Risk of Incident Venous Thromboembolism Among Patients With Bullous Pemphigoid or Pemphigus Vulgaris: A Nationwide Cohort Study With Meta-Analysis

Abstract

Background Bullous pemphigoid (BP) and pemphigus vulgaris (PV) share similar pathophysiology with venous thromboembolism (VTE) involving platelet activation, immune dysregulation, and systemic inflammation. Nevertheless, their associations have not been well established. Methods and Results To examine the risk of incident VTE among patients with BP or PV, we performed a nationwide cohort study using Taiwan's National Health Insurance Research Database and enrolled 12 162 adults with BP or PV and 12 162 controls. A Cox regression model considering stabilized inverse probability weighting was used to calculate the hazard ratios (HRs) for incident VTE associated with BP or PV. To consolidate the findings, a meta-analysis that incorporated results from the present cohort study with previous literature was also conducted. Compared with controls, patients with BP or PV had an increased risk for incident VTE (HR, 1.87 [95% CI, 1.55-2.26]; P<0.001). The incidence of VTE was 6.47 and 2.20 per 1000 person-years in the BP and PV cohorts, respectively. The risk for incident VTE significantly increased among patients with BP (HR, 1.85 [95% CI, 1.52-2.24]; P<0.001) and PV (HR, 1.99 [95% CI, 1.02-3.91]; P=0.04). In the meta-analysis of 8 studies including ours, BP and PV were associated with an increased risk for incident VTE (pooled relative risk, 2.17 [95% CI, 1.82-2.62]; P<0.001). Conclusions BP and PV are associated with an increased risk for VTE. Preventive approaches and cardiovascular evaluation should be considered particularly for patients with BP or PV with concomitant risk factors such as hospitalization or immobilization.

Keywords: bullous pemphigoid; cohort study; meta‐analysis; pemphigus vulgaris; systematic review; venous thromboembolism.

Figure 1. Cumulative incidence curves for venous thromboembolism in the overall, bullous pemphigoid, and pemphigus vulgaris cohorts.

BP indicates bullous pemphigoid; and PV, pemphigus vulgaris.

Figure 2. Forest plots of the meta‐analysis.

The meta‐analysis illustrated a significant association of bullous pemphigoid or pemphigus vulgaris with venous thromboembolism, deep vein thrombosis, and pulmonary embolism. IV indicates inverse variance; and VTE, venous thromboembolism.