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

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.

Fig. 1

Hazard ratios (HR) for (a) mortality endpoints; major adverse cardiovascular events (MACE) include myocardial infarction, stroke, cardiogenic shock, cardiac arrest and congestive heart failure, (b) acute atheromatous events, (c) vascular diseases and (d) structural cardiac diseases are shown comparing patients with prurigo nodularis with controls. Bars show mean hazard ratios ±95%-confidence interval. ∗p < 0.003125 (Log-rank test). (e) Kaplan-Meyer curves showing survival probabilities regarding mortality and MACE (f) over time for patients with PN (blue) and controls (black). n = 64,801 per group.

Fig. 2

Hazard ratios (HR) for (a) mortality endpoints (MACE, major adverse cardiovascular events), (b) acute atheromatous events, (c) vascular diseases and (d) structural cardiac diseases are shown comparing either prurigo nodularis patients with skin of colour (blue symbols) or white (black symbols) patients with prurigo nodularis with matched controls. Bars show mean hazard ratios ±95%-confidence interval. ∗p < 0.003125 (Log-rank test). n = 13,612 per group.

Fig. 3

Hazard ratios (HR) for (a) mortality endpoints (MACE, major adverse cardiovascular events), (b) acute atheromatous events, (c) vascular diseases and (d) structural cardiac diseases are shown comparing either male (blue symbols) or female (black symbols patients with prurigo nodularis with matched controls. Bars show mean hazard ratios ±95%-confidence interval. ∗p < 0.003125 (Log-rank test). n = 38,250 per group.

Fig. 4

Hazard ratios (HR) for (a) mortality endpoints (MACE, major adverse cardiovascular events), (b) acute atheromatous events, (c) vascular diseases and (d) structural cardiac diseases are shown comparing patients with prurigo nodularis treated with standard therapies but not dupilumab with patients treated with dupilumab. Bars show mean hazard ratios ±95%-confidence interval. ∗p < 0.003125 (Log-rank test). (e) Kaplan-Meyer curves showing survival probabilities regarding mortality over time for patients with prurigo nodularis treated with dupilumab (blue) or only with other approved medications (black, see Supplementary Table S1 for a list of included drugs). (f) Frequency of the number of dupilumab injections registered in the dupilumab-treated group; dotted line shows mean value (8.086), median: 3 injections. n = 1454 per group.

Supplementary Fig. S1

Supplementary Fig. S2