Abstract / Summary
Background: Atopic dermatitis (AD) is generally considered polygenic but may occur as a predominant manifestation of inborn errors of immunity (IEI). Although dupilumab is effective in pediatric AD, evidence in IEI-associated severe atopic skin disease remains limited, with no longitudinal comparative studies available. We aimed to characterize clinical phenotype and compare effectiveness, quality-of-life, and safety of dupilumab in pediatric patients with severe polygenic AD and IEI-associated severe atopic skin disease.
Methods: This multicenter retrospective observational study within the Italian Society of Pediatric Research Network included children and adolescents who initiated dupilumab before 18 years of age. Given IEI rarity, we accepted a numerically unbalanced but clinically meaningful cohort. Clinical outcomes were assessed longitudinally using EASI, pruritus NRS, and CDLQI scores. Achievement and maintenance of EASI-50/75/90 re-sponses were evaluated, together with adverse events and treatment discontinuation.
Results: Among 127 patients, 116 had polygenic AD and 11 had IEI-associated disease. IEI patients more frequently had disease onset within 6 months (64% vs. 29%; p=0.037), severe recurrent infections (100% vs. 0%; p< 0.001), very elevated sIgE (91% vs. 14%; p< 0.001), and higher baseline EASI (median 50 vs. 25; p< 0.001). EASI, pruritus, and CDLQI improved significantly over time. EASI-50/75/90 were achieved by 88.2%/81.9%/66.1% and maintained by 84.3%/69.3%/47.2%. IEI patients showed steeper EASI decline but achieved EASI-75/90 later. Dupilumab was well tolerated with no unexpected safety signals.
Conclusions: Dupilumab provided rapid, sustained improvement across both groups. Despite greater baseline severity and slower deep clearance achievement, IEI patients demonstrated substantial durable benefit, supporting dupilumab use in selected IEI-associated atopic manifestations.