Pediatric patients with early-onset atopic dermatitis could be at significantly increased risk of developing pediatric uveitis, according to a new study.
Using data from the TriNetX Research Network, investigators analyzed de-identified records from more than 100,000 pediatric patients who were diagnosed with atopic dermatitis (AD) prior to age 2 between January 1, 2004, and December 14, 2024. They were matched 1:1 to controls. The average follow-up was 6 years in the AD cohort and 6.6 years in the control cohort.
Inclusion criteria for AD diagnosis required at least one follow-up claim within 1 year and prescription of standard AD treatments, such as oral antihistamines, topical corticosteroids, or topical calcineurin inhibitors. Patients with prior uveitis or specified infectious and autoimmune diseases were excluded.
Pediatric uveitis occurred in 0.08% of the AD cohort compared with 0.05% of the control group. The hazard ratio (HR) for developing uveitis in the AD group was 1.92, and the investigators found that the risk for iridocyclitis (anterior uveitis) was also elevated (HR = 2.09).
Patients with severe AD had a markedly higher risk of developing uveitis compared with those with nonsevere AD. Those with severe AD had 0.40% incidence (HR = 3.64), whereas those with nonsevere AD had 0.08% incidence. Severity was defined by the use of systemic immunosuppressive or biologic medications such as dupilumab, methotrexate, or upadacitinib within 1 year of diagnosis.
“[F]ollowing the introduction of dupilumab for AD treatment,” wrote lead study author Yung-Yu Chu, MD, of the Department of Ophthalmology at Chi Mei Medical Center in Tainan, Taiwan, and colleagues, “recent case reports have focused predominantly on dupilumab-associated uveitis. Studies have suggested that the underlying mechanism of dupilumab-associated uveitis may involve the upregulation of interferon gamma and the Th1 immune response, resulting from the inhibition of interleukin (IL)-4 and IL-13 signaling by dupilumab. Notably, these cases of uveitis typically resolved after discontinuation of dupilumab and/or treatment with local or systemic corticosteroids,” they added.
The investigators found that, after excluding dupilumab users, the AD group still had increased uveitis risk (HR = 1.77). Excluding those with autoimmune diseases yielded similar results (HR = 1.52). This finding, they explained, “indicat[ed] the risk is independent of dupilumab use.”
“Previous studies have identified elevated levels of inflammatory cytokines and eosinophil-derived cytotoxic major basic protein in the aqueous humor of patients with AD,” the study authors wrote. “Such inflammation may subsequently lead to uveitis, particularly in the anterior segment of the eye,” they continued. They further explained that this inflammation may explain why only the risk of iridocyclitis remained elevated across the primary, sensitivity, and AD severity analyses.
The investigators acknowledged that reliance on ICD-10 codes may have introduced misclassification bias, and that the retrospective design introduced other limitations. Some uveitis subtypes—such as retinal vasculitis, sympathetic uveitis, and panuveitis—were too rare for separate analysis. Larger studies are needed to both clarify the risks of uveitis subtypes in AD and to validate the overall findings of this research.
They concluded: “These findings support the potential need to consider ophthalmologic monitoring in [pediatric patients] with early-onset AD to try to detect and subsequently manage uveitis if it develops.”
No conflicts of interest were reported.
Source: JAMA Ophthalmology