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. 2025 Mar 17;317(1):575.
doi: 10.1007/s00403-025-04090-5.

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

Giuseppina Caiazzo #  1 , Maddalena Napolitano #  2 , Maria Quaranta  2 , Vincenzo Picone  3 , Gabriella Fabbrocini  2 , Cataldo Patruno  4
Affiliations

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

Giuseppina Caiazzo et al. Arch Dermatol Res. .

Abstract

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.

Keywords: Atopic dermatitis; Dupilumab; Elderly; Endotype; Phenotype.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study has been approved by ethics committee of University of Naples Federico II and Informed consent was obtained from all individual participants involved in the study (N26/21). Consent for publication: This manuscript contains original unpublished work and is not being submitted for publication elsewhere. Competing interests: Napolitano M. acted as speaker, consultant and advisory board member for Sanofi, Abbvie, Leo Pharma; Patruno C. acted as investigator, speaker, consultant, and advisory board member for AbbVie, Eli Lilly, Novartis, Pfizer and Sanofi: Caiazzo G., Picone V., Quaranta M. have nothing to disclose. Disclosures: Napolitano M. acted as speaker, consultant and advisory board member for Sanofi, Abbvie, Leo Pharma; Patruno C. acted as investigator, speaker, consultant, and advisory board member for AbbVie, Eli Lilly, Novartis, Pfizer and Sanofi: Caiazzo G., Picone V., Quaranta M. have nothing to disclose. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Figures

Fig. 1
Fig. 1
Gene expression profile of patients with phenotype non-flexural. Interleukin (IL)-13, IL-4, IL-31,IL-22, periostin, CXCL1 and IL-17 A, gene expression in skin of healthy subjects (HS), and in lesional (LES) and nonlesional (NLES) skin at baseline (W0) and after 52 weeks of dupilumab (W52). Values are normalized to the housekeeping gene 18 S and expressed as mean ± SD. Statistical significance was assessed using Mann–Whitney test
Fig. 2
Fig. 2
Gene expression profile of patients with phenotype flexural. Interleukin (IL)-13, IL-4, IL-31,IL-22, periostin, CXCL1 and IL-17 A, gene expression in skin of healthy subjects (HS), and in lesional (LES) and nonlesional (NLES) skin at baseline (W0) and after 52 weeks of dupilumab (W52). Values are normalized to the housekeeping gene 18 S and expressed as mean ± SD. Statistical significance was assessed using Mann–Whitney test
Fig. 3
Fig. 3
Immunofluorescence analysis in non flexural phenotype group of patients. IL-17, IL-22 IL-13, IL-4 and periostin cutaneous protein expression in lesional skin at W0 and W52 by immunofluorescence assay. Cell nuclei are counterstained with DAPI (blue). Magnification 20X
Fig. 4
Fig. 4
Protein levels of patients with e non-flexural (a) and flexural (b) phenotype. Interleukin (IL)-13, IL-4, IL-31, IL-17 A, IL-22 and CXCL1 circulating levels at W0 and W52 assessed by ELISA
See this image and copyright information in PMC

References

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