CSU Linked With Significantly Higher Rates of Atopic Comorbidities

There is a strong association between chronic spontaneous urticaria (CSU) and a range of atopic diseases, according to a case-control study published in JEADV Clinical Practice.¹ The findings emphasize a shared Th2-driven immunologic pathway between CSU and atopic disorders, reinforcing the potential for type 2 inflammation–targeted therapies in comprehensive patient management.

CSU is a mast cell-driven condition characterized by recurring wheals or angioedema that lasts longer than 6 weeks without an identifiable trigger.² While prior literature has suggested a co-occurrence with atopic disorders, the new study sought to re-evaluate this link within a diverse, nationwide cohort.¹

“Despite the influence various environmental and demographic factors may have on the development and severity of atopic disorders, the relationship between CSU and atopic disease in diverse populations remains unclear,” the authors wrote. “Thus, there is a significant need in the dermatologic literature to re-evaluate the link between CSU and atopic comorbidities utilizing diverse cohorts.”

The study employed a matched, case-control design using data from the All of Us (AoU) program, a National Institutes of Health database including health data from across the US focusing on groups that are historically underrepresented in research. Participants were enrolled between May 2018 and October 2023, and the final analysis identified 1171 CSU cases and 4684 matched controls who were balanced for age, sex, race, ethnicity, and smoking status. The control group was then screened against the CSU group for rates of common atopic conditions, including allergic rhinitis, asthma, atopic dermatitis, nasal polyps, and food and drug allergies.

Patients with CSU had significantly higher rates of every atopic comorbidity studied when compared with controls. The most notable difference was observed in allergic rhinitis, which affected 58% of CSU cases compared with 13.2% of controls (P < .001). The prevalence of asthma was also significantly higher in the CSU group (46.2%) vs controls (13.2% [P < .001]), as was atopic dermatitis (12.6% vs 1.7% [P < .001]). Patients with CSU also experienced higher rates of nasal polyps (3.8% vs 0.7% [P = .001]) and food and drug allergies.

Multivariable logistic regression analyses were adjusted for 3 common autoimmune comorbidities: hypothyroidism, systemic lupus erythematosus, and rheumatoid arthritis. Even after adjustment, the significant association between CSU and all atopic comorbidities was persistent.

“These findings have important clinical implications,” the authors wrote. “Patients with CSU and atopic comorbidities may significantly benefit from more comprehensive management strategies that intervene on shared inflammatory intermediates.”

Study limitations included the retrospective design and reliance on accurate electronic health record documentation, as well as the potential that the cohort may not be fully representative of the US population despite efforts to include historically underrepresented populations.

Still, the documented overlap strengthens the hypothesis that CSU and atopic disorders share an immunological basis, marked by the upregulation of Th2 cytokines such as interleukin (IL)-4 and IL-13 signaling. This shared pathology suggests that patients with co-occurring CSU and atopic disease may significantly benefit from type 2–targeted therapies.

“This study elucidates a strong association between CSU and various atopic comorbidities within a diverse cohort of patients from across the United States,” the authors wrote. “Dermatologists should perform a thorough review of systems to identify potential targets for therapeutic intervention and optimize comprehensive patient care.”

References

1. Cortes JA, Adjei-Frimpong NA, Fakhouri SK, Delacqua F, Oldenburg R. Atopic comorbidities associated with chronic spontaneous urticaria: a case-control analysis of the All of Us research program. JEADV Clin Prac. Published online October 8, 2025. doi:10.1002/jvc2.70181

2. Lang DM. Chronic Urticaria. N Engl J Med. 2022;387(9):824-831. doi:10.1056/NEJMra2120166