Increased cardiovascular risks and mortality in prurigo nodularis: a global cohort study

Henning Olbrich; Khalaf Kridin; Gema Hernández; Henner Zirpel; Christian D Sadik; Patrick Terheyden; Diamant Thaçi; Ralf J Ludwig; Katharina Boch

doi:10.1016/j.ebiom.2024.105123

Increased cardiovascular risks and mortality in prurigo nodularis: a global cohort study

EBioMedicine. 2024 Apr 16:103:105123. doi: 10.1016/j.ebiom.2024.105123. Online ahead of print.

Authors

Henning Olbrich¹, Khalaf Kridin², Gema Hernández³, Henner Zirpel⁴, Christian D Sadik⁵, Patrick Terheyden⁵, Diamant Thaçi⁴, Ralf J Ludwig⁶, Katharina Boch⁷

Affiliations

¹ Department of Dermatology, University of Lübeck, Lübeck, Germany. Electronic address: henning.olbrich@uksh.de.
² Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel; Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
³ TriNetX, LLC, Cambridge, MA, USA.
⁴ Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lübeck, Germany.
⁵ Department of Dermatology, University of Lübeck, Lübeck, Germany.
⁶ Department of Dermatology, University of Lübeck, Lübeck, Germany; Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel; Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lübeck, Germany.
⁷ Department of Dermatology, University of Kiel, Kiel, Germany.

Abstract

Background: Prurigo nodularis (PN) presents with intensely itchy hard nodules. Despite being limited to the skin, PN was noted to be associated with systemic diseases including diabetes and chronic renal failure. In previous smaller retrospective studies, several cardiac and vascular diseases were found more frequently in patients with PN. However, small cohort sizes, partially discrepant outcomes, missing data, and incomplete risk assessment limit these findings.

Methods: Electronic health records (EHR)s of 64,801 patients (59.44% females) with PN and an equal sized propensity-matched control group were retrieved. In these cohorts, the risks to develop cardiac and vascular diseases and mortality following the diagnosis of PN were determined. Sub-analyses included stratification for sex, ethnicity, and treatments.

Findings: PN was associated with a higher risk for a broad range of acute cardiac events including heart failure and myocardial infarction. For example, the hazard ratio of myocardial infarction was 1.11 (95%-CI: 1.041-1.184, p = 0.0015) following PN diagnosis. Also, all-cause mortality was higher in patients with PN. Further, chronic vascular as well as structural heart diseases, e.g., peripheral arterial disease, chronic ischaemic heart disease and valval disorders were found more frequently following a PN diagnosis. Risks were more pronounced in white and female patients. Having established an increased risk for death and cardiovascular disease, we next addressed if dupilumab that has been recently licenced for use in this indication can modulate these risks. The risk of death but not of any cardiovascular disease was slightly reduced in patients with PN treated with dupilumab as opposed to those treated with systemic therapies other than dupilumab. The study is limited by retrospective data collection and reliance on ICD10-disease classification.

Interpretation: PN is associated with higher mortality and an increased risk for the development of a wide range of cardiac and vascular diseases. Health care professionals should take this into account when managing patients with PN.

Funding: This work was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft and the State of Schleswig-Holstein.

Keywords: Cardiovascular disease; Mortality; Myocardial infarction; Prurigo nodularis; Stroke; TriNetX.