Mortality in adult patients with chronic spontaneous urticaria: A real-world cohort study

Background: Chronic spontaneous urticaria (CSU), a common and debilitating disease, is widely held not to be life limiting, but the mortality of CSU has not been investigated. Objective: We sought to assess all-cause mortality in patients with CSU, risk for comorbidities that are leading causes of death, and impact of guideline-recommended urticaria treatments on mortality rates. Methods: This was a retrospective population-based cohort study of electronic health records of 272,190 adult patients with CSU and 12,728,913 controls without urticaria from the US collaborative network TriNetX. Results: The study included 264,680 propensity score–matched patients with CSU (mean [SD] age = 47.5 [19.8] years; 71.5% female) and a corresponding number of controls without urticaria. Patients with CSU had higher 3-month (hazard ratio [HR] 2.10, 95% CI 1.97-2.22), 1-year (HR 1.77, 95% CI 1.71-1.83), and 5-year (HR 1.69, 95% CI 1.65-1.73) all-cause mortality (all P < .0001). Compared with controls, patients with CSU exhibited higher risk and rates of the leading causes of death in the United States, including suicidal ideations/suicide attempts (HR 3.14, 95% CI 3.00-3.28) and malignant neoplasms (HR 2.09, 95% CI 2.02-2.16). The risk of mortality appeared to be more pronounced in White and younger patients with CSU. All-cause mortality rates at 5 years were significantly lower in patients treated with second-generation H₁ antihistamines versus untreated patients (1.0% vs 2.3%; HR 1.84, P < .0001) and omalizumab-treated patients versus antihistamine-treated patients (0.7% vs 2.6%; HR 3.99, P = .0003). Conclusions: CSU is associated with increased mortality likely due to comorbidities, especially suicide, and effective CSU treatment may reduce mortality. These findings should be investigated in additional studies and in other populations.