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Peer-reviewedCC BY 4.0PLOS One

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

  • Kimberly Smart1
  • Andrea Ure2
  • Nicole Johnsen3
  • Shaliz Aflatooni4
  • Julian A. Cortes5
  • Gabriela Palma6
  • Yvonne Nong7
  • Andrea J. Borba
  • Paul C. Levins
  • April W. Armstrong
7 affiliations
  1. 1Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
  2. 2University of California, Davis School of Medicine, Sacramento, California, United States of America
  3. 3David Geffen School of Medicine at the University of California, Los Angeles, California, United States of America
  4. 4USF Morsani College of Medicine, Tampa, Florida, United States of America
  5. 5University of California, San Diego School of Medicine, San Diego, California, United States of America
  6. 6Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York, United States of America
  7. 7Division of Dermatology, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California, United States of America
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Abstract

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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Cite

BibTeXRIS
BibTeX
@article{smart2026moderatetosevere,
  title = {{Moderate-to-severe chronic spontaneous urticaria is associated with increased risk of immune-mediated diseases: A population-based study}},
  author = {Kimberly Smart and Andrea Ure and Nicole Johnsen and Shaliz Aflatooni and Julian A. Cortes and Gabriela Palma and Yvonne Nong and Andrea J. Borba and Paul C. Levins and April W. Armstrong},
  journal = {PLOS One},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pone.0358883},
  url = {https://doi.org/10.1371/journal.pone.0358883},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Moderate-to-severe chronic spontaneous urticaria is associated with increased risk of immune-mediated diseases: A population-based study
AU  - Kimberly Smart
AU  - Andrea Ure
AU  - Nicole Johnsen
AU  - Shaliz Aflatooni
AU  - Julian A. Cortes
AU  - Gabriela Palma
AU  - Yvonne Nong
AU  - Andrea J. Borba
AU  - Paul C. Levins
AU  - April W. Armstrong
PY  - 2026
DA  - 2026/09/23
JO  - PLOS One
DO  - 10.1371/journal.pone.0358883
UR  - https://doi.org/10.1371/journal.pone.0358883
AB  - 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.
SN  - 1932-6203
ER  -