol. 2023:jdv.19569. doi:10.1111/jdv.19569