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

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.