Phenotype-endotype relationship in elderly atopic dermatitis and effects of dupilumab therapy: prospective study.

Atopic dermatitis is a chronic inflammatory systemic disease that can persist or start in adulthood, even in elderly age, with several clinical phenotypes. The aim of this study was to evaluate the relationship between phenotype and endotype in elderly patients, and the long-term effects of dupilumab on molecular signature in these patients. A total of 50 elderly patients had been treated with dupilumab during the follow up period. Regarding effectiveness parameters, mean EASI score at Week 0 was 25.12 ± 4.23 and significantly reduced to 2.42 ± 3.15 at Week 52 (p < 0.05). Regarding safety, none of the registered adverse events led to the discontinuation of dupilumab therapy. Moreover, after 52 weeks of dupilumab treatment, Th2 cytokines expression was decreased, with IL-13 and IL-31 downregulated in both patient groups at Week 52, at both gene and protein levels when compared with Week 0. Our data also revealed a significant increase in both IL-4 gene expression and protein production at Week 52 when compared with Week 0. Unexpectedly, our results also revealed that IL-22 cutaneous expression was significantly increased, while circulating levels were decreased at Week 52 when compared to Week 0. In conclusion, our results highlight the effectiveness of dupilumab at a late time point as Week 52. Of note, a dumping of the Th2- and Th17- immune response at both systemic and in situ level and a possible remodelling role of IL-22 in the skin is suggested.