Moderate-to-severe chronic spontaneous urticaria is associated with increased risk of immune-mediated diseases: A population-based study

Smart K, Ure A, Johnsen N, Aflatooni S et al. PLoS One. 2026 Sep 23;21(9):e0358883. doi: 10.1371/journal.pone.0358883.

Abstract

Forest plot showing odds ratios (ORs) and 95% confidence
intervals for immune-mediated comorbidities among patients
with chronic spontaneous urticaria (CSU).

Chronic spontaneous urticaria (CSU) is characterized by the idiopathic appearance of wheals and/or angioedema lasting more than six weeks. There is a critical need to evaluate whether the severity of CSU influences the risk of future immune-mediated comorbidities. We aim to evaluate if patients with moderate-to-severe chronic spontaneous urticaria (CSU) have an increased risk of developing immune-mediated comorbidities compared with matched patients with mild CSU.

We conducted a retrospective cohort study using the TriNetX US Collaborative Network database from 2014–2026. We propensity matched patients with ≥2 ICD-10 diagnoses of idiopathic urticaria treated with omalizumab, dupilumab, or cyclosporine (moderate-to-severe disease) to age-, sex-, race-, ethnicity-, comorbidity-, and family history-matched counterparts who were never treated with biologics or cyclosporine (mild disease). After matching, 16,413 patients were included in the moderate-to-severe group, and 16,413 patients were included in the mild group. Patients with moderate-to-severe CSU had a significantly increased risk of developing rheumatoid arthritis OR=1.34 (95% CI: 1.12 to 1.60, p = 0.001) and Sjögren’s syndrome OR=1.04 (1.63–2.56, p < 0.0001), after adjusting for clinical factors and multiple hypothesis testing (Bonferroni’s alpha ≤0.00333). Moderate-to-severe CSU is associated with an increased risk of rheumatoid arthritis and Sjögren’s syndrome compared to mild CSU.

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