Atopic comorbidities associated with chronic spontaneous urticaria: a case-control analysis of the All of Us research program

Cortes JA, Adjei-Frimpong NA, Fakhouri SK, Delacqua F, Oldenburg R. JEADV Clin Prac. Published online October 8, 2025. doi:10.1002/jvc2.70181

ABSTRACT

Background

Chronic spontaneous urticaria (CSU) is a mast cell-driven condition defined by recurrent wheals and/or angioedema lasting over 6 weeks without an identifiable trigger. Though CSU is known to co-occur with atopic diseases and share Th2-dominant immunologic pathways, prior studies have not adequately addressed these relationships in diverse populations.

Objectives

To examine associations between CSU and atopic comorbidities in the All of Us (AoU) research program, a diverse, nationwide National Institutes of Health cohort focused on increasing enrollment from historically underrepresented groups.

Methods

We conducted a matched, case-control study of AoU participants aged ≧ 18 years enrolled between May 6, 2018 and October 1, 2023. CSU cases were identified using SNOMED codes 51611005 and 42265009. Controls were matched 4:1 by age, sex, race, ethnicity, and smoking status.

We compared rates of atopic dermatitis, allergic rhinitis, asthma, nasal polyps, food allergy, and drug allergy. Multivariable logistic regression adjusted for hypothyroidism, systemic lupus erythematosus, and rheumatoid arthritis given known associations with CSU.

Results

Multivariable analysis controlling for hypothyroidism,
systemic lupus erythematosus, and rheumatoid
arthritis.

We identified 1171 CSU cases and 4684 matched controls with no significant demographic differences. CSU patients had significantly higher rates of atopic dermatitis (12.6% vs. 1.7%, p < 0.001), allergic rhinitis (58% vs. 13.2%, p < 0.001), asthma (46.2% vs. 13.2%, p < 0.001), nasal polyps (3.8% vs. 0.7%, p < 0.001), and food and drug allergies (p < 0.001). These associations persisted after multivariable adjustment (p < 0.001).

Conclusions

This study demonstrates a strong association between CSU and atopic disease in a racially and socioeconomically diverse cohort. Our findings highlight shared Th2-driven pathways underlying CSU and atopy and reinforce the potential utility of type 2 targeted therapies (e.g., dupilumab) in patients with CSU and comorbid atopic disease. Clinicians should screen CSU patients for atopic disease to help guide comprehensive, targeted therapy.

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