Infusion of Pituitary Adenylate Cyclase–Activating Polypeptide-38 in Patients with Rosacea Induces Flushing and Facial Edema that Can Be Attenuated by Sumatriptan
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- 1-s2.0-S0022202X21001196-main
Forlagets udgivne version, 1,75 MB, PDF-dokument
Background: The pathogenesis of rosacea is incompletely understood. Signaling neuropeptides, including PACAP, a regulator of vasodilation and edema, are upregulated in rosacea skin. Here, we evaluated PACAP38-induced rosacea features and examined whether a 5-HT1B/1D receptor agonist could reduce these features. Methods: A total of 35 patients with erythematotelangiectatic rosacea received an intravenous infusion of 10 pmol/kg/minute of PACAP38 followed by an intravenous infusion of 4 mg sumatriptan or placebo (saline) on two study days in a double-blind, randomized, placebo-controlled, and cross-over trial. Results: PACAP38 increased facial skin blood flow by 90%, dilated the superficial temporal artery by 56%, and induced prolonged flushing and facial edema. Compared with placebo, sumatriptan reduced PACAP38-induced facial skin blood flow for 50 minutes (P = 0.023), constricted the superficial temporal artery for 80 minutes (P = 0.010), and reduced duration of flushing (P = 0.001) and facial edema (P < 0.001). Conclusions: We established a clinical experimental model of rosacea features and showed that sumatriptan was able to attenuate PACAP38-induced rosacea flushing and edema. Findings support a key role of PACAP38 in rosacea flushing pathogenesis. It remains unknown whether PACAP38 inhibition can improve rosacea. Trial register: The trial was registered at ClinicalTrials.gov NCT03878784 in March 2019.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Investigative Dermatology |
| Vol/bind | 141 |
| Udgave nummer | 7 |
| Sider (fra-til) | 1687-1698 |
| Antal sider | 12 |
| ISSN | 0022-202X |
| DOI | |
| Status | Udgivet - jul. 2021 |
Bibliografisk note
Funding Information:
This study was supported unconditionally by Novo Nordisk Foundation, Denmark (NNF170C0029698) and Augustinus Foundation, Denmark (17-2523). We especially want to thank all patients that volunteered for this study. We would also like to thank medical students Ingrid Marie Furberg and Nanna Bov? for helping with analysis of thermal images, Anne Luise Haulund Vollesen and Thien Phu Do for helping with blinding in the study, and laboratory technicians Winnie Gr?nning (Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark) and Lene Elkj?r (Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, University of Copenhagen) for expert assistance. MA had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of data analysis. Conceptualization: NKFW, CEC, AE, JPT, MA; Data Curation: NKFW, CEC, MA; Formal Analysis: NKFW, CEC, MA; Funding Acquisition: NKFW, MA; Investigation: NKFW, HC, DGZ; Methodology: NKFW, CEC, AE, JPT, MA; Project Administration: NKFW, MA; Resources: NKFW, CEC, AE, JPT, MA; Software: NKFW, CEC, MA; Supervision: CEC, AE, JPT, MA; Validation: NKFW, HG, CEC, MA; Visualization: NKFW, CEC, MA; Writing - Original Draft Preparation: NKFW, CEC, MA; Writing - Review and Editing: NKFW, CEC, HC, DGZ, HG, AE, JPT, MA
Publisher Copyright:
© 2021 The Authors
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 285800886